# Lasia spinosa Chemical Composition and Therapeutic Potential: A Literature-Based Review

Authors: Rajib Hossain; Cristina Quispe; Jesús Herrera-Bravo; Md. Shahazul Islam; Chandan Sarkar; Muhammad Torequl Islam; Miquel Martorell; Natália Cruz-Martins; Ahmed Al-Harrasi; Ahmed Al-Rawahi; Javad Sharifi-Rad; Manshuk Ibrayeva; Sevgi Durna Daştan; Mohammed M. Alshehri; Daniela Calina; William C. Cho
Journal: Oxidative Medicine and Cellular Longevity
 (2021)

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## Abstract

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: “Lasia spinosa,” then combined with “ethnopharmacological use,” “phytochemistry,” and “pharmacological activity.” This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans.


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## Body

## 1. Introduction

Traditional, herbal, and Ayurvedic medicine comprise an important and prestigious form of treatment for various diseases and conditions in different locations all over the world from the beginning of human civilization on Earth [1]. Several plants and their corresponding preparations have been used for various therapeutic purposes for a long time ago. The history of traditional, herbal, and Ayurvedic medicine is the eldest to establish a treatment pattern [1].Lasia spinosa (L.) Thwaites, often known as Chengmora/Sibru in Assames, Kata-kachu in Bengali, Janum-Saru in Manipuri, Kohila/Mahakohila/Engilikohila in Sri Lanka, Zawangzang in Mizoram, and Laksmana in Sanskrit [2–4], belongs to the Araceae family [5]. It is found in Asia-Bangladesh, China, the Indian subcontinent, Myanmar, Thailand, Indo-China, Indonesia, and Papua New Guinea [6].Briefly,L. spinosa is an aquatic or terrestrial plant, short-stemmed spiny heirs with underground rhizome that usually occurs in wet forests, open marshes, wetlands, or in permanently standing water [7]. L. spinosa is a large marsh plant with the stem stout 1 m high and the leaves broadly arrow-shaped in outlines, 20-30 cm long deeply divided into 4-6 pairs of narrow side lobes. The petiole is 30-40 cm long, veins beneath the petiole and peduncle prickly [8]. Morpho-anatomical feature of L. spinosa has been recently reported by Lakshmi et al. [9]. The plant is harvested from the wild for its edible leaves and various medicinal uses. Sometimes, it is also cultivated as a vegetable crop along ponds margins [10]. Recently, it has been reported that Fusarium fujikuroi caused leaf spot on L. spinosa in China [11].With regards to their biological effects, the tender leaves and rhizomes of this plant, used as a vegetable and in indigenous medicine, have been recommended for a variety of conditions [12–15].Given the multiple potentialities of this plant, this review provides up-to-date data onL. spinosa chemical composition and biological effects based on the scientific reports found in the databases.


## 2. Review Methodology

In this study, the literature on botanical classification ofL. spinosa, ethnomedicinal applications, secondary metabolites, biological properties were compiled, reviewed, and summarized. For the compilation of all written papers on this species, scientific search engines such as PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, Scifnder, and Google Scholar have been used. In this study, the literature on botanical classification of Lasia spinosa, ethnomedicinal applications, secondary metabolites, and biological properties were compiled, reviewed, and summarized. For searching, the next MeSH terms were used: “Phytotherapy”, “Plants”, “Medicinal”, “Plant Extracts/administration & dosage”, “Plant Extracts/isolation & purification”, “Plant/chemistry”, “Structure-Activity Relationship”, “Disease Models”, “Animal”, and “Plant Extracts/toxicity”. Using the Chemsketch version 12.01 program, chemical structures were drawn. The scientific names of the plants have been verified according to the PlantList [16, 17].Inclusion criteria: works published in English on Lasia spinosa that highlighted the following data: chemical compounds isolated from each genus, preclinical pharmacological research highlighting molecular mechanisms, andin vitro/in vivo pharmacological studies that contained the concentration and dose at which the chemical compounds studied were pharmacologically active and toxicological data. The most important results obtained were summarized in the tables.Exclusion criteria: abstracts, letters to the editor, papers in languages other than English, studies that did not have dose-effect correlations, and studies that did not have proven molecular mechanisms which underline the pharmacology.


## 3. Ethnopharmacology

L. spinosa is a medicinally important plant, traditionally used by different ethnic communities all over the world. There are various reports on L. spinosa medicinal and economical properties. Often used for treating colic, tuberculosis of lymph nodes, swollen lymph nodes, rheumatism/rheumatoid arthritis, injuries, snake bites, and insect bites, this plant is also recommended as effective for the treatment of sore throat, constipation, to purify the blood, on lung inflammation, bleeding cough, and uterine cancer [14, 18–20]. Rhizomes (roots) are most often used as a remedy for hemorrhoids in Sri Lanka and Malays and to confer protection for some of the above conditions, because of their high fibre content and antioxidant compounds [15].Besides, leaves and stalks have demonstrated profound antihelminthic, anticestode, and antinematode efficacy [12, 15, 18, 19, 21, 22]. The root decoction is also useful in gastrointestinal diseases and stomachache [4], while also stimulating liver function [22]. Paste from tender leaves is externally used in burns [4].


## 4. Phytochemical Profile

L. spinosa whole plant contains several essential phytochemicals, including alkaloids, flavonoids, tannin, saponins, steroids, terpenoids, and varying amounts of micronutrients, like zinc (Zn), magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), manganese (Mn), and molybdenum (Mo) (Table 1).Table 1
Amounts of micronutrients ofLasia spinosa in ppm (parts per million) [2].
ElementsAmounts (ppm)Zn7.442±0.01Mg6.228±0.11Fe17.06±0.87Cu0.316±0.02Mn1.334±0.08Mo1.180±0.06Nutritional analysis ofL. spinosa showed that it contains proteins (17.6 kcal/100 g), fats (1.16 kcal/100 g), and carbohydrates (35.7 kcal/100 g), with a nutritive value of 224 kcal/100 g [2, 23]. In another study, the protein, fats, and carbohydrate content on a dry weight basis were 17.9, 3.8, and 45.5 g/100 g edible portion for protein, fats, and carbohydrate, respectively, for L. spinosa leaf, with a nutritive value of 288.5 kcal/100 g [24]. L. spinosa roots/rhizome contains dietary fibre, Ca, and provitamin A carotenoids [18, 25]. L. spinosa leaf contains 15.4 g of fibre, 250 mg of Ca, 19.2 mg of Fe, and 455 mg of vitamin C for 100 g edible portion on a dry weight basis [24, 26].In fresh weight, other studies reported content of proteins, fats, and carbohydrates of3.68±0.28, 0.44±0.03, and 4.78±0.38g/100g, respectively, the mineral content of 158.08±3.98, 321.73±7.00, 73.17±2.37, 53.86±3.86, and 0.92±0.08mg/100g for Ca, K, P, Mg, and Fe, and 2.99±0.11 and 0.28±0.01mg/100g of vitamins C and E, respectively [27].When specifically addressing the different extracts prepared fromL. spinosa, hexane extracts leaves and root contains the alkaloid berberine [28], lignan (e.g., lyoniresinol, meridional, secoisolariciresinol; 5,5′-dimethoxysecoiso-lariciresinol; 2-(4-hydroxy-3,5-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl)-1,2-butanediol; (7′S,8S,8R)-4,4′-dihydroxy-3,3′5,5′-tetra methoxy-7′,9-eproxylignan-9′-ol-7-one; 5,5′-dimethoxy-lariciresinol; 5′-methyoxlariciresinol, dihydrodehydrodiconifery alcohol; syringaresinol) [27–29], aldehyde (e.g., p-hydroxy benzaldehyde) [30], phenolic (e.g., procyanidin A1) [31] and other compounds (e.g., 4-hydroxybenzoic acid, 2-(4′- methoxyphenyl)-ethanol, 4-methoxyphenyl alcohol, 1-tetracosane) [30], from stem carotenoids (e.g., α-carotene, β-carotene, β-carotene-5,6, 5′, 6′-diepoxide; 5, 6, 5′, 6′-diepoxy-5, 8, 5′,8′-tetrahydro-β, cis-neoxanthin, and unidentified carotenoids I, II, III, and IV) are isolated [24, 32, 33].The aerial parts ofL. spinosa contain terpenoids (e.g., limonene, aqualene, caryophyllene), volatile oil (e.g., methyl octadec-6,9-dien-12-ynoate, α-glyceryl-linolenate α-pinene, α-selinene, camphene, δ-3-carene, camphor) [21, 34], phenolic compounds (e.g., 4-hydroxybenzoic acid, morin, cinnamic acid, syringic acid, gentisic aid) [21, 28, 34], fatty acids (e.g., methyl ester of oleic acid, palmitic acid, stearic acid, epoxyoleic acid) [34], steroids (e.g., spinasterone, β-sitosterol, γ-sitosterol, stigmasterol, campesterol, crinosterol) [21, 34], alkane (e.g., hexatriacontane and heptacosane) [35].The whole plant contains phenolics (e.g., gentisic acid, isovanilic acid, syringic acid, chlorogenic acid, p-hydroxy benzoic acid, (+)-catechin) [28], flavonoids including flavonoid glycosides and flavonoid aglycones (e.g., vitexin, vitexin-2”-O-β-D-glucopyranoside; isorhamnetin 3-O-rutinoside, morin, apigenin, 3′-methyl-quercetin-3-O-α-L-rhamnopyranosyl-(1/6) β-D-glucopyranoside; triglochinin) [28, 32, 35], and ketone (e.g., hexahydrofarnesyl acetone) (21).The chemical structures of such compounds are shown in Table2 and Figure 1.Table 2
Phytochemical profile ofLasia spinosa.
Plant partsPhytochemical classCompoundsRef.LeaveAlkaloidsBerberine[25]Leaf and root/rhizomeAldehydep-Hydroxy benzaldehyde[26]Other compounds4-Hydroxybenzoic acid, 2-(4′-methoxyphenyl)-ethanol, 4-methoxyphenethyl alcohol, 1-tetracosaneStemCarotenoidα-Carotene, β-carotene, β-carotene-5,6, 5′, 6′-diepoxide; 5, 6, 5′, 6′-diepoxy-5, 8, 5′,8′-tetrahydro-β, cis-neoxanthin[24, 31] Priyadarshani and Jansz, [25]Aerial partsTerpinoidLimonene,β-elemene, squalene, caryophyllene[21]; Rahman et al., [23]Volatile oilMethyl octadec-6,9-dien-12-ynoate,α-glyceryl-linolenate α-pinene, α-selinene, camphene, δ-3-carene, camphor[21]; Rahman et al., [23]Phenolics4-Hydroxybenzoic acid, morin, cinnamic acid, syringic acid, gentisic acidRahman et al., [23]; [21, 28]Fatty acidsMethyl ester of oleic acid, palmitic acid, stearic acid, epoxyoleic acidRahman et al., [23]SteroidSpinasterone,β-sitosterol, γ-sitosterol, stigmasterol, campesterol, crinosterol,Rahman et al., [23]; [21]AlkaneHexatriacontane, heptacosaneRahman et al., [23]Root/rhizomeLignanLyoniresinol, meridinol, secoisolariciresinol; 5,5′-dimethoxysecoiso-lariciresinol; 2-(4-hydroxy-3,5-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl)-1,2-butanediol; (7′S,8S,8R)-4,4′-dihydroxy-3,3′5,5′-tetramethoxy-7′,9-eproxylignan-9′-ol-7-one; 5,5′-dimethoxy-lariciresinol; 5′-methyoxlariciresinol, dihydrodehydrodiconifery alcohol; syringaresinolAlam et al., [36]; [28, 29, 32]PhenolicProcyanidin A1[30]Whole plantPhenolicGentisic acid, isovanilic acid, syringic acid, chlorogenic acid, p-hydroxy benzoic acid, (+)-catechin[28]Flavonoids (glycosides and aglycones)Vitexin, vitexin 2”-O-β-D-glucopyranoside; isorhamnetin 3-O-rutinoside, morin, apigenin, 3′-methyl quercetin-3-O-α-L-rhamnopyranosyl-(1/6) β-D-glucopyranoside; triglochinin[27, 28, 31]KetoneHexahydrofarnesyl acetone[21]Figure 1
Chemical structures of the most important phytochemicals found in different parts ofLasia spinosa.


## 5. Pharmacological Properties: Mechanisms and Targeted Molecular Pathways

### 5.1. Antioxidant

Oxidative stress is the basis of premature ageing of the body, the basis of disease, and is triggered by free radicals [29] more precisely occurs as a result of the imbalance between the amount of reactive oxygen produced in the body and its ability to eliminate it [30, 31]. Oxidative stress can be alleviated by approaching a balanced lifestyle that includes a healthy diet and sports [32]. Physical exercise reduces cellular oxidation by deep oxygenating tissues, eliminating stress, and relaxing the body [33]. On the other hand, the diet has a very important role, and the best treatment against oxidative stress is antioxidants [34]. They are found in many herbs and can kill free radicals [35, 37]. Medicinal plants usually contain a high level of antioxidants that can counteract the oxidative stress process linked to a disease [38, 39].The free radical scavenging activity ofL. spinosa leaves extracts on 1,1-diphenyl-2-picrylhydrazyl (DPPH) had been assessed and showed significant antioxidant activities [40]. The ethyl acetate fraction showed the highest free radical scavenging activity (IC50=16.42μg/mL) when compared to the positive control-butylated hydroxytoluene (BHT). At the same time, the aqueous fraction also exhibited moderate antioxidant potential (IC50=73.20μg/mL) [40]. In DPPH and ABTS assay, ethanol extract (leaves) showed antioxidant activity (SC50=17.25μg/mL and 16.47 μg/mL, respectively). Antioxidant activity is due to the presence of high levels of polyphenolic compounds [38]. In a study performed with different extracts of L. spinosa aerial parts, the highest free radical scavenging activity (DPPH) was stated to the methanol extract (IC50=0.48±0.04μg/mL), whereas in the metal chelating activity of ferrous ions (Fe2+) assay, the highest activity was observed for hexane extract (IC50=0.55±0.08μg/mL) [23]. In another study, the antiradical activity (1/EC50) of L. spinosa leaf determined by the DPPH method was 0.1 [24]. The same study reported a total phenolic content of 6.4 mg gallic equivalents/g and total flavonoid content of 4.4 retinol equivalent in L. spinosa leaf [24]. In other studies, L. spinosa showed a total phenolic content of 2.1 mg gallic equivalents/g and low antioxidant activity, through ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays, in comparison to indigenous vegetables from Southern Thailand, such as young cashew leaves (Anacardium occidentale L.) and Mon-pu (Glochidion zeylanicum (Gaertn.) A.Juss.) [27].


### 5.2. Anti-Inflammatory

Inflammation is part of the complex biological response of body tissues to harmful stimuli such as pathogens, damaged cells, or irritants [41] and a protective response involving immune system cells, molecular mediators, among others [42–44].In lipopolysaccharide-induced RAW 264.7 macrophages, the anti-inflammatory activity ofL. spinosa leaf extract was addressed [45], is stated that it can activate the nuclear factor- (NF-) κappa B, and nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 (Nrf2/HO-1) pathways and to suppress mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways. Furthermore, L. spinosa leaf extract suppresses the upregulation enzyme iNOS (NOS2), COX2, and proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and increases cytokines (IL-10) which produced anti-inflammatory effect [40].In another study, the anti-inflammatory activity ofL. spinosa hydroalcoholic extract in xylene-induced ear oedema model mice was assessed, being stated a significant inhibitory effect on oedema formation 17.1% at 250 mg/kg and 27.9% at 500 mg/kg. An inhibitory potential was also stated in a carrageenan-induced paw oedema model rat, and it was highest at 3 h, with 26.72% inhibition at 250 mg/kg and 38.70% at 500 mg/kg, when compared to the standard drugs (diclofenac sodium (10 mg/kg): 29.52%, and phenylbutazone (100 mg/kg): 40.47%) (Figure 2) [46].Figure 2
Diagram with molecular mechanisms of anti-inflammatory effect ofLasia spinosa.


### 5.3. Antimicrobial

An antimicrobial agent is that able to kill or stop microorganisms’ growth. For that, antibacterial and antifungals are used to fight bacterial and fungal infections, respectively [47–49]. Specifically addressing antibacterial, their prolonged use is closely related to a marked decrease in the number of enteric bacteria, thus, having a major negative impact on health and wellbeing [50, 51]. In this sense, the consumption of probiotics and a prebiotics-rich diet may help to replace the destroyed gut microbiota [52]. Stool transplants may also be proposed for patients with difficulty in recovering from prolonged antibiotic treatment, as for recurrent Clostridium difficile infections [53, 54].The organic extracts (hexane, chloroform, ethyl acetate; 300μg/disc) and essential oil of L. spinosa aerial parts showed potent antibacterial activity against Escherichia coli, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis in comparison of standard antibiotics (tetracycline 30 μg/disc, streptomycin 30 μg/disc, and erythromycin 15 μg/disc), except for methanol extract [23]. In another study, L. spinosa leaves methanol extract showed moderate antimicrobial properties against Bacillus subtilis, E. coli, Bacillus cereus, S. aureus, Candida albicans, Aspergillus niger, and Vibrio para hemolyticus at 400 μg/disc by disc diffusion assay [36]. In other studies, the methanol extract of L. spinosa edible parts did not show antimicrobial activity against C. albicans [46].


### 5.4. Cytotoxic

Cytotoxicity destroys cancer cells or prevents them from multiplying [55–57]. This cytotoxicity is done in different ways: some bioactive compounds can affect the genetic material of cells, and others act by blocking the access of malignant cells to the nutrients needed for division and multiplication [58, 59].The cytotoxic potential ofL. spinosa extracts has also been assessed. Brine shrimp lethality bioassay technique was applied to determine the cytotoxic potential of crude extracts. The aqueous extract from L. spinosa leaves showed moderate cytotoxicity (LC50=98.66μg/mL) in brine shrimp lethality bioassay [40], while the methanol extract from the whole plant led to significant cytotoxic effects (IC50=13.49μg/mL) on brine shrimp [36].


### 5.5. Antidiarrheal

In the castor oil-induced diarrheal mice model, both standard antimotility drug loperamide and hydroalcoholic extract fromL. spinosa root significantly reduced the number of stools in a dose-dependent manner compared to the negative control group. The mean number of stools found was 11.6 for 250 mg/kg and 8.2 for 500 mg/kg b.w., whereas for the standard drug (5 mg/kg) was of 5.6.L. spinosa root extract at 250 mg/kg b.w, causing a little increase in the latent period, but at 500 mg/kg b.w. led to a significant increase [46]. L. spinosa root extract exhibited a potent antidiarrheal activity, supporting their traditional use for diarrhea.


### 5.6. Antihelminthic

Helminthic infections continue to be the major people’s health hazard, especially in those living in tropical developing countries [60]. L. spinosa leaves methanol extract significantly exhibited paralysis and triggered worms’ death, especially at high doses (100 mg/mL) against Pheritimaposthuma [61], in a hymenolepisdiminuta–rat animal model [12] and infected mice with Trichinellaspiralis (800 mg/kg; p.o.) [19].


### 5.7. Antidiabetic

Diabetes mellitus is a chronic metabolic disease with numerous complications, like retinopathy, neuropathy, and peripheral vascular insufficiency. Several synthetic agents are available for diabetes treatment, but several side effects have been reported [62]. Plant-based medicinal products have been used since ancient times to manage diabetes in traditional medicine in many countries all over the world. L. spinosa stem hydroalcoholic extract have revealed antidiabetic activity at 200 and 400 mg/kg (p.o.) in dexamethasone (10 mg/kg s.c.)-induced diabetic albino rats by preventing serum glucose levels rise triggered by dexamethasone [63] and significantly reducing the triglycerides levels [64]. This extract also ameliorated hyperglycemia, and it likely has greater therapeutic potential as they may also exert beneficial effects on the clinical course of noninsulin-dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease [63]. A study developed by Shafie et al. [65] showed inhibitory effects of different parts (leaves, stems, and roots) of L. spinosa extracts (aqueous hot/cold, ethanol) against pancreatic lipase, α-amylase, and α-glucosidase.


### 5.8. Antihyperlipidemic

L. spinosa leaves have also the potential to prevent hyperlipidemia-induced pancreatitis in rats at concentrations of 400 and 800 mg/kg (p.o.) while exerting cardioprotective effects by significantly increasing serum high-density lipoprotein-cholesterol (HDL-c) at 100 mg/kg, p.o., and Triton-X 100 at 480 mg/kg, i.p. in an induced hyperlipidemic animal model [3].


### 5.9. Antinociceptive

Antinociception is the action or process of blocking the detection of a painful or injurious stimulus by sensory neurons, and antinociceptives are agents that block painful stimulus [66, 67]. The acetic acid-induced writhing test is used for detecting both central and peripheral analgesia, whereas the hot plate is most sensitive to centrally acting analgesics [68]. In acetic acid-induced writhing and hot plate-induced pain in mice the hydroalcoholic extract of L. spinosa roots revealed antinociceptive activity in mice, being stated 37% and 50% writhing inhibition at 250 mg/kg and 500 mg/kg b.w., respectively, while increased pain threshold [46]. On the other hand, the methanol extract from L. spinosa leaves at 400 mg/kg led to a significant decrease in the number of writhes and elongated the reaction time in the acetic acid writhing method and radiant heat tail flicking method, respectively [69].


### 5.10. Gastroprotective

A study revealed thatL. spinosa leaves ethanol extract has gastroprotective effects. In albino rats with indomethacin (5 mg/kg, p.o.) and cold restrain stress-induced ulcers, 3 doses (100, 200, and 400 mg/kg, p.o.) of L. spinosa extract were tested, with gastroprotective effects being mainly conferred by the extractability to create a defensive layer in stomach, through scavenging free radicals and inhibiting lipid peroxidation [70]. In gastric secretion studies, L. spinosa significantly evidenced a tendency to decrease gastric juice, free acidity, and total acidity [70]. Thus, after isolation of the individual compounds present in the extract, those responsible for the observed effect can be used both to treat ulcers and to reduce their severity.


### 5.11. Effect on Reproductive Activity

Testosterone plays an important role in Sertoli and Leydig cell proliferation and hyperplasia that can increase the testis size [71]. Testosterone is also involved in spermatogenesis and the growth and development of testis and male accessory reproductive glands [64]. The hydroalcoholic extract of L. spinosa rhizomes was revealed to be able to increase the serum testosterone levels and sperm count in male rats at 40 g/kg b.w. These data were confirmed afterward by an increase in testicular weight and sperm count, with the increase in the absolute weight of testis being attributed to the elevation of androgen biosynthesis leading to an increase in serum testosterone levels [64].The most important pharmacological properties are summarized in Table3 and Figure 3.Table 3
Pharmacological activities ofLasia spinosa.
ActivitySourcesTest systemDose testedPositive valueResultsRef.AntioxidantEthyl acetate extract (leaves)DPPHIC50=73.20μg/mLBHTIC50=23.19μg/mLModerate potential[40]Ethanol extract (leaves)DPPHABTSDPPH,IC50=17,25μg/mL; ABTSSC50=16.47μg/mLVitamin CDose=5.38μg/mLTroloxDose=3.17μg/mL↑ antioxidant activity due to the presence of high levels of polyphenolic compounds[45]Hexane, chloroform, ethyl acetate, and methanol extracts (aerial parts)DPPHChelating activity of ferrous ions (Fe2+)IC50=0.48±0.04μg/mL (methanolic)IC50=0.55±0.08μg/mL (hexane)Not studied↑ antioxidant activity[23]Anti-inflammatoryEthanol extract (leaves)Lipopolysaccharide-induced RAW 264.7 macrophagesin vitroDose=50, 100, 200, 400 μg/mLL-NAMEDose=100μM↑ NF-κB, ↑ Nrf2/HO-1↓MAPK, ↓ PI3K/Akt[45]Hydroalcoholic extract (roots)Carrageenan-induced paw edema model rats and xylene-induced ear edema micein vivoDose=250, 500 mg/kg bw, i.p.n=6NalbuphineDose=10mg/kg↓oedema formation[46]AntimicrobialMethanol extract (leaves)Disc diffusion assayin vitroDose=400μg/discKanamycinDose=30μg/discModerate antimicrobial activity againstBacillus subtilis, Escherichia coli, Bacillus cereus, Staphylococcus aureus, Candida albicans, Aspergillus niger, and Vibrio parahemolyticus[36]Hexane, chloroform, ethyl acetate, and methanol extracts (aerial parts) and essential oilDisc diffusion assayin vitroDose=300μg/discTetracyclineDose=30μg/discStreptomycinDose=30μg/discErythromycineDose=15μg/discPotent antibacterial activity againstEscherichia coli, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis, with the exception of methanolic extract[23]CytotoxicityHydromethanolic extract (leaves)Brine shrimp lethality bioassayin vitroLC50=98.663μg/mLVincristine sulphateLC50=0.544μg/mlModerate cytotoxic effect[40]Methanol extract (whole plant)Triton-X 100 (480 mg/kg, i.p.) induced hyperlipidemic rat modelin vivoIC50=13.49μg/mLVincristine sulphateLC50=20μg/ml↑cytotoxicity[36]Dose=200, 400, 800 mg/kg, p.o.n=6Triton-X 100Dose=480mg/kg↓triglycerides, ↓LDL-C↓VLDL-CAntidiarrhealHydroalcoholic extract (roots)Castor oil-induced diarrhea mice modelin vivo250 and 500 mg/kg b.w., i.p.n=6LoperamideDose=5mg/kg↓number of stools↑latent period of diarrhea[46]AnthelminticMethanol extract (leaves)Pheritima posthuman in vivoDose=25, 50, 100 mg/mL, n=6AlbendazoleDose=10mg/ml↑paralysis, ↑worm death, especially at 100 mg/ml[61]Extract (leaves)Hymenolepis diminuta rat model in vivoDose=200, 400, 800, 1600 mg/kg, p.o.,n=6PraziquantelDose=5−10mg/kg↓eggs per gram of feces↓worm recovery rates[12]AntidiabeticHydroalcoholic extract (stem)Dexamethasone 10 mg/kg s.c. induced diabetes ratsin vivoDose=200, 400 mg/kg, p.o.n=6Dexamethasonedose=10mg/kg↑antidiabetic activity[63]AntihyperlipidemicMethanol extract (leaves)Cholestero,l 100 mg/kg p.o, induced hyperlipidemic rat modelin vivoDose=200, 400, 800 mg/kg, p.o.n=6CholesterolDose=100mg/kg↓cholesterol[3]Triton-X 100, 480 mg/kg, i.p. induced hyperlipidemic rat modelin vivoDose=200, 400, 800 mg/kg, p.o.n=6Triton-X 100Dose=480mg/kg↓triglycerides↓LDL-C↓VLDL-CAntinociceptiveHydroalcoholic extract (roots)Acetic acid-induced writhing and hot plate-induced pain in micein vivoDose=250, 500 mg/kg b.w., i.p.n=6Diclofenac sodiumDose=10mg/kg50% writhing inhibition↑pain threshold[46]Methanol extract (leaves)Acetic acid writhing method and radiant heat tail flicking methodin vivoDose=200, 400 mg/kg, p.o.n=5Diclofenac sodiumDose=50mg/kg↓number of writhes ↑reaction time at dose 400 mg/kg[69]GastroprotectiveEthanol extract (leaves)Indomethacin, 5 mg/kg b.w., p.o.Cold restraint stress-induced ulcers in rats in vivoDose=100, 200, 400 mg/kg, p.o.n=5Indomethacindose=5mg/kgDevelopment of a defensive layer; ↑free radical scavenging activity; ↓LPO[70]Reproductive activityHydroalcoholic extract (rhizomes)Male ratsin vivoDose=5, 10, 20, 40 g/kg b.w., p.o.n=5Distilled water↑serum testosterone[64]Abbreviations: ABTS: 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid; BHT: butylatedhydroxytoluene; DPPH: 1,1-diphenyl-2-pecrylhydrazyl; HO-1: heme-oxygenase-1; L-NAME: N-Nitro-L-arginine methyl ester; LDL-C: low-density lipoprotein cholesterol; MAPK: mitogen-activated protein kinase; NF-κB: kappa B; Nrf2: nuclear factor erythroid 2-related factor 2; PI3K/Akt: phosphoinositide-3-kinase/protein kinase B; VLDL-C: very-low-density lipoprotein cholesterol.Figure 3
Summarized scheme with traditional uses and the most representative biological properties ofL. spinosa.


## 5.1. Antioxidant

Oxidative stress is the basis of premature ageing of the body, the basis of disease, and is triggered by free radicals [29] more precisely occurs as a result of the imbalance between the amount of reactive oxygen produced in the body and its ability to eliminate it [30, 31]. Oxidative stress can be alleviated by approaching a balanced lifestyle that includes a healthy diet and sports [32]. Physical exercise reduces cellular oxidation by deep oxygenating tissues, eliminating stress, and relaxing the body [33]. On the other hand, the diet has a very important role, and the best treatment against oxidative stress is antioxidants [34]. They are found in many herbs and can kill free radicals [35, 37]. Medicinal plants usually contain a high level of antioxidants that can counteract the oxidative stress process linked to a disease [38, 39].The free radical scavenging activity ofL. spinosa leaves extracts on 1,1-diphenyl-2-picrylhydrazyl (DPPH) had been assessed and showed significant antioxidant activities [40]. The ethyl acetate fraction showed the highest free radical scavenging activity (IC50=16.42μg/mL) when compared to the positive control-butylated hydroxytoluene (BHT). At the same time, the aqueous fraction also exhibited moderate antioxidant potential (IC50=73.20μg/mL) [40]. In DPPH and ABTS assay, ethanol extract (leaves) showed antioxidant activity (SC50=17.25μg/mL and 16.47 μg/mL, respectively). Antioxidant activity is due to the presence of high levels of polyphenolic compounds [38]. In a study performed with different extracts of L. spinosa aerial parts, the highest free radical scavenging activity (DPPH) was stated to the methanol extract (IC50=0.48±0.04μg/mL), whereas in the metal chelating activity of ferrous ions (Fe2+) assay, the highest activity was observed for hexane extract (IC50=0.55±0.08μg/mL) [23]. In another study, the antiradical activity (1/EC50) of L. spinosa leaf determined by the DPPH method was 0.1 [24]. The same study reported a total phenolic content of 6.4 mg gallic equivalents/g and total flavonoid content of 4.4 retinol equivalent in L. spinosa leaf [24]. In other studies, L. spinosa showed a total phenolic content of 2.1 mg gallic equivalents/g and low antioxidant activity, through ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays, in comparison to indigenous vegetables from Southern Thailand, such as young cashew leaves (Anacardium occidentale L.) and Mon-pu (Glochidion zeylanicum (Gaertn.) A.Juss.) [27].


## 5.2. Anti-Inflammatory

Inflammation is part of the complex biological response of body tissues to harmful stimuli such as pathogens, damaged cells, or irritants [41] and a protective response involving immune system cells, molecular mediators, among others [42–44].In lipopolysaccharide-induced RAW 264.7 macrophages, the anti-inflammatory activity ofL. spinosa leaf extract was addressed [45], is stated that it can activate the nuclear factor- (NF-) κappa B, and nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 (Nrf2/HO-1) pathways and to suppress mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways. Furthermore, L. spinosa leaf extract suppresses the upregulation enzyme iNOS (NOS2), COX2, and proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and increases cytokines (IL-10) which produced anti-inflammatory effect [40].In another study, the anti-inflammatory activity ofL. spinosa hydroalcoholic extract in xylene-induced ear oedema model mice was assessed, being stated a significant inhibitory effect on oedema formation 17.1% at 250 mg/kg and 27.9% at 500 mg/kg. An inhibitory potential was also stated in a carrageenan-induced paw oedema model rat, and it was highest at 3 h, with 26.72% inhibition at 250 mg/kg and 38.70% at 500 mg/kg, when compared to the standard drugs (diclofenac sodium (10 mg/kg): 29.52%, and phenylbutazone (100 mg/kg): 40.47%) (Figure 2) [46].Figure 2
Diagram with molecular mechanisms of anti-inflammatory effect ofLasia spinosa.


## 5.3. Antimicrobial

An antimicrobial agent is that able to kill or stop microorganisms’ growth. For that, antibacterial and antifungals are used to fight bacterial and fungal infections, respectively [47–49]. Specifically addressing antibacterial, their prolonged use is closely related to a marked decrease in the number of enteric bacteria, thus, having a major negative impact on health and wellbeing [50, 51]. In this sense, the consumption of probiotics and a prebiotics-rich diet may help to replace the destroyed gut microbiota [52]. Stool transplants may also be proposed for patients with difficulty in recovering from prolonged antibiotic treatment, as for recurrent Clostridium difficile infections [53, 54].The organic extracts (hexane, chloroform, ethyl acetate; 300μg/disc) and essential oil of L. spinosa aerial parts showed potent antibacterial activity against Escherichia coli, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis in comparison of standard antibiotics (tetracycline 30 μg/disc, streptomycin 30 μg/disc, and erythromycin 15 μg/disc), except for methanol extract [23]. In another study, L. spinosa leaves methanol extract showed moderate antimicrobial properties against Bacillus subtilis, E. coli, Bacillus cereus, S. aureus, Candida albicans, Aspergillus niger, and Vibrio para hemolyticus at 400 μg/disc by disc diffusion assay [36]. In other studies, the methanol extract of L. spinosa edible parts did not show antimicrobial activity against C. albicans [46].


## 5.4. Cytotoxic

Cytotoxicity destroys cancer cells or prevents them from multiplying [55–57]. This cytotoxicity is done in different ways: some bioactive compounds can affect the genetic material of cells, and others act by blocking the access of malignant cells to the nutrients needed for division and multiplication [58, 59].The cytotoxic potential ofL. spinosa extracts has also been assessed. Brine shrimp lethality bioassay technique was applied to determine the cytotoxic potential of crude extracts. The aqueous extract from L. spinosa leaves showed moderate cytotoxicity (LC50=98.66μg/mL) in brine shrimp lethality bioassay [40], while the methanol extract from the whole plant led to significant cytotoxic effects (IC50=13.49μg/mL) on brine shrimp [36].


## 5.5. Antidiarrheal

In the castor oil-induced diarrheal mice model, both standard antimotility drug loperamide and hydroalcoholic extract fromL. spinosa root significantly reduced the number of stools in a dose-dependent manner compared to the negative control group. The mean number of stools found was 11.6 for 250 mg/kg and 8.2 for 500 mg/kg b.w., whereas for the standard drug (5 mg/kg) was of 5.6.L. spinosa root extract at 250 mg/kg b.w, causing a little increase in the latent period, but at 500 mg/kg b.w. led to a significant increase [46]. L. spinosa root extract exhibited a potent antidiarrheal activity, supporting their traditional use for diarrhea.


## 5.6. Antihelminthic

Helminthic infections continue to be the major people’s health hazard, especially in those living in tropical developing countries [60]. L. spinosa leaves methanol extract significantly exhibited paralysis and triggered worms’ death, especially at high doses (100 mg/mL) against Pheritimaposthuma [61], in a hymenolepisdiminuta–rat animal model [12] and infected mice with Trichinellaspiralis (800 mg/kg; p.o.) [19].


## 5.7. Antidiabetic

Diabetes mellitus is a chronic metabolic disease with numerous complications, like retinopathy, neuropathy, and peripheral vascular insufficiency. Several synthetic agents are available for diabetes treatment, but several side effects have been reported [62]. Plant-based medicinal products have been used since ancient times to manage diabetes in traditional medicine in many countries all over the world. L. spinosa stem hydroalcoholic extract have revealed antidiabetic activity at 200 and 400 mg/kg (p.o.) in dexamethasone (10 mg/kg s.c.)-induced diabetic albino rats by preventing serum glucose levels rise triggered by dexamethasone [63] and significantly reducing the triglycerides levels [64]. This extract also ameliorated hyperglycemia, and it likely has greater therapeutic potential as they may also exert beneficial effects on the clinical course of noninsulin-dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease [63]. A study developed by Shafie et al. [65] showed inhibitory effects of different parts (leaves, stems, and roots) of L. spinosa extracts (aqueous hot/cold, ethanol) against pancreatic lipase, α-amylase, and α-glucosidase.


## 5.8. Antihyperlipidemic

L. spinosa leaves have also the potential to prevent hyperlipidemia-induced pancreatitis in rats at concentrations of 400 and 800 mg/kg (p.o.) while exerting cardioprotective effects by significantly increasing serum high-density lipoprotein-cholesterol (HDL-c) at 100 mg/kg, p.o., and Triton-X 100 at 480 mg/kg, i.p. in an induced hyperlipidemic animal model [3].


## 5.9. Antinociceptive

Antinociception is the action or process of blocking the detection of a painful or injurious stimulus by sensory neurons, and antinociceptives are agents that block painful stimulus [66, 67]. The acetic acid-induced writhing test is used for detecting both central and peripheral analgesia, whereas the hot plate is most sensitive to centrally acting analgesics [68]. In acetic acid-induced writhing and hot plate-induced pain in mice the hydroalcoholic extract of L. spinosa roots revealed antinociceptive activity in mice, being stated 37% and 50% writhing inhibition at 250 mg/kg and 500 mg/kg b.w., respectively, while increased pain threshold [46]. On the other hand, the methanol extract from L. spinosa leaves at 400 mg/kg led to a significant decrease in the number of writhes and elongated the reaction time in the acetic acid writhing method and radiant heat tail flicking method, respectively [69].


## 5.10. Gastroprotective

A study revealed thatL. spinosa leaves ethanol extract has gastroprotective effects. In albino rats with indomethacin (5 mg/kg, p.o.) and cold restrain stress-induced ulcers, 3 doses (100, 200, and 400 mg/kg, p.o.) of L. spinosa extract were tested, with gastroprotective effects being mainly conferred by the extractability to create a defensive layer in stomach, through scavenging free radicals and inhibiting lipid peroxidation [70]. In gastric secretion studies, L. spinosa significantly evidenced a tendency to decrease gastric juice, free acidity, and total acidity [70]. Thus, after isolation of the individual compounds present in the extract, those responsible for the observed effect can be used both to treat ulcers and to reduce their severity.


## 5.11. Effect on Reproductive Activity

Testosterone plays an important role in Sertoli and Leydig cell proliferation and hyperplasia that can increase the testis size [71]. Testosterone is also involved in spermatogenesis and the growth and development of testis and male accessory reproductive glands [64]. The hydroalcoholic extract of L. spinosa rhizomes was revealed to be able to increase the serum testosterone levels and sperm count in male rats at 40 g/kg b.w. These data were confirmed afterward by an increase in testicular weight and sperm count, with the increase in the absolute weight of testis being attributed to the elevation of androgen biosynthesis leading to an increase in serum testosterone levels [64].The most important pharmacological properties are summarized in Table3 and Figure 3.Table 3
Pharmacological activities ofLasia spinosa.
ActivitySourcesTest systemDose testedPositive valueResultsRef.AntioxidantEthyl acetate extract (leaves)DPPHIC50=73.20μg/mLBHTIC50=23.19μg/mLModerate potential[40]Ethanol extract (leaves)DPPHABTSDPPH,IC50=17,25μg/mL; ABTSSC50=16.47μg/mLVitamin CDose=5.38μg/mLTroloxDose=3.17μg/mL↑ antioxidant activity due to the presence of high levels of polyphenolic compounds[45]Hexane, chloroform, ethyl acetate, and methanol extracts (aerial parts)DPPHChelating activity of ferrous ions (Fe2+)IC50=0.48±0.04μg/mL (methanolic)IC50=0.55±0.08μg/mL (hexane)Not studied↑ antioxidant activity[23]Anti-inflammatoryEthanol extract (leaves)Lipopolysaccharide-induced RAW 264.7 macrophagesin vitroDose=50, 100, 200, 400 μg/mLL-NAMEDose=100μM↑ NF-κB, ↑ Nrf2/HO-1↓MAPK, ↓ PI3K/Akt[45]Hydroalcoholic extract (roots)Carrageenan-induced paw edema model rats and xylene-induced ear edema micein vivoDose=250, 500 mg/kg bw, i.p.n=6NalbuphineDose=10mg/kg↓oedema formation[46]AntimicrobialMethanol extract (leaves)Disc diffusion assayin vitroDose=400μg/discKanamycinDose=30μg/discModerate antimicrobial activity againstBacillus subtilis, Escherichia coli, Bacillus cereus, Staphylococcus aureus, Candida albicans, Aspergillus niger, and Vibrio parahemolyticus[36]Hexane, chloroform, ethyl acetate, and methanol extracts (aerial parts) and essential oilDisc diffusion assayin vitroDose=300μg/discTetracyclineDose=30μg/discStreptomycinDose=30μg/discErythromycineDose=15μg/discPotent antibacterial activity againstEscherichia coli, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis, with the exception of methanolic extract[23]CytotoxicityHydromethanolic extract (leaves)Brine shrimp lethality bioassayin vitroLC50=98.663μg/mLVincristine sulphateLC50=0.544μg/mlModerate cytotoxic effect[40]Methanol extract (whole plant)Triton-X 100 (480 mg/kg, i.p.) induced hyperlipidemic rat modelin vivoIC50=13.49μg/mLVincristine sulphateLC50=20μg/ml↑cytotoxicity[36]Dose=200, 400, 800 mg/kg, p.o.n=6Triton-X 100Dose=480mg/kg↓triglycerides, ↓LDL-C↓VLDL-CAntidiarrhealHydroalcoholic extract (roots)Castor oil-induced diarrhea mice modelin vivo250 and 500 mg/kg b.w., i.p.n=6LoperamideDose=5mg/kg↓number of stools↑latent period of diarrhea[46]AnthelminticMethanol extract (leaves)Pheritima posthuman in vivoDose=25, 50, 100 mg/mL, n=6AlbendazoleDose=10mg/ml↑paralysis, ↑worm death, especially at 100 mg/ml[61]Extract (leaves)Hymenolepis diminuta rat model in vivoDose=200, 400, 800, 1600 mg/kg, p.o.,n=6PraziquantelDose=5−10mg/kg↓eggs per gram of feces↓worm recovery rates[12]AntidiabeticHydroalcoholic extract (stem)Dexamethasone 10 mg/kg s.c. induced diabetes ratsin vivoDose=200, 400 mg/kg, p.o.n=6Dexamethasonedose=10mg/kg↑antidiabetic activity[63]AntihyperlipidemicMethanol extract (leaves)Cholestero,l 100 mg/kg p.o, induced hyperlipidemic rat modelin vivoDose=200, 400, 800 mg/kg, p.o.n=6CholesterolDose=100mg/kg↓cholesterol[3]Triton-X 100, 480 mg/kg, i.p. induced hyperlipidemic rat modelin vivoDose=200, 400, 800 mg/kg, p.o.n=6Triton-X 100Dose=480mg/kg↓triglycerides↓LDL-C↓VLDL-CAntinociceptiveHydroalcoholic extract (roots)Acetic acid-induced writhing and hot plate-induced pain in micein vivoDose=250, 500 mg/kg b.w., i.p.n=6Diclofenac sodiumDose=10mg/kg50% writhing inhibition↑pain threshold[46]Methanol extract (leaves)Acetic acid writhing method and radiant heat tail flicking methodin vivoDose=200, 400 mg/kg, p.o.n=5Diclofenac sodiumDose=50mg/kg↓number of writhes ↑reaction time at dose 400 mg/kg[69]GastroprotectiveEthanol extract (leaves)Indomethacin, 5 mg/kg b.w., p.o.Cold restraint stress-induced ulcers in rats in vivoDose=100, 200, 400 mg/kg, p.o.n=5Indomethacindose=5mg/kgDevelopment of a defensive layer; ↑free radical scavenging activity; ↓LPO[70]Reproductive activityHydroalcoholic extract (rhizomes)Male ratsin vivoDose=5, 10, 20, 40 g/kg b.w., p.o.n=5Distilled water↑serum testosterone[64]Abbreviations: ABTS: 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid; BHT: butylatedhydroxytoluene; DPPH: 1,1-diphenyl-2-pecrylhydrazyl; HO-1: heme-oxygenase-1; L-NAME: N-Nitro-L-arginine methyl ester; LDL-C: low-density lipoprotein cholesterol; MAPK: mitogen-activated protein kinase; NF-κB: kappa B; Nrf2: nuclear factor erythroid 2-related factor 2; PI3K/Akt: phosphoinositide-3-kinase/protein kinase B; VLDL-C: very-low-density lipoprotein cholesterol.Figure 3
Summarized scheme with traditional uses and the most representative biological properties ofL. spinosa.


## 6. Toxicological Data and Clinical Gaps

Oral administration in an acute analysis of 5, 10, 20, and 40 gm/kg of an extract, there were no mortality or physiological changes demonstrated. In the subchronic assay for 28 gm/kg, administration of 5 or 20 gm/kg of extract for 28 gm/kg, no animal deaths were announced that day. No differences in haematological parameters were noticed in either case [52].Therapeutic limitation of natural bioactive compounds fromLasia spinosa results from the relatively reduced bioavailability of bioactive compounds. In addition, numerous interactions with other prescription drugs may occur. Interactions between medicinal plants interfere with the metabolism or elimination of the drug/chemotherapy from the body. Drug metabolism/elimination is mediated by enzymes that metabolize drugs in the cytochrome P450 (CYP) family and drug transport proteins. These interactions can change the concentration of drugs in the body [72].Interactions between plants and drugs may occur due to inhibition or activation by plant phytochemicals of CYP enzymes or drug transport proteins that metabolize the drug [73]. Some therapeutic pharmacological agents must be activated by CYP to be effective. Once CYPs are inhibited, such drugs that need to be activated will be ineffective. There may be interactions between plants and drugs that lead to increased elimination of drugs due to CYP activation, which could lead to subtherapeutic exposure to drugs and could lead to therapy failure [74]. Some plant-drug interactions due to CYP inhibition may lead to the accumulation of cytotoxic drugs due to delayed clearance and may increase drug toxicity due to high doses of drugs. Cancer patients are already taking several medications at the same time due to other conditions associated with cancer and comorbidities, which present a risk of drug interactions [75]. The use of herbs/herbal products may further increase the risk of these potentially harmful interactions that interfere with the impact of the drug.


## 7. Overall Conclusions and Future Perspectives

Natural plant sources have contributed to many drug developments. In this study, we comply with the traditional uses, pharmacological properties, and chemical constituents ofL. spinosa, information that can be useful for further research. Many phytochemicals present in L. spinosa may be responsible for its biological effects in various test systems, but more studies are needed to identify and characterize the active compounds responsible for the pharmacological activities of this hopeful medicinal plant. Future directions must be oriented to toxicological studies which are scarce, and there are necessary new reports to ensure the safety of this plant. Besides, clinical studies are required to confirm the preclinical biological effects in humans.



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