# Lippia javanica (Burm.f.) Spreng.: Traditional and Commercial Uses and Phytochemical and Pharmacological Significance in the African and Indian Subcontinent

Authors: Alfred Maroyi
Journal: Evidence-Based Complementary and Alternative Medicine
 (2017)

---

## Abstract

Lippia javanicaoccurs naturally in central, eastern, and southern Africa and has also been recorded in the tropical Indian subcontinent. The potential ofL. javanica as herbal or recreational tea and herbal medicine and its associated phytochemistry and biological properties are reviewed. The extensive literature survey revealed thatL. javanica is used as herbal tea and has ethnomedicinal applications such as in colds, cough, fever, malaria, wounds, diarrhoea, chest pains, bronchitis, and asthma. Multiple classes of phytochemicals including volatile and nonvolatile secondary metabolites such as alkaloids, amino acids, flavonoids, iridoids, and triterpenes as well as several minerals have been identified fromL. javanica. Scientific studies onL. javanica indicate that it has a wide range of pharmacological activities which include anticancer, antiamoebic, antidiabetic, antimalarial, antimicrobial, antioxidant, antiplasmodial, and pesticidal effects. Although many of the traditional uses ofL. javanica have been validated by phytochemical and pharmacological studies, there are still some gaps where current knowledge could be improved.Lippia javanicais popular as both herbal and recreational tea, but there is need for more precise studies to evaluate the safety and clinical value of its main active crude and pure compounds and to clarify their mechanisms of action.


---

## Body

## 1. Introduction

Lippia javanica(Burm.f.) Spreng. (Verbenaceae) (Figure 1(a)) has a long history of traditional uses in tropical Africa as indigenous herbal tea or tisane (Figure 1(b)), refreshing beverage, or food additive based on its perceived health and medicinal properties.Lippia javanicais rich in volatile oil, particularly caryophyllene, carvone, ipsenone, ipsdienone, limonene, linalool, myrcene, myrcenone, ocimenone,p-cymene, piperitenone, sabinene, and tagetenone [1–5]. Research by Viljoen et al. [3] revealed that the essential oil profiles ofL. javanicaare characterized by inter- and intraspecies variations because they are produced by different metabolic pathways. Using cluster analysis, Viljoen et al. [3] identified five chemotypes ofL. javanicain South Africa and Swaziland, myrcenone-rich type (36–62%), carvone-rich type (61–73%), piperitenone-rich type (32–48%), ipsdienone-rich type (42–61%), and linalool-rich type (>65%). The relative proportion of the chemical constituents ofL. javanicaessential oil is important as this determines the biological properties of the species chemotypes.Figure 1
(a)Lippia javanica(Burm.f.) Spreng. flowers and leaves (photo: BT Wursten) and (b)L. javanica herbal tea traded as Zumbani in Zimbabwe (http://specialityfoods.co.zw/product/zumbani/).
(a) (b)Lippia javanica belongs to theVerbena or vervain family (Verbenaceae) comprising approximately 32 genera and 840 species [97]. The genusLippia L. is named after Augustin Lippi (1678–1701), an Italian botanist and natural historian who was killed in Ethiopia at the age of 23 [98]. Phylogenetic relationships within family Verbenaceae demonstrated that genusLippia and other closely related genera, namely,Aloysia Paláu,Lantana L., andPhyla Lour., are not monophyletic [97]. The boundaries separating these four genera are historically weak, with many taxonomic researchers including species belonging toAloysia, Lantana, andPhyla in the genusLippia [99].LippiaandLantana genera are the most difficult to separate, as species of these two genera show similarities in their inflorescences that are spicate, often subcapitate during anthesis and elongating in fruit and pedunculated [98]. According to de Campos et al. [100], the genusLippia comprises about 200 species of herbs, shrubs, and small trees distributed throughout south and central America and tropical Africa. Only 15Lippiaspecies have been recorded in tropical Africa [101]. The specific name “javanica” was given by the Dutch Botanist Nicolaas Laurens Burman (1734–1793) in 1768, who mistakenly thought that the type specimen was collected in Java, Indonesia [102]. He placed the species in the genusVerbena,and the German botanist Sprengel (1766–1833) transferred Burman’s name to the genusLippia in 1825 [103].Lippia javanica is morphologically similar toL. scaberrimaSond. but is much taller and its bracts are shorter than the flowers (Figure 1(a)), whileL. scaberrima has many stems arising from ground level and is usually less than 0.5 metres high, and its bracts are not longer than the flowers [104].Lippia javanica is an erect woody perennial herb or shrub of up to 4.5 m tall, with strong aromatic leaves which give off a lemon-like fragrance when crushed [105]. Stems are brownish, usually erect or spreading with short stiff tubercle-based whitish hairs and small glands, and branched with inflorescences in nearly all axils. Leaves are opposite or in whorls of 3, blades lanceolate to oblong and densely pubescent, rounded and then cuneate at the base, and crenate-serrate or closely serrulate on the margins except near the leaf base [106]. Flowers occur in conical or oblong spikes, purple or dull-reddish in fruit, dark brownish on drying [101, 106]. The flowers are sessile or with short peduncles, lower bracts of spikes ovate and upper bracts smaller, pubescent, glandular, and densely spreading [101]. The calyx is 2-lobed, half as long as the corolla, pubescent, and densely spreading. The corolla is white, yellowish-white to greenish (Figure 1(a)), usually with a yellow throat, glandular and pubescent outside in the upper half, tube narrowly funnel-shaped from a narrow base [101, 106]. Anthers are sulphur-yellow and nutlets are brown and half ovoid [101, 106].Lippia javanicaoccurs naturally in central, eastern, and southern Africa (Figure 2) and has also been recorded in the tropical Indian subcontinent [12, 13, 23, 39, 47, 61]. In sub-Saharan Africa, the species is native to Angola, Botswana, Central African Republic, Democratic Republic of Congo, Ethiopia, Kenya, Malawi, Mozambique, South Africa, Swaziland, Tanzania, Uganda, Zambia, Zanzibar, and Zimbabwe.Lippia javanicahas been recorded in low to high altitude (0–2350 m above sea level) woodlands and wooded grasslands, scrub bushland, and grassy rocky kopjes, in riverine vegetation, and on margins of dambos and swampy ground, sometimes on termite mounds, in montane grasslands, and on evergreen forest margins, also in disturbed ground beside roads, forest clearings, plantations, and cultivated land and becoming a weed in derived rangelands [101, 106]. This shows that the plant is highly adaptable to a wide range of climatic, soil, and vegetation conditions.Figure 2
Lippia javanica naturally occurs in central, eastern, and southern Africa.


## 2. Traditional Uses ofLippia javanica

Lippia javanicais used for a wide variety of traditional uses (Table 1). Based on literature, the most important traditional applications include its uses as herbal tea and ethnomedicinal applications for (in descending order of importance) colds, cough, fever or malaria, wounds, repelling mosquitos, diarrhoea, chest pains, bronchitis, and asthma (Figure 3). These different uses are discussed in the following seven sections: Food Uses; Respiratory Problems; Gastrointestinal Diseases; Fever, Malaria, and Insect Repellent; Wounds, Injuries, Pain, and Skin Infections; Ethnoveterinary Uses; and Other Uses.Table 1
Traditional uses ofLippia javanica in central, eastern, and southern Africa.
Use Plant part(s) used Mode of use Country practised Reference(s) Food uses Food additive Leaves, twigs Leaves and twigs boiled together with maize, cassava, groundnuts, and common tea (Camellia sinensis(L.) Kuntze) Kenya [6] Herbal tea Leaves Leaves can be sun dried for later use Botswana, South Africa, and Zimbabwe [7–11] Leafy vegetable Leaves Eaten as vegetable with meat or fish India [12, 13] Respiratory problems Asthma Leaves, twigs Decoction taken orally or smoke inhaled South Africa, Zimbabwe [14–17] Blocked nose Leaves Leaf decoction ofL. javanica alone taken orally or mixed with any of these species: Brachylaena unifloraHarv., Clausena anisata(Willd). Hook.f. ex Benth., Clematis brachiataThunb., Combretum molleR. Br. ex G. Don,Eucalyptus grandisW. Hill, Helichrysum kraussiiSch. Bip., Krauseola mosambicinaPax & Hoffm., Plectranthus neochilus Schltr., Senecio serratuloidesDC.,or Trichilia emeticaVahl taken orally South Africa [18] Bronchitis Leaves, roots, and stems Leaf infusion ofL. javanica alone taken orally or applied to skin as ointment or leaf and stem infusion of L. javanica mixed with leaves of Artemisia afra Jacq. ex Willd. taken orally Botswana, South Africa [15, 19–22] Chest pains Leaves, roots Leaves and roots ofL. javanica alone chewed or decoction taken orally or used in washes and poultices or smoke inhaled or “imbiza,” decoction prepared fromL. javanica and Cyrtanthus obliquus (L. f.) Aiton, taken orally or leaf decoction of L. javanica mixed with leaves of any of these species: Brachylaena transvaalensisHutch. ex E. Phillips & Schweick., C. brachiata, E. grandis,H. kraussii,orT. emetica taken orally or leaf juice taken orally with cloves of Allium sativumL. Bangladesh, Ethiopia, and South Africa [14, 18, 23–27] Colds Leaves, twigs Leaf infusion ofL. javanica alone taken orally or inhaled or applied as an ointment or “imbiza,” decoction prepared fromL. javanica and C. obliquus, taken orally Botswana, Kenya, South Africa, and Zimbabwe [15, 16, 19, 21, 27–32] Cough Leaves, stems, and twigs Leaves ofL. javanica alone chewed or infusion inhaled or taken orally or applied as an ointment or leaf and stem infusion of L. javanica mixed with leaves of any of these species: Acanthospermum glabratum(DC.) Wild., A. afra, B. uniflora, B. transvaalensis, Bridelia catharticaBertol., C. anisata, C. brachiata, C. molle, E. grandis, H. kraussii, K. mosambicina, P. neochilus, Psidium guajavaL., S. serratuloides, Terminalia sericeaBurch. ex DC., Tetradenia riparia(Hochst.) Codd, or T. emeticataken orally Botswana, Ethiopia, South Africa, and Zimbabwe [15, 16, 18–21, 26, 30, 32] Influenza Leaves, roots Decoction taken orally Mozambique, South Africa [7, 33–36] Lung infections Leaves Infusions taken orally South Africa [37] Measles Leaves, stems Leaf decoction ofL. javanica alone taken orally or body washed with infusion or leaf and stem infusion of L. javanicamixed with leaves of A. afrataken orally Kenya, South Africa, and Zimbabwe [14, 20, 38] Pneumonia Leaves Ointment rubbed on chest and abdomen Zimbabwe [14] Respiratory disorders Leaves Decoction taken orally India, South Africa [39–41] Runny nose Leaves, roots Leaf and root decoction ofL. javanica alone taken orally or leaf decoction of L. javanica mixed with leaves of any of these species: B. transvaalensis, B. cathartica,C. anisata, C. brachiata, E. grandis, Hypoxisspp., K. mosambicina; P. guajava, S. serratuloides, P. neochilus,orT. emeticataken orally South Africa [18] Shortness of breath (dyspnoea) Leaves Decoction taken orally or body washed with decoction Zimbabwe [14] Sore throat Leaves Leaf decoction ofL. javanica alone taken orally or leaf decoction of L. javanica mixed with leaves of E. grandisor T. ripariataken orally South Africa [18] Tonsillitis Leaves Leaf decoction ofL. javanica alone taken orally or leaf decoction of L. javanicamixed with leaves of E. grandistaken orally South Africa [18] Tuberculosis Leaves Leaf decoction ofL. javanica alone taken orally or “imbiza,” decoction prepared fromL. javanica and C. obliquus, taken orally South Africa, Uganda [24, 42, 43] Gastrointestinal diseases Amoebiasis Leaves, twigs Decoction taken orally Kenya [6] Anthelmintics Leaf Infusions taken orally South Africa [40] Diarrhoea Leaves, roots Decoction taken orally Kenya, Mozambique, South Africa [17, 29, 34, 37, 44] Gangrenous rectitis Leaves Infusions taken orally South Africa [45] Prophylactic against diarrhoea Leaves Infusion taken orally South Africa [40] Vomiting Leaves Decoction taken orally Zanzibar, Tanzania [46] Fever, malaria, and as insect repellent Fever Leaves, stems, and twigs Leaf and twig decoction ofL. javanica alone taken orally or leaf and stem infusion of L. javanica mixed with leaves of any of these species: A. afra, B. transvaalensis, C. anisata, C. molle, E. grandis,P. guajava, S. serratuloides, T. riparia,or T. emetica takenorally South Africa, Zimbabwe [14, 16, 18, 20] Getting rid of lice, insects, and lice and as mosquito repellent Leaves, twigs, and whole plant Used in washes and poultices or as steam or sprayed or burnt to chase away mosquitoes Ethiopia, South Africa, and Zimbabwe [4, 26, 34, 47–51] Malaria Leaves, roots Decoction taken orally Mozambique, South Africa [17, 33, 52] Prophylactic against malaria Leaves Infusion taken orally South Africa [40] Wounds, injuries, pain, and skin infections Abdominal pains Leaves Leaves chewed and juice swallowed Zimbabwe [14] Acne Leaves Not specified Botswana [22] Antidotes Roots Used as antidote for food poisoning Botswana [22] Backache Roots Infusion taken orally South Africa, Zimbabwe [14, 20] Bleeding from the nose (epistaxis) Leaves Fresh leaves inserted into nose or powdered leaves sniffed South Africa, Zimbabwe [14, 53] Boils Leaves Infusion taken orally South Africa [54] Chicken pox Leaves Used in washes and poultices or as steam South Africa [50] Earache Leaves Decoction taken orally mixed with leaves ofE. grandis South Africa [18] Febrile rashes Leaves Infusions taken orally South Africa [40] Headache, migraine Leaves, roots Leaf and root decoction ofL. javanica alone taken orally or leaf decoction of L. javanicamixed with leaves of any of these species: B. cathartica,C. brachiata, E. grandis, T. riparia,and T. emeticataken orally Kenya, South Africa, and Zimbabwe [14, 18, 33, 34, 38] Inflammation Leaves Not specified South Africa [41] Pubic sores Leaves Decoction taken orally mixed with leaves ofAcanthospermum australe (Loefl.) Kuntze Swaziland [55] Scabies Leaves, roots Infusion taken orally or used in washes and poultices or as steam South Africa, Zimbabwe [14, 50, 54] Shingles Leaves, twigs, and roots Applied as an ointment South Africa [15] Skin disorders, such as heat rash scratches, stings, and bites Leaves, twigs Applied as an ointment or “imbiza,” decoction prepared fromL. javanica and C. obliquus, taken orally South Africa [21, 27] Sores Leaves Decoction ofL. javanica mixed with bark of Acacia burkeiBenth., Ozoroa engleriR. Fern. & A. Fern., Sclerocarya birrea(A. Rich.) Hochst., Syzygium cordatum Hochst. ex Krauss, and Tabernaemontana elegansStapf taken orally South Africa [56] Sore eyes, cataracts Leaves, roots Juice squeezed into eyes Botswana, Zimbabwe [14, 22] Sprained joints Roots Root powder applied to scarifications around sprained joints South Africa [20] Ulcers Leaves Juice taken orally with cloves ofA. sativum Bangladesh [23] Wounds Leaves Fresh leaves wrapped around wound to enhance healing or infusion taken orally Kenya, South Africa [54, 57] Ethnoveterinary uses Disinfecting suspected anthrax-infested meat Whole plant Whole plants used to disinfect suspected anthrax-infested meat South Africa [20] Getting rid of ticks and other ectoparasites Leaves, twigs, and whole plant Crushed leaves mixed with water and sprayed, twigs used as bedding in fowl runs South Africa, Zimbabwe [58–60] Lice repellant Whole plant Whole plant used to repel lice in poultry India [61] Milk preservative Stem Stem applied to milk gourd before milk fermentation Kenya [62] Other uses Anaemia in pregnancy Leaves Decoction taken orally Zanzibar, Tanzania [46] Broom Whole plant Whole plants cut and tied together to make rough brooms South Africa [53] Cancer Leaves “Imbiza,” decoction prepared fromL. javanica and C. obliquus, taken orally South Africa [27] Ceremonial Leaves, whole plant Used before and after funerals or placed on patients’ bed after circumcision Kenya, South Africa [31, 58, 63] Convulsions Leaves Leaves rubbed on face Zimbabwe [14, 64] Diabetes Leaves “Imbiza,” decoction prepared fromL. javanica and C. obliquus, taken orally South Africa [27] Fatigue or tiredness Leaves Leaf decoction ofL. javanica mixed with leaves of A. glabratum or E. grandisor T. ripariataken orally South Africa [18] Fence Whole plant Planted around homesteads Ethiopia [26] Fodder Leaves Leaves eaten by goats Kenya [31] Fuelwood Whole plant Whole plant used as fuelwood Zanzibar, Tanzania [46] Human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) symptoms Leaves “Imbiza,” decoction prepared fromL. javanica and C. obliquus which is taken orally South Africa [65, 66] Kidney problems Root 50 g root powder boiled in 2 litres of water; patient takes a cup of this mixture once per day for 3 days Swaziland [67] Madness Leaves, whole plant Body washed with leaf infusion Malawi, Zimbabwe [14, 68] Marasmic infants Roots Infusions used to bath infants South Africa, Zimbabwe [14, 20] Night blindness Leaves Face washed with infusion Zimbabwe [14] Nightmares Not specified Not specified Zimbabwe [64] Pre-, intra-, and postpartum complications Stem, roots Smear powder of root or stem Kenya [69] Preventing odours or being used indoors to freshen air Leaves, whole plant Leaves sprinkled in toilets to prevent odours or whole plant placed in vase or room Kenya, South Africa [31, 35, 58] Protection against dogs and crocodiles Leaves Leaves smeared on body South Africa [70] Psychotropic behaviour Leaves Infusion taken orally Swaziland [71] Removing bad luck Leaves Face and hands washed with infusion ofL. javanica leaves mixed with C. molle leaves Swaziland [72] Sleepless nights Leaves Leaf decoction ofL. javanica mixed with leaves of E. grandis and T. ripariataken orally South Africa [18] To drive away bad spirits Leaves Body washed with infusion Zimbabwe [14] To prevent infants from contracting illness caused by father or mother committing adultery Leaves Leaves rubbed on forehead, elbows, and knees after committing adultery Zimbabwe [14] Venereal diseases Roots Decoction taken orally Mozambique [44] Weak joints Leaves Decoction taken orally Zimbabwe [14]Figure 3
Main ethnobotanical applications ofLippia javanica in central, eastern, and southern Africa. An ethnobotanical use is counted only once per publication.


### 2.1. Food Uses

Leaves and twigs ofLippia javanica are used as food additives in Kenya [6] and leafy vegetable in India [12, 13].Lippia javanica is popular as herbal tea, particularly in Botswana, South Africa, and Zimbabwe [7–11].Lippia javanica herbal tea is prepared by steeping fresh or dried leaves, stems, or twigs in boiling water and letting them stand for two to five minutes to release flavour, with or without milk and sugar added according to taste. A stronger brew, known as a decoction, is prepared by boiling fresh or dried leaves, stems, or twigs for more than five minutes. The herbal tea prepared fromL. javanicaleaves, stems, or twigs has a lemon or vanilla aroma and is often used as a common tea (i.e.,C. sinensis) substitute or a few leaves, stems, or twigs are added toC. sinensis to provide a lemon or vanilla aroma. According to Sõukand and Kalle [87], herbal tea or tisane is an English term used to denote a decoction or infusion made of herbs for medicinal purposes. WhenL. javanica is used as medicinal herbal tea, it is consumed for a limited number of days to treat a specific condition like asthma in Zimbabwe [14], bronchitis in South Africa [19], chest pains in Zimbabwe and South Africa [14, 24], colds in Kenya, South Africa, and Zimbabwe [19, 20, 28–30], cough in South Africa and Zimbabwe [19, 20, 30, 53], and other diseases (see Table 1). From literature, it seemsL. javanicaherbal tea evolved over the years from medicinal tea decoctions or infusions to nonmedicinal uses, where the herbal tea is now drunk for recreation and enjoyment. According to Shikanga et al. [7],L. javanicatea is appreciated throughout its distributional range as a general health tonic and also because it is naturally caffeine-free and has a calming and relaxing effect. Research done by other workers, for example, Manenzhe et al. [2], Shikanga et al. [7], Parrant [8], Olivier et al. [81], Motlhanka and Makhabu [9], and Bhebhe et al. [10, 11], revealed thatL. javanica is a popular recreational tea in southern Africa, consumed on a daily basis within a food context, while medicinal infusions or tisanes ofL. javanica are taken for a specific medical purpose. During the past 20 years, the use of herbal teas has increased globally [107] because of their functional properties and consumer interest in the health promoting properties of such beverages [108]. The other advantage associated withL. javanica usage is that the leaves can be sun-dried and later boiled in water and drunk as herbal tea [9].Most ofL. javanica used as herbal tea in rural and periurban communities in central, eastern, and southern Africa is still collected from the wild, although small-scale cultivation has become necessary as it is marketed as herbal tea in Botswana under the brand name “Mosukudu” or “Mosukujane” [109] and in Zimbabwe as “Zumbani” (Figure 1(b)). Although considerable quantities ofL. javanicaare sold in local markets in Botswana and Zimbabwe and also traded on the Internet, there is no data on present production levels, traded volumes, values, and export figures in these two countries. Research by Whiteside [110] showed that sales ofL. javanicatea bags generated an income of R20300.00 (US$5718) during 1994/1995 in Botswana. There is increased demand forL. javanica herbal tea especially in the light of growing health consciousness worldwide, with the estimated potential demand for the species and its products around 100 tonnes per year on the local market and 1000 tonnes per year on the export market (http://bio-innovation.org/work/fever-tea-tree/). Considering the rapid growth of the herbal tea industry worldwide and the increasing demand forL. javanicaproducts, there is need for the improvement ofL. javanicaproducts as well as development of new products. Therefore,L. javanica has potential to make the transition from limited local use to commercial and international product.Lippia javanica has been identified as one of the few plant species that should be integrated in the domestication process in farming systems in sub-Saharan Africa to support medicinal, nutritional, and income security of local communities [107, 111]. According to Van Wyk [111],L. javanica is of commercial value as herbal tea and health drinks. Therefore, commercialization ofL. javanicais unlikely to be viable if the product is sorely harvested from the wild. In the same line commercialization ofL. javanicamight be more worthy if other products other than tea are derived from the plant.


### 2.2. Respiratory Problems

The different parts ofL. javanica, for example, the leaves and twigs, are used for the treatment of asthma, coughs, colds, influenza, pneumonia, tuberculosis, and bronchial problems in Bangladesh, Botswana, Ethiopia, Kenya, South Africa, and Zimbabwe [14–16, 19, 20, 23, 25, 26, 28–32, 53, 112]. In Bangladesh, leaf infusion ofL. javanica is taken orally mixed with 3-4 pieces of cloves ofA. sativum, 2-3 times daily as remedy for chest pains [23]. In Ethiopia, leaves ofL. javanica are chewed with butter as remedy for chest pains and cough [26]. In India,L. javanica leaf decoction is taken orally as remedy for respiratory disorders [39]. In Kenya, leaves are sniffed [31] or half glass of hot leaf infusion is taken orally three times a day [28, 29] as remedy for colds and cough. Research done by Davids et al. [19] in South Africa revealed that about 50 g of leaves is added to a cup of boiling water to produce an infusion which is taken orally as remedy for coughs, colds, and bronchial problems or the infusion is applied to the skin or mixed with Vaseline to make an ointment. In South Africa, leaf or twig decoction is taken orally for asthma, colds, and cough [16, 53], leaves are used in washes and poultices for chest pains [25], and leaves are boiled for 5 minutes and one cup of extract is taken orally thrice a day for chest pains and tuberculosis [24, 42]. According to York [18], two handfuls ofL. javanica leaves are boiled in two litres of water and patient is steamed once or twice a day to treat coughs, chest pain, headaches, fever, chills, a sore throat, or a blocked nose. This decoction can also be taken orally by drinking half a cup daily [18]. Alternatively, a handful ofL. javanica roots or leaves are mixed with a handful leaves ofA. glabratum orB. transvaalensisorB. uniflora orB. cathartica orC. anisata orC. brachiata orC. molleorE. grandisorH. kraussiiorHypoxisspp. orK. mosambicinaorP. neochilusorP. guajavaorS. serratuloidesorT. sericeaorT. ripariaorT. emeticato treat blocked nose, chest pain, cough, earache, fatigue, fever, influenza, headache, runny nose, sleepless nights, sore throat, tiredness, and tonsillitis [18]. Leaf and stem infusion ofL. javanica are taken orally together withA. afra by the Zulu people in South Africa as remedy for bronchial ailments, colds, and cough [20]. “Imbiza,” a popular herbal decoction prepared fromL. javanicaandC. obliquus,is used by the Zulu people in South Africa as herbal tonic and an immune booster and also for the treatment of cancer, chest pains, colds, diabetes, HIV or AIDS symptoms, skin infections, and tuberculosis [27]. In some communities in South Africa,L. javanica leaf or root infusion is taken orally as remedy for influenza and malaria [33] and respiratory disorders [40, 41]. In Zimbabwe, leaf or root decoction is taken orally or smoke of burnt leaves and roots is inhaled as remedy for chest pains [14] and leaf and twigs are boiled in water and infusion is taken orally as remedy for colds and cough [30]. According to Gelfand et al. [14], Shona people in Zimbabwe rub leaf ointment ofL. javanica on the chest and abdomen as remedy for pneumonia and leaf decoction is taken orally and body washed with leaf decoction as remedy for shortness of breath or dyspnoea. In South Africa, a leaf and stem infusion ofL. javanicaare taken orally together with leaves ofA. afra as remedy for measles [20].Based on literature, inhalation of smoke fromL. javanica appears to be a popular remedy for asthma, chest pains, colds, and chronic coughs in Botswana, South Africa, and Zimbabwe [14, 15, 20, 32]. In Botswana,L. javanica leaf infusion vapour is inhaled as remedy for colds and cough [32]. In South Africa, for example, leaves and twigs are burned and smoke is inhaled as remedy for asthma and cough [15] or steam from leaf infusions is inhaled or hot leaf infusions are taken orally against colds and cough [20]. In Zimbabwe, smoke of burnt leaves and roots is inhaled as remedy for chest pains [14].


### 2.3. Gastrointestinal Diseases

The leaf and root decoction or infusions ofL. javanica are used as remedies of the digestive system diseases such as cholera, diarrhoea, and dysentery. For example, in Mozambique, root decoction is taken orally as remedy for a type of diarrhoea commonly known as “chinhamucaca” which is characterized by milky diarrhoea accompanied by vomiting in children [44]. Leaf decoction is used as herbal medicine for diarrhoea in Kenya [113]. In South Africa, the leaves ofL. javanica are crushed and mixed with cold or hot water and the mixture is then sieved and a quarter of a cup (75 mL) is taken twice a day until diarrhoea subsides [34]. The Venda people in South Africa use leaf infusions as prophylactic against diarrhoea [40]. Research done by Palgrave et al. [37] in South Africa revealed that tea infusions of theL. javanica leaves are used as remedies for HIV/AIDS opportunistic infections such as lung infections and diarrhoea. Previous research in Mozambique [114], South Africa [115], and Zimbabwe [116] showed that gastrointestinal disorders, particularly cholera, diarrhoea, and dysentery are among human diseases often treated with herbal medicines. For those patients diagnosed as having intestinal worms in Venda, South Africa, a leaf infusion ofL. javanicaleaves is used as an anthelmintic [40]. Therefore, these findings illustrate that herbal medicines includingL. javanica can play an important role in basic health care of local communities through treatment and management of cholera, diarrhoea, and dysentery.


### 2.4. Fever, Malaria, and Insect Repellent

Traditionally,L. javanicais commonly used to treat fever and malaria and repel insects throughout its distributional range [4, 14, 16, 17, 33–35, 40, 48–50, 58–60]. In South Africa, a decoction of fresh or air dried leaves is used to wash or steam body parts infested with lice [50]. In India, the whole plant is used to repel lice in poultry [61]. In South Africa and Zimbabwe, whole plant or leaves are burnt to repel mosquitoes [4, 34, 35, 48, 49, 58]. In South Africa and Zimbabwe,L. javanicais widely used to get rid of ticks and other ectoparasites; for example, ticks are sprayed with crushed leaves mixed with water or twigs are used as bedding in fowl runs [58–60]. Leaf and twig decoction ofL. javanicaare taken orally as remedy for fever [16]. The Venda people in South Africa use leaf infusions ofL. javanicaas prophylactic against malaria [40]. In Zimbabwe, leaf decoction is taken orally as remedy for fever [14].Lippia javanicais also cultivated on a commercial scale by a rural community in Giyani, the Limpopo province, South Africa, for the production of mosquito-repellent candles [117]. Clinical studies using human volunteers showed thatL. javanica repels no less than 95% of mosquitos, whereas most mosquito repellents repel only 42% of them [118]. Based on these findings, the Council for Scientific and Industrial Research (CSIR), South Africa, signed a benefit sharing agreement with traditional healers allowing for the commercial cultivation ofL. javanica aimed at establishing an indigenous oil industry for rural development and large-scale production of antimosquito candles and other insect repellents. The mosquito repellent is registered as a patent under the Fertilisers, Farm Feeds and Stock Remedies Act (Act 36 of 1947) as a pest repellent [119]. These findings and the establishment of a large-scale production of antimosquito candles and other insect repellents strengthen the view thatL. javanica is a potential source of antipesticidal agents and to some extent validate the traditional use of the plant species for insect pest control. Pesticidal plants such asL. javanica are increasingly being used as alternatives where synthetic products are unaffordable or are not available or are ineffective. A number of studies have indicated that the use ofL. javanica as a pesticide is a long-standing tradition passed down from generation to generation [120].


### 2.5. Wounds, Injuries, Pain, and Skin Infections

Lippia javanicais used as remedy for a variety of skin infections and injuries in Kenya, South Africa, Swaziland, and Zimbabwe. In South Africa, leaf infusions are used to treat skin disorders, such as boils, chicken pox, febrile rashes, heat rashes, measles, scabies, scratches, and stings [20, 21, 40, 50, 54]. In Kenya, about 50 g of fresh leaves is wrapped around a fresh wound to enhance healing [57] and, in South Africa, leaf infusions are taken orally as remedy for wounds [54]. In South Africa, powder from burnt roots ofL. javanicais applied to scarifications made around sprained joints to facilitate healing [20]. In Kenya and Zimbabwe, leaf infusion is taken orally to treat measles or a patient is washed with leaf infusion [14, 38]. The Zulu people in South Africa take a mixture of chopped handful leaves ofL. javanicawith the same amount of bark ofA. burkei,O. engleri,S. birrea,S. cordatum, andT. elegans boiled in two litres of water as an enema for the treatment of sores [56]. In Swaziland, about 30 g ofL. javanicaleaves and similar amount ofAcanthospermum australe Kuntze are boiled in 5 litres of water and decoction is taken as remedy for sores [55]. In Zimbabwe, root ashes ofL. javanicamixed with fat are applied to the skin of a patient with scabies [14]. Wound healing is a process which involves distinct overlapping phases of coagulation, inflammation, proliferation, and tissue remodelling [121]. The same authors argued that a set of complex biochemical events takes place in a closely orchestrated cascade to repair the wound and any errors in the wound healing process can lead to delayed healing or formation of hypertrophic scars. Abubakar [122] argued that colonization of wounds by opportunistic microorganisms usually delays the wound healing process and/or may lead to infectious condition. Therefore, application ofL. javanica on wounds and skin infections leads to disinfection, debridement, and provision of a suitable environment for aiding the wound healing process.Lippia javanica has potential for therapeutic use in wound and skin diseases management, but there is need for research on the safety, phytochemistry, and biological properties of the species.


### 2.6. Ethnoveterinary Uses

The leaves, stems, twigs, and whole plants ofL. javanica are used as ethnoveterinary medicine in India, Kenya, South Africa, and Zimbabwe. The Xhosa people in the Eastern Cape province, South Africa, useL. javanicaleaves for the disinfection of meat that has been infected with anthrax [20]. In Kenya, the stem ofL. javanica is used to preserve milk by applying it to the gourd before milk fermentation [62]. In India, whole plants are used as lice repellants while, in South Africa and Zimbabwe, crushed leaves mixed with water are used to get rid of ticks and twigs are used as bedding in fowl runs to get rid of ectoparasites [58–60].


### 2.7. Other Uses

Lippia javanica is used as a good luck charm, to treat persons experiencing bad dreams, to ward off evil spirits, to protect one from lightening, and to protect the home (Table 1). In Zimbabwe,L. javanicaleaves are prepared as an infusion to treat persons experiencing nightmares [64]. In both South Africa and Zimbabwe, evil spirits are cleansed by washing the body of an affected person by leaf infusion ofL.javanica [14, 123]. In Swaziland, 50 g leaves ofL. javanica andC. molle are ground into a powder and 5 litres of water is added and face and hands are washed to remove bad luck when exposed to a corpse [71]. In South Africa, the whole plant is placed on a patient’s bed after the circumcision ceremony [58], to prevent odours and freshen surrounding air. A mixture ofL. javanica leaves and roots is used to clean tools and hands before and after funerals, the stems and leaves are used as brooms to sweep grave sites, and the entire plant is also used when coming from the mortuary to remove bad spirits [58, 124]. The corpse is washed withL. javanica infusion after death to prevent odours forming or if the corpse has an odour, women place pieces ofL. javanica in the nostrils of the corpse and sweep the room with twigs where the person was sleeping [58]. In KwaZulu Natal, South Africa, if the meat started to smell it will be boiled withL.javanica leaves to take away the smell [58]. The Xhosa people in the Eastern Cape province, South Africa, useL. javanicaleaves for the disinfection of meat that has been infected with anthrax [20]. In KwaZulu Natal, South Africa, leaves are sprinkled in toilets to prevent odours [58]. Leaves ofL.javanica are sprinkled in houses for pleasant smell in the Limpopo province, South Africa [35], and Kenya [31]. In KwaZulu Natal, South Africa, it is believed that a person can repel snakes by placing a small stem with leaves on his or her head [58]. In Malawi, Swaziland, and Zimbabwe, people showing sign of mental disorder, madness, or hysterical outbursts are required to wash their bodies with leaf infusions [14, 67, 68, 71].


## 2.1. Food Uses

Leaves and twigs ofLippia javanica are used as food additives in Kenya [6] and leafy vegetable in India [12, 13].Lippia javanica is popular as herbal tea, particularly in Botswana, South Africa, and Zimbabwe [7–11].Lippia javanica herbal tea is prepared by steeping fresh or dried leaves, stems, or twigs in boiling water and letting them stand for two to five minutes to release flavour, with or without milk and sugar added according to taste. A stronger brew, known as a decoction, is prepared by boiling fresh or dried leaves, stems, or twigs for more than five minutes. The herbal tea prepared fromL. javanicaleaves, stems, or twigs has a lemon or vanilla aroma and is often used as a common tea (i.e.,C. sinensis) substitute or a few leaves, stems, or twigs are added toC. sinensis to provide a lemon or vanilla aroma. According to Sõukand and Kalle [87], herbal tea or tisane is an English term used to denote a decoction or infusion made of herbs for medicinal purposes. WhenL. javanica is used as medicinal herbal tea, it is consumed for a limited number of days to treat a specific condition like asthma in Zimbabwe [14], bronchitis in South Africa [19], chest pains in Zimbabwe and South Africa [14, 24], colds in Kenya, South Africa, and Zimbabwe [19, 20, 28–30], cough in South Africa and Zimbabwe [19, 20, 30, 53], and other diseases (see Table 1). From literature, it seemsL. javanicaherbal tea evolved over the years from medicinal tea decoctions or infusions to nonmedicinal uses, where the herbal tea is now drunk for recreation and enjoyment. According to Shikanga et al. [7],L. javanicatea is appreciated throughout its distributional range as a general health tonic and also because it is naturally caffeine-free and has a calming and relaxing effect. Research done by other workers, for example, Manenzhe et al. [2], Shikanga et al. [7], Parrant [8], Olivier et al. [81], Motlhanka and Makhabu [9], and Bhebhe et al. [10, 11], revealed thatL. javanica is a popular recreational tea in southern Africa, consumed on a daily basis within a food context, while medicinal infusions or tisanes ofL. javanica are taken for a specific medical purpose. During the past 20 years, the use of herbal teas has increased globally [107] because of their functional properties and consumer interest in the health promoting properties of such beverages [108]. The other advantage associated withL. javanica usage is that the leaves can be sun-dried and later boiled in water and drunk as herbal tea [9].Most ofL. javanica used as herbal tea in rural and periurban communities in central, eastern, and southern Africa is still collected from the wild, although small-scale cultivation has become necessary as it is marketed as herbal tea in Botswana under the brand name “Mosukudu” or “Mosukujane” [109] and in Zimbabwe as “Zumbani” (Figure 1(b)). Although considerable quantities ofL. javanicaare sold in local markets in Botswana and Zimbabwe and also traded on the Internet, there is no data on present production levels, traded volumes, values, and export figures in these two countries. Research by Whiteside [110] showed that sales ofL. javanicatea bags generated an income of R20300.00 (US$5718) during 1994/1995 in Botswana. There is increased demand forL. javanica herbal tea especially in the light of growing health consciousness worldwide, with the estimated potential demand for the species and its products around 100 tonnes per year on the local market and 1000 tonnes per year on the export market (http://bio-innovation.org/work/fever-tea-tree/). Considering the rapid growth of the herbal tea industry worldwide and the increasing demand forL. javanicaproducts, there is need for the improvement ofL. javanicaproducts as well as development of new products. Therefore,L. javanica has potential to make the transition from limited local use to commercial and international product.Lippia javanica has been identified as one of the few plant species that should be integrated in the domestication process in farming systems in sub-Saharan Africa to support medicinal, nutritional, and income security of local communities [107, 111]. According to Van Wyk [111],L. javanica is of commercial value as herbal tea and health drinks. Therefore, commercialization ofL. javanicais unlikely to be viable if the product is sorely harvested from the wild. In the same line commercialization ofL. javanicamight be more worthy if other products other than tea are derived from the plant.


## 2.2. Respiratory Problems

The different parts ofL. javanica, for example, the leaves and twigs, are used for the treatment of asthma, coughs, colds, influenza, pneumonia, tuberculosis, and bronchial problems in Bangladesh, Botswana, Ethiopia, Kenya, South Africa, and Zimbabwe [14–16, 19, 20, 23, 25, 26, 28–32, 53, 112]. In Bangladesh, leaf infusion ofL. javanica is taken orally mixed with 3-4 pieces of cloves ofA. sativum, 2-3 times daily as remedy for chest pains [23]. In Ethiopia, leaves ofL. javanica are chewed with butter as remedy for chest pains and cough [26]. In India,L. javanica leaf decoction is taken orally as remedy for respiratory disorders [39]. In Kenya, leaves are sniffed [31] or half glass of hot leaf infusion is taken orally three times a day [28, 29] as remedy for colds and cough. Research done by Davids et al. [19] in South Africa revealed that about 50 g of leaves is added to a cup of boiling water to produce an infusion which is taken orally as remedy for coughs, colds, and bronchial problems or the infusion is applied to the skin or mixed with Vaseline to make an ointment. In South Africa, leaf or twig decoction is taken orally for asthma, colds, and cough [16, 53], leaves are used in washes and poultices for chest pains [25], and leaves are boiled for 5 minutes and one cup of extract is taken orally thrice a day for chest pains and tuberculosis [24, 42]. According to York [18], two handfuls ofL. javanica leaves are boiled in two litres of water and patient is steamed once or twice a day to treat coughs, chest pain, headaches, fever, chills, a sore throat, or a blocked nose. This decoction can also be taken orally by drinking half a cup daily [18]. Alternatively, a handful ofL. javanica roots or leaves are mixed with a handful leaves ofA. glabratum orB. transvaalensisorB. uniflora orB. cathartica orC. anisata orC. brachiata orC. molleorE. grandisorH. kraussiiorHypoxisspp. orK. mosambicinaorP. neochilusorP. guajavaorS. serratuloidesorT. sericeaorT. ripariaorT. emeticato treat blocked nose, chest pain, cough, earache, fatigue, fever, influenza, headache, runny nose, sleepless nights, sore throat, tiredness, and tonsillitis [18]. Leaf and stem infusion ofL. javanica are taken orally together withA. afra by the Zulu people in South Africa as remedy for bronchial ailments, colds, and cough [20]. “Imbiza,” a popular herbal decoction prepared fromL. javanicaandC. obliquus,is used by the Zulu people in South Africa as herbal tonic and an immune booster and also for the treatment of cancer, chest pains, colds, diabetes, HIV or AIDS symptoms, skin infections, and tuberculosis [27]. In some communities in South Africa,L. javanica leaf or root infusion is taken orally as remedy for influenza and malaria [33] and respiratory disorders [40, 41]. In Zimbabwe, leaf or root decoction is taken orally or smoke of burnt leaves and roots is inhaled as remedy for chest pains [14] and leaf and twigs are boiled in water and infusion is taken orally as remedy for colds and cough [30]. According to Gelfand et al. [14], Shona people in Zimbabwe rub leaf ointment ofL. javanica on the chest and abdomen as remedy for pneumonia and leaf decoction is taken orally and body washed with leaf decoction as remedy for shortness of breath or dyspnoea. In South Africa, a leaf and stem infusion ofL. javanicaare taken orally together with leaves ofA. afra as remedy for measles [20].Based on literature, inhalation of smoke fromL. javanica appears to be a popular remedy for asthma, chest pains, colds, and chronic coughs in Botswana, South Africa, and Zimbabwe [14, 15, 20, 32]. In Botswana,L. javanica leaf infusion vapour is inhaled as remedy for colds and cough [32]. In South Africa, for example, leaves and twigs are burned and smoke is inhaled as remedy for asthma and cough [15] or steam from leaf infusions is inhaled or hot leaf infusions are taken orally against colds and cough [20]. In Zimbabwe, smoke of burnt leaves and roots is inhaled as remedy for chest pains [14].


## 2.3. Gastrointestinal Diseases

The leaf and root decoction or infusions ofL. javanica are used as remedies of the digestive system diseases such as cholera, diarrhoea, and dysentery. For example, in Mozambique, root decoction is taken orally as remedy for a type of diarrhoea commonly known as “chinhamucaca” which is characterized by milky diarrhoea accompanied by vomiting in children [44]. Leaf decoction is used as herbal medicine for diarrhoea in Kenya [113]. In South Africa, the leaves ofL. javanica are crushed and mixed with cold or hot water and the mixture is then sieved and a quarter of a cup (75 mL) is taken twice a day until diarrhoea subsides [34]. The Venda people in South Africa use leaf infusions as prophylactic against diarrhoea [40]. Research done by Palgrave et al. [37] in South Africa revealed that tea infusions of theL. javanica leaves are used as remedies for HIV/AIDS opportunistic infections such as lung infections and diarrhoea. Previous research in Mozambique [114], South Africa [115], and Zimbabwe [116] showed that gastrointestinal disorders, particularly cholera, diarrhoea, and dysentery are among human diseases often treated with herbal medicines. For those patients diagnosed as having intestinal worms in Venda, South Africa, a leaf infusion ofL. javanicaleaves is used as an anthelmintic [40]. Therefore, these findings illustrate that herbal medicines includingL. javanica can play an important role in basic health care of local communities through treatment and management of cholera, diarrhoea, and dysentery.


## 2.4. Fever, Malaria, and Insect Repellent

Traditionally,L. javanicais commonly used to treat fever and malaria and repel insects throughout its distributional range [4, 14, 16, 17, 33–35, 40, 48–50, 58–60]. In South Africa, a decoction of fresh or air dried leaves is used to wash or steam body parts infested with lice [50]. In India, the whole plant is used to repel lice in poultry [61]. In South Africa and Zimbabwe, whole plant or leaves are burnt to repel mosquitoes [4, 34, 35, 48, 49, 58]. In South Africa and Zimbabwe,L. javanicais widely used to get rid of ticks and other ectoparasites; for example, ticks are sprayed with crushed leaves mixed with water or twigs are used as bedding in fowl runs [58–60]. Leaf and twig decoction ofL. javanicaare taken orally as remedy for fever [16]. The Venda people in South Africa use leaf infusions ofL. javanicaas prophylactic against malaria [40]. In Zimbabwe, leaf decoction is taken orally as remedy for fever [14].Lippia javanicais also cultivated on a commercial scale by a rural community in Giyani, the Limpopo province, South Africa, for the production of mosquito-repellent candles [117]. Clinical studies using human volunteers showed thatL. javanica repels no less than 95% of mosquitos, whereas most mosquito repellents repel only 42% of them [118]. Based on these findings, the Council for Scientific and Industrial Research (CSIR), South Africa, signed a benefit sharing agreement with traditional healers allowing for the commercial cultivation ofL. javanica aimed at establishing an indigenous oil industry for rural development and large-scale production of antimosquito candles and other insect repellents. The mosquito repellent is registered as a patent under the Fertilisers, Farm Feeds and Stock Remedies Act (Act 36 of 1947) as a pest repellent [119]. These findings and the establishment of a large-scale production of antimosquito candles and other insect repellents strengthen the view thatL. javanica is a potential source of antipesticidal agents and to some extent validate the traditional use of the plant species for insect pest control. Pesticidal plants such asL. javanica are increasingly being used as alternatives where synthetic products are unaffordable or are not available or are ineffective. A number of studies have indicated that the use ofL. javanica as a pesticide is a long-standing tradition passed down from generation to generation [120].


## 2.5. Wounds, Injuries, Pain, and Skin Infections

Lippia javanicais used as remedy for a variety of skin infections and injuries in Kenya, South Africa, Swaziland, and Zimbabwe. In South Africa, leaf infusions are used to treat skin disorders, such as boils, chicken pox, febrile rashes, heat rashes, measles, scabies, scratches, and stings [20, 21, 40, 50, 54]. In Kenya, about 50 g of fresh leaves is wrapped around a fresh wound to enhance healing [57] and, in South Africa, leaf infusions are taken orally as remedy for wounds [54]. In South Africa, powder from burnt roots ofL. javanicais applied to scarifications made around sprained joints to facilitate healing [20]. In Kenya and Zimbabwe, leaf infusion is taken orally to treat measles or a patient is washed with leaf infusion [14, 38]. The Zulu people in South Africa take a mixture of chopped handful leaves ofL. javanicawith the same amount of bark ofA. burkei,O. engleri,S. birrea,S. cordatum, andT. elegans boiled in two litres of water as an enema for the treatment of sores [56]. In Swaziland, about 30 g ofL. javanicaleaves and similar amount ofAcanthospermum australe Kuntze are boiled in 5 litres of water and decoction is taken as remedy for sores [55]. In Zimbabwe, root ashes ofL. javanicamixed with fat are applied to the skin of a patient with scabies [14]. Wound healing is a process which involves distinct overlapping phases of coagulation, inflammation, proliferation, and tissue remodelling [121]. The same authors argued that a set of complex biochemical events takes place in a closely orchestrated cascade to repair the wound and any errors in the wound healing process can lead to delayed healing or formation of hypertrophic scars. Abubakar [122] argued that colonization of wounds by opportunistic microorganisms usually delays the wound healing process and/or may lead to infectious condition. Therefore, application ofL. javanica on wounds and skin infections leads to disinfection, debridement, and provision of a suitable environment for aiding the wound healing process.Lippia javanica has potential for therapeutic use in wound and skin diseases management, but there is need for research on the safety, phytochemistry, and biological properties of the species.


## 2.6. Ethnoveterinary Uses

The leaves, stems, twigs, and whole plants ofL. javanica are used as ethnoveterinary medicine in India, Kenya, South Africa, and Zimbabwe. The Xhosa people in the Eastern Cape province, South Africa, useL. javanicaleaves for the disinfection of meat that has been infected with anthrax [20]. In Kenya, the stem ofL. javanica is used to preserve milk by applying it to the gourd before milk fermentation [62]. In India, whole plants are used as lice repellants while, in South Africa and Zimbabwe, crushed leaves mixed with water are used to get rid of ticks and twigs are used as bedding in fowl runs to get rid of ectoparasites [58–60].


## 2.7. Other Uses

Lippia javanica is used as a good luck charm, to treat persons experiencing bad dreams, to ward off evil spirits, to protect one from lightening, and to protect the home (Table 1). In Zimbabwe,L. javanicaleaves are prepared as an infusion to treat persons experiencing nightmares [64]. In both South Africa and Zimbabwe, evil spirits are cleansed by washing the body of an affected person by leaf infusion ofL.javanica [14, 123]. In Swaziland, 50 g leaves ofL. javanica andC. molle are ground into a powder and 5 litres of water is added and face and hands are washed to remove bad luck when exposed to a corpse [71]. In South Africa, the whole plant is placed on a patient’s bed after the circumcision ceremony [58], to prevent odours and freshen surrounding air. A mixture ofL. javanica leaves and roots is used to clean tools and hands before and after funerals, the stems and leaves are used as brooms to sweep grave sites, and the entire plant is also used when coming from the mortuary to remove bad spirits [58, 124]. The corpse is washed withL. javanica infusion after death to prevent odours forming or if the corpse has an odour, women place pieces ofL. javanica in the nostrils of the corpse and sweep the room with twigs where the person was sleeping [58]. In KwaZulu Natal, South Africa, if the meat started to smell it will be boiled withL.javanica leaves to take away the smell [58]. The Xhosa people in the Eastern Cape province, South Africa, useL. javanicaleaves for the disinfection of meat that has been infected with anthrax [20]. In KwaZulu Natal, South Africa, leaves are sprinkled in toilets to prevent odours [58]. Leaves ofL.javanica are sprinkled in houses for pleasant smell in the Limpopo province, South Africa [35], and Kenya [31]. In KwaZulu Natal, South Africa, it is believed that a person can repel snakes by placing a small stem with leaves on his or her head [58]. In Malawi, Swaziland, and Zimbabwe, people showing sign of mental disorder, madness, or hysterical outbursts are required to wash their bodies with leaf infusions [14, 67, 68, 71].


## 3. Phytochemical Constituents and Nutritional Composition ofLippia javanica

Multiple classes of phytochemicals including volatile and nonvolatile secondary metabolites, such as alkaloids, amino acids, flavonoids, iridoids, and triterpenes as well as several minerals, have been identified fromL. javanica [1–5, 7, 13, 27, 73, 78, 81, 83–86, 88–94, 120, 123, 125–127]. Leaves, flowers, and twigs ofL. javanica have a wide variety of the so-called classic nutrients, such as minerals, carbohydrates, proteins, fats, and vitamins (Table 2).Lippia javanica leaves are a good source of minerals such as cadmium, calcium, chromium, cobalt, copper, iron, magnesium, manganese, selenium, and zinc [27]. These authors assessed the levels of the elements inL. javanica leaves and found the elements to be in the decreasing order of Ca > Mg > Fe > Zn > Mn > Cu > Se > Cr > Pb > Co > Cd for total concentrations and Ca > Mg > Fe > Zn > Cu > Cr > Pb for water extractable forms. These results corroborate an observation made by Sedaghathoor et al. [128] that Ca and Mg are among the most abundant elements in tea plants. These mineral elements are important in human nutrition sinceL. javanica is used as herbal tea and food additive (Table 1). Calcium, magnesium, iron, manganese, and zinc play a major role in activating some enzymes and regulating many responses of cells to stimuli [129]. Some of the mineral elements identified fromL. javanica leaves are required by the human body for repair of worn out cell tissues and strong bones and teeth and building of red blood cells and other related tissues. Therefore, sinceL. javanica has appreciable concentrations of mineral elements such as calcium, magnesium, iron, manganese, and zinc (Table 2) which are essential for enzyme metabolism, these mineral elements could enhance the nutritional and curative properties of the species.Table 2
Nutritional composition ofLippia javanica leaves.
Caloric and nutritional composition Values Reference Ash 1.60 ± 0.001 g [13] Calorific value 50.64 ± 5.63 kcal [13] Crude fat 0.16 ± 0.001 g [13] Crude fibre 2.63 ± 0.002 g [13] Crude protein 1.22 ± 0.0004 g [13] Dry matter 15.46 ± 1.40 g [13] Moisture 90.44 ± 0.26 g [13] Total carbohydrate 6.55 ± 0.26 g [13] Vitamin C 22.42 ± 0.001 mg [13] Ca 2856–9225μg g−1 [27] Mg 1598–5619μg g−1 [27] Fe 75–750μg g−1 [27] Mn 40.1 ± 1.16 μg g−1 [27] Zn 15.6–27.3μg g−1 [27] Cu 3.0–8.5μg g−1 [27] Cr 0–2.7μg g−1 [27] Se 2.57 ± 0.19 μg g−1 [27] Pb 0.38–1.19μg g−1 [27] Cd 0.53 ± 0.05 μg g−1 [27] Co 0.19 ± 0.01 μg g−1 [27]Bhebhe et al. [10] determined the total phenolic and tannin content and radical scavenging activities ofL. javanica, comparing it withAspalathus linearis (Burm.f.) R. Dahlgren (Rooibos™), a commercial South African herbal tea, and other popular herbal teas in Zimbabwe (Table 3).Adansonia digitata L.,Fadogia ancylantha Schweinf.,Ficus sycomorus L., andMyrothamnus flabellifolius Welw. are indigenous herbal teas consumed in Zimbabwe. The tannin content ofL. javanica is very low when compared toA. linearis (Rooibos) (Table 3).Lippia javanicahas higher radical scavenging activity thanA. linearis (Table 3) which is probably due to higher total phenolic content in comparison toA. linearis which is a popular herbal tea consumed by 10% of the global herbal tea market [10]. In another study, Bhebhe et al. [11] determined and compared the effect of several solvents, namely, hot water, 50% methanol, ethanol, 50% ethanol, acetone, 50% acetone, and ethyl acetate, on phenolic composition and free radical scavenging activity in common black tea,C. sinensis, and five other well-known herbal teas includingL. javanica. In all the seven solvents used,L. javanica had higher total phenolic content thanC. sinensis implying thatL. javanica is competitive to the black tea in terms of phenolic content. Shikanga et al. [7] found leaf extracts ofL. javanica to have higher phenolic content of 14.8 mg/g gallic acid equivalent of dry weight than flowers (9.9 mg/g) and twigs (8.3 mg/g). Phenolic compounds found in plants are known to play an important role as antioxidants in exhibiting the medicinal properties such as antibiotic, anti-inflammatory, anticancer, and antiallergic properties [10, 66, 130, 131].Table 3
Total phenolic content (TPC) as gallic acid equivalents (GAE) and tannin content as leucocyanidin equivalents (LE) and free radical scavenging activity (FRSA) of herbal tea extracts (after Bhebhe et al. [10]).
Plant species TPC g GAE/100 g Tannin content of LE/100 g Percentage FRSA I C 50 g/mL Lippia javanica 12.46 ± 4.31 0.12 ± 0.01 83.77 ± 0.8 0.016 Aspalathus linearis 6.69 ± 0.83 0.94 ± 0.04 67.27 ± 0.25 0.053 Adansonia digitata 0.79 ± 0.28 1.69 ± 0.01 43.07 ± 1.0 0.132 Fadogia ancylantha 2.88 ± 0.48 0.20 ± 0.12 70.0 ± 0.40 0.051 Ficus sycamores 14.02 ± 0.01 1.98 ± 0.12 86.13 ± 0.85 0.009 Myrothamnus flabellifolius 4.75 ± 0.33 1.04 ± 0.01 80.93 ± 0.75 0.019The compounds isolated fromL. javanica are documented and listed in Appendix A and their structures are presented in Appendix B. Simple phenolic compounds and caffeic acid and its derivatives are some of the compounds that have been identified inL. javanicaand examples include coumarin1, 3,4-dihydroxy-β-phenylethoxy-O-[4′′-β-caffeoyl-α-rhamnopyranosyl-(1‴,3′′)-O-β-glucopyranoside], commonly referred to as verbascoside2, and 3,4-dihydroxy-β-phenylethoxy-O-[6′′-β-caffeoyl-α-rhamnopyranosyl-(1‴,3′′)-O-β-glucopyranoside] commonly referred to as isoverbascoside3 isolated by Olivier et al. [81] from the aerial parts of the species. Nonvolatile diterpenes, known as iridoid-glycosides, have also been isolated fromL. javanica by Rimpler and Sauerbier [82] represented by theveside-Na4 and theveridoside5. Mujovo et al. [83] isolated a long chain alkane “4-ethylnonacosane”6 and four flavanones apigenin7, cirsimaritin8, 6-methoxyluteolin 4′-methyl ether9, and 6-methoxyluteolin 3′,4′,7-trimethyl ether10 from ethanolic extracts ofL. javanica leaves. Madzimure et al. [120] identified an array of phenolic glycosides and flavonoids which include crassifolioside11, luteolin12, diosmetin13, chrysoeriol14, tricin15, isothymusin16, eupatorin17, 5-dimethyl noboletin18, genkwanin19, salvigenin20, and an alkaloid xanthine22. Ludere et al. [84] isolated lippialactone21 from the ethyl acetate extract of aerial parts ofL. javanica. Neidlein and Staehle [85] and Dlamini [86] isolated 19 amino acids, compounds23 to41 in Appendix A, fromL. javanica. At least 131 different classes of essential oil compounds (compounds42–172 in Appendices A and B) have been isolated fromL. javanicaby several researchers [3–5, 83, 85, 86, 88–94, 123]. Hutchings and van Staden [96] isolated a toxic triterpenoid saponin, icterogenin173, fromL. javanica leaves. These different classes of essential oil compounds have been associated with various therapeutic activities such as anaesthetic, analgesic, anti-inflammatory, antimicrobial, cardiovascular, decongestant, digestive, expectorant, hepatoprotective, and sedative activities as well as stimulant of nervous system and tonifying effects [132]. Meanwhile flavonoids possess several pharmacological properties including antibacterial, anticancer, anti-inflammatory, antioxidant, antiviral, and hepatoprotective effects [133] which play important roles in human health. Flavonoid such as apigenin7 is reported to possess antibacterial [134] and hepatoprotective [135] properties. Apigenin7 and luteolin12 are reported to possess anti-inflammatory and analgesic effects [133], affecting the function of enzyme systems involved in the generation of inflammatory processes, especially tyrosine and serine-threonine protein kinases [136, 137]. It has also been reported that apigenin7 prevents HIV-1 activation via a novel mechanism that involves inhibition of viral transcription [138] and luteolin12 demonstrated synergistic effects with another flavonoid kaempferol against herpes simplex virus [133]. Kamiya [139] documented the importance of essential amino acids such as lysine, valine, isoleucine, and histidine in terms of the risks to health if they are deficient. The author also documented their biological effects which include muscle protein maintenance, potentiation of immune function, tissue repair acceleration after burn or trauma, protecting liver from toxic agents, lowering blood pressure, modulating cholesterol metabolism, and stimulating insulin or growth hormone secretion. Therefore,L. javanica leaves and other plant parts which have shown to be rich in flavonoid and polyphenolic compounds, amino acids, and essential oil could play an important role in the treatment and management of diseases such as hypertension and inflammation listed in Table 1.


## 4. Pharmacological Activities

Scientific studies onL. javanica indicate that it has a wide range of pharmacological activities (Table 4), which include anticancer [140], antidiabetic [141], antimalarial [4, 49, 142], antimicrobial [2, 3, 7, 17, 73–75, 77, 83, 84, 126, 143], antioxidant [7, 10, 11, 75, 77, 125], antiplasmodial [2, 79, 80, 84, 144, 145], and pesticidal effects [1, 2, 59, 95, 120, 146–150] and cytotoxicity [2, 73, 79, 120] activities. Table 4 summarizes some of the pharmacological studies undertaken onL. javanica extracts aimed at evaluating some of the ethnomedicinal uses of the species documented throughout its distributional range (see Table 1). Some of the listed pharmacological activities may not relate directly to the documented ethnomedicinal uses of the species but may provide some insight into the species’ potential therapeutic value and bioactive properties and application.Table 4
Summary of pharmacological activities of the extracts isolated from different parts ofLippia javanica.
Activity tested Extract Plant part Model Effect Reference Antiamoebic Piperitenone162 Leaves Microdilution assay Active with IC50 value of 25 μg/mL against E. histolytica [73]  Antibacterial Piperitenone162 Leaves Microdilution assay Active with MIC value of 50μg/mL against A. calcoaceticus, M. kristinae (50 μg/mL), S. typhi (25 μg/mL), and S. aureus(12 μg/mL) [73]  Antibacterial (Antiproteus) Methanol Leaves Disc diffusion assay Active withMIC value of 313μg/mLagainst P. mirabilis and 926 μg/mL against P. vulgaris [74] Water Leaves Disc diffusion assay Exhibited weak activity againstP.mirabilis with MIC value of 1873 μg/mL and 1768 μg/mL against P. vulgaris [74]  Antibacterial Acetone Leaves Microdilution assay Active againstE. coliwithMIC value of 0.64 mg/mL, E. faecalis(0.64), P. aeruginosa(0.32), and S. aureus(0.64). Total activity MIC values were as follows: E. coli(127 mg/mL), E. faecalis(127 mg/mL), P. aeruginosa(253 mg/mL), and S. aureus(127 mg/mL) [75] Acetone Leaves Microdilution assay Active againstB. cereus withMIC value of 3 mg/mL, Bacillus pumilus (6 mg/mL), B. subtilis(>12 mg/mL), S. aureus (12 mg/mL), E. faecalis (6 mg/mL), E. cloacae (6 mg/mL), E. coli (6 mg/mL), Pantoea agglomerans (12 mg/mL), P. aeruginosa (12 mg/mL), Shigella flexneri (1.5 mg/mL), Aeromonas hydrophila (12 mg/mL), P. mirabilis (>12 mg/mL), K. pneumoniae (12 mg/mL), Salmonella choleraesuis (6 mg/mL), and Serratia marcescens(>12 mg/mL) [17] Hexane Leaves Microdilution assay Active againstB. cereus withMIC value of 12 mg/mL, B. pumilus(12 mg/mL), B. subtilis (12 mg/mL), S. aureus (6 mg/mL), E. faecalis (12 mg/mL), E. cloacae (12 mg/mL), E. coli (6 mg/mL), P. agglomerans (12 mg/mL), P. aeruginosa (12 mg/mL), S. flexneri (6 mg/mL), A. hydrophila (12 mg/mL), P. mirabilis (12 mg/mL), K. pneumoniae (12 mg/mL), S. choleraesuis (6 mg/mL), and antiamoebic effect (12 mg/mL) [17] Methanol Leaves Microdilution assay Active againstB. cereus withMIC values of 1.5 mg/mL, B. pumilus(6 mg/mL), B. subtilis (>12 mg/mL), S. aureus (12 mg/mL), E. faecalis (3 mg/mL), E. cloacae (6 mg/mL), E. coli (6 mg/mL), P. agglomerans (12 mg/mL), P. aeruginosa (12 mg/mL), S. flexneri (1.5 mg/mL), A. hydrophila (6 mg/mL), P. mirabilis (>12 mg/mL), K. pneumoniae (12 mg/mL), S. choleraesuis (6 mg/mL), and S. marcescens (12 mg/mL) [17] Essential oil Leaves Microdilution assay Active againstB. cereus withMIC values of 6 mg/mL, B. pumilus (6 mg/mL), B. subtilis (3 mg/mL), S. aureus (1.5 mg/mL), E. faecalis (3 mg/mL), E. cloacae (12 mg/mL), E. coli (6 mg/mL), P. agglomerans (6 mg/mL), P. aeruginosa (12 mg/mL), S. flexneri (3 mg/mL), A. hydrophila (3 mg/mL), P. mirabilis (>12 mg/mL), K. pneumoniae (3 mg/mL), S. choleraesuis (1.5 mg/mL), and S. marcescens (>12 mg/mL) [17] Methanol Leaves Microdilution assay Active againstE. faecalis with MIC value of 0.14 mg/mL [7] Methanol Leaves Microdilution assay Active againstE. coliwith MIC value of 0.31 mg/mL [7] Methanol Leaves Microdilution assay Active againstP. aeruginosa with MIC value of 0.42 mg/mL [7] Methanol Leaves Microdilution assay Active againstS. aureus with MIC value of 0.13 mg/mL [7]  Antifungal Acetone Leaves Microdilution assay Active againstC. albicans with MIC value of >7.5 mg/mL, C. krusei (1.88 mg/mL), and C. neoformans (>7.5 mg/mL) [7] Hexane Leaves Microdilution assay Active againstC. albicanswith MIC value of >3.75 mg/mL, C. krusei(3.75 mg/mL), and C. neoformans (>7.5 mg/mL) [7] Acetone Leaves Microdilution assay Active againstC. kruseiwith MFC value of 7.5 mg/mL [7] Dichloromethane Aerial parts Microdilution assay Active againstFusarium proliferatumwith MIC value of 0.14 mg/mL and Fusarium verticillioides (0.19 mg/mL) [76] Hexane Aerial parts Microdilution assay Active againstF. proliferatumwith MIC value of 0.23 mg/mL and F. verticillioides (0.45 mg/mL) [76] Methanol Aerial parts Microdilution assay Active againstF. proliferatum with MIC value of 1.77 mg/mL and F. verticillioides (0.43 mg/mL) [76] Methanol Aerial parts Microdilution assay Active againstF. proliferatum with MIC value of >2.50 mg/mL and F. verticillioides (>2.50 mg/mL) [76]  Antimycobacterial Acetone Leaves Microdilution assay Active with MIC value of 0.47 mg/mL and total activity of 10 mL/g againstM. smegmatis [77] Dichloromethane Leaves Microdilution assay Active with MIC value of 1.25 mg/mL and total activity of 23 mL/g againstM. smegmatis [77] Hexane Leaves Microdilution assay Active with MIC value of 0.62 mg/mL and total activity of 13 mL/g againstM. smegmatis [77] Methanol Leaves Microdilution assay Active with MIC value of 1.25 mg/mL and total activity of 7 mL/g againstM. smegmatis [77]  Antioxidant Water Leaves DPPH assay Exhibited activity with EC50 value of 358 μg/mL [7] Water Leaves — Exhibited activity with 209 ascorbic acid equivalent (mg/g dry weight) [7] Water Leaves ABTS assay Active with TEAC value of 1.5 mmol/100 g [78] Water Leaves DPPH assay Active with TEAC value of 1462.54 mmol/100 g [78] Water Leaves FRAP assay Active with TEAC value of 2.38 mmol/100 g [78]  Antiplasmodial Hexane, chloroform Roots Microdilution assay Active againstP. falciparumchloroquine sensitive with IC50 value of 12.25±0.72 μg/mL [79] Ethyl acetate Roots Microdilution assay Active againstP. falciparumchloroquine sensitive with IC50 value of 12.12±0.79 μg/mL [79] Methanol Roots Microdilution assay Active againstP. falciparumchloroquine sensitive with IC50 value of 1.35±0.06 μg/mL [79] Hexane, chloroform Roots Microdilution assay Active againstP. falciparumchloroquine resistant with IC50 value of 18.59±0.26 μg/mL [79] Ethyl acetate Roots Microdilution assay Active againstP. falciparumchloroquine resistant with IC50 value of 15.80±0.26 μg/mL [79] Methanol Roots Microdilution assay Active againstP. falciparumchloroquine resistant with IC50 value of 1.75±0.17 μg/mL [79] Dichloromethane Roots pLDH assay Active againstP. falciparumwithIC50 value of 3.8 μg/mL [80] Dichloromethane/methanol Roots pLDH assay Active againstP. falciparumwithIC50 value of 27 μg/mL [80] Methanol Roots pLDH assay Active againstP. falciparumwithIC50 value of 24 μg/mL [80] Water Roots pLDH assay Active againstP. falciparum withIC50 value of >100 μg/mL [80] Dichloromethane Stems pLDH assay Active againstP. falciparumwithIC50 value of 4.5 μg/mL [80] Dichloromethane/methanol Stems pLDH assay Active againstP. falciparumwithIC50 value of 21.8 μg/mL [80] Methanol Stems pLDH assay Active againstP. falciparumwith IC50 value of 29.8 μg/mL [80] Water Stems pLDH assay Active againstP. falciparumwithIC50 value of >100 μg/mL [80]  Free radical scavenging activity Water — DPPH assay Active with IC50 value of 0.059±0.02 g/mL [11] 50% methanol — DPPH assay Active with IC50 value of 0.04±0.001 g/mL [11] Ethanol — DPPH assay Active with IC50 value of 0.025±0.001 g/mL [11] 50% ethanol — DPPH assay Active with IC50 value of 0.027±0.005 g/mL [11] Acetone — DPPH assay Active with IC50 value of 0.057±0.004 g/mL [11] 50% acetone — DPPH assay Active with IC50 value of 0.022±0.001 g/mL [11] Ethyl acetate — DPPH assay Active with IC50 value of 0.066±0.001 g/mL [11]  Toxicity Methanol Leaf Brine shrimp lethality assay 40% mortality recorded after 48 h exposure towardsArtemia nauplii [74] Methanol Roots Brine shrimp lethality assay Active againstP. falciparumchloroquine sensitive with IC50 value of 843.0 μg/mL [79] Methanol Roots Brine shrimp lethality assay Active againstP. falciparumchloroquine resistant with IC50 value of 650.3 μg/mL [79]


### 4.1. Anticancer Activity

Fouche et al. [140] reported anticancer activity of dichloromethane root extract ofL. javanica against three human cells, exhibiting TGI value of 1.82 μg/mL for breast MDA-MB-435, 1.86 μg/mL for breast MDA-N, and 2.09 μg/mL for melanoma MALME-3M. Based on literature, a couple of terpenoid compounds that have been isolated fromL. javanica are known to have antitumor properties. For example, linalool120 is known to have antitumor activity which plays a protective role against hepatotoxicity and the compound has anti-inflammatory activities as well [151]. Research by Yang et al. [152] showed limonene92 to have inhibitory effect on pancreatic and mammary tumors. Another terpenoid compound, α-pinene44, is known to inhibit translocation of NF-κB or p65 protein into nuclei of LPS-stimulated THP-1 cells [153]. These findings serve as a scientific validation for the use ofL. javanica as a component of a herbal concoction known in KwaZulu Natal province as “imbiza,” prepared by mixingL. javanica withC. obliquus as herbal medicine for cancer [27].


### 4.2. Antidiabetic Activity

Arika et al. [141] determined the in vivo antidiabetic activity of aqueous leaf extracts ofL. javanica in white male alloxan-induced albino mice. The aqueous leaf extracts ofL. javanicaat all dose levels significantly lowered the blood glucose levels in both oral and intraperitoneal routes. The antidiabetic effect ofL. javanicacould have been due to the observed presence of flavonoids. The polyhydroxylated flavonol enhances lipogenesis and glucose uptake in the adipocytes and flavanoids have demonstrated insulinmimetic properties as the compound is known to be effective at controlling blood sugar levels. These findings strengthen the view thatL. javanica is a potential source of antidiabetic agents and to some extent validate the traditional use of the plant species mixed withC. obliquus to form a herbal concoction known in KwaZulu Natal province, South Africa, as “imbiza” used against diabetes [27].


### 4.3. Antimalarial Activity

Govere et al. [142] found that topical application ofL. javanica alcohol extract leads to 76.7% protection againstAnopheles arabiensis for 4 hours.Lippia javanicahas been used as a mosquito repellent by the rural communities in Zimbabwe for a long time and previous studies have shown that essential oils from the species have very strong and lasting repellent activity against femaleA. arabiensis[64]. Research by Lukwa et al. [4] revealed that topical application of 5 mg/cm2 ofL. javanicaleads to 100% protection againstAnopheles aegyptifor 8 hours. Mavundza et al. [154] screened dichloromethane and ethanol leaf extracts ofL. javanica for adulticidal activity againstA. arabiensis. The authors observed dichloromethane and ethanol activities of 45% and 55% mosquito mortality, respectively. These findings strengthen the view thatL. javanica is a potential source of antimalarial agents and to some extent validate the traditional use of the plant species as mosquito repellent in India [47], South Africa [34, 49, 58], and Zimbabwe [4, 48].


### 4.4. Antioxidant Activity

Leaf infusions ofL. javanicaexhibited antioxidant activity with EC50 value of 358 μg/mL and contained 14.8 mg/mL of dry weight gallic acid equivalent phenolic compounds [7]. The EC50 value of 358 μg/mL obtained forL. javanica by Shikanga et al. [7] compares well to those of many commercial teas, including antioxidant capacity of Rooibos Fresh Pack™ herbal teas(A. linearis) with the best antioxidant activity of 333 μg/mL. The high antioxidant activities displayed byL. javanica infusions can be partially attributed to the high levels of verbascoside2 (1.5 mg/g dry weight) reported by Olivier et al. [81] in the leaf extract of the species. Earlier research by Muchuweti et al. [125] reported 74.4% inhibition of the DPPH radical by an ethanolic leaf extract ofL. javanica. Lekganyane et al. [75] reported antioxidant activity inL. javanicaand the acetone extracts of the species displayed antioxidant activity on BEA chromatogram [77]. Bhebhe et al. [10] reported the antioxidant activities ofL. javanica based on the DPPH, reducing power and inhibition of phospholipid peroxidation assays. Free radical scavenging activity ofL. javanica is attributed to phenolic compounds since these compounds have an ideal structural chemistry for free radical scavenging activity [155]. Bhebhe et al. [11] determined the effect of several solvents on the free radical scavenging activity ofL. javanica using the DPPH assay. Free radical scavenging activity expressed as IC50 ranged from 0.022 ± 0.001 g/mL to 0.066 ± 0.001 g/mL; see Table 4.


### 4.5. Antiplasmodial Activity

Prozesky et al. [144] evaluatedL. javanica leaf acetone extract for in vitro antiplasmodial activity using PfUP1, a chloroquine resistant strain of the malaria parasitePlasmodium falciparum by means of the flow cytometric test. The IC50 value forL. javanica was 4.26 μg/mL. Manenzhe et al. [2] evaluated essential oil, piperitenone162, isolated fromL. javanica for antiplasmodial activity using chloroquine diphosphate as positive control and found it active against a chloroquine sensitive strain ofP. falciparum in micromolar concentrations with IC50 of 8 μg/mL. Clarkson et al. [80] evaluatedL. javanica roots and stems extracts for in vitro activity againstP. falciparumusing the parasite lactase dehydrogenase (pLDH) assay and chloroquine diphosphate (Sigma) as the positive control. The dichloromethane, methane, and water extracts showed IC50 values ranging from 3.8 to >100 μg/mL; see Table 4. Omolo et al. [145] screened the essential oil ofL. javanica for fumigant toxicity toAnopheles gambiae which exhibited LD50 of 4.3 × 10−3 mg cm−3. Ayuko et al. [79] showed thatL. javanica root extracts have antiplasmodial activity againstP. falciparum with IC50 ranging from 1.35 to 18.59 μg/mL; see Table 4. Lippialactone21, derived from the ethyl acetate extract of aerial parts ofL. javanica, exhibited some activity against the chloroquine sensitive D10 strain ofP. falciparum with an IC50 value of 9.1 μg/mL and is also mildly cytotoxic [84]. Compared to chloroquine, the compound is approximately 2000 times less active against the D10 strain ofP. falciparum[84].


### 4.6. Antimicrobial Activities

Lippia javanica is widely used in the treatment of a wide range of infectious diseases caused by microorganisms. Viljoen et al. [3] determined the antimicrobial properties ofL. javanica by evaluating the time kill studies of the species’ essential oil using the disc diffusion assay on three respiratory pathogensKlebsiella pneumoniae,Cryptococcus neoformans,andBacillus cereus. This study showed that the killing rate was greatest forK. pneumoniae followed by C. neoformansand very little reduction of microbial populations was observed forB. cereus. The efficacy ofL. javanicaoil forK. pneumoniaeshowed a killing rate within 30 minutes for the concentrations 0.25, 0.5, 0.75, and 1%,C. neoformansshowed a killing rate for concentrations 0.5, 0.75, and 1% within 1 hour, and the lowest concentration of 0.25% took 8 hours before a bactericidal effect was noted whileB. cereusshowed some reduction in colonies [3]. The positive antimicrobial activity ofL. javanica as revealed by the time kill study could be attributed to linalool120 which averages between 65 and 70% in yield [3, 5, 88, 90] and has known antimicrobial properties [93, 156–159]. These findings somehow corroborate the traditional use ofL. javanicaas herbal medicine for a wide range of bacterial and fungal respiratory ailments indicated in Table 1.Manenzhe et al. [2] evaluated essential oil, piperitenone162, isolated fromL. javanica for antibacterial activity on cultures ofBacillus subtilis, Staphylococcus aureus,andEscherichia coliusing imipenem, cefazolin, and ampicillin as positive controls. The authors found piperitenone162to inhibitS. aureus andE. coliat 1% dilution. Acetone, hexane, and methanol leaf extracts and essential oil isolated fromL. javanica showed some activity against fifteen Gram-positive and Gram-negative bacteria with MIC values ranging from 1.5 to >12 mg/mL [60]; see Table 4. In a similar study, Samie et al. [73] demonstrated that a pure compound piperitenone162isolated fromL. javanica has antibacterial activities againstAcinetobacter calcoaceticus, Micrococcus kristinae, Salmonella typhi, andS. aureus using dimethyl sulphoxide and kanamycin as controls, with MIC values ranging from 12 to 50 μg/mL; see Table 4. Shikanga et al. [7] evaluated the antibacterial activity ofL. javanicamethanolic leaf extract againstS. aureus, Enterococcus faecalis, E. coli,andPseudomonas aeruginosausing the serial microdilution method with gentamycin (Virbac®) and acetone as positive and negative controls, respectively.Lippia javanica displayed antibacterial activities with MIC values ranging from 0.13 to 0.42 mg/mL against all four pathogens; see Table 4. The obtained minimum inhibitory concentrations are promising, since natural products with MIC values below 1 mg/mL are generally considered to be noteworthy findings [160]. Lippialactone21, derived from the ethyl acetate extract of aerial parts ofL. javanica, exhibited some activity against theE. coliandS. aureusat a concentration of 10 mg/mL [84]. Lekganyane et al. [75] reported antibacterial activity ofL. javanica acetone leaf extracts againstE. coli,E. faecalis,P. aeruginosa,andS. aureuswith MIC values ranging from 0.32 to 0.64 mg/mL and total activity of the same species ranging from 127 to 253 mg/mL; see Table 4. Methanol and water leaf extracts ofL. javanicaexhibited some antiproteus activity againstProteus mirabilis andProteus vulgaris with MIC values <2000 μg/mL with standard discs of ampicillin (2 μg) and chloramphenicol (10 μg) as positive controls [74]. Some of the antibacterial properties ofL. javanicacan be attributed to the phytochemical constituents of the species; for example, the phenolic compound apigenin7 is a well-known antibacterial agent [7, 134]. Apigenin7was shown to be highly active againstVibrio cholera andE. faecalis [161], while Basile et al. [162] reported the inhibition ofS. typhi, P. mirabilis, andP. aeruginosaby the compound. Therefore, results from these antibacterial evaluations ofL. javanica give credence to the use of the species’ infusions against bacterial infections and other related diseases.Shikanga et al. [126] investigated the antifungal activities of leaf extracts and essential oil compounds isolated fromL. javanica leafy extracts against a Guazatine®-resistant strain ofPenicillium digitatum. The methanolic leafy extracts, isoverbascoside3 and verbascoside2compounds, isolated fromL. javanica inhibited fungal growth at concentrations above 0.6 mg·mL−1, causing significant inhibition of mycelial growth. Verbascoside2 is well-known for its antimicrobial properties and has been found to inhibit viruses, bacteria, and fungi [163]. Similarly, Samie et al. [143] investigated antifungal effects of acetone and hexane leaf extracts ofL. javanica againstCandida albicans, Candida krusei,andC. neoformans isolated from AIDS patients using the microdilution method with nystatin, Roche, and DMSO as positive and negative controls, respectively. Noteworthy moderate antifungal activities were recorded fromC. krusei with MIC value of 1.88 mg/mL and other recorded MFC and MIC values for other species ranged from 1.88 mg/mL to >7.5 mg/mL; see Table 4. Thembo et al. [76] investigated the antifungal activity of aqueous and organic extracts ofL. javanicausing a serial microdilution assay. Generally, extracts ofL. javanica exhibited weak activity; see Table 4.


### 4.7. Antimycobacterial Activity

Mujovo et al. [83] evaluatedL. javanicacompounds against a drug-sensitive strain ofMycobacterium tuberculosis using the radiometric respiratory techniques. Of all the isolated compounds, only one triterpenoid carboxylic acid, euscaphic acid172, exhibited antimycobacterial activity with MIC value of 50 μg mL−1 against this strain. In a similar study, the leaf extract ofL. javanica exhibited antimycobacterial activity againstM. smegmatis in an evaluation which used microdilution assay and rifampicin as control [77]. Acetone extract was the best extractant with MIC value of 0.47 mg/mL; it extracted antibacterial agents which was indicated by the lowest MIC value [77]. Masoko and Nxumalo [77] also evaluated the total activity ofL. javanicawhich averaged 13 mL/g suggesting that the extract prepared from one gram ofL. javanicacould be diluted to a volume of 13 mL and will still inhibitM. smegmatis efficiently. According to Semenya and Maroyi [115], tuberculosis caused byM. tuberculosisis a serious disease requiring effective strategies and tools to control and manage it. Therefore, preliminary evaluations done by Mujovo et al. [83] and Masoko and Nxumalo [77] serve as a scientific validation for the use ofL. javanica in traditional medicine for treatment of tuberculosis and other respiratory ailments in South Africa [24, 27, 115] and Uganda [43] as well as their efficiency in tuberculosis drug discovery.


### 4.8. Antiviral Activity

Mujovo et al. [83] found that (E)-2(3)-tagetenone epoxide42and piperitenone162 inhibited the HIV-1 reverse transcriptase enzyme by 91% and 53%, respectively, at 100 μg mL−1 based on a nonradioactive HIV RT colorimetric ELISA kit. Little is known about the HIV RT activity ofL. javanicaextracts or compounds, but flavonoids are known to be active against viral RT and also as potent inhibitors of the cellular alpha and beta DNA polymerase [83], while luteolin12 is active against HIV RT [164, 165].Lippia javanica is traditionally used to treat HIV/AIDS symptoms in South Africa [65, 66] and several viral and HIV/AIDS opportunistic diseases and infections such as bronchitis [15, 19–22], chicken pox [50], diarrhoea [17, 34, 37, 44, 113], measles [14, 20, 38], pneumonia [14], shingles [15], and venereal diseases [44]. Despite significant advances in the utilization ofL. javanica in southern Africa over the years for numerous viral diseases (Table 1), very little antiviral evaluations have been done on crude extracts and purified compounds of the species. There is need, therefore, for more pharmacological research asL. javanica could be harbouring potent (RT) inhibitors which could be useful for the development of new pharmaceutical products important for use against viral diseases and infections.


### 4.9. Pesticidal Effects

Magano et al. [95] evaluated the repellent effects of hexane extracts ofL. javanicaessential oil using the in vitro tick climbing repellency bioassay on adults ofHyalomma marginatum rufipes Koch ticks. The authors found that 107 mg/mL caused repellency index of 100% at one hour and 30 minutes. In a similar study by Madzimure et al. [120],L. javanicaaqueous leaf extracts at 10% and 20% w/v were effective at controlling cattle ticks (Amblyomma species,Boophilus species,Hyalomma species,Rhipicephalus appendiculatus, andRhipicephalus evertsi evertsi) and were as good as the positive control amitraz-based acaricide Trickbuster®. These authors found no parasites on microscopic examination of the Giemsa-stained thin blood smear collected from treated cattle implying that the animals did not suffer from clinical tick-borne diseases. Similarly, Nyahangare et al. [59] tested the pesticidal activity ofL. javanica water extracts against cattle ticks. The authors found no significant difference between cattle treated with a commercial synthetic acaricide and those underL. javanicatreatment. Martinez-Velazquez et al. [166] evaluated pesticidal effects of two essential oils, namely, γ-terpinene82 and ρ-cymene99, isolated fromLippia graveolens Kunth against 10-day-oldRhipicephalus (Boophilus) microplus(Canestrini) tick larvae using the larval packet test bioassay. The two essential oils produced high mortality ranging from 90 to 100% in all tested concentrations of 20 to 1.25% (v/v). Therefore,L. javanica can provide an effective tick control option where synthetic products are unavailable or unaffordable particularly in remote rural areas in sub-Saharan Africa.Lippia javanica is popular for tick control and management among resource-poor smallholder farmers in South Africa [58, 95] and Zimbabwe [59, 60, 120]. While these preliminary evaluations may serve as confirmation thatL. javanica has some bioactivities against ticks, a comprehensive method of tick control is required for the resource-constrained smallholder farmers based on ethnopharmacological properties ofL. javanica.McGaw et al. [146] screenedL. javanica for the anthelmintic test systems using the free living nematodeCaenorhabditis elegans. The crude ethanol and hexane extracts showed some activity at a concentration of 2 mg/mL, with the 7-day incubation assay appearing to be more sensitive than the shorter assay. Earlier research by Mwangi et al. [1] indicated thatL. javanicawas active againstAedes aegyptilarvae andSitophilus zeamaisMotschulsky (maize weevil). Katsvanga and Chigwiza [147] reported thatL. javanica is an effective natural pesticide which can be used to control aphid species(Brevicoryne brassicae). In their study, Katsvanga and Chigwiza [147] found that 1 : 1 powdered aqueous leaf extract ofL. javanica reducedB. brassicae by 53.2% against 78.3% and 96.7% of two synthetic pesticides, Aphid kill and Bexadust “L,” respectively. Chikukura et al. [149] foundL. javanica powdered leaf extracts to have insecticidal properties with potential to control grain damage by 21–33%. Mashela et al. [148] reported that the application of groundL. javanica leaves to soil in nematode-infested(Meloidogyne incognita) pots reduced the nematode numbers by 79–92% and significantly increased fresh fruit yield, dry shoot mass, plant height, and stem diameter of the tomato plants, as well as levels of potassium, nitrogen, and manganese in leaf tissue. Muzemu et al. [150] evaluated water extracts ofL. javanica leaf powder for pesticidal effects against rape (Brassica napus L.) aphids,B. brassicae, and tomato (Solanum lycopersicum Lam.) red spider mites, andTetranychus evansi as alternatives to conventional pesticides.Lippia javanicareducedB. brassicae andTetranychus evansiby 12.5% and 63%, respectively [150]. The study demonstrated thatL. javanica has pesticidal effects onB. brassicae andT. evansi. The reduced number ofB. brassicae andT. evansi could be due toL. javanica’s extracts having repellent, toxic, and antifeedant effects since the species has essential oils with pesticidal properties [2]. Therefore, these findings indicate thatL. javanicahas both nematicidal and plant growth-promoting properties.


### 4.10. Toxicity and Cytotoxicity Activity

Lippia javanica is known to cause liver damage and photosensitisation in livestock, resulting in stock losses [167]. Triterpenoids isolated from the genusLippia are icterogenic and cause jaundice as a result of liver damage [167]. The characteristic swelling, yellowing, and later peeling of unpigmented skin are due to the presence of phylloerythrin, a photodynamic porphyrin that reacts with sunlight and causes severe cell damage [167]. The compound is normally formed when chlorophyll is broken down by microorganisms in the rumen, but it now accumulates in the liver as a result of the damage caused by triterpenoids [167]. In view of the known toxicity ofLippia species, the prolonged use of high doses ofL. javanica is potentially harmful [167].Lippia javanica showed low toxicity after 48 h exposure with the percentage of mortality below 50% [74].Ayuko et al. [79] evaluated the toxicity ofL. javanica using a brine shrimp cytotoxicity assay with LC50 value of 1138 ± 1.33 μg/mL. Ayuko et al. [79] found the cytotoxicity to antiplasmodial activity ratios for the methanolic extracts of the two tested strains to be 843.0 and 650.3, and since these are greater than 100, it may be concluded that the extracts are of low toxicity. Samie et al. [73] demonstrated that a pure compound piperitenone162 isolated fromL. javanicaessential oil has low cytotoxicity activity against intestinal adenocarcinoma cells (i.e., the HCT-8 monolayers with IC50 of 265.6 ± 5.3 μg/mL). Lukwa [64] evaluated the toxicity ofL. javanica aqueous leaf extracts using sexually mature BALB/c mice with the placebo as control. Within 48 hours, all mice fed with theL. javanica leaf aqueous extract at 12.5–37.5% v/v were lethargic, and the overall mortality was 37.5%. Previous research by Manenzhe et al. [2] showed that hydrodistillation ofL. javanica leaves, flowers, and stems produced oil that was poisonous againstP. falciparumwhen diluted to 1% (v/v). These findings imply that, despite its apparent safety, water extracts ofL. javanica leaves may have deleterious health implications on humans and animals if consumed at very high doses.Many compounds that have been isolated fromL. javanica including phenolic glycosides, flavonoids, and essential oils are not known to have acute toxic properties with the exception of icterogenin173.Icterogenin173has been shown to inhibit biliary excretion in rabbits [168]. Reports in literature indicate that the consumption of xanthine22has resulted in mammalian toxicity. According to Madzimure et al. [64], xanthine22is a demethylated derivative of caffeine with pharmacological actions such as central nervous system (CNS) stimulation, relaxation of smooth muscle (especially bronchial muscle), myocardial stimulation, peripheral vasoconstriction, and diuresis. Considering the widespread use ofL. javanica as herbal tea and medicine, it is important to determine if any toxicological effects can occur from its chronic or subchronic usage.


### 4.11. Other Activities

Mpofu et al. [169] determined the effect of inclusion ofL. javanica leaf meal in broiler diets on growth performance, carcass characteristics, and fatty acid profiles. The authors found that theL. javanica fed broilers had higher total polyunsaturated fatty acids and n-3 fatty acids. The findings from the study showed that inclusion ofL. javanica in broiler diets at 5 g/kg feed has positive influences on growth performance, carcass characteristics, and fatty acid profiles of broiler meat and, therefore,L. javanica has potential as growth-promoting feed additive in broilers. Samie et al. [73] evaluated antiamoebic activity of a pure compound piperitenone162 isolated fromL. javanicaessential oil againstEntamoeba histolytica using microdilution method with metronidazole as the positive control, diluents (i.e., culture medium with an appropriate concentration of dimethyl sulphoxide as the negative control), and a blank (i.e., culture medium without dimethyl sulphoxide). Samie et al. [73] demonstrated that piperitenone162 had marked antiamoebic activity with IC50 value of 25 μg/mL. More research is required asL. javanicacould be harbouring potent antiamoebic properties which could be useful for managing amoebiasis, an infection that remains a significant cause of morbidity and mortality worldwide.


## 4.1. Anticancer Activity

Fouche et al. [140] reported anticancer activity of dichloromethane root extract ofL. javanica against three human cells, exhibiting TGI value of 1.82 μg/mL for breast MDA-MB-435, 1.86 μg/mL for breast MDA-N, and 2.09 μg/mL for melanoma MALME-3M. Based on literature, a couple of terpenoid compounds that have been isolated fromL. javanica are known to have antitumor properties. For example, linalool120 is known to have antitumor activity which plays a protective role against hepatotoxicity and the compound has anti-inflammatory activities as well [151]. Research by Yang et al. [152] showed limonene92 to have inhibitory effect on pancreatic and mammary tumors. Another terpenoid compound, α-pinene44, is known to inhibit translocation of NF-κB or p65 protein into nuclei of LPS-stimulated THP-1 cells [153]. These findings serve as a scientific validation for the use ofL. javanica as a component of a herbal concoction known in KwaZulu Natal province as “imbiza,” prepared by mixingL. javanica withC. obliquus as herbal medicine for cancer [27].


## 4.2. Antidiabetic Activity

Arika et al. [141] determined the in vivo antidiabetic activity of aqueous leaf extracts ofL. javanica in white male alloxan-induced albino mice. The aqueous leaf extracts ofL. javanicaat all dose levels significantly lowered the blood glucose levels in both oral and intraperitoneal routes. The antidiabetic effect ofL. javanicacould have been due to the observed presence of flavonoids. The polyhydroxylated flavonol enhances lipogenesis and glucose uptake in the adipocytes and flavanoids have demonstrated insulinmimetic properties as the compound is known to be effective at controlling blood sugar levels. These findings strengthen the view thatL. javanica is a potential source of antidiabetic agents and to some extent validate the traditional use of the plant species mixed withC. obliquus to form a herbal concoction known in KwaZulu Natal province, South Africa, as “imbiza” used against diabetes [27].


## 4.3. Antimalarial Activity

Govere et al. [142] found that topical application ofL. javanica alcohol extract leads to 76.7% protection againstAnopheles arabiensis for 4 hours.Lippia javanicahas been used as a mosquito repellent by the rural communities in Zimbabwe for a long time and previous studies have shown that essential oils from the species have very strong and lasting repellent activity against femaleA. arabiensis[64]. Research by Lukwa et al. [4] revealed that topical application of 5 mg/cm2 ofL. javanicaleads to 100% protection againstAnopheles aegyptifor 8 hours. Mavundza et al. [154] screened dichloromethane and ethanol leaf extracts ofL. javanica for adulticidal activity againstA. arabiensis. The authors observed dichloromethane and ethanol activities of 45% and 55% mosquito mortality, respectively. These findings strengthen the view thatL. javanica is a potential source of antimalarial agents and to some extent validate the traditional use of the plant species as mosquito repellent in India [47], South Africa [34, 49, 58], and Zimbabwe [4, 48].


## 4.4. Antioxidant Activity

Leaf infusions ofL. javanicaexhibited antioxidant activity with EC50 value of 358 μg/mL and contained 14.8 mg/mL of dry weight gallic acid equivalent phenolic compounds [7]. The EC50 value of 358 μg/mL obtained forL. javanica by Shikanga et al. [7] compares well to those of many commercial teas, including antioxidant capacity of Rooibos Fresh Pack™ herbal teas(A. linearis) with the best antioxidant activity of 333 μg/mL. The high antioxidant activities displayed byL. javanica infusions can be partially attributed to the high levels of verbascoside2 (1.5 mg/g dry weight) reported by Olivier et al. [81] in the leaf extract of the species. Earlier research by Muchuweti et al. [125] reported 74.4% inhibition of the DPPH radical by an ethanolic leaf extract ofL. javanica. Lekganyane et al. [75] reported antioxidant activity inL. javanicaand the acetone extracts of the species displayed antioxidant activity on BEA chromatogram [77]. Bhebhe et al. [10] reported the antioxidant activities ofL. javanica based on the DPPH, reducing power and inhibition of phospholipid peroxidation assays. Free radical scavenging activity ofL. javanica is attributed to phenolic compounds since these compounds have an ideal structural chemistry for free radical scavenging activity [155]. Bhebhe et al. [11] determined the effect of several solvents on the free radical scavenging activity ofL. javanica using the DPPH assay. Free radical scavenging activity expressed as IC50 ranged from 0.022 ± 0.001 g/mL to 0.066 ± 0.001 g/mL; see Table 4.


## 4.5. Antiplasmodial Activity

Prozesky et al. [144] evaluatedL. javanica leaf acetone extract for in vitro antiplasmodial activity using PfUP1, a chloroquine resistant strain of the malaria parasitePlasmodium falciparum by means of the flow cytometric test. The IC50 value forL. javanica was 4.26 μg/mL. Manenzhe et al. [2] evaluated essential oil, piperitenone162, isolated fromL. javanica for antiplasmodial activity using chloroquine diphosphate as positive control and found it active against a chloroquine sensitive strain ofP. falciparum in micromolar concentrations with IC50 of 8 μg/mL. Clarkson et al. [80] evaluatedL. javanica roots and stems extracts for in vitro activity againstP. falciparumusing the parasite lactase dehydrogenase (pLDH) assay and chloroquine diphosphate (Sigma) as the positive control. The dichloromethane, methane, and water extracts showed IC50 values ranging from 3.8 to >100 μg/mL; see Table 4. Omolo et al. [145] screened the essential oil ofL. javanica for fumigant toxicity toAnopheles gambiae which exhibited LD50 of 4.3 × 10−3 mg cm−3. Ayuko et al. [79] showed thatL. javanica root extracts have antiplasmodial activity againstP. falciparum with IC50 ranging from 1.35 to 18.59 μg/mL; see Table 4. Lippialactone21, derived from the ethyl acetate extract of aerial parts ofL. javanica, exhibited some activity against the chloroquine sensitive D10 strain ofP. falciparum with an IC50 value of 9.1 μg/mL and is also mildly cytotoxic [84]. Compared to chloroquine, the compound is approximately 2000 times less active against the D10 strain ofP. falciparum[84].


## 4.6. Antimicrobial Activities

Lippia javanica is widely used in the treatment of a wide range of infectious diseases caused by microorganisms. Viljoen et al. [3] determined the antimicrobial properties ofL. javanica by evaluating the time kill studies of the species’ essential oil using the disc diffusion assay on three respiratory pathogensKlebsiella pneumoniae,Cryptococcus neoformans,andBacillus cereus. This study showed that the killing rate was greatest forK. pneumoniae followed by C. neoformansand very little reduction of microbial populations was observed forB. cereus. The efficacy ofL. javanicaoil forK. pneumoniaeshowed a killing rate within 30 minutes for the concentrations 0.25, 0.5, 0.75, and 1%,C. neoformansshowed a killing rate for concentrations 0.5, 0.75, and 1% within 1 hour, and the lowest concentration of 0.25% took 8 hours before a bactericidal effect was noted whileB. cereusshowed some reduction in colonies [3]. The positive antimicrobial activity ofL. javanica as revealed by the time kill study could be attributed to linalool120 which averages between 65 and 70% in yield [3, 5, 88, 90] and has known antimicrobial properties [93, 156–159]. These findings somehow corroborate the traditional use ofL. javanicaas herbal medicine for a wide range of bacterial and fungal respiratory ailments indicated in Table 1.Manenzhe et al. [2] evaluated essential oil, piperitenone162, isolated fromL. javanica for antibacterial activity on cultures ofBacillus subtilis, Staphylococcus aureus,andEscherichia coliusing imipenem, cefazolin, and ampicillin as positive controls. The authors found piperitenone162to inhibitS. aureus andE. coliat 1% dilution. Acetone, hexane, and methanol leaf extracts and essential oil isolated fromL. javanica showed some activity against fifteen Gram-positive and Gram-negative bacteria with MIC values ranging from 1.5 to >12 mg/mL [60]; see Table 4. In a similar study, Samie et al. [73] demonstrated that a pure compound piperitenone162isolated fromL. javanica has antibacterial activities againstAcinetobacter calcoaceticus, Micrococcus kristinae, Salmonella typhi, andS. aureus using dimethyl sulphoxide and kanamycin as controls, with MIC values ranging from 12 to 50 μg/mL; see Table 4. Shikanga et al. [7] evaluated the antibacterial activity ofL. javanicamethanolic leaf extract againstS. aureus, Enterococcus faecalis, E. coli,andPseudomonas aeruginosausing the serial microdilution method with gentamycin (Virbac®) and acetone as positive and negative controls, respectively.Lippia javanica displayed antibacterial activities with MIC values ranging from 0.13 to 0.42 mg/mL against all four pathogens; see Table 4. The obtained minimum inhibitory concentrations are promising, since natural products with MIC values below 1 mg/mL are generally considered to be noteworthy findings [160]. Lippialactone21, derived from the ethyl acetate extract of aerial parts ofL. javanica, exhibited some activity against theE. coliandS. aureusat a concentration of 10 mg/mL [84]. Lekganyane et al. [75] reported antibacterial activity ofL. javanica acetone leaf extracts againstE. coli,E. faecalis,P. aeruginosa,andS. aureuswith MIC values ranging from 0.32 to 0.64 mg/mL and total activity of the same species ranging from 127 to 253 mg/mL; see Table 4. Methanol and water leaf extracts ofL. javanicaexhibited some antiproteus activity againstProteus mirabilis andProteus vulgaris with MIC values <2000 μg/mL with standard discs of ampicillin (2 μg) and chloramphenicol (10 μg) as positive controls [74]. Some of the antibacterial properties ofL. javanicacan be attributed to the phytochemical constituents of the species; for example, the phenolic compound apigenin7 is a well-known antibacterial agent [7, 134]. Apigenin7was shown to be highly active againstVibrio cholera andE. faecalis [161], while Basile et al. [162] reported the inhibition ofS. typhi, P. mirabilis, andP. aeruginosaby the compound. Therefore, results from these antibacterial evaluations ofL. javanica give credence to the use of the species’ infusions against bacterial infections and other related diseases.Shikanga et al. [126] investigated the antifungal activities of leaf extracts and essential oil compounds isolated fromL. javanica leafy extracts against a Guazatine®-resistant strain ofPenicillium digitatum. The methanolic leafy extracts, isoverbascoside3 and verbascoside2compounds, isolated fromL. javanica inhibited fungal growth at concentrations above 0.6 mg·mL−1, causing significant inhibition of mycelial growth. Verbascoside2 is well-known for its antimicrobial properties and has been found to inhibit viruses, bacteria, and fungi [163]. Similarly, Samie et al. [143] investigated antifungal effects of acetone and hexane leaf extracts ofL. javanica againstCandida albicans, Candida krusei,andC. neoformans isolated from AIDS patients using the microdilution method with nystatin, Roche, and DMSO as positive and negative controls, respectively. Noteworthy moderate antifungal activities were recorded fromC. krusei with MIC value of 1.88 mg/mL and other recorded MFC and MIC values for other species ranged from 1.88 mg/mL to >7.5 mg/mL; see Table 4. Thembo et al. [76] investigated the antifungal activity of aqueous and organic extracts ofL. javanicausing a serial microdilution assay. Generally, extracts ofL. javanica exhibited weak activity; see Table 4.


## 4.7. Antimycobacterial Activity

Mujovo et al. [83] evaluatedL. javanicacompounds against a drug-sensitive strain ofMycobacterium tuberculosis using the radiometric respiratory techniques. Of all the isolated compounds, only one triterpenoid carboxylic acid, euscaphic acid172, exhibited antimycobacterial activity with MIC value of 50 μg mL−1 against this strain. In a similar study, the leaf extract ofL. javanica exhibited antimycobacterial activity againstM. smegmatis in an evaluation which used microdilution assay and rifampicin as control [77]. Acetone extract was the best extractant with MIC value of 0.47 mg/mL; it extracted antibacterial agents which was indicated by the lowest MIC value [77]. Masoko and Nxumalo [77] also evaluated the total activity ofL. javanicawhich averaged 13 mL/g suggesting that the extract prepared from one gram ofL. javanicacould be diluted to a volume of 13 mL and will still inhibitM. smegmatis efficiently. According to Semenya and Maroyi [115], tuberculosis caused byM. tuberculosisis a serious disease requiring effective strategies and tools to control and manage it. Therefore, preliminary evaluations done by Mujovo et al. [83] and Masoko and Nxumalo [77] serve as a scientific validation for the use ofL. javanica in traditional medicine for treatment of tuberculosis and other respiratory ailments in South Africa [24, 27, 115] and Uganda [43] as well as their efficiency in tuberculosis drug discovery.


## 4.8. Antiviral Activity

Mujovo et al. [83] found that (E)-2(3)-tagetenone epoxide42and piperitenone162 inhibited the HIV-1 reverse transcriptase enzyme by 91% and 53%, respectively, at 100 μg mL−1 based on a nonradioactive HIV RT colorimetric ELISA kit. Little is known about the HIV RT activity ofL. javanicaextracts or compounds, but flavonoids are known to be active against viral RT and also as potent inhibitors of the cellular alpha and beta DNA polymerase [83], while luteolin12 is active against HIV RT [164, 165].Lippia javanica is traditionally used to treat HIV/AIDS symptoms in South Africa [65, 66] and several viral and HIV/AIDS opportunistic diseases and infections such as bronchitis [15, 19–22], chicken pox [50], diarrhoea [17, 34, 37, 44, 113], measles [14, 20, 38], pneumonia [14], shingles [15], and venereal diseases [44]. Despite significant advances in the utilization ofL. javanica in southern Africa over the years for numerous viral diseases (Table 1), very little antiviral evaluations have been done on crude extracts and purified compounds of the species. There is need, therefore, for more pharmacological research asL. javanica could be harbouring potent (RT) inhibitors which could be useful for the development of new pharmaceutical products important for use against viral diseases and infections.


## 4.9. Pesticidal Effects

Magano et al. [95] evaluated the repellent effects of hexane extracts ofL. javanicaessential oil using the in vitro tick climbing repellency bioassay on adults ofHyalomma marginatum rufipes Koch ticks. The authors found that 107 mg/mL caused repellency index of 100% at one hour and 30 minutes. In a similar study by Madzimure et al. [120],L. javanicaaqueous leaf extracts at 10% and 20% w/v were effective at controlling cattle ticks (Amblyomma species,Boophilus species,Hyalomma species,Rhipicephalus appendiculatus, andRhipicephalus evertsi evertsi) and were as good as the positive control amitraz-based acaricide Trickbuster®. These authors found no parasites on microscopic examination of the Giemsa-stained thin blood smear collected from treated cattle implying that the animals did not suffer from clinical tick-borne diseases. Similarly, Nyahangare et al. [59] tested the pesticidal activity ofL. javanica water extracts against cattle ticks. The authors found no significant difference between cattle treated with a commercial synthetic acaricide and those underL. javanicatreatment. Martinez-Velazquez et al. [166] evaluated pesticidal effects of two essential oils, namely, γ-terpinene82 and ρ-cymene99, isolated fromLippia graveolens Kunth against 10-day-oldRhipicephalus (Boophilus) microplus(Canestrini) tick larvae using the larval packet test bioassay. The two essential oils produced high mortality ranging from 90 to 100% in all tested concentrations of 20 to 1.25% (v/v). Therefore,L. javanica can provide an effective tick control option where synthetic products are unavailable or unaffordable particularly in remote rural areas in sub-Saharan Africa.Lippia javanica is popular for tick control and management among resource-poor smallholder farmers in South Africa [58, 95] and Zimbabwe [59, 60, 120]. While these preliminary evaluations may serve as confirmation thatL. javanica has some bioactivities against ticks, a comprehensive method of tick control is required for the resource-constrained smallholder farmers based on ethnopharmacological properties ofL. javanica.McGaw et al. [146] screenedL. javanica for the anthelmintic test systems using the free living nematodeCaenorhabditis elegans. The crude ethanol and hexane extracts showed some activity at a concentration of 2 mg/mL, with the 7-day incubation assay appearing to be more sensitive than the shorter assay. Earlier research by Mwangi et al. [1] indicated thatL. javanicawas active againstAedes aegyptilarvae andSitophilus zeamaisMotschulsky (maize weevil). Katsvanga and Chigwiza [147] reported thatL. javanica is an effective natural pesticide which can be used to control aphid species(Brevicoryne brassicae). In their study, Katsvanga and Chigwiza [147] found that 1 : 1 powdered aqueous leaf extract ofL. javanica reducedB. brassicae by 53.2% against 78.3% and 96.7% of two synthetic pesticides, Aphid kill and Bexadust “L,” respectively. Chikukura et al. [149] foundL. javanica powdered leaf extracts to have insecticidal properties with potential to control grain damage by 21–33%. Mashela et al. [148] reported that the application of groundL. javanica leaves to soil in nematode-infested(Meloidogyne incognita) pots reduced the nematode numbers by 79–92% and significantly increased fresh fruit yield, dry shoot mass, plant height, and stem diameter of the tomato plants, as well as levels of potassium, nitrogen, and manganese in leaf tissue. Muzemu et al. [150] evaluated water extracts ofL. javanica leaf powder for pesticidal effects against rape (Brassica napus L.) aphids,B. brassicae, and tomato (Solanum lycopersicum Lam.) red spider mites, andTetranychus evansi as alternatives to conventional pesticides.Lippia javanicareducedB. brassicae andTetranychus evansiby 12.5% and 63%, respectively [150]. The study demonstrated thatL. javanica has pesticidal effects onB. brassicae andT. evansi. The reduced number ofB. brassicae andT. evansi could be due toL. javanica’s extracts having repellent, toxic, and antifeedant effects since the species has essential oils with pesticidal properties [2]. Therefore, these findings indicate thatL. javanicahas both nematicidal and plant growth-promoting properties.


## 4.10. Toxicity and Cytotoxicity Activity

Lippia javanica is known to cause liver damage and photosensitisation in livestock, resulting in stock losses [167]. Triterpenoids isolated from the genusLippia are icterogenic and cause jaundice as a result of liver damage [167]. The characteristic swelling, yellowing, and later peeling of unpigmented skin are due to the presence of phylloerythrin, a photodynamic porphyrin that reacts with sunlight and causes severe cell damage [167]. The compound is normally formed when chlorophyll is broken down by microorganisms in the rumen, but it now accumulates in the liver as a result of the damage caused by triterpenoids [167]. In view of the known toxicity ofLippia species, the prolonged use of high doses ofL. javanica is potentially harmful [167].Lippia javanica showed low toxicity after 48 h exposure with the percentage of mortality below 50% [74].Ayuko et al. [79] evaluated the toxicity ofL. javanica using a brine shrimp cytotoxicity assay with LC50 value of 1138 ± 1.33 μg/mL. Ayuko et al. [79] found the cytotoxicity to antiplasmodial activity ratios for the methanolic extracts of the two tested strains to be 843.0 and 650.3, and since these are greater than 100, it may be concluded that the extracts are of low toxicity. Samie et al. [73] demonstrated that a pure compound piperitenone162 isolated fromL. javanicaessential oil has low cytotoxicity activity against intestinal adenocarcinoma cells (i.e., the HCT-8 monolayers with IC50 of 265.6 ± 5.3 μg/mL). Lukwa [64] evaluated the toxicity ofL. javanica aqueous leaf extracts using sexually mature BALB/c mice with the placebo as control. Within 48 hours, all mice fed with theL. javanica leaf aqueous extract at 12.5–37.5% v/v were lethargic, and the overall mortality was 37.5%. Previous research by Manenzhe et al. [2] showed that hydrodistillation ofL. javanica leaves, flowers, and stems produced oil that was poisonous againstP. falciparumwhen diluted to 1% (v/v). These findings imply that, despite its apparent safety, water extracts ofL. javanica leaves may have deleterious health implications on humans and animals if consumed at very high doses.Many compounds that have been isolated fromL. javanica including phenolic glycosides, flavonoids, and essential oils are not known to have acute toxic properties with the exception of icterogenin173.Icterogenin173has been shown to inhibit biliary excretion in rabbits [168]. Reports in literature indicate that the consumption of xanthine22has resulted in mammalian toxicity. According to Madzimure et al. [64], xanthine22is a demethylated derivative of caffeine with pharmacological actions such as central nervous system (CNS) stimulation, relaxation of smooth muscle (especially bronchial muscle), myocardial stimulation, peripheral vasoconstriction, and diuresis. Considering the widespread use ofL. javanica as herbal tea and medicine, it is important to determine if any toxicological effects can occur from its chronic or subchronic usage.


## 4.11. Other Activities

Mpofu et al. [169] determined the effect of inclusion ofL. javanica leaf meal in broiler diets on growth performance, carcass characteristics, and fatty acid profiles. The authors found that theL. javanica fed broilers had higher total polyunsaturated fatty acids and n-3 fatty acids. The findings from the study showed that inclusion ofL. javanica in broiler diets at 5 g/kg feed has positive influences on growth performance, carcass characteristics, and fatty acid profiles of broiler meat and, therefore,L. javanica has potential as growth-promoting feed additive in broilers. Samie et al. [73] evaluated antiamoebic activity of a pure compound piperitenone162 isolated fromL. javanicaessential oil againstEntamoeba histolytica using microdilution method with metronidazole as the positive control, diluents (i.e., culture medium with an appropriate concentration of dimethyl sulphoxide as the negative control), and a blank (i.e., culture medium without dimethyl sulphoxide). Samie et al. [73] demonstrated that piperitenone162 had marked antiamoebic activity with IC50 value of 25 μg/mL. More research is required asL. javanicacould be harbouring potent antiamoebic properties which could be useful for managing amoebiasis, an infection that remains a significant cause of morbidity and mortality worldwide.


## 5. Conclusion

Lippia javanica has been used in African and Asian countries as herbal tea and medicine for many centuries. Utilization ofL. javanica because of its flavour and medicinal properties forms the basis of the current demand for the plant species in central, eastern, and southern Africa. Research onL. javanica over the past decade on health promoting properties has greatly contributed to the increased consumption of the species as herbal or recreational tea. The focus of this research has been on phytochemical compounds, particularly phenolic content and antioxidant and free radical scavenging activities. Phenolic compounds present inL. javanica are largely responsible for the antioxidant properties possessed by the species. More research in this regard is required and future research should focus on more comprehensive chemical characterization of both crude and pure extracts and evaluate potential for commercialization and development of nutraceutical products based on traditional uses ofL. javanica.Most of the pharmacological researches conducted onL. javanica so far have focused on the phytochemistry and biological properties of leaves, and little or no research has been done on roots and other plant parts. Therefore, future research on the species should focus on other plant parts, for example, flowers, roots, and stems, as well as organ-to-organ, age, and seasonal variation evaluations in the phytochemical content and pharmacological activities of the species.The recent increase in the demand forL. javanicaproducts may partly be ascribed to growing body of scientific evidence indicating important health benefits.Lippia javanicais widely sold as herbal tea in Botswana, South Africa, and Zimbabwe. Leaves and stems ofL. javanica are also sold as herbal medicines in the medicinal plant “muthi” markets in South Africa [35, 170]. For local people who rely on herbal medicines as part of their primary healthcare as well as cultural beliefs, they preferL. javanica harvested from the wild and unprocessed plant parts sold in informal medicinal “muthi” markets [170]. In the past, there were no records of overexploitation ofL. javanica wild populations in southern Africa, resulting in Raimondo et al. [171] listing the species as Least Concern (LC) under the IUCN Red List Categories and Criteria version 3.1 of threatened species (http://www.iucnredlist.org). Recently, signs of overharvesting have been noted, where local people or plant traders have uprooted whole plants to supply medicinal plant “muthi” markets or use the plants as herbal medicines, brooms, or herbal tea. Therefore, large-scale commercial utilization ofL. javanica is not sustainable if the species is harvested from the wild. Currently,L. javanica is cultivated on a commercial scale in Kenya [28] and South Africa [117] for essential oil production for the mosquito-repellent candles and perfume industry. Cultivation ofL. javanicais therefore, a solution to the sustainability problems associated with harvesting of the species from the wild, and this option is also necessary for establishing commercial scale medicinal production and processing and trade enterprises. The success of commercial cultivation ofL. javanicawill depend on how the species is marketed as herbal tea and medicine and source of essential oil and health care products and as a source of functional foods.Significant research has been made in the past 50 years into the chemistry and pharmacology ofL. javanica. These studies have shownL. javanica to display various chemical and different biological activities some of which justify its ethnopharmacological utilization in variety of cultures. In the light of the evidence thatL. javanica is combined with other plant species in traditional medicine, it will be valuable to investigate the possibility of synergistic effects of the different extracts. Deep phytochemical studies ofL. javanica and its phytochemical properties, especially the mechanisms of action of its bioactive constituents to illustrate the correlation between ethnomedicinal uses and pharmacological activities, should be the focus of further research on the species. There is need for extensive in vivo experiments to validate the existing pharmacological activities. However, becauseL. javanica contains potentially toxic compounds, its toxicological properties need to be properly established via proper quality control of product development to ensure that potentially toxic components are kept below tolerance levels.



---

*Source: 6746071-2017-01-01.xml*