Review Article | Open Access
Shuaibu Babaji Sanusi, Mohd Fadzelly Abu Bakar, Maryati Mohamed, Siti Fatimah Sabran, Muhammad Murtala Mainasara, "Southeast Asian Medicinal Plants as a Potential Source of Antituberculosis Agent", Evidence-Based Complementary and Alternative Medicine, vol. 2017, Article ID 7185649, 39 pages, 2017. https://doi.org/10.1155/2017/7185649
Southeast Asian Medicinal Plants as a Potential Source of Antituberculosis Agent
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 significant in 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.
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 of Mycobacterium tuberculosis (MTB) are the common cause of this deadly infectious disease . 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 . It is unfortunate that more than 75% of TB cases are found in adults . 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 .
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 the Mycobacterium species develops resistance to the TB drugs .
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 with Mycobacterium 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 . 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 . 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.  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 . In 2003, Copp  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) . In another review, Okunade et al.  discussed 88 natural products and their synthetic analogues, mainly from plant source, and fungi as well as some aquatic organisms that displayed substantial activity against M. tuberculosis and other mycobacterial species in in vitro bioassays . In their review, Pauli et al.  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 . A review by Jachak and Jain  described recent target-based natural compounds that displayed antimycobacterial action . Gautam et al.  reviewed different species of plant from a vast array of families that have exhibited antimycobacterial activity. Gupta et al. , in their review article, identified sixty-four medicinal plants used by traditional people in the treatment of leprosy .
Some antitubercular plants from Ayurveda as well as foreign origin have been reviewed by Arya  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 . The most recent among all the reviews is by Chinsembu  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 .
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 . 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 .
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 . 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 from Dracaena angustifolia using this method [23, 32, 38].
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, 38]. 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 of Mycobacterium. Example of such is M. smegmatis (ATCC 607) . Other avirulent substitutes to work with instead of virulent strains of MTB are the slow-growing strains such as M. tuberculosis H37Ra (ATCC 25177) and M. 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, 38].
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 . Agar diffusion assays need to be avoided with Mycobacteria, since these organisms with high lipid content in their cell wall are usually more sensitive to compounds of less-polarity . 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 .
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 100–200 µl 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 of Mycobacteria [32, 38].
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 of Mycobacteria, the growth can be evaluated quantitatively by the broth medium turbidity. However, the proneness of clumps formation makes the assay very challenging . 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, 38].
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 . 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 .
The cell-wall-attacking characteristic of the test extracts is revealed in electron microscopy studies. Because the main part of the cell wall of Mycobacteria 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 of Mycobacteria 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 .
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 . 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 .
Although many productive outcomes can be revealed in genomic studies, it is only the proteomic analysis that can obtain the exact cellular information . 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 . With the aid of a technique called two-dimensional gel electrophoresis coupled with mass spectrometry (2DE-MS), about 263 proteins were identified in M. bovis BCG and MTB strains . 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 .
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 in in vitro assay (MIC values ranging from 10 to 100 µg/ml). These plant species are Aegle 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., and Zingiber officinale Roscoe.
Some bioactive compounds that were isolated from the reviewed medicinal plants exhibited good anti-TB activity (MIC values ranged between <1 and 50 µg/ml). Active compound, Abruquinone B, from Abrus precatorius L. exhibited MIC of 12.5 µg/ml. From Aglaia 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 from Alpinia 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 from Anisochilus harmandii Doan ex Suddee & A. J. Paton all showed MIC value of 50 µg/ml. Lakoochins A and B isolated from Artocarpus 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 from Artocarpus rigidus Wall. showed MIC values of 6.25, 12.5, 12.5, 25, and 50 µg/ml, respectively. Active compounds obtained from Camchaya 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 from Casearia 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 from Chisocheton penduliflorus Planch. ex Hiern. Fluroclausine A and heptazoline isolated from Clausena guillauminii Tanaka all showed MIC of 25 µg/ml. Dentatin, O-methylated clausenidin, and 3-methoxycarbonylcarbazole isolated from Clausena excavata Burm. f. all showed MIC value of 50 µg/ml. 1-(2-Hydroxy-4-methoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)propane isolated from Combretum 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 from Cordia globifera W. W. Smith. The bioactive compounds of Croton 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), and ent-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 from Croton kongensis are ent-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), and ent-8,9-seco-7α,11β-diacetoxykaura-8(14),16-dien-9,15-dione (MIC, 25.0 µg/ml). Flavanone, dalparvone, and dalparvinene isolated from Dalbergia parviflora Roxb. showed MIC values of 12.5, 50, and 50 µg/ml respectively. 3β-hydroxy-21-O-acetyl-24-methylenecycloartane from Dasymaschalon dasymaschalum (Blume) I. M. Turner exhibited MIC of 50 µg/ml. Bioactive compounds isolated from Dendrolobium 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-oxobenzopyrano[,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 from Derris indica L. Betulinic acid from Diospyros decandra Lour., showing MIC of 25 µg/ml. From Diospyros ehretioides Wall. ex G. Don, palmarumycins JC2 (MIC, 6.25 µg/ml) and isodiospyrol A (MIC, 50 µg/ml) were isolated. Diospyrin, isolated from Diospyros glandulosa Lace, showed MIC value of 6.25 µg/ml. Betulinaldehyde isolated from Diospyros 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 from Eriosema chinense Vogel. From Erythrina 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 from Erythrina subumbrans Merr. (E)-((E)-3-(4-methoxyphenyl)allyl)3-(4-hydroxyphenyl)acrylate from Etlingera pavieana (Pierre ex Gagnep.) R. M. Sm., exhibited MICs of 50 µg/ml. 3′-formyl-2′,4′-dihydroxy-6′-methoxychalcone, a bioactive compound from Friesodielsia discolor (Craib) D. Das, showed MICs of 6.25 µg/ml. From Garcinia 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 from Goniothalamus 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 from Goniothalamus laoticus (Finet & Gagnep.) Bân. Coronarin E and 16-Hydroxylabda-8(17),11,13-trien-15,16-olide isolated from Hedychium ellipticum Buch.-Ham. ex Sm. showed MICs of 12.5 and 6.25 µg/ml, respectively. Caniojane isolated from Jatropha integerrima Jacq. demonstrated MIC of 25 µg/ml. Bioactive compounds, sandaracopimaradien-1α-ol and 2α-acetoxysandaracopimaradien-1α-ol isolated from Kaempferia marginata Carey, showed MICs of 25 and 50 µg/ml, respectively. From Morinda 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 from Momordica 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 from Pedilanthus tithymaloides (L.) Poit. demonstrated 12.5 and 50 µg/ml MIC. From Piper 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 from Polyalthia cerasoides (Roxb.) Benth. ex Bedd. Debilisone B, Debilisone C, and Debilisone E isolated from Polyalthia 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 from Premna odorata Blanco and Rothmannia wittii (Craib) Bremek. showed 8 and 12.5 µg/ml MIC values, respectively. The compounds chabamide and piperine isolated from Piper 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 from Sapium indicum L. From Sesbania 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 from Tiliacora triandra (Colebr.) Diels exhibited MIC ranging between 0.7 and 6.2 µg/ml. From Uvaria valderramensis Cabuang, Exconde & Alejandro, valderramenols A, grandiuvarone, and reticuline were isolated and showed MICs of 10, 32, and 32 µg/ml, respectively. Globospiramine obtained from Voacanga globosa Merr. exhibited 4 and 5.2 MICs. Compound nummularines H isolated from Ziziphus mauritiana Lam. exhibited MIC of 4.5 μg/ml. 6-Gingerol from Zingiber officinale Roscoe demonstrated MIC value of 33 μg/ml.
Generally, some of the reviewed plant species such as Alpinia 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, and Ziziphus 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.
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 significant in 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.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
The authors are very grateful to Universiti Tun Hussein Onn Malaysia (UTHM) for providing the research grants (UTHM Contract Grant Vot no. U555 and also Incentive Grant for Publication (IGSP) Vot no. U673) that supported the study.
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