# Southeast Asian Medicinal Plants as a Potential Source of Antituberculosis Agent

Authors: Shuaibu Babaji Sanusi; Mohd Fadzelly Abu Bakar; Maryati Mohamed; Siti Fatimah Sabran; Muhammad Murtala Mainasara
Journal: Evidence-Based Complementary and Alternative Medicine
 (2017)

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## Abstract

Despite all of the control strategies, tuberculosis (TB) is still a major cause of death globally and one-third of the world’s population is infected with TB. The drugs used for TB treatment have drawbacks of causing adverse side effects and emergence of resistance strains. Plant-derived medicines have since been used in traditional medical system for the treatment of numerous ailments worldwide. There were nine major review publications on antimycobacteria from plants in the last 17 years. However, none is focused on Southeast Asian medicinal plants. Hence, this review is aimed at highlighting the medicinal plants of Southeast Asian origin evaluated for anti-TB. This review is based on literatures published in various electronic database. A total of 132 plants species representing 45 families and 107 genera were reviewed; 27 species representing 20.5% exhibited most significantin vitro anti-TB activity (crude extracts and/or bioactive compounds 0–<10 µg/ml). The findings may motivate various scientists to undertake the project that may result in the development of crude extract that will be consumed as complementary or alternative TB drug or as potential bioactive compounds for the development of novel anti-TB drug.


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## Body

## 1. Introduction

Tuberculosis (TB) is an ancient disease and it is among the world’s most deadly epidemics. Like any other infectious disease, TB can happen to anyone and spares no age, sex, and nationality [1, 2]. Several strains ofMycobacterium tuberculosis (MTB) are the common cause of this deadly infectious disease [3]. This disease is endemic in every country in the world, and death due to TB is more common when compared to other bacterial disease [1, 3, 4]. About two billion individuals are latently infected with TB, but only 10% of these infected persons fall sick with active disease during their lifetime [5–8]. It has been estimated that around nine million persons develop TB and almost 2 million die from it annually [9–12]. About 5.5 million of the cases occur in Asia, 1.5 million in Africa, 745,000 in the Middle East, and 600,000 in Latin America [13]. It is unfortunate that more than 75% of TB cases are found in adults [14]. Unprecedented decision was taken in 1993 by WHO to declare TB as a public health emergency [10, 15], and it is the first disease that has ever been declared as a global emergency by WHO [16].In order to combat TB, chemotherapy is used, which is the modern TB treatment. The drugs used include rifampicin, isoniazid, ethambutol, pyrazinamide, and streptomycin for TB treatment. However, these drugs have drawbacks of causing adverse side effects and the TB-causing bacterium can gain easy resistance against these drugs. Besides that, there is a chance of “relapse” due to noncompliance with medication within the first year of treatment. Consequently, this results in a more serious condition where theMycobacterium species develops resistance to the TB drugs [1].The TB resistance can be categorized into two types: the multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB). Firstly, MDR-TB arises when the strain that is resistant to the first-line standard TB drugs (isoniazid and rifampicin) is involved. More than 4% of TB patients globally are infected withMycobacterium strains that are resistant to first-line drugs. Secondly, XDR-TB happens when the mycobacterial strain is resistant to the first-line drugs, fluoroquinolone, as well as other injectable second-line drugs such as kanamycin, capreomycin, and amikacin. According to the WHO report on surveillance and response to MDR-TB and XDR-TB, approximately 310,000 MDR-TB cases occurred in pulmonary TB patients documented in 2011 while 84 countries were recorded having at least one XDR-TB case [17–20]. In 2012, around 480,000 people have been reported to develop MDR-TB and about 170,000 people died as a result [20, 21]. These forms of TB diseases are often more fatal, costly, and difficult to treat. The second-line drugs used in drug resistant TB have notable side effects, but have about 50% cure rate [22]. Although fluoroquinolones such as ofloxacin and norfloxacin have been used and are considered safer than the aforementioned second-line drugs, however, they also have their own drawback of being more costly.Due to aforementioned disadvantages, the prospective efficacy of medicinal plants has motivated doctors and scientists to turn to folk medicines for treatment of various chronic diseases, including TB [22]. Hence, the urgent need arises towards the search of a component with a higher anti-TB activity, with easy availability and without side effects [1, 6, 23].Owing to their chemical diversity and significant role in the drug sighting and development, medicinal plants proffer a great hope to overcome these needs. The medicinal plants have been comprehensively used either as crude extracts or pure materials. However, very few species of medicinal plants have been thoroughly explored for their medicinal properties [24–26]. The plant-derived medicines have been utilized in traditional medical system for the treatment of different illnesses worldwide. Around 75% of the global populace solely depends on medicinal plants for primary health care [27, 28]. Consequently, there is so much interest in plant medicine during the last few decades leading to numerous species of medicinal plant being investigated for their pharmacological activities.In the last 17 years, there were nine major review publications on antimycobacteria from natural products. Newton et al. [29] published a review paper on natural compounds with antimycobacteria derived from plant source, describing their potency in crude extracts as well as pure compounds from 123 plant species [29]. In 2003, Copp [30] published a review article that covered a wide range of natural bioactive products, with reported antimycobacterial activity within a period of twelve years (i.e., from 1990 to 2002) [30]. In another review, Okunade et al. [31] discussed 88 natural products and their synthetic analogues, mainly from plant source, and fungi as well as some aquatic organisms that displayed substantial activity againstM. tuberculosis and other mycobacterial species inin vitro bioassays [31]. In their review, Pauli et al. [32] offered cross-linkage to the literatures of bioactive pure compounds with anti-TB and summarized more current advances in mycobacteriology and natural compounds chemistry tools innovation as well as their prospective to influence the primary steps in TB drug discovery process [32]. A review by Jachak and Jain [33] described recent target-based natural compounds that displayed antimycobacterial action [33]. Gautam et al. [23] reviewed different species of plant from a vast array of families that have exhibited antimycobacterial activity. Gupta et al. [34], in their review article, identified sixty-four medicinal plants used by traditional people in the treatment of leprosy [34].Some antitubercular plants from Ayurveda as well as foreign origin have been reviewed by Arya [35] to give a scientific account on usage of antitubercular plants. Consequently, various phytochemicals such as alkaloids, flavonoids, tannins, xanthones, triterpenes, and quinones were involved in antitubercular activity [35]. The most recent among all the reviews is by Chinsembu [20] in 2016. The review focused on antimycobacterial natural products derived from both endophytes as well as medicinal plants of Africa, Asia, Europe, South America, and Canada. Several plant species disclosed in the review demonstrated a putative anti-TB activity. Numerous antimycobacterial bioactive compounds have, as well, been isolated. They include 1-epicatechol, allicin, anthocyanidin, anthraquinone glycosides, arjunic acid, benzophenanthridine alkaloids, beta-sitosterol, crinine, decarine, ellagic acids, ellagitannin punicalagin, friedelin, galanthimine, gallic acid, glucopyranosides, hydroxybenzoic acids, iridoids, leucopelargonidol, neolignans, phenylpropanoids, taraxerol, and termilignan B. The chemicals may offer leads on new and more effective drugs to minimize the predicament TB and lessen the drug resistant strains as well [20].All the above review articles hardly highlighted any medicinal plant of Southeast Asian source. Even though there is an increasing availability of modern medicine in the Southeast Asia region, the use of traditional medicine remains popular [36]. Due to the enormous diversity of its flora, Southeast Asian region has a great potential for the discovery of novel active compounds. The countries in the region such as Malaysia, Indonesia, Brunei, and Thailand have a long history of using medicinal plant that proffers substantial pharmaceutical prospects [37].


## 2. Methodology

Related Scientific studies published in journals, books, and reports were reviewed. Relevant literatures were searched in Google Scholar and various electronic databases including Science Direct, IEEE Xplore, Scopus, SciFinder, and MEDLINE using a specific search terms including “TB”, “medicinal plants”, “anti-TB”, “Malaysia OR Philippines OR Indonesia Singapore OR Thailand OR Brunei OR Cambodia OR Laos OR Myanmar (Burma) OR Vietnam”. This review discussed studies from year 2000 to 2016.


## 3. Bioassay Guidance for Evaluating the Activity of Antituberculosis

Bioassay-guided fractionation is the modern practice presently used in identifying the active compound(s) present in crude extract(s). Due to the fact that the procedure comprises alternating stages of biological screening and active compound fractionation, in the last 20 years, sensitivity of fractionation techniques of pure natural compound has dramatically improved due to the vast advancements in chromatography. Consequently, this creates new paths for both yet to be investigated materials and previously studied genera. Hence, the new paths were given access to unanticipated chemical varieties and novel biological products [32]. To provide effective direction in discovery program of drug from natural resources, the development of novel phytochemical approaches becomes crucial in a bioassay-directed drug discovery. Another step is bioassay which should be selected wisely in relation to the crucial terminus, that is, the antibiotic screening on virulent mycobacterial strain in vivo. Interestingly, three effective antimycobacterial products have been sequestered fromDracaena angustifolia using this method [23, 32, 218].


### 3.1. Target Organism

It is obvious that the ideal organism to be targeted in the effort to discover anti-TB is the actual etiologic agent,Mycobacterium tuberculosis (MTB). The prominent pathogenic strain, MTB H37Rv (ATCC 27294), has fairly represented drug sensitivity profile of most drug sensitive clinical isolated strains. In primary screening, employing MDR strains of MTB is not crucial due to the fact that they are never “superbugs” that have resistant capacity to various drugs by the virtue of a particular mechanisms, such as effusion pump in some bacteria. However, they are rather the consequence of peculiar step by step mutations to particular drugs. Hence, it is anticipated that they would be susceptible to any novel biologically active product, which does not attack the same site as TB drugs currently in use do [23, 32, 218]. Due to its virulence, the pathogenic strain of MTB must be processed or handled only in a laboratory with biosafety level 3 (BL-3) set-up. In the BL-3 laboratory, individual working is required to don on a protective gear. Most researchers opted to employ avirulent, fast growing, and saprophytic strain ofMycobacterium. Example of such isM. smegmatis (ATCC 607) [218]. Other avirulent substitutes to work with instead of virulent strains of MTB are the slow-growing strains such asM. tuberculosis H37Ra (ATCC 25177) andM. bovis BCG (ATCC 35743). The above species are closely related to pathogenic MTB H37Rv strain in their antimycobacterial susceptibility profile as well as genetic configuration. For this, strains require the employment of a class 2 biosafety cabinet when working with these organisms [23, 218].


### 3.2.In Vitro Bioassays for Anti-TB Screening

#### 3.2.1. Agar Diffusion

The conventional diffusion assays (well or disk) were applied in various antimicrobial evaluation of compounds from natural sources only to indicate the presence or absence of growth inhibition at unspecified concentrations gradient and hence are never quantifiable when evaluating crude materials or novel products. The sizes of the zones of inhibition can be only interpreted as indicative of either microbial sensitivity or resistance with well characterized antibiotics. This is because the size of inhibition zone depends on both the rate of diffusion of biologically active agent and the growth rate of the targeted organism [32]. Agar diffusion assays need to be avoided withMycobacteria, since these organisms with high lipid content in their cell wall are usually more sensitive to compounds of less-polarity [218]. Therefore, the diffusion of such compounds will be very slow compared to polar compounds with the same molecular weight on the aqueous agar. This might consequently produce smaller inhibition zones. Furthermore, polar active compounds of low molecular weight could diffuse to equilibrium prior to appearance of colonies in slow-growing mycobacterial strain. And if, at the equilibrium, the concentration is below the MIC, the zone of inhibition will never appear [218].


#### 3.2.2. Micro and Macro Agar Dilution

When screening extracts with known concentrations, fractions in an agar enable the MIC value to be determined and its activity to be quantified. Except in some fastidious species, many mycobacterial strains such as MTB tend to produce colonies effectively on Middlebrook 7H10 or 7H11 agar supplemented with Oleic acid, Albumin, Dextrose, and Catalase (OADC). The sample to be tested is added to the semisolid media at final concentration of 1% v/v or subsequently either 100–200µl medium to 96-well microplates, 1.5 ml to 24-well microplates, 4 ml to 6-well microplates, or 20 ml into usual Petri dishes of 150 mm diameter. Following the hardening of the medium, the inoculum can then be dropped on the surface of the agar using a micro pipette. Some of the volumes of inoculum recommended are as follows: 1–5 µl for 96-well plates, 10 µl for 6- or 24-well plates, and 100 µl for normal Petri dishes. The plates are then incubated at 37°C overnight, after which they should then be inverted for the remaining period of incubation. The major shortcoming with such a bioassay is that it requires a minimum of 18 days to produce a visible colony ofMycobacteria [32, 218].


#### 3.2.3. Microbroth Dilution

Evaluation of susceptibility (bioactivity) of natural products using microplates with 96 wells proffers an edge because it requires little sample, is cheap, and is high-throughput. The mycobacterial species are often cultured in Middlebrook 7H9 broth supplemented with glycerol (0.5%), casitone (0.1%), Tween-80 (0.05%), and ADC (10%). In many strains ofMycobacteria, the growth can be evaluated quantitatively by the broth medium turbidity. However, the proneness of clumps formation makes the assay very challenging [23]. Nevertheless, the utilization of indicator dye like Alamar blue renders this technique more sensitive and rapid. The results of this assay can be read visually, although the reduced form of the dye is quantifiable using calorimeter. This is done by measuring the absorbance at 570 nm and then subtracting absorbance at 600 nm. On the other hand, the second approach has been proven to be more sensitive. Microbroth dilution tests should also be carried out using either resazurin or tetrazolium dyes. Therefore, a high-throughput assay of anti-TB is possible through using a microplate, spectrophotometrically or fluorometrically. These are quantitative assays that could detect even partial inhibition, making it possible to determine the relative activity of fractions from crude extracts using different concentrations [32, 218].


## 3.1. Target Organism

It is obvious that the ideal organism to be targeted in the effort to discover anti-TB is the actual etiologic agent,Mycobacterium tuberculosis (MTB). The prominent pathogenic strain, MTB H37Rv (ATCC 27294), has fairly represented drug sensitivity profile of most drug sensitive clinical isolated strains. In primary screening, employing MDR strains of MTB is not crucial due to the fact that they are never “superbugs” that have resistant capacity to various drugs by the virtue of a particular mechanisms, such as effusion pump in some bacteria. However, they are rather the consequence of peculiar step by step mutations to particular drugs. Hence, it is anticipated that they would be susceptible to any novel biologically active product, which does not attack the same site as TB drugs currently in use do [23, 32, 218]. Due to its virulence, the pathogenic strain of MTB must be processed or handled only in a laboratory with biosafety level 3 (BL-3) set-up. In the BL-3 laboratory, individual working is required to don on a protective gear. Most researchers opted to employ avirulent, fast growing, and saprophytic strain ofMycobacterium. Example of such isM. smegmatis (ATCC 607) [218]. Other avirulent substitutes to work with instead of virulent strains of MTB are the slow-growing strains such asM. tuberculosis H37Ra (ATCC 25177) andM. bovis BCG (ATCC 35743). The above species are closely related to pathogenic MTB H37Rv strain in their antimycobacterial susceptibility profile as well as genetic configuration. For this, strains require the employment of a class 2 biosafety cabinet when working with these organisms [23, 218].


## 3.2.In Vitro Bioassays for Anti-TB Screening

### 3.2.1. Agar Diffusion

The conventional diffusion assays (well or disk) were applied in various antimicrobial evaluation of compounds from natural sources only to indicate the presence or absence of growth inhibition at unspecified concentrations gradient and hence are never quantifiable when evaluating crude materials or novel products. The sizes of the zones of inhibition can be only interpreted as indicative of either microbial sensitivity or resistance with well characterized antibiotics. This is because the size of inhibition zone depends on both the rate of diffusion of biologically active agent and the growth rate of the targeted organism [32]. Agar diffusion assays need to be avoided withMycobacteria, since these organisms with high lipid content in their cell wall are usually more sensitive to compounds of less-polarity [218]. Therefore, the diffusion of such compounds will be very slow compared to polar compounds with the same molecular weight on the aqueous agar. This might consequently produce smaller inhibition zones. Furthermore, polar active compounds of low molecular weight could diffuse to equilibrium prior to appearance of colonies in slow-growing mycobacterial strain. And if, at the equilibrium, the concentration is below the MIC, the zone of inhibition will never appear [218].


### 3.2.2. Micro and Macro Agar Dilution

When screening extracts with known concentrations, fractions in an agar enable the MIC value to be determined and its activity to be quantified. Except in some fastidious species, many mycobacterial strains such as MTB tend to produce colonies effectively on Middlebrook 7H10 or 7H11 agar supplemented with Oleic acid, Albumin, Dextrose, and Catalase (OADC). The sample to be tested is added to the semisolid media at final concentration of 1% v/v or subsequently either 100–200µl medium to 96-well microplates, 1.5 ml to 24-well microplates, 4 ml to 6-well microplates, or 20 ml into usual Petri dishes of 150 mm diameter. Following the hardening of the medium, the inoculum can then be dropped on the surface of the agar using a micro pipette. Some of the volumes of inoculum recommended are as follows: 1–5 µl for 96-well plates, 10 µl for 6- or 24-well plates, and 100 µl for normal Petri dishes. The plates are then incubated at 37°C overnight, after which they should then be inverted for the remaining period of incubation. The major shortcoming with such a bioassay is that it requires a minimum of 18 days to produce a visible colony ofMycobacteria [32, 218].


### 3.2.3. Microbroth Dilution

Evaluation of susceptibility (bioactivity) of natural products using microplates with 96 wells proffers an edge because it requires little sample, is cheap, and is high-throughput. The mycobacterial species are often cultured in Middlebrook 7H9 broth supplemented with glycerol (0.5%), casitone (0.1%), Tween-80 (0.05%), and ADC (10%). In many strains ofMycobacteria, the growth can be evaluated quantitatively by the broth medium turbidity. However, the proneness of clumps formation makes the assay very challenging [23]. Nevertheless, the utilization of indicator dye like Alamar blue renders this technique more sensitive and rapid. The results of this assay can be read visually, although the reduced form of the dye is quantifiable using calorimeter. This is done by measuring the absorbance at 570 nm and then subtracting absorbance at 600 nm. On the other hand, the second approach has been proven to be more sensitive. Microbroth dilution tests should also be carried out using either resazurin or tetrazolium dyes. Therefore, a high-throughput assay of anti-TB is possible through using a microplate, spectrophotometrically or fluorometrically. These are quantitative assays that could detect even partial inhibition, making it possible to determine the relative activity of fractions from crude extracts using different concentrations [32, 218].


## 3.2.1. Agar Diffusion

The conventional diffusion assays (well or disk) were applied in various antimicrobial evaluation of compounds from natural sources only to indicate the presence or absence of growth inhibition at unspecified concentrations gradient and hence are never quantifiable when evaluating crude materials or novel products. The sizes of the zones of inhibition can be only interpreted as indicative of either microbial sensitivity or resistance with well characterized antibiotics. This is because the size of inhibition zone depends on both the rate of diffusion of biologically active agent and the growth rate of the targeted organism [32]. Agar diffusion assays need to be avoided withMycobacteria, since these organisms with high lipid content in their cell wall are usually more sensitive to compounds of less-polarity [218]. Therefore, the diffusion of such compounds will be very slow compared to polar compounds with the same molecular weight on the aqueous agar. This might consequently produce smaller inhibition zones. Furthermore, polar active compounds of low molecular weight could diffuse to equilibrium prior to appearance of colonies in slow-growing mycobacterial strain. And if, at the equilibrium, the concentration is below the MIC, the zone of inhibition will never appear [218].


## 3.2.2. Micro and Macro Agar Dilution

When screening extracts with known concentrations, fractions in an agar enable the MIC value to be determined and its activity to be quantified. Except in some fastidious species, many mycobacterial strains such as MTB tend to produce colonies effectively on Middlebrook 7H10 or 7H11 agar supplemented with Oleic acid, Albumin, Dextrose, and Catalase (OADC). The sample to be tested is added to the semisolid media at final concentration of 1% v/v or subsequently either 100–200µl medium to 96-well microplates, 1.5 ml to 24-well microplates, 4 ml to 6-well microplates, or 20 ml into usual Petri dishes of 150 mm diameter. Following the hardening of the medium, the inoculum can then be dropped on the surface of the agar using a micro pipette. Some of the volumes of inoculum recommended are as follows: 1–5 µl for 96-well plates, 10 µl for 6- or 24-well plates, and 100 µl for normal Petri dishes. The plates are then incubated at 37°C overnight, after which they should then be inverted for the remaining period of incubation. The major shortcoming with such a bioassay is that it requires a minimum of 18 days to produce a visible colony ofMycobacteria [32, 218].


## 3.2.3. Microbroth Dilution

Evaluation of susceptibility (bioactivity) of natural products using microplates with 96 wells proffers an edge because it requires little sample, is cheap, and is high-throughput. The mycobacterial species are often cultured in Middlebrook 7H9 broth supplemented with glycerol (0.5%), casitone (0.1%), Tween-80 (0.05%), and ADC (10%). In many strains ofMycobacteria, the growth can be evaluated quantitatively by the broth medium turbidity. However, the proneness of clumps formation makes the assay very challenging [23]. Nevertheless, the utilization of indicator dye like Alamar blue renders this technique more sensitive and rapid. The results of this assay can be read visually, although the reduced form of the dye is quantifiable using calorimeter. This is done by measuring the absorbance at 570 nm and then subtracting absorbance at 600 nm. On the other hand, the second approach has been proven to be more sensitive. Microbroth dilution tests should also be carried out using either resazurin or tetrazolium dyes. Therefore, a high-throughput assay of anti-TB is possible through using a microplate, spectrophotometrically or fluorometrically. These are quantitative assays that could detect even partial inhibition, making it possible to determine the relative activity of fractions from crude extracts using different concentrations [32, 218].


## 4. Electron and Fluorescence Microscopy Studies

Electron and fluorescence microscopy have been used effectively to examine the morphological changes during the growth of microorganisms. In addition, they can also be employed in an attempt to locate the target of action of the test extract-treated mycobacterial samples [219]. The scanning electron microscope (SEM) provides a relatively easy technique of surface morphology study of microorganisms at high magnification with a resolution of around 15 to 20 nm under ideal conditions. One of the largely untapped potentials of this apparatus is the study of the morphological changes after bacterial exposure to antimicrobial agents [220].The cell-wall-attacking characteristic of the test extracts is revealed in electron microscopy studies. Because the main part of the cell wall ofMycobacteria is comprised of lipids, it is assumed that the extracts must possess some effect on them. The target suspected is obviously mycolic acid (predominant lipid). It has been shown that a loss of acid fastness occurs when the cells ofMycobacteria are grown in the presence of antibiotics. The staining characteristics of this bacterial cell can be mainly attributed to the mycolic acids presence. Thus, when investigating the staining properties of cultures treated with extract, the culture is grown as for SEM studies. The auramine rhodamine dye is then used to stain the cells and visualized using a fluorescence microscope [219].


## 5. Genomics Studies and Proteomics Analysis

The systematic study of the whole set of cellular genetic material is called genomics. This will proffer enormous potential in both drug target and antigen discovery. Furthermore, it enhances novel antibacterial agents and vaccine development through DNA sequencing, as well as bioinformatics analysis. In TB study, it was first practiced on MTB H37Rv strain. Its bioinformatic investigation showed the attribution of accurate functions (~40% of the 4,000 genes). Once the functional information is available, it usually enables researchers to pinpoint a possible drug target on the basis of their proposed biological role or their resemblance to known bacterial drug targets [221]. In antibiotic drug discovery, expression of genome-based profiling may represent a useful tool for three applications: (i) target identification, (ii) antibiotics mechanism-of-action (MOA) studies, and (iii) new types of cell assays development for the purpose of drug screening [222].Although many productive outcomes can be revealed in genomic studies, it is only the proteomic analysis that can obtain the exact cellular information [223]. The term proteomics denotes the proteins expressed by a genome. It addresses the protein, which is the final genomic product. The advantage of proteomics is in the overcoming of a major shortcoming of DNA chip technology. It has been proven to be vital in the novel antimycobacterial drug development [224]. With the aid of a technique called two-dimensional gel electrophoresis coupled with mass spectrometry (2DE-MS), about 263 proteins were identified inM. bovis BCG and MTB strains [225]. For protein patterns analysis, it is still the analytical technique available with the best resolution and has appeared as robust and efficient for rapid protein identification. It is assisted by the database of total genome sequence [226].


## 6. Southeast Asian Medicinal Plants with Anti-TB Activity

Despite the huge medicinal plant research efforts from Southeast Asian region, literature search showed that very little research work has been carried out on anti-TB plants and published by researchers from the region. Considering the abundant biodiversity and traditional ethnomedicinal knowledge in Southeast Asia, there is vast potential to institute a dedicated anti-TB screening programme. This review paper describes the Southeast Asian medicinal plants from a wide array of families that have been evaluated for anti-TB activity in the region so far.They have been computed in a table form describing the plant species, families, part of plants and solvents used,in vitro activity, and ethnopharmacological uses (see Table 1). Interestingly, these plants species were found mentioned in various traditional medicines. Out of the 132 plants species (from 45 different families and 107 genera) discussed in this review, 114 species (87%) had reported role in the treatment of TB or TB-like symptoms in ethnomedicine (Table 1). More specifically, 24 species (18.2%) were reported for TB, 14 species (10.6%) for leprosy, and 76 species (57.6%) for TB-related diseases such as asthma, bronchitis, coughing, whooping cough, pulmonary infectious, fever, and chest diseases in ethnomedicine. It was found that crude extracts from 32 species representing 24.2% of all (132 species) plants demonstrated significant anti-TB activity inin vitro assay (MIC values ranging from 10 to 100 µg/ml). These plant species areAegle marmelos (L.) Correa,Alpinia galanga (L.) Sw.,Alpinia purpurata K. Schum.,Alpinia zerumbet (Pers.) B. L. Burtt & R. M. Sm.,Annona reticulate L.,Artocarpus rigidus Blume,Boesenbergia pandurata (Roxb.) Schltr.,Clausena excavata Burm. f.,Clausena harmandiana (Pierre) Guillaumin,Croton kongensis Gagnep.,Eclipta prostrata (L.) L.,Eriosema chinense Vogel,Feroniella lucida Swingle,Glycosmis pentaphylla (Retz.) DC.,Gynura divaricata (L.) DC.,Haplophragma adenophyllum (Wall. ex G. Don) Dop,Heliotropium indicum Linn.,Marsypopetalum modestum (Pierre) B. Xue,Micromelum minutum Wight & Arn.,Morinda citrifolia Linn,Orthosiphon stamineus Benth.,Piper betle L.,Piper chaba Hunter,Piper nigrum L.,Piper sarmentosum Roxb.,Rollinia mucosa (Jacq.) Baill.,Solanum spirale Roxb.,Tinospora crispa (L.) Hook. F. & Thomson,Uvaria microcarpa Champ. ex Benth.,Uvaria rufa Blume,Vitex trifolia L., andZingiber officinale Roscoe.Table 1
Southeast Asian medicinal plants screened for anti-TB.
Scientific name
Family
Local name
Part used: extract/active compound
Activity
Traditional uses (references)
Abrus precatorius L.
Leguminosae
Akar saga
Not stated
The extract exhibited at 500µg/ml concentration of 90.0% and inhibition against both H37Rvand MDR strain in LRP assay [38].
Bronchitis, cough, TB [18].
Aerial part: dichloromethane/Abruquinone B (1) was isolated from the extract
Compound1obtained showed anti-TB activity against H37Ra strain with MIC of 12.5 µg/ml [39].
Abutilon indicum (L.) Sweet
Malvaceae
Giling-gilingan
Leaves: dichloromethane and methanol/β-amyrin 3-palmitate (1), squalene (2), β-sitosterol (3), and stigmasterol (4) were isolated from the extract
All the isolated compounds (1, 2 and a 1 : 1 mixture of 3 and 4) showed inhibition at MIC of >128 µg/ml [40].
Cough and leprosy [40].
Acanthus ebracteatusVahl.
Acanthaceae
Nguag-plaa-moa
Leaves, stem: chloroform methanol water
All the chloroform, methanol, water extract of leaves and stem showed activity against H37Ra strain in MABA at MIC of 1000µg/ml [41].
Asthma, cough [42, 43].
Aegle marmelos(L.) Correa
Rutaceae
Mak toum
90% ethanol
The extract was active against H37Rv at MIC 54.88 µg/ml [44].
Cough, respiratory infection, intermittent fever [44–46].
Fruits and flowers: 90% ethanol
The activity against H37Rv strain in MABA was observed at the MIC of 47.8 to >100 µg/ml from 90% ethanolic extract [47].
Ageratum conyzoides L.
Asteraceae
Babadaton
Whole plant: 80% methanol
Methanolic extract of whole plant exhibited inhibition against H37Rv at the MIC 1600 µg/ml in TEMA [48].
Asthma, pneumonia, fever [49, 50].
Aglaia erythrosperma Pannell
Meliaceae
Fruits and leaves: 95%/cabraleadiol (1), cabraleahydroxylactone (2), ethyl eichlerianoate (3), eichlerialactone (4), aglinin A (5), cabralealactone (6), aglaialactone (7), flavagline (8) were isolated from the extract
Compounds3, 4,7showed anti-TB activity against H37Ra strain with the MIC of 25 µg/ml which is better than compounds 1, 2, 6,8with the MIC value of 50 µg/ml, while compound 5 showed weaker activity (MIC, >200 µg/ml) [51].
Nil.
Allium odorum L.
Liliaceae
Kucai
Leaves: 80% methanol
The extract was active against H37Rv strain at MIC 1600µg/ml [48].
Asthma, cough [52].
Aloe veraL.
Aloaceae
Lidah buaya
Leaves: 80% methanol
The extract showed activity against H37Rv strain at the MIC of 1600µg/ml [48].
Asthma, bronchitis [53].
Alpinia galanga (L.) Sw.
Zingiberaceae
Khaa, Lengkuas,
Rhizome: chloroform methanol waterCompound 1′acetoxychavicol acetate (1) was isolated from chloroform extract of rhizome
The crude chloroform, methanol, water extract of the rhizomes exhibited activity against H37Ra strain at MIC of 0.12, 1000, and 1000µg/ml, respectively. The MIC value for the isolated compound (1) was 0.024 µg/ml [41].
TB, bronchitis, pain in chest, whooping cough, asthma, sore throat [54–57].
Leaves: 80% methanol
The extract showed inhibition against H37Rv strain at the MIC 1600 µg/ml [48].
Alpinia purpurata K. Schum.
Zingiberaceae
Luyang pula
Leave: methanol/compoundsβ-sitosteryl-β-D-galactoside (1), β-sitosteryl-3-O-6′-palmityl-β-D-glucoside (2), kumatakenin (3) were isolated from the extract
At 100µg/ml, the methanolic extract of leaves showed 90% inhibition against H37Rv. All isolated compounds 1, 2, 3showed MIC > 128 µg/ml [58].
Cough [59].
Alpinia zerumbet (Pers.) B. L. Burtt & R. M. Sm.
Zingiberaceae
Rhizomes: methanol
At 100µg/ml, the methanolic extract of rhizomes showed 80% inhibition against H37Rv [58].
Common cold [59].
Alstonia scholaris(L.) R. Brown
Apocynaceae
Dita
Leaves: methanol/19,20E-vallesamine (1), a mixture of angustilobine B N4-oxide (2), N4-methyl angustilobine B (3), 20S-tubotaiwine (4), 6,7-seco-angustilobine B (5), (+)-manilamine (6) were obtained from the extract
Only4 exhibited activity at MIC of 100 µg/ml, against, while all other compounds like 1, 2, 3, 5,6showed activity with >128 µg/ml [60].
Fever [60].
Amaranthus tricolor L.
Amaranthaceae
Bayam
Whole plant: 80% methanol
Methanolic extract of whole plant exhibited inhibition against H37Rv strain at the MIC 1600 µg/ml in TEMA [48].
Cough [61].
Andrographis paniculata Nees
Acanthaceae
Hempedu Bumi
Herbs: aqueous
At 5 mg/ml the extract exhibited 100.0% inhibition against H37Rv and 93.7% against MDR strain [62].
Leprosy, sore throat [63].
Angiopteris evecta (J. R. Forst.) Hoffm.
Marattiaceae
Paku gajah
Leaves: 80% methanol
The extract exhibited activity against H37Rv strain at the MIC of 400µg/ml [48].
Cough, fever [64].
Anisochilus harmandii Doan ex Suddee & A. J. Paton
Lamiaceae
Chroomuay
Aerial part: hexane and EtOAc/pimaric acid (1), 9α-13α-epidioxyabiet-8(14)-en-18-oic acid (2), 15-hydrooxydehydroabietic acid (3) were isolated from the extract
1, 2, 3 all showed anti-TB activity at MIC, 50 µg/ml [65].
Nil.
Annona muricata L.
Annonaceae
Sirsak
Leaves: aqueous
The extract at concentration of 5 mg/ml showed 82.1% inhibition against H37Rv and 50.0% against MDR strain [62].
Asthma, cough [66, 67].
Annona reticulataL.
Annonaceae
Kantaloht (peurak)
90% ethanol
The crude extract exhibited activity at the MIC of 49.17µg/ml against H37Rv [44].
Cough, high fever [44, 68].
Anomianthus dulcis (Dunal) J. Sinclair
Annonaceae
Num Wua
Stem bark: 80% ethanol, dichloromethane and water/(2S)-5-hydroxy-6,7-dimethoxyflavanone (1), 9-methoxyliriodenine (4), Liriodenine (5) were isolated from the extract
Compounds (5), (1), (4) demonstrated anti-TB activity against H37Ra using MABA with the MIC values of 100, 200, 200 µg/ml, respectively [69].
Fever [69].
Artocarpus lakoocha Roxb.
Moraceae
Ma-Haad
Roots: dichloromethane/Lakoochins A (1) and B (2) were isolated from the extract
Compound1 and 2 showed anti-TB activity against H37Ra strain with the MICs of 12.5 and 50 µg/ml, respectively [70].
Sore throat [71].
Artocarpus rigidus subsp. Rigidus
Moraceae
Tampang
Root bark: flavonoid 7-demethylartonol E (1), chromone artorigidusin (2), xanthone artonol B (3), flavonoid artonin F (4), flavonoid cycloartobiloxanthone (5), xanthone artoindonesianin C (6), all isolated from n-hexane, chloroform, methanol extracts
All the isolated compounds showed activity again H37Ra in MABA with compound4 being the most active compound (MIC 6.25 µg/ml). This was followed by compounds 2 and 6(MIC 12.5 µg/ml) and compounds 5, 1,3with the MIC of 25, 50, 100 µg/ml, respectively [72].
Asthma, cough [73].
Averrhoa bilimbi L.
Oxalidaceae
Belimbing masam
Fruits, leaves: 80% methanol
The methanol extracts of both fruit and leaves exhibited inhibition against H37Rv at the MIC 1600 µg/ml in TEMA [48].
Whooping cough and fever [74].
Barleria lupulinaLindl.
Acanthaceae
Sa-let-pangpon
Leaves: chloroform methanol water
Chloroform, methanol, water extract of leaves all exhibited activity against H37Ra strain at the MIC of 1000µg/ml.
Cough, fever [75, 76].
Stem: chloroform methanol water
Chloroform extract of stem exhibited inhibition at MIC of 500µg/ml against H37Ra strain while methanol and water extract showed activities at 1000 µg/ml [41].
Blumea balsamifera DC.
Asteraceae
Sembung utan
Not stated
At 500µg/ml, the extract exhibited 96.0 and 82.0% inhibition against H37Rvand MDR, respectively, in LRP assay [38].
Cough [77].
Boesenbergia pandurata (Roxb.) Schltr.
Zingiberaceae
Krachai
Rhizome: chloroform methanol water
Both methanol and water extracts of rhizome exhibited inhibitory activity in MABA against H37Ra strain at the MIC of 62.5µg/ml, while chloroform extract showed activity at 1000 µg/ml MIC [41].
Cough [78].
Camchaya calcarea Kitamura
Asteraceae
Whole plant: dichloromethane/goyazensolides (1), lychnophorolides A (2), centratherin or lychnophorolides B (3), isogoyazensolides (4), isocentratherin (5), 5-epi- isogoyazensolides (7), 5-epi-isocentratherin (8), 1(10),E,4Z,11(13)-germacratriene-12,6-olide-15-oic acid (9), caffeic acid methyl ester (10) were isolated from the extract
Compound4 was the most active against H37Ra strain with MIC value of 1.5 µg/ml, followed by compounds 1, 2, 5, 7,8 with the same MIC value of 3.1 µg/ml. Compounds 3, 9,10showed less activities with the MIC values of 6.2, 50, and 25 µg/ml, respectively [79].
Nil.
Capsicum annum L.
Solanaceae
Cili
Fruit: 80% methanol
The extract showed activity against H37Rv strain at the MIC of 1600µg/ml [48].
Cough, anorexia, asthma, sore throat [80].
Casearia grewiifolia Vent.
Flacourtiaceae
Kruai pa
Stem bark: hexane and dichloromethane/bioactive compounds, Caseargrewiin A (1), Caseargrewiin B (2), Caseargrewiin C (3), Caseargrewiin D (4), rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (5) and rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (6) were isolated from the extract
1, 2, 4, 5,6 all exhibited good anti-TB activity against H37Ra strain with MICs of 12.5 µg/ml while 3 showed moderate activity with MIC of 25 µg/ml [81].
Fever [81].
Catharanthus roseus (L.) G. Don
Apocynaceae
Kemunting cina
Leaves: 80% methanol
The extract was active against H37Rv at MIC 1600 µg/ml [48].
Asthma, TB [82].
Ceiba pentandra (L.) Gaertn.
Bombacaceae
Kabu
Fruit: 80% methanol
The extract exhibited anti-TB activity against H37Rv strain at the MIC of 1600µg/ml [48].
Bronchitis, fever [83].
Centella asiatica (L.) Urb.
Apiaceae
Pegaga
Whole plant: 80% methanol
The extract showed activity against H37Rv strain at the MIC of 1600µg/ml [48].
TB, leprosy, asthma [84].
Herbs: aqueous
78.5 and 50.0% inhibition were observed at 5 mg/ml concentration against H37Rv and MDR, respectively [62].
Chisocheton penduliflorus Planch. ex Hiern
Meliaceae
Wood and leaves: 95% methanol/cabraleadiol (1), allo-aromadendrane-10β, 14-diol (2), allo-aromadendrane-10α, 14-diol (3) eichlerialactone (4), cabraleahydroxylactone (5), cabralealactone (6), allo-aromadendrane-10β,13,14-triol (7) were isolated from the extract
Compound4showed good anti-TB activity against H37Ra with the MIC value of 25 µg/ml, better than 1, 2, 5, 6,7 with the MICs of 50 µg/ml, while compound 3 showed weaker activity (MIC, 100 µg/ml) [85].
Nil.
Chromolaena odorata (L.) R. M. King & H. Rob.
Asteraceae
Agonoi
Flowers: isosakuranetin (1), 4′-hydroxy-5,6,7-trimethoxyflavanone (2), acacetin (3), luteolin (4), all isolated from chloroform extract
The compounds isolated exhibited activities against H37Ra at different MIC values (µg/ml) 174.8 (1), 606.0 (2), 704.2 (3), 699.3 (4) [86].
Cough [87].
Citrus aurantiifolia (Christm.) Swingle
Rutaceae
Limau nipis
Not stated
In LRP assay, extract at 500µg/ml showed 98.0% inhibition against H37Rv strain and 36.0% against MDR strain [38].
Sore throats, bronchitis, asthma [88, 89].
Citrus microcarpa Bunge
Rutaceae
Limau kasturi
Leaves: 80% methanol
The extract exhibited anti-TB activity against H37Rv strain at the MIC of 1600µg/ml in TEMA [48].
Cough [90].
Clausena excavate Burm. f.
Rutaceae
Sun Soak
Dentatin (1), nordentatin (2), clausenidin (3), O-methylated clausenidin (4), 3-formylcarbazole (5), mukonal (6), 3-methoxycarbonylcarbazole (7), 2-hydroxy-formyl-7-methoxycarbazole (8), clauszoline (9); compounds 1, 2, 6, 7, 8,9 where isolated from the chloroform extract of rhizomes; compound 3was isolated from crude hexane extract of rhizome. Methylation of compound 3 gave rise to compound 4; compound 10 was isolated from crude chloroform extract of the root
Compounds1, 4,7, isolated, were more active against H37Ra with MIC of 50 µg/ml; this is followed by 2, 5, 8,9 with MIC of 100 µg/ml, while compounds 3 and 6 are with MIC of 200 µg/ml [91].
TB [92].
Clausena guillauminii Tanaka
Rutaceae
Roots: acetone/fluroclausine A (1) and heptazoline (2) were obtained from the extract
Using the green fluorescent protein microplate assay (GFPMA), both1 and 2 exhibited anti-TB activity against H37Ra strain with the same IC50 value of 25 µg/ml [93].
Cough [94].
Clausena harmandiana(Pierre) Guillaumin
Rutaceae
Song Fa
Fruits and flowers: 90% ethanol
MICs of 83.1 to >100µg/ml were observed when 90% ethanolic extract of fruits and flowers was tested against H37Rv in MABA [47].
Cough [94].
Clerodendrum indicum (L.) Kuntze
Verbenaceae
Bunga pagoda
Flowers: 80% methanol
The extract exhibited anti-TB activity against H37Rv strain at the MIC of 1600µg/ml [48].
Cough, asthma [95].
Clitoria ternatea L.
Leguminosae
Bunga kelentik
Whole plant: 80% methanol
At MIC = 1600µg/ml, the extract showed anti-TB activity against H37Rv strain [48].
Asthma, leprosy, TB [96].
Coccinia grandis (L.) Voigt
Cucurbitaceae
Phak tamlueng
Leaves: chloroform methanol water
In MABA, chloroform, methanol, water extract of leaves all exhibited activity against H37Ra strain at the MIC of 1000µg/ml [41].
Asthma, cough, bronchitis [97, 98].
Coleus atropurpureusL. Benth
Lamiaceae
Piladang
Compound 2′,5′-dimethyl benzopelargonolactone was isolated from the chloroform fraction of leaf
The isolate was active against H37Rv strain at the MIC of 200 µg/ml [99].
Bronchitis, TB [99].
Colocasia esculenta (L.) Schott
Colocasieae
Keladi cina
Leaf: 80% methanol
The methanol extract of leaves showed activity against H37Rv strain with the MIC value 1600 µg/ml [48].
Asthma, coughing with sputum [100].
Combretum griffithii Van Heurck & Müll. Arg.
Combretaceae
Khamin khruea
Stem: methanol/1-(2-hydroxy-4-methoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)propane (1) were isolated from the extract
1 exhibited anti-TB activity against H37Ra strain with the MIC of 3.13 µg/mL [101].
Coughing, leprosy [102].
Cordia globifera W. W. Smith
Boraginaceae
Sak Hin
Root: dichloromethane/Globiferin (1), cordiachrome B (2), cordiachrome C (3), cordiaquinol C (4), alliodorin (5), elaeagin (6), cordiachromene (7) were isolated from the extract
Compounds1, 2,3 displayed good activity (MIC, 6.2, 12.5, 1.5 µg/ml resp.) using MABA against H37Ra, followed by 5, 6,7 (MIC, 12.5 µg/ml) and then 4 with MIC of 25 µg/ml [103].
Cough [104].
Costus speciosus (J. Koenig) Sm.
Costaceae
Setawar halia
Stem and flowers: 80% methanol
The methanol extract of Stem and flowers exhibited anti-TB activity against H37Rv strain with the MIC value 800 µg/ml [48].
Asthma, bronchitis [105].
Croton kongensis Gagnep.
Euphorbiaceae
Plao Ngeon, Khổ sâm bắc bộ
Leaves: crude dichloromethane extract.ent-8,9-seco-7α,11β-diacetoxykaura-8(14),16-dien-9,15-dione (1), ent-8,9-seco-8,14-epoxy-7α-hydroxy-11β-acetoxy-16-kauren-9,15-dione (2), ent-8,9-seco-7α-hydroxy-11β-acetoxykaura-8(14),16-dien-9,15-dione (3), all were isolated from dichloromethane extract of leaves
Dichloromethane crude extract exhibited activity against H37Ra strain with the MIC value 12.5µg/ml in MABA. The isolated compounds 2 and 3 showed better activity with the MIC value 6.25 µg/ml than compound 1 with 25.0 µg/ml MIC [106].
Leprosy, weight loss [107].
Whole plants, leaves: ethanol, ethyl acetate, methylene chloride, n-Hexane/ent-1β,7α,14β-triacetoxykaur-16-en-15-one (1), ent-7α,18-dihydroxykaur-16-en-15-one (2), ent-16(S)-18-acetoxy-7α- hydroxykaur-15-one (3), ent-18-acetoxy-7α-hydroxykaur-16-en-15-one (4), ent-1β,14β-diacetoxy-7α-hydroxykaur-16-en-15-one (5), ent-1β-acetoxy-7α,14β-dihydroxykaur-16-en-15-one (6), ent-7α,14β-dihydroxykaur-16-en-15-one (7) were all isolated from ethanol, ethyl acetate, methylene extract of whole plants and leaves
The activities against H37Ra strain were observed at the MIC of 25–50, >50, 6.25–12.5, 12.5–25µg/ml from ethanol, ethyl acetate, methylene chloride, n-Hexane crude extracts of whole plants and leave using microtiter resazurin assay. Isolated compound 1 exhibited the highest activity with MIC values of 0.78, 1.56, 3.12–12.5 µg/ml against H37Ra, H37Rv, other resistant strains of M. tb screened. Both compounds 2and3exhibited MIC at 1.56 µg/ml. Compounds 4, 5, 6,7 on the other hand showed MIC value 3.12–6.25 against H37Ra and H37Rv and other resistant strains of M. tb [108].
Curcuma aeruginosa Roxb.
Zingiberaceae
Waan mahaamek
Rhizomes: water/essential oil
Using GFPMA, essential oil showed weaker anti-TB activity against H37Ra strain with 2500µg/ml MIC value [109].
Dyspepsia [109].
Dalbergia parviflora Roxb.
Leguminosae
Sak Kee
Stem: hexane, ethyl acetate, methanol/Flavanone (1), dalparvone (2), dalparvinene (6) were isolated from the extract
Using GFPMA, compound1 exhibited good anti-TB activity against H37Ra strain with the MIC of 12.5 µg/ml, while compounds 2 and 6 showed activity with the MICs of 50 µg/ml [110].
Expectorant [110].
Dasymaschalon dasymaschalum (Blume) I. M. Turner
Annonaceae
Buu ngong
Leaves: ethyl acetate/3β-hydroxy-21-O-acetyl-24-methylenecycloartane (1) was obtained from the extract
Compound1 displayed activity against H37Ra strain with the MIC value of 50 µg/ml [111].
Nil.
Dendrolobium lanceolatum (Dunn) Schindl.
Leguminosae
Kraduk-Khiat
Root: hexane and dichloromethane/Flavanones 1 (1), flavanones (2), flavan (3), dibenzocycloheptene derivative (4), 4′-hydroxy-7,8-(2′′,2′′-dimethylpyran)flavan (5) isolated from the extract.
Compound1 exhibited highest activity against H37Ra strain with MIC of 6.3 µg/ml, followed by 2 (MIC, 12.5 µg/ml) and then 3 and 5 with MICs of 25 µg/ml [112].
Nil.
Derris indica L
Leguminosae
Root and stem: dichloromethane extract/3-methoxy-(3′′,4′′-dihydro-3′′,4′′-diacetoxy)-2′′,2′′-dimethylpyrano-(7,8:5′′,6′′)-flavone (1), 2′-methoxy-4′,5′-methylenedioxyfurano [7,8:4′′,5′′]-flavone (2), 8,4′-dimethoxy-7-O-γ,γ-dimethylally-lisoflavone (3), 3,4-methylenedioxy-10-methoxy-7-oxo[2]benzopyrano[4,3-b]benzopyran (4), desmethoxy kanugin (5), karanjin (6), lacheolatin B (7), pongachromene (8), 3,7-dimethoxyflavone (9), pachycarin D (10), maackiain (11), medicarpin (12) karanjachromene (13), pinnatin (14) isolated from this extract
4, 13,14 (6.25, 12.5, 12.5 µg/ml, resp.) showed stronger activity compared to 1, 5,7, 9, 10 (25, 50, 50, 50, 50 µg/ml resp.) that showed moderate activity, with 3, 8, 10,12 (100, 100, 200, 100 µg/ml resp.) showing weaker activity against H37Ra strain using MABA [113].
Bronchitis and whooping cough [23].
Diospyros decandra Lour.
Ebenaceae
Chan
Betulinic acid (1) and 2-oxo-3β,19α-dihydroxy-24-nor-urs-12-en-28-oic acid (2)
1 and 2exhibited moderate to weak anti-TB activity against H37Ra strain with MIC of 25 and 200 µg/ml, respectively [114].
Fever [114].
Diospyros ehretioides Wall. ex G. Don
Ebenaceae
Nom ngua
Fruits: dichloromethane/palmarumycins JC1 (1), palmarumycins JC2 (2), isodiospyrin (3), isodiospyrol A (4) were isolated from the extract
Compound2exhibited good (MIC = 6.25 µg/ml) anti-TB activity against H37Ra, followed by compound 4(MIC = 50 µg/ml). Compounds 1and 3 showed weak activity (MICs ≥ 200 µg/ml) [115].
Nil.
Diospyros glandulosa Lace
Ebenaceae
Kluai ruesi
Diospyrin, isolated from dichloromethane extract of wood
Diospyrin isolated showed activity against H37Ra in MABA with the MIC of 6.25µg/ml [116].
Nil.
Diospyros rhodocalyx Kurz
Ebenaceae
Tako Na
Betulinaldehyde, obtained from dichloromethane extract of wood
Betulinaldehyde exhibited inhibitory activity in microbroth dilution assay against H37Ra with the MIC of 25µg/ml [116].
Nil.
Eclipta prostrata(L.) L.
Asteraceae
Kra-meng
Whole plant: chloroform methanol water
Water, chloroform, methanol extracts of whole plant exhibited inhibition in MABA against H37Ra strain at the MICs of 62.5, 125, 1000µg/ml respectively [41].
Asthma and TB [117].
Eriosema chinense Vogel
Leguminosae
ToonKhonklong
Roots: hexane, dichloromethane, methanol/Khonklonginol A (1), B (2), F (6), H (8), lupinifolinol (9), dehydrolupinifolinol (10), flemichin D (11), eriosemaone A (12), lupinifolin (13) were obtained from the extract
Crude hexane extract showed anti-TB activity against H37Ra strain with the MIC value of 50µg/ml using MABA. Compounds 10, 11, 12,13demonstrated good anti-TB activity against H37Ra strain with the same MIC value of 12.5 µg/ml. Compounds 1, 8,9 exhibited moderate activity with the same MIC value of 25 µg/ml. Compounds 2 and 6 showed activity at MIC values of 50 and 100 µg/ml, respectively [118].
Nil.
Erythrina fusca Lour.
Fabaceae
Thong long
Stem bark: hexane and ethyl acetate/sandwicensin (1), erythrisenegalone (2), lonchocarpol A (3), lupinifolin (4) were isolated from the extract
Compounds1, 2, 3,4 demonstrated anti-TB activity against H37Ra with MICs of 100, 50, 50, 25 µg/ml, respectively [119].
Antibacterial [120].
Erythrina subumbrans Merr.
Leguminosae
Bark: n-hexane, dichloromethane and methanol/1-methoxyerythrabyssin II (1) was isolated from the extractStem: n-hexane and dichloromethane/erystagallin A (1), erycristagallin (2), 5-hydroxysophoranone (3), erysubin F (4) were isolated from the extract
Compound 1 showed activity against H37Ra strain with 50 µg/ml MIC value [121]. All compounds 1, 2, 3, 4 exhibited anti-TB activity against H37Ra with the MICs of 12.5 µg/ml [122].
Cough [122].
Etlingera elatior (Jack) R. M. Sm.
Zingiberaceae
Bunga kantan
Rhizomes: methanol/Stigmasterol (1) and β-sitosterol (2) were isolated from the extract
At 100µg/ml, the methanolic extract of rhizomes showed 86% inhibition against H37Rv. The isolated compounds 1 and 2 exhibited MIC > 128 µg/ml [58].
Nil.
Etlingera pavieana (Pierre ex Gagnep.) R. M. Sm.
Zingiberaceae
Rhizomes: dichloromethane/(E)-((E)-3-(4-methoxyphenyl)allyl)3-(4-hydroxyphenyl)acrylate (1) was isolated from the crude extract
Compound1 demonstrated anti-TB activity with the MIC value of 50.00 µg/ml [123].
Fever and cough [123].
Fernandoa adenophylla(Wall. Ex G. Don) Steenis
(Bignoniaceae)
Khae Pa
Fruits and flowers: 90% ethanol
In microbroth dilution assay, the extract exhibited inhibition at MIC of 79.7 to >100µg/ml [47].
Skin diseases [124].
Feroniella lucidaSwingle
Rutaceae
Sung(mak)/kohk sung
90% ethanol
The extract showed inhibition against H37Rv at MIC value 91.54 µg/ml in MABA [44].
Cough, TB [44, 125].
Fruits and flowers: 90% ethanol
In MABA, 90% ethanolic extract of fruits and flowers exhibited activity against H37Rv strain with MIC ranging from 90.4 to >100µg/ml [44].
Ficus carica L.
Moraceae
Ara
Leaves: 80% methanol
There was anti-TB activity against H37Rv strain at 1600µg/ml [48].
Asthma, cough [126].
Flemingia strobilifera (L.) W. T. Aiton
Fabaceae
Serengan
Leaves: 80% methanol
At MIC = 1600µg/ml, the extract showed anti-TB activity against H37Rv strain [48].
TB [127].
Friesodielsia discolor (Craib) D. Das
Annonaceae
Leave: dichloromethane and ethyl acetate/3′-formyl-2′,4′-dihydroxy-6′-methoxychalcone (1) was isolated from the extract
Compound1 exhibited anti-TB activity against H37Ra strain with 6.25 µg/ml MIC value [128].
Nil.
Garcinia mangostanaL.
Clusiacea
Mangkhud
Fruits:α-mangostin (1), β-mangostin (2), γ-mangostin (3), garcinone D (4), mangostenol (5), garcinone B (6), mangostanin (7), mangostanol (8), mangostenone A (9), tovophyllin B (10), demethylcalabaxanthone (11), trapezifolixanthone (12), mangostinone (13) all isolated from chloroform, methanol extract
Compounds isolated showed activities against H37Ra in microbroth dilution at different MIC values (µg/ml) 6.25 (1), 6.25 (2), 25 (3), 25 (4), 100 (5), 6.25 (6), 25 (7), 200 (8), 25 (9) 25 (10), 12.5 (11), 12.5 (12), 200 (13) [129].
Fever [130].
Glycosmis pentaphylla (Retz.) DC.
Rutaceae
Xom Xeuan
Fruits and flowers: 90% ethanol
The 90% ethanol extracts of fruits and flowers exhibited activities against H37Rv strain with the MIC of 93.5 to >100 µg/ml in MABA [47].
Cough [131].
Goniothalamus gitingensis Elmer
Annonaceae
Leaves/Liriodenine (1) was isolated from the extract
1 showed anti-TB with the MIC of 16 µg/ml [132].
Nil.
Goniothalamus laoticus (Finet & Gagnep.) Bân
Annonaceae
Khao-Lam-dong
Flowers: goniotriol (1), (+)-altholactone (2), howiininA (3) and an aporphine alkaloid; (−)-nordicentrine (4), all isolated from n-hexane, ethyl acetate, methanol extracts
In microbroth dilution, the isolated compound4 showed the best activity against H37Ra with MIC of 12.5 µg/ml, followed by compounds 2 and 3 both with the MIC of 6.25 µg/ml, and then compound 1 with 100 µg/ml [133].
Cold [134].
Gynura divaricata (L.) DC.
Asteraceae
Leaves: hexane, dichloromethane, methanol/essential oil
The essential oil showed inhibitory effect against H37Ra strain with the MIC value of 50µg/ml [135].
Bronchitis and pulmonary TB [135].
Gynura pseudochina (L.) D.C. var. hispida Thv.
Asteraceae
Waan Mahaakaan
Whole plant: chloroform methanol water
At the MIC of 200µg/ml, chloroform extract of whole plant exhibited activity against H37Ra strain while both methanol and water extracts exhibited activity at 1000 µg/ml MIC, respectively [41].
Asthma, fever, AIDS [136, 137].
Haplophragma adenophyllum (Wall. ex G. Don) Dop
Bignoniaceae
Kay pa
90% ethanol
In MABA, the MIC of 83.25µg/ml was observed against H37Rv [44].
Cough [44].
Hedychium ellipticum Buch.-Ham. ex Sm.
Zingiberaceae
Rhizomes: n-hexane and dichloromethane/Coronarin E (1) and 16-Hydroxylabda-8(17),11,13-trien-15,16-olide (7) were isolated from the extract
Compounds1and7exhibited good anti-TB activity against H37Ra strain using GFPMA with the MIC value of 12.5 and 6. 25 µg/ml, respectively [138].
Bronchitis [139].
Heliotropium indicum Linn.
Boraginaceae
Yaa Nguang Chaang
Leaves: water
The crude extract showed activity against H37Ra strain using MABA with the MIC of 20.8µg/ml [140].
Asthma [140].
Hibiscus rosa-sinensis L.
Malvaceae
Bunga raya
Leaves: 80% methanol
The extract exhibited anti-TB activity against H37Rv strain at the MIC of 1600µg/ml [48].
Cough, leprosy, bronchial catarrh [141].
Hymenocardia wallichii Tul
Euphorbiaceae
Stem: dichloromethane, methanol, hexane/Squalene were isolated from the extract
Squalene displayed anti-TB activity against H37Ra strain with the MIC value of 100µg/ml [142].
Nil.
Hyptis suaveolens (L.) Poit.
Lamiaceae
Maeng luk kha
Whole plant: hexane, chloroform and methanol/8α,9α-epoxysuaveolic acid (2), suaveolic acid (4), suaveolol (5) were isolated from the extract
Compounds2, 4, 5 displayed weak anti-TB activities (MIC 100–200 µg/ml) against H37Ra strain using MABA [143].
Fever and respiratory tract infections [143].
Jasminum sambac (L.) Aiton
Oleaceae
Melor
Leaves: 80% methanol
At MIC = 1600µg/ml, the crude extract showed inhibition against H37Rv strain [48].
Cough, Leprosy [144].
Jatropha curcas L.
Euphorbiaceae
Jarak
Leaves: 80% methanol
The extract showedin vitro activity against H37Rv strain at the MIC of 1600 µg/ml [48].
Leprosy [145].
Jatropha integerrima Jacq.
Euphorbiaceae
Roots: dichloromethane and ethanol/caniojane were isolated from the extract
Caniojane exhibited anti-TB activity against H37Ra strain using MABA with 25µg/ml MIC value [146].
Styptic [147].
Justicia gendarussa Burm. f.
Acanthaceae
Urat sugi
Leaves: 80% methanol
The extract exhibited anti-TB activity against H37Rv strain at the MIC of 1600µg/ml [48].
Respiratory disorders [148].
Kaempferia galangal L.
Zingiberaceae
Kencur
Not stated
In LRP assay, the extract at 500µg/ml exhibited 69.0% inhibition against both H37Rv and MDR strain [38].
Asthma, cough [149].
Kaempferia marginata Carey
Zingiberaceae
Tup mup
Whole plant: dichloromethane and/(1R,2S,5S,9S,10S,11R,13R)-1,2,11-trihydroxy-pimara-8(14),15-diene (2), (1S,5S,7R,9R,10S,11R,13R)-1,7,-11-trihydroxypimara-8(14),15-diene (3), (1R,2S,5S,7S,9R,10S,13R)-1,2-dihydroxypimara-8(14),15- diene-7-one (6), sandaracopimaradien-1α-ol,2α-acetoxysandaracopimaradien-1α-ol, sandaracopimaradien-1α,2α-diol were isolated from the extract
Compounds sandaracopimaradien-1α-ol and 2α-acetoxysandaracopimaradien-1α-ol exhibited ant-TB activity against H37Ra strain with the MIC values of 25 and 50 µg/ml, respectively.Compounds 2, 3, 6, sandaracopimaradien-1α,2α-diol were less active (MICs of > 100 µg/ml) [150].
Fever [150].
Lantana camaraL.
Verbenaceae
Kembang telek
Not stated
At 500µg/ml, the extract exhibited 94.0 and 79.0% inhibition against H37Rv and MDR, respectively, in LRP assay [38].
TB, leprosy, asthma [151, 152].
Lepisanthes rubiginosa (Roxb.) Leenh.
Sapindaceae
Mertajam
Leaves: 80% methanol
In broth microdilution assay, the extract showed inhibition against H37Rv strain at 1600µg/ml [48].
TB [153].
Licuala spinosa Thunb.
Arecaceae
Palas tikus
Leaves: 80% methanol
In TEMA, the extract showed inhibition against H37Rv strain at 1600µg/ml [48].
TB [48].
Limnophila geoffrayi Bonati
Scrophulariaceae
Prod Ka yaeng
Flavones nevadensin (1) and isothymusin (2), all were isolated from chloroform extract of aerial part
Both compounds1 and 2 showed activities against H37Ra in MABA at the MIC = 200 µg/ml [154].
Expectorant [155].
Marsypopetalum modestum (Pierre) B. Xue
Annonaceae
Tin Tang Tia
Fruits and flowers: 90% ethanol
The extract of fruits and flowers exhibited activities at MIC ranging between 0.05 and 11.9µg/ml in MABA against H37Rv [47].
Nil.
Micromelum minutum Wight & Arn.
Rutaceae
Sa Mat Khao
Fruits and flowers: 90% ethanol
The activity against H37Rv strain in MABA was observed at the MIC of 45.7 to >100 µg/ml from 90% ethanolic extract [47].
Cough, fever [156].
Momordica charantiaL.
Cucurbitaceae
Ampalaya
Leaves: ethanol/2,4-bis(2-phenylpropan-2-yl)phenol (1) isolated from the extract
Compound1 exhibited anti-TB activity against H37Rv strain MIC value of 14 µg/ml using MABA [157].
Leprosy [158].
Morinda citrifolia Linn.
Rubiaceae
Noni
Leaves: ethanol and hexane/(E)-phytol (1), cycloartenol (2), stigmasta-4-en-3-one (3), stigmasta-4-22-dien-3-one (4), β-sitosterol (5), stigmasterol (6), campesta-6,22-dien-5α,8α-epidioxy-3β-ol (7) were isolated from the extract
At 100µg/ml, the crude extract of ethanol and hexane fractions displayed 89 and 95% inhibition, respectively, against H37Rv strain.2 : 1 mixture of compounds 3 and 4 exhibited good activity (MIC = 2 µg/ml) against H37Rv strain followed by 7(MIC = 2.5 µg/ml) and then 1 and 6 (MICs = 32 µg/ml). Compound 2 and 5 were less active with MIC values of 64 and 128 µg/ml, respectively [159].
Respiratory infection [159].
Morus alba L.
Moraceae
Merbatu
Leaves and fruit: 80% methanol
In broth microdilution assay, the extract showed inhibition against H37Rv strain at 1600µg/ml [48].
Cough [160].
Murraya paniculata (L.) Jack
Rutaceae
Kaeo
Leaves: chloroform methanol water
Chloroform extract of leaves at the MIC of 250µg/ml showed activity against H37Ra strain while both methanol and water extracts exhibited activity at 1000 µg/ml MIC, respectively [41].
Cough, asthma, expectorant [161–163].
Orthosiphon stamineus Benth.
Lamiaceae
Misai Kuching
Leaves: hexane, chloroform, ethyl acetate
The hexane, chloroform, ethyl acetate extracts of leaves exhibited activity with the MICs of 25.00, 3.12, 6.25µg/ml [164].
Loss of weigh [165].
Passiflora foetida L.
Passifloraceae
Letup-letup
Whole plant: 80% methanol
There was inhibition against H37Rv at MIC = 1600 µg/ml [48].
Cough [166].
Pedilanthus tithymaloides (L.) Poit.
Euphorbiaceae
Sa yaek
Leaves: methanol, water, hexane/1α,13β,14α-trihydroxy-3β,7β-dibenzoyloxy-9β,15β-diacetoxyjatropha-5,11E-diene (1), 1α,7β,13β,14α-tetrahydroxy-3β-benzoyloxy-9β,15β-diacetoxyjatropha-5,11E-diene (2), 1α,8β,9β,14α,15β-pentaacetoxy-3β-benzoyloxy-7-oxojatropha-5,12-diene (3), 7,8β,9β,14α,15β-pentaacetoxy-3β-benzoyloxy-1α,5β-dihydroxyjatropha-6(7),12-diene (4), 1α,7,8β,9β,14α,15β-hexaacetoxy-3β-benzoyloxy-5β-hydroxyjatropha-6(7),12-diene (5) were obtained from the extract
Compound1 showed stronger (12.5 µg/ml) activity compared to 2, 3, 4, and 5 (100, 50, 100, and 50 µg/ml resp.) against H37Ra in MABA [167].
Nil.
Petiveria alliacea L.
Phytolaccaceae
Singawalang
96% ethanol: leaves
The ethanolic extract of leaves exhibited activity against drug sensitive and resistant strains of H37Rv at the MIC of 1280 µg/ml [168].
Antibacterial [169].
Not stated
At 500µg/ml, the extract exhibited 98.0 and 76.0% inhibition against H37Rv and MDR, respectively, in LRP assay [38].
Phyllanthus acidus (L.) Skeels
Euphorbiaceae
Cermai
Leaves: 80% methanol
The extract exhibited anti-TB activity against H37Rv strain at the MIC = 1600µg/ml [48].
Cough [170].
Piper betle L.
Piperaceae
Plu, Daun sirih
Leaves:chloroform methanol water
Chloroform extract of leaves was more active against H37Ra strain with MIC value 62.5µg/ml than the methanol and water extract both with activity at MIC of 1000 µg/ml [41].
Asthma, leprosy cough, dyspnea, bronchitis [171–173].
Piper chabaHunter
Piperaceae
Dee plee
Fruit: chloroform, methanol, water; compound Piperine (1) was isolated from chloroform crude extract of fruit
Inhibition against H37Ra strain was observed at MIC (µg/ml) of 16, 25, 1000 with respect to the chloroform, methanol, water extract of fruit in MABA. Compound 1 isolated exhibited activity at MIC of 50 µg/ml [41].
Asthma [174].
Stem: n-hexane/chabamide (1) was isolated from the extract
Compound1 exhibited anti-TB activity with the MIC value of 12.5 µg/ml against H37Ra strain [175].
Piper nigrum L.
Piperaceae
Lada hitam
Fruit: 80% methanol
The extract exhibited anti-TB activity against H37Rv strain at the MIC of 1600µg/ml [48].
Asthma, bronchitis, TB, sore throat [176, 177].
Leaves: ethyl acetate n-hexane water
Ethyl acetate, n-hexane, water extract fraction of leaves exhibited inhibition against H37Rv strain using TEMA at the MIC values of 25, 50, 100µg/ml, respectively [176].
Piper sarmentosumRoxb.
Piperaceae
Kadok, Cha-plu
Whole plant: 80% methanol
At the MIC = 800µg/ml, the extract showed inhibition against H37Rv strain [48].
Cough [178].
Leaves: petroleum ether, Chloroform, methanol
The methanol extract of leaves showed more activity against MTB (MIC 12.5µg/ml) in TEMA than both petroleum ether and Chloroform extracts (MIC 25 µg/ml). The ethyl acetate and chloroform fractions of methanol extract exhibited MICs at 3.12 µg/ml [179].
Leaves: aqueous, ethanol
The aqueous and ethanol extracts of leaves exhibited anti-TB activity MIC/MBC 12.5µg/ml. Methanolic extract was fractionated with ethyl acetate; the fraction of ethyl acetate exhibited anti-TB activity with MIC/MBC 3.12 µg/ml [180].
Fruits: hexane and methanol/pellitorine (1), guineensine (2), brachystamide B (3), sarmentine (4), brachyamide B (5), sarmentosine (8), 1-(3,4-methylenedioxyphenyl)-1E-tetradecene (11) were isolated from the extract
Compounds1 and 11 were more active (MICs = 25 µg/ml) against H37Ra strain followed by 2, 4, 5 (MICs = 50 µg/ml); then 3 and 8 showed weaker activities with the MIC values of 100 and 200 µg/ml, respectively [181].
Pistia stratiotes L.
Araceae
Water lettuce
Whole plant: 80% methanol
The inhibition against H37Rv was observed at the MIC of 1600µg/ml [48].
Leprosy, TB [182].
Pluchea indica (L.) Less.
Asteraceae
Beluntas
FlowerLeaves: 80% methanol
In TEMA, the extracts of flowers and leaves showed inhibitory activities against H37Rv strain at the MIC of 800µg/ml each [48].
TB [183].
Leaves: aqueous
The extract showed 100% inhibition against H37Rv and MDR at 5 mg/ml [62].
Polyalthia cerasoides(Roxb.) Benth. ex Bedd
Annonaceae
Sai den
Root: hexane, EtOAc, MeOH/Bidebiline E (1), octadeca-9,11,13-triynoic acid (2), α-humulene (3) were isolated from the extract
Isolated compounds1, 2,3 showed anti-TB activity against H37Ra strain with MICs of 6.25 µg/ml [184].
Fever [184].
Polyalthia debilis (Piere) Finet & ganep
Annonaceae
Kon Krok
Root: methanol/Debilisone B (1), Debilisone C (2), Debilisone E (3)
Compounds1, 2, 3 showed moderate anti-TB activity against H37Ra strain with MIC values of 25.0, 12.5, 25.0 µg/ml, respectively [185].
TB [186].
Premna odorataBlanco
Lamiaceae
Alagaw
Leaves: methanol and dichloromethane/1-heneicosyl formate (1) was isolated from the extract
Crude methanolic extract showed inhibition against H37Rv strain with >128µg/ml MIC. Compound 1 showed good anti-TB activity (8 µg/ml) [187].
TB [187].
Rhoeo spathacea (Sw.) Stearn
Commelinaceae
Nil
Leaves: 80% methanol
At 5 mg/ml, the extract exhibited 100% inhibition against H37Rv and MDR [62].
TB, asthma [188].
Rollinia mucosa(Jacq.) Baill.
Annonaceae
Khanthaloht
Fruits and flowers: 90% ethanol
Fruits and flowers extract were active at MIC ranging between 43.9 and 75.2µg/ml in MABA [47].
Nil.
Rothmannia wittii (Craib) Bremek.
Rubiaceae
Muk Mo
Bark and fruits: n-Hexane and ethyl acetate/A compound 6β-hydroxy-10-O-acetylgenipin (1) was isolated from the extract
Compound1 displayed activity against H37Ra using MABA with MIC value of 12.50 µg/ml [189].
Fever [189].
Sapium indicum L.
Euphorbiaceae
Fruit: hexane/compounds 12-(2-N-methylaminobenzoyl)-4β,5,20-trideoxyphorbol-13-acetate (1), 12-(2-N-methylaminoben-zoyl)-4α,5,20-trideoxyphorbol-13-acetate (2), sapintoxin A (3), α- saponine (4), sapintoxin C (5), 12-(2-N-methylaminobenzoyl)-4α,20-dideoxy-5-hydroxyphorbol-13-acetate (6) sapintoxin B (7), 12-(2′-N-methylaminobenzoyl)-4α-deoxy-5,20-dihydroxyphorbol-13-acetate (8), 12-(2-methylaminobenzoyl)-4-deoxyphorbaldehyde-13-acetae (9) were isolated from extract
Compound3(MIC, 3.12 µg/ml) was the most active compound against H37Ra using MABA, followed by 7 (MIC, 12.5 µg/ml) and then followed by 5, 8,9 (MIC, 25 µg/ml). Compound 1 showed moderate activity (MIC, 50 µg/ml) while 2, 4,6 showed weak activity (200, >200, >200 MIC, µg/ml, respectively) [190].
Fever [191].
Selaginella plana (Desv. ex Poir.) Hieron.
Selaginellaceae
Paka merak
Whole plant: 80% methanol
Inin vitro assay, the extract showed activity against H37Rv at 1600 µg/ml MIC [48].
Coughing and asthma [48].
Sesbania grandiflora (L.) Poir.
Leguminosae
Geti
Fruit: 80% methanol
The extract exhibited inhibition against H37Rv strain at the MIC of 1600µg/ml [48].
Sore throat [192].
Root: methanol/isovestitol (1), medicarpin (2), sativan (3), betulinic acid (4)
The methanol crude extract exhibited anti-TB activity against H37Rv with MIC value of 625 μg/ml. Isolated compounds 1-3 exhibited MIC of 50 µg/ml while compound 4 showed activity at MIC of 100 µg/ml [193].
Solanum spiraleRoxb.
Solanaceae
Pak dit
Fruit: water
Essential oil extracted showed anti-TB activity against H37Ra strain with MIC value of 50µg/ml [194].
Fevers and colds [194].
Solanum torvum Sw.
Solanaceae
Terung pipit
Fruit: 80% methanol
There was inhibition at the MIC of 1600μg/mL against H37Ra strain [48].
Cough [195].
Spilanthes acmella(L.) Murray
Asteraceae
Raan
Whole plant: chloroform methanol water
The chloroform, methanol, water extract of whole plant exhibited inhibition in MABA, against H37Ra strain at the MIC of 500, 1000, 1000µg/ml, respectively [41].
TB, cough, sore throats [196, 197].
Spondias pinnata (L.f.) Kurz
Anacardiaceae
Loloh cemcem
Chloroform, 80% ethanol.
The extracts were active against MDR strain of Lowenstein-Jensen medium with 100% inhibition at concentration of 100 mg/ml [198].
Chronic cough [198].
Tabernaemontana coronaria (L.) Willd.
Apocynaceae
Jasmine
Leaves: 80% methanol
At the MIC of 800µg/ml, the extract showed inhibition against H37Rv strain [48].
TB [48].
Tiliacora triandra (Colebr.) Diels
Menispermaceae
Ya-nang
Roots: tiliacorinine (1), 2′-nortiliacorinine (2), tiliacorine (3), 13′-bromo-tiliacorinine (4) were isolated from the extract
Compounds1, 2, 3,4 demonstrated anti-TB activity against MDR-MTB strains with the MIC values ranging from 0.7 to 6.2 µg/ml [199].
Fever [200].
Tinospora crispa(L.) Hook. F. & Thomson
Menispermaceae
Kheuah Khao Ho
Fruits and flowers: 90% ethanol
In microbroth dilution assay, the extract exhibited inhibition at MIC of 2.43 to 96.2µg/ml [47].
Coughs, asthma leprosy [201, 202].
Trigonostemon reidioides (Kurz) Craib
Euphorbiaceae
Lot Thanong
Root: n-hexane, EtOAc, MeOH/Compounds trigonoreidon A (1), trigonoreidon B (2), trigonoreidon C (3), trigonostemon C (7), spruceanol (8), trigonostemone (9), rediocide A (10), rediocide B (11), rediocide C (12), rediocide F (13), rediocide G (14) were isolated from the extract
Among the tested compounds,12 and 14 were the two most active compounds against H37Ra strain with the MICs of 3.84 µM, followed by 13, with the MIC of 3.91 µM. Compounds 11 and 10 were active and moderately active with the MICs of 7.86 and 15.72 µM, respectively. Compounds 1,2,3,7,8, 9exhibited weak activity with MICs of 183.57, 168.71, 88.55, 83.79, 72.58, 38.30 µM, respectively [203].
Asthma [203].
Uvaria microcarpaChamp. ex Benth.
Annonaceae
Phii Phouan
Fruits and flowers: 90% ethanol
The extract showed inhibition at MIC ranging from 43.2 to >100µg/ml against H37Rv [47].
Nil.
Uvaria rufaBlume
Annonaceae
Mak Phii Phouan, Susung kalabaw
Fruits and flowers: 90% ethanol
The activity against H37Rv strain was observed at the MIC ranging from 33.1 to >100 µg/ml in MABA [47].
TB [204].
Methanol, ethyl acetate, n-butanol Kaempferol (1), quercitrin (2) isolated from methanolic extract of leave
All three extracts showed inhibition in MIC value >128µg/ml in MABA.Mixture of 1 and 2 exhibited activities against H37Rv with MIC of 64 µg/ml using microplate Alamar Blue assay [205].
Uvaria valderramensis Cabuang, Exconde & Alejandro
Annonaceae
Usog
Leaves: dichloromethane and methanol/valderramenols A (1), grandiuvarone (2), andreticuline (3) isolated from the extract
Compound1 showed better activity (10 µg/ml) while 2 and 3 exhibited lesser activity (32 µg/ml) against H37Rv using MABA [206].
Vitex trifoliaL.
Verbenaceae
Phi sua
90% ethanol
The extract showed inhibition at MIC value of 8.02µg/ml against H37Rv [44].
Asthma, cough [44, 207].
Fruits and flowers: 90% ethanol
Inin vitro assays, 90% ethanolic fruit and flower extract exhibited activity against H37Rv strain at the MIC ranging from 77.6 to >100 µg/ml [47].
Voacanga globosa Merr.
Apocynaceae
Bayag-usa
Leaves: dichloromethane and methane/Globospiramine (1) was isolated from the extract
1 demonstrated potent anti-TB activity against H37Rv strain as demonstrated in MABA (MIC = 4 µg/ml) and low-oxygen recovery assay (MIC = 5.2 µg/ml) [208].
TB [209].
Zingiber officinale Roscoe
Zingiberaceae
Halia, Luya
Rhizome: 80% methanol/6-shogaol (1) and 6-gingerol (2) were isolated from the extract
In TEMA, the extract of methanol showed inhibition against H37Rvstrain at the MIC of 1600 µg/ml [48]. At 100 µg/ml, the methanolic extract of rhizomes showed 61% inhibition against H37Rv. The isolated compound 2 (MIC 33 µg/ml) showed more activity than 1 (MIC 64 µg/ml) [58].
Cough, asthma [210].
Zingiber zerumbet(L.) Roscoe ex Sm.
Zingiberaceae
Haeo dam
Rhizome: chloroform methanol water
In MABA, the chloroform, methanol, water extract of rhizome exhibited inhibition against H37Ra strain at the MIC of 125, 1000, 1000µg/ml, respectively [41].
Leprosy, cough, asthma, chest pain, loss of appetite [211, 212].
Ziziphus mauritiana Lam.
Rhamnaceae
Phut-sa
Root: mauritine M (1) and nummularines H (2), all isolated from ethanol extracts
Isolated compounds exhibited activities against H37Ra at the MIC 72.8µg/ml (1) and 4.5 µg/ml (2) [213].
Asthma, bronchitis [214, 215].
Ziziphus oenoplia (L.) Mill.
Rhamnaceae
Root: hexane, ethyl acetate and methanol/Ziziphine N and Q were isolated from the extract
Ziziphine N and Q showed weak anti-TB activity against H37Ra strain with the same MIC value of 200µg/ml [216].
Asthma, fever [217].Some bioactive compounds that were isolated from the reviewed medicinal plants exhibited good anti-TB activity (MIC values ranged between <1 and 50µg/ml). Active compound, Abruquinone B, fromAbrus precatorius L. exhibited MIC of 12.5 µg/ml. FromAglaia erythrosperma Pannell, ethyl eichlerianoate, eichlerialactone, and aglaialactone (all showing MIC of 25 µg/ml) and cabraleadiol, cabraleahydroxylactone, cabralealactone, and flavagline (all showing MIC values of 50 µg/ml) were obtained. 1′Acetoxychavicol acetate isolated fromAlpinia galanga (L.) Sw. exhibited MIC value of 0.024 µg/ml. Pimaric acid, 9α-13α-epidioxyabiet-8 (14)-en-18-oic acid, and 15-hydrooxydehydroabietic acid obtained fromAnisochilus harmandii Doan ex Suddee & A. J. Paton all showed MIC value of 50 µg/ml. Lakoochins A and B isolated fromArtocarpus lakoocha Roxb. showed MICs of 12.5 and 50 µg/ml, respectively. Flavonoid artonin F, chromone artorigidusin, xanthone artoindonesianin C, flavonoid cycloartobiloxanthone, and flavonoid 7-demethylartonol E isolated fromArtocarpus rigidus Wall. showed MIC values of 6.25, 12.5, 12.5, 25, and 50 µg/ml, respectively. Active compounds obtained fromCamchaya calcarea Kitamura are isogoyazensolides (MIC, 1.5 µg/ml), goyazensolides, lychnophorolides A, isocentratherin, isogoyazensolides and 5-epi-isocentratherin (with the same MIC value of 3.1 µg/ml), lychnophorolides B, 1(10),E,4Z,11(13)-germacratriene-12,6-olide-15-oic acid, and caffeic acid methyl ester (MICs, 6.2, 50, and 25 µg/ml resp.). Caseargrewiin A, Caseargrewiin B, Caseargrewiin D, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene, and rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (all showing MIC value of 12.5 µg/ml) and Caseargrewiin C (showing MIC of 25 µg/ml) were isolated fromCasearia grewiifolia Vent. Cabraleadiol, allo-aromadendrane-10β, 14-diol, cabraleahydroxylactone, cabralealactone, allo-aromadendrane-10β, 13, 14-triol (all displaying MICs of 50 µg/ml), and eichlerialactone (MIC, 25 µg/ml) were obtained fromChisocheton penduliflorus Planch. ex Hiern. Fluroclausine A and heptazoline isolated fromClausena guillauminii Tanaka all showed MIC of 25 µg/ml. Dentatin, O-methylated clausenidin, and 3-methoxycarbonylcarbazole isolated fromClausena excavata Burm. f. all showed MIC value of 50 µg/ml. 1-(2-Hydroxy-4-methoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)propane isolated fromCombretum griffithii Van Heurck & Müll. Arg. showed MIC of 3.13 µg/ml. Globiferin, cordiachrome B, cordiachrome C (showing MICs of 6.2, 12.5, and 1.5 µg/ml resp.), alliodorin, elaeagin, cordiachromene (same MIC value of 12.5 µg/ml), and cordiaquinol C (MIC, 25 µg/ml) were isolated fromCordia globifera W. W. Smith. The bioactive compounds ofCroton kongensis Gagnep.,ent-1β,7α,14β-triacetoxykaur-16-en-15-one (MICs, 0.78, 1.56, and 3.12–12.5 µg/ml),ent-7α,18-dihydroxykaur-16-en-15-one (MIC, 1.56 µg/ml), andent-16(S)-18-acetoxy-7α-hydroxykaur-15-one exhibited MIC of 1.56 µg/ml. Furthermore, ent-18-acetoxy-7α-hydroxykaur-16-en-15-one, ent-1β,14β-diacetoxy-7α-hydroxykaur-16-en-15-one, ent-1β-acetoxy-7α,14 β-dihydroxykaur-16-en-15-one, and ent-7α,14β-dihydroxykaur-16-en-15-one showed MIC values ranging from 3.12 to 6.25 µg/ml. Other active compounds isolated fromCroton kongensis areent-8,9-seco-8,14-epoxy-7α-hydroxy-11β-acetoxy-16-kauren-9,15-dione (MIC, 6.25 µg/ml),ent-8,9-seco-7α-hydroxy-11β-acetoxykaura-8(14),16-dien-9,15-dione (MIC, 6.25 µg/ml), andent-8,9-seco-7α,11β-diacetoxykaura-8(14),16-dien-9,15-dione (MIC, 25.0 µg/ml). Flavanone, dalparvone, and dalparvinene isolated fromDalbergia parviflora Roxb. showed MIC values of 12.5, 50, and 50 µg/ml respectively. 3β-hydroxy-21-O-acetyl-24-methylenecycloartane fromDasymaschalon dasymaschalum (Blume) I. M. Turner exhibited MIC of 50 µg/ml. Bioactive compounds isolated fromDendrolobium lanceolatum (Dunn) Schindl., Flavanones 1, flavanones, flavan, and 4′-hydroxy-7,8-(2′′,2′′-dimethylpyran)flavan, exhibited MICs of 6.3, 12.5, 25, and 25 µg/ml, respectively. Compounds 3,4-methylenedioxy-10-methoxy-7-oxo[2]benzopyrano[4,3-b]benzopyran, karanjachromene, pinnatin, 3-methoxy-(3′′,4′′-dihydro-3′′,4′′-diacetoxy)-2′′,2′′-dimethylpyrano-(7,8 : 5′′,6′′)-flavone, desmethoxy kanugin, lacheolatin B, 3,7-dimethoxyflavone, and pachycarin D (showing MIC values of 6.25, 12.5, 12.5, 25, 50, 50, 50, and 50 µg/ml, resp.) were isolated fromDerris indica L. Betulinic acid fromDiospyros decandra Lour., showing MIC of 25 µg/ml. FromDiospyros ehretioides Wall. ex G. Don, palmarumycins JC2 (MIC, 6.25 µg/ml) and isodiospyrol A (MIC, 50 µg/ml) were isolated. Diospyrin, isolated fromDiospyros glandulosa Lace, showed MIC value of 6.25 µg/ml. Betulinaldehyde isolated fromDiospyros rhodocalyx Kurz exhibited MIC value of 25 µg/ml. Dehydrolupinifolinol (MIC, 12.5 µg/ml), flemichin D (MIC, 12.5 µg/ml), eriosemaone A (MIC, 12.5 µg/ml), lupinifolin (MIC, 12.5 µg/ml), Khonklonginol A (MIC, 25 µg/ml), Khonklonginol H (MIC, 25 µg/ml), lupinifolinol (MIC, 25 µg/ml), and Khonklonginol B (MIC, 50 µg/ml) were isolated fromEriosema chinense Vogel. FromErythrina fusca Lour., erythrisenegalone (50 µg/ml MIC), lonchocarpol A (50 µg/ml MIC), and lupinifolin (25 µg/ml MIC) were isolated. Bioactive compounds erystagallin A, erycristagallin, 5-hydroxysophoranone, erysubin F (all showing MICs of 12.5 µg/ml), and 1-methoxyerythrabyssin II (showing MICs of 50 µg/ml) were obtained fromErythrina subumbrans Merr. (E)-((E)-3-(4-methoxyphenyl)allyl)3-(4-hydroxyphenyl)acrylate fromEtlingera pavieana (Pierre ex Gagnep.) R. M. Sm., exhibited MICs of 50 µg/ml. 3′-formyl-2′,4′-dihydroxy-6′-methoxychalcone, a bioactive compound fromFriesodielsia discolor (Craib) D. Das, showed MICs of 6.25 µg/ml. FromGarcinia mangostana L., α-mangostin (MIC, 6.25 µg/ml), β-mangostin (MIC, 6.25 µg/ml), γ-mangostin (MIC, 25 µg/ml), garcinone D (MIC, 25 µg/ml), garcinone B (MIC, 6.25 µg/ml), mangostanin (MIC, 25 µg/ml), mangostenone A (MIC, 25 µg/ml), tovophyllin B (MIC, 25 µg/ml), demethylcalabaxanthone (MIC, 12.5 µg/ml), and trapezifolixanthone (MIC, 12.5 µg/ml) were identified as active compounds. Active compound Liriodenine isolated fromGoniothalamus gitingensis Elmer exhibited MIC of 16 µg/ml. Active compounds (+)-altholactone (MIC, 6.25 µg/ml), howiininA (MIC, 6.25 µg/ml), and (−)-nordicentrine (12.5 µg/ml) were isolated fromGoniothalamus laoticus (Finet & Gagnep.) Bân. Coronarin E and 16-Hydroxylabda-8(17),11,13-trien-15,16-olide isolated fromHedychium ellipticum Buch.-Ham. ex Sm. showed MICs of 12.5 and 6.25 µg/ml, respectively. Caniojane isolated fromJatropha integerrima Jacq. demonstrated MIC of 25 µg/ml. Bioactive compounds, sandaracopimaradien-1α-ol and 2α-acetoxysandaracopimaradien-1α-ol isolated fromKaempferia marginata Carey, showed MICs of 25 and 50 µg/ml, respectively. FromMorinda citrifolia Linn., campesta-6,22-dien-5α,8α-epidioxy-3β-ol (2.5 µg/ml), (E)-phytol (32 µg/ml), and stigmasterol (32 µg/ml) were obtained. Active compounds 2,4-bis(2-phenylpropan-2-yl)phenol isolated fromMomordica charantia L. showed 14 µg/ml MIC. 1α,13β,14α-trihydroxy-3β,7β-dibenzoyloxy-9β,15β-diacetoxyjatropha-5,11E-diene and 1α,8β,9β,14α,15β-pentaacetoxy-3β-benzoyloxy-7-oxojatropha-5,12-diene isolated fromPedilanthus tithymaloides (L.) Poit. demonstrated 12.5 and 50 µg/ml MIC. FromPiper sarmentosum Roxb., pellitorine, 1-(3,4-methylenedioxyphenyl)-1E-tetradecene, guineensine, sarmentine, and brachyamide B showed MICs of 25, 25, 50, 50, and 50 µg/ml, respectively. Bidebiline E (6.25 µg/ml), octadeca-9,11,13-triynoic acid (6.25 µg/ml), and α-humulene (6.25 µg/ml) were isolated fromPolyalthia cerasoides (Roxb.) Benth. ex Bedd. Debilisone B, Debilisone C, and Debilisone E isolated fromPolyalthia debilis (Piere) Finet & ganep exhibited MIC values of 25, 12.5, and 25 µg/ml, respectively. 1-Heneicosyl formate and 6β-hydroxy-10-O-acetylgenipin fromPremna odorata Blanco andRothmannia wittii (Craib) Bremek. showed 8 and 12.5 µg/ml MIC values, respectively. The compounds chabamide and piperine isolated fromPiper chaba Hunter exhibited MIC values of 12.5 and 50 µg/ml, respectively. Bioactive compounds sapintoxin A (3.12 µg/ml), sapintoxin B (12.5 µg/ml), sapintoxin C (25 µg/ml), 12-(2′-N-methylaminobenzoyl)-4α-deoxy-5,20-dihydroxyphorbol-13-acetate (25 µg/ml), 12-(2-methylaminobenzoyl)-4-deoxyphorbaldehyde-13-acetae (25 µg/ml), and 12-(2-N-methylaminobenzoyl)-4β,5,20-trideoxyphorbol-13-acetate (50 µg/ml) were isolated fromSapium indicum L. FromSesbania grandiflora (L.) Poir., isovestitol (50 μg/ml), medicarpin (50 μg/ml), and sativan (50 μg/ml) were isolated as active compounds. Tiliacorinine, 2′-nortiliacorinine, tiliacorine, and 13′-bromo-tiliacorinine fromTiliacora triandra (Colebr.) Diels exhibited MIC ranging between 0.7 and 6.2 µg/ml. FromUvaria valderramensis Cabuang, Exconde & Alejandro, valderramenols A, grandiuvarone, and reticuline were isolated and showed MICs of 10, 32, and 32 µg/ml, respectively. Globospiramine obtained fromVoacanga globosa Merr. exhibited 4 and 5.2 MICs. Compound nummularines H isolated fromZiziphus mauritiana Lam. exhibited MIC of 4.5 μg/ml. 6-Gingerol fromZingiber officinale Roscoe demonstrated MIC value of 33 μg/ml.Generally, some of the reviewed plant species such asAlpinia galanga,Artocarpus rigidus,Camchaya calcarea,Combretum griffithii,Cordia globifera,Croton kongensis,Dendrolobium lanceolatum,Derris indica,Diospyros glandulosa,Diospyros ehretioides,Friesodielsia discolor,Garcinia mangostana,Goniothalamus laoticus,Hedychium ellipticum,Marsypopetalum modestum,Morinda citrifolia,Orthosiphon stamineus,Piper sarmentosum,Polyalthia cerasoides,Premna odorata,Sapium indicum,Tiliacora triandra,Trigonostemon reidiodes,Voacanga globosa,Tinospora crispa,Vitex trifolia, andZiziphus mauritiana proved to be potential source of anti-TB (crude and/or bioactive compound exhibited anti-TB activities at MIC values ranging from 0 to <10 µg/ml) and as such should be considered for further development as either crude extract that will be consumed as complementary or alternative TB drug or as potential bioactive compounds for the development of novel anti-TB drug.


## 7. Conclusion

There has been an increase in demand for the phytopharmaceuticals worldwide due to the fact that allopathic drugs have more side effects. This review makes an attempt to compile some of the anti-TB plants of Southeast Asian origin from wide range of families and genera that have exhibited significantin vitro anti-TB activities and a number of bioactive compounds from different groups of chemicals have been isolated. As stated earlier, about 2 million individuals worldwide die from TB yearly. Therefore, the findings may encourage numerous researchers to embark on the project that potentially leads to the development of standardized crude extracts that will be consumed as either complementary or alternative TB drug. The findings might as well motivate various researchers to undertake the project that may further identify and characterize the active components from these plant species in order to search for the novel natural product leads useful for new anti-TB drug discovery and development.



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*Source: 7185649-2017-07-03.xml*