Potent anti-mycobacterial and immunomodulatory activity of some bioactive molecules of Indian ethnomedicinal plants that have the potential to enter in TB management

Tuberculosis (TB) is one of the deadliest infectious diseases of human civilization. Approximately one-third of global population is latently infected with the TB pathogen Mycobacterium tuberculosis (M.tb). The discovery of anti-TB antibiotics leads to decline in death rate of TB. However, the evolution of antibiotic-resistant M.tb-strain and the resurgence of different immune-compromised diseases re-escalated the death rate of TB. WHO has already cautioned about the chances of pandemic situation in TB endemic countries until the discovery of new anti-tubercular drugs, that is, the need of the hour. Analysing the pathogenesis of TB, it was found that M.tb evades the host by altering the balance of immune response and affects either by killing the cells or by creating inflammation. In the pre-antibiotic era, traditional medicines were only therapeutic measures for different infectious diseases including tuberculosis. The ancient literatures of India or ample Indian traditional knowledge and ethnomedicinal practices are evidence for the treatment of TB using different indigenous plants. However, in the light of modern scientific approach, anti-TB effects of those plants and their bioactive molecules were not established thoroughly. In this review, focus has been given on five bioactive molecules of different traditionally used Indian ethnomedicinal plants for treatment of TB or TB-like symptom. These compounds are also validated with proper identification and their mode of action with modern scientific approaches. The effectiveness of these molecules for sensitive or drug-resistant TB pathogen in clinical or preclinical studies was also evaluated. Thus, our specific aim is to highlight such scientifically validated bioactive compounds having anti-mycobacterial and immunomodulatory activity for future use as medicine or adjunct-therapeutic molecule for TB management.     

α-Sulfonamidophosphonates as new anti-mycobacterial chemotypes: Design,development of synthetic methodology,and biological evaluation

Tuberculosis (TB) is the leading cause of death worldwide due to bacterial infection. The scarcity of effective drugs to treat the disease and the compounded problems due to the development of resistance to the available therapeutics and TB-HIV synergism drive medicinal chemists to search for new anti-Mtb chemotypes. Towards this endeavor, the α-sulfonamidophosphonate moiety has been identified as new anti-Mtb chemotype through the scaffold hopping as the design strategy, development of an effective synthetic methodology using green chemistry tools, and evaluation of anti-TB activity of the synthesized compounds against Mtb (Mycobacterium tuberculosis) H37Rv. Out of the sixteen compounds, five have been found to have MIC values of 1.56 μg/mL and one 3.125 μg/mL. The five most active compounds are non-cytotoxic to RAW 264.7 (mouse leukemic monocyte macrophage) cell lines. The compounds are found to possess acceptable values of the various parameters for drug likeness in accordance with the Lipinski rule with the topological surface area (tPSA) of >70 that suggest eligibility of these new molecular entities for further consideration as potential drug candidates.     

Anti-tuberculosis lead molecules from natural products targeting <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> ClpC1

Tuberculosis (TB) is a serious and potentially fatal disease caused by Mycobacterium tuberculosis (M. tb). The occurrence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tb is a significant public health concern because most of the anti-TB drugs that have been in use for over 40 years are no longer effective for the treatment of these infections. Recently, new anti-TB lead compounds such as cyclomarin A, lassomycin, and ecumicin, which are cyclic peptides from actinomycetes, have shown potent anti-TB activity against MDR and XDR M. tb as well as drug-susceptible M. tb in vitro. The target molecule of these antibiotics is ClpC1, a protein that is essential for the growth of M. tb. In this review, we introduce the three anti-TB lead compounds as potential anti-TB therapeutic agents targeting ClpC1 and compare them with the existing anti-TB drugs approved by the US Food and Drug Administration.     

Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants

Multidrug-resistant tuberculosis (MDR-TB) and TB–HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40?years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.     

Medicinal plants used in Jeddah,Saudi Arabia: Phytochemical screening

Ethnobotanical and phytochemical studies are useful to discover new drugs. Phytochemical screening is an important step in the detection of the bioactive components existing in medicinal plants that are used in traditional medicine. Very few phytochemical studies investigating medicinal plants used in traditional medicine exist in Saudi Arabia. Eighty-five medicinal plants used in traditional medicine in Jeddah, Saudi Arabia are investigated here for the first time. This research aims to screen of 85 medicinal plants used in traditional medicine in Jeddah for the presence of secondary metabolites, and to answer the following question: Is the ethnomedicinal importance of medicinal plants used in Jeddah conform to their secondary metabolite content. Ethnobotanical fieldwork took place in Jeddah from August 2018 to September 2019. Eighty-five different plant species belonging to 37 families were identified. Screening of 85 medicinal plants was performed for the presence of alkaloids, glycosides, flavonoids, tannins, saponins and resins using standard methods. The most commonly distributed phytochemical compounds among medicinal plants used were glycosides (82%; 70 species), tannins (68%; 58 species), alkaloids (56%; 48 species), saponins (52%, 44 species) and flavonoids (35%; 30 species). On the other hand, the least commonly distributed compounds were resins (31%; 26 species). All the six groups of secondary metabolites were found in seeds of Cuminum cyminum L., Pimpinella anisum L. and Trigonella foenum-graecum L. It can be said that the ethnomedicinal importance of these 85 medicinal plants used in Jeddah conform to their secondary metabolite content. More research should be carried out on the quantitative analysis of phytochemicals in these 85 medicinal plants used in traditional medicine in Jeddah. Furthermore, there is a need to focus phytochemical screening on ethnobotanical studies to complete research into traditional medicine which leads to the discovery of new drugs.     

Elaeagnus umbellata: A miraculous shrub with potent health-promoting benefits from Northwest Himalaya

Medicinal plants encompassing a series of bioactive compounds have gained significant importance for use in the treatment of different diseases. Of them, Elaeagnus umbellata Thunb. (Deciduous shrub found in dappled shade, and sunny hedge) exhibits high medicinal value, with a widespread distribution across the Pir Panjal region of the Himalayas. Fruits serve as an excellent source of vitamins, minerals, and other essential compounds that exhibits hypolipidemic, hepatoprotective, and nephroprotective effects. The phytochemical fingerprint of berries revealed them to have a high content of polyphenols (with major proportion of anthocyanins), followed by monoterpenes and vitamin C. Extract of fruits help in regulating the digestion and absorption of glucose and reduces inflammation and oxidative stress. The phytosterols upholding anticoagulant activity serve the purpose of causing decrease in angina and the blood cholesterol levels. Phytochemicals such as eugenol, palmitic acid, and methyl palmitate exhibit potent antibacterial activity against broad range of disease-causing agents. Additionally, a high percentage of essential oils attribute it with the property of being effective against heart ailments. The present study highlights the importance of E. umbellata in traditional medicinal practices, and summarizes the knowledge of its bioactive constituents and a snapshot vision of remarkable biological activities like antimicrobial, antidiabetic, antioxidant, etc towards understanding its role in the development of efficient drug regimens for use in the treatment of different diseases. It also underlines the need to explore the plant on nutritional aspects to strengthen the existing knowledge pertaining to health promoting potential of E. umbellata.     

Medicinal history of North American Veratrum

Plants belonging to the genus Veratrum have been used throughout history for their medicinal properties. During the nineteenth and twentieth centuries, phytochemical investigations revealed a host of steroidal alkaloids in Veratrum species, some of which are potent bioactives. This review discusses Veratrum species that grow in North America with a focus on the medicinal history of these plants and the steroidal alkaloids they contain. While significant reviews have been devoted to singularly describing the plant species within the genus Veratrum (botany), the staggering breadth of alkaloids isolated from these and related plants (phytochemistry), and the intricacies of how the various alkaloids act on their biological targets (physiology and biochemistry), this review will straddle the margins of the aforementioned disciplines in an attempt to provide a unified, coherent picture of the Veratrum plants of North America and the medicinal uses of their bioactive steroidal alkaloids.     

Bioassay-guided isolation of three anthelmintic compounds from Warburgia ugandensis Sprague subspecies ugandensis, and the mechanism of action of polygodial

Parasitic helminths continue to pose problems in human and veterinary medicine, as well as in agriculture. Resistance to current anthelmintics has prompted the search for new drugs. Anthelmintic metabolites from medicinal plants could be good anthelmintic drug candidates. However, the compounds active against nematodes have not been identified in most medicinal plants with anthelmintic activity. In this study, we aimed to identify the active compounds against helminths in Warburgia ugandensis Sprague subspecies ugandensis (Canellaceae) and study the underlying mechanism of action. A bioassay-guided isolation of anthelmintic compounds from the plant was performed using a Caenorhabditis elegans (C. elegans) test model with a WMicrotracker instrument to monitor motility. Three active compounds were purified and identified by nuclear magnetic resonance and high resolution MS: warburganal (IC₅₀: 28.2?±?8.6?μM), polygodial (IC₅₀: 13.1?±?5.3?μM) and alpha-linolenic acid (ALA, IC₅₀: 70.1?±?17.5?μM). A checkerboard assay for warburganal and ALA as well as polygodial and ALA showed a fractional inhibitory concentration index of 0.41 and 0.37, respectively, suggesting that polygodial and ALA, as well as warburganal and ALA, have a synergistic effect against nematodes. A preliminary structure–activity relationship study for polygodial showed that the α,β-unsaturated 1,4-dialdehyde structural motif is essential for the potent activity. None of a panel of C. elegans mutant strains, resistant against major anthelmintic drug classes, showed significant resistance to polygodial, implying that polygodial may block C. elegans motility through a mechanism which differs from that of currently marketed drugs. Further measurements showed that polygodial inhibits mitochondrial ATP synthesis of C. elegans in a dose-dependent manner (IC₅₀: 1.8?±?1.0?μM). Therefore, we believe that the underlying mechanism of action of polygodial is probably inhibition of mitochondrial ATP synthesis. In conclusion, polygodial could be a promising anthelmintic drug candidate worth considering for further development.     

Design,synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties

Out of the prominent global ailments, tuberculosis (TB) is still one of the leading causes of death worldwide due to infectious disease. Development of new drugs that shorten the current tuberculosis treatment time and have activity against drug resistant strains is of utmost importance. Towards these goals we have focused our efforts on developing novel anti-TB compounds with the general structure of 1-adamantyl-3-phenyl urea. This series is active against Mycobacteria and previous lead compounds were found to inhibit the membrane transporter MmpL3, the protein responsible for mycolic acid transport across the plasma membrane. However, these compounds suffered from poor in vitro pharmacokinetic (PK) profiles and they have a similar structure/SAR to inhibitors of human soluble epoxide hydrolase (sEH) enzymes. Therefore, in this study the further optimization of this compound class was driven by three factors: (1) to increase selectivity for anti-TB activity over human sEH activity, (2) to optimize PK profiles including solubility and (3) to maintain target inhibition. A new series of 1-adamantyl-3-heteroaryl ureas was designed and synthesized replacing the phenyl substituent of the original series with pyridines, pyrimidines, triazines, oxazoles, isoxazoles, oxadiazoles and pyrazoles. This study produced lead isoxazole, oxadiazole and pyrazole substituted adamantyl ureas with improved in vitro PK profiles, increased selectivity and good anti-TB potencies with sub μg/mL minimum inhibitory concentrations.     

New classes of alanine racemase inhibitors identified by high-throughput screening show antimicrobial activity against Mycobacterium tuberculosis

Background

In an effort to discover new drugs to treat tuberculosis (TB) we chose alanine racemase as the target of our drug discovery efforts. In Mycobacterium tuberculosis, the causative agent of TB, alanine racemase plays an essential role in cell wall synthesis as it racemizes L-alanine into D-alanine, a key building block in the biosynthesis of peptidoglycan. Good antimicrobial effects have been achieved by inhibition of this enzyme with suicide substrates, but the clinical utility of this class of inhibitors is limited due to their lack of target specificity and toxicity. Therefore, inhibitors that are not substrate analogs and that act through different mechanisms of enzyme inhibition are necessary for therapeutic development for this drug target.

Methodology/Principal Findings

To obtain non-substrate alanine racemase inhibitors, we developed a high-throughput screening platform and screened 53,000 small molecule compounds for enzyme-specific inhibitors. We examined the ‘hits’ for structural novelty, antimicrobial activity against M. tuberculosis, general cellular cytotoxicity, and mechanism of enzyme inhibition. We identified seventeen novel non-substrate alanine racemase inhibitors that are structurally different than any currently known enzyme inhibitors. Seven of these are active against M. tuberculosis and minimally cytotoxic against mammalian cells.

Conclusions/Significance

This study highlights the feasibility of obtaining novel alanine racemase inhibitor lead compounds by high-throughput screening for development of new anti-TB agents.     

The Diversity and Anti-Microbial Activity of Endophytic Actinomycetes Isolated from Medicinal Plants in Panxi Plateau,China

Traditional Chinese medicinal plants are sources of biologically active compounds, providing raw material for pharmaceutical, cosmetic and fragrance industries. The endophytes of medicinal plants participate in biochemical pathways and produce analogous or novel bioactive compounds. Panxi plateau in South-west Sichuan in China with its unique geographical and climatological characteristics is a habitat of a great variety of medicinal plants. In this study, 560 endophytic actinomycetes were isolated from 26 medicinal plant species in Panxi plateau. 60 isolates were selected for 16S rDNA-RFLP analysis and 14 representative strains were chosen for 16S rDNA sequencing. According to the phylogenetic analysis, seven isolates were Streptomyces sp., while the remainder belonged to genera Micromonospora, Oerskovia, Nonomuraea, Promicromonospora and Rhodococcus. Antimicrobial activity analysis combined with the results of amplifying genes coding for polyketide synthetase (PKS-I, PKS-II) and nonribosomal peptide synthetase (NRPS) showed that endophytic actinomycetes isolated from medicinal plants in Panxi plateau had broad-spectrum antimicrobial activity and potential natural product diversity, which further proved that endophytic actinomycetes are valuable reservoirs of novel bioactive compounds.     

Bioprospecting of <Emphasis Type="Italic">Diaporthe terebinthifolii</Emphasis> LGMF907 for antimicrobial compounds

Antibiotic-resistant bacteria have been observed with increasing frequency over the past decades, driving the search for new drugs and stimulating the interest in natural products sources. Endophytic fungi from medicinal plants represent a great source of novel bioactive compounds useful to pharmaceutical and agronomical purposes. Diaporthe terebinthifolii is an endophytic species isolated from Schinus terebinthifolius, a plant used in popular medicine for several health problems. The strain D. terebinthifolii LGMF907 was previously reported by our group to produce secondary metabolites with biological activity against phytopathogens. Based on these data, strain LGMF907 was chosen for bioprospecting against microorganisms of clinical importance and for characterization of major secondary metabolites. In this study, different culture conditions were evaluated and the biological activity of this strain was expanded. The crude extracts demonstrated high antibacterial activity against Escherichia coli, Micrococcus luteus, Saccharomyces cerevisiae, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant S. aureus. The compounds diaporthin and orthosporin were characterized and also showed activity against the clinical microorganisms evaluated. This study discloses the first isolation of diaporthin and orthosporin from D. terebinthifolii, and revealed the potential of this endophytic fungus to produce secondary metabolites with antimicrobial activity.     

Exploring antifungal activities of acetone extract of selected Indian medicinal plants against human dermal fungal pathogens

A broad spectrum of medicinal plants was used as traditional remedies for various infectious diseases. Fungal infectious diseases have a significant impact on public health. Fungi cause more prevalent infections in immunocompromised individuals mainly patients undergoing transplantation related therapies, and malignant cancer treatments. The present study aimed to investigate the in vitro antifungal effects of the traditional medicinal plants used in India against the fungal pathogens associated with dermal infections. Indian medicinal plants (Acalypha indica, Lawsonia inermis Allium sativum and Citrus limon) extract (acetone/crude) were tested for their antifungal effects against five fungal species isolated from skin scrapings of fungal infected patients were identified as including Alternaria spp., Curvularia spp., Fusarium spp., Trichophyton spp. and Geotrichum spp. using well diffusion test and the broth micro dilution method. All plant extracts have shown to have antifungal efficacy against dermal pathogens. Particularly, Allium sativum extract revealed a strong antifungal effect against all fungal isolates with the minimum fungicidal concentration (MFC) of 50–100 μg/mL. Strong antifungal activity against Curvularia spp., Trichophyton spp., and Geotrichum spp. was also observed for the extracts of Acalypha indica, and Lawsonia inermis with MFCs of 50–800 μg/mL respectively. The extracts of Citrus limon showed an effective antifungal activity against most of the fungal strains tested with the MFCs of 50–800 μg/mL. Our research demonstrated the strong evidence of conventional plants extracts against clinical fungal pathogens with the most promising option of employing natural-drugs for the treatment of skin infections. Furthermore, in-depth analysis of identifying the compounds responsible for the antifungal activity that could offer alternatives way to develop new natural antifungal therapeutics for combating resistant recurrent infections.     

Simple dihydrosphyngosine analogues with potent activity against MDR-Mycobacterium tuberculosis

Fifteen dihydrosphingosine analogues have been synthesized and tested in vitro against Mycobacterium tuberculosis (MTB). Two ether (3 and 4b) and one diamine (8b) derivatives have displayed high mycobactericidal potency, with similar MIC values of 1.25 μg/mL, against the virulent strain H37Rv, as well as against a clinical isolate resistant to the five first-line anti-TB drugs. The three compounds, tested on other eleven cultured MTB strains with different multi-drug-resistance (MDR) patterns, retained their MIC values for most strains, or even lowered it, as in the case of compound 4b, which, assayed on strain No. 332, also resistant to all first-line anti-TB drugs, attained the MIC value of 0.78 μg/mL.     

Design,synthesis and biological activity of novel substituted 3-benzoic acid derivatives as MtDHFR inhibitors

The enzyme dihydrofolate reductase from M. tuberculosis (MtDHFR) has a high unexploited potential to be a target for new drugs against tuberculosis (TB), due to its importance for pathogen survival. Preliminary studies have obtained fragment-like molecules with low affinity to MtDHFR which can potentially become lead compounds. Taking this into account, the fragment MB872 was used as a prototype for analogue development by bioisosterism/retro-bioisosterism, which resulted in 20 new substituted 3-benzoic acid derivatives. Compounds were active against MtDHFR, with IC₅₀ values ranging from 7 to 40 μM, where compound 4e not only had the best inhibitory activity (IC₅₀ = 7 μM), but also was 71-fold more active than the original fragment MB872. The 4e inhibition kinetics indicated an uncompetitive mechanism, which was supported by molecular modeling which suggested that the compounds can access an independent backpocket from the substrate and competitive inhibitors. Thus, based on these results, substituted 3-benzoic acid derivatives have strong potential to be developed as novel MtDHFR inhibitors and also anti-TB agents.     

N-γ-(L-glutamyl)-L-selenomethionine shows neuroprotective effects against Parkinson's disease associated with SKN-1/Nrf2 and TRXR-1 in Caenorhabditis elegans

Background: Parkinson's disease (PD) is a common neurodegenerative disease, yet fundamental treatments for the disease remain sparse. Thus, the search for potentially efficacious compounds from medicinal plants that can be used in the treatment of PD has gained significant interest.Purpose: In many medicinal plants, selenium is primarily found in an organic form. We investigated the neuroprotective potential of an organic form of selenium, N-γ-(L-glutamyl)-L-selenomethionine (Glu-SeMet) in a Caenorhabditis elegans PD model and its possible molecular mechanisms.Methods: We used a C. elegans pharmacological PD strain (BZ555) that specifically expresses green fluorescent protein (GFP) in dopaminergic neurons and a transgenic PD strain (NL5901) that expresses human α-synuclein (α-syn) in muscle cells to investigate the neuroprotective potential of Glu-SeMet against PD.Results: We found that Glu-SeMet significantly ameliorated 6-hydroxydopamine (6-OHDA)-induced dopaminergic neuron damage in the transgenic BZ555 strain, with corresponding improvements in slowing behavior and intracellular ROS levels. In addition, compared with clinical PD drugs (L-DOPA and selegiline), Glu-SeMet demonstrated stronger ameliorated effects on 6-OHDA-induced toxicity. Glu-SeMet also triggered the nuclear translocation of SKN-1/Nrf2 and significantly increased SKN-1, GST-4, and GCS-1 mRNA levels in the BZ555 strain. However, Glu-SeMet did not increase mRNA levels or ameliorate the damage to dopaminergic neurons when the BZ555 strain was subjected to skn-1 RNA interference (RNAi). Glu-SeMet also upregulated the mRNA levels of the selenoprotein TRXR-1 in both the BZ555 and BZ555; skn-1 RNAi strains and significantly decreased α-syn accumulation in the NL5901 strain, although this was not observed in the NL5901; trxr-1 strain.Conclusion: We found that Glu-SeMet has a neuroprotective effect against PD in a C. elegans PD model and that the anti-PD effects of Glu-SeMet were associated with SKN-1/Nrf2 and TRXR-1. Glu-SeMet may thus have the potential for use in therapeutic applications or supplements to slow the progression of PD.     

An integrated assessment of wild vegetable resources in Inner Mongolian Autonomous Region, China

Mwingi District lies within the Kenyan Arid and Semiarid lands (ASALs) in Eastern Province. Although some ethnobotanical surveys have been undertaken in some arid and semiarid areas of Kenya, limited studies have documented priority medicinal plants as well as local people's awareness of conservation needs of these plants. This study sought to establish the priority traditional medicinal plants used for human, livestock healthcare, and those used for protecting stored grains against pest infestation in Mwingi district. Further, the status of knowledge among the local people on the threat and conservation status of important medicinal species was documented. This study identified 18 species which were regarded as priority traditional medicinal plants for human health. In terms of priority, 8 were classified as moderate, 6 high, while 4 were ranked highest priority species. These four species are Albizia amara (Roxb.) Boiv. (Mimosacaeae), Aloe secundiflora (Engl. (Aloaceae), Acalypha fruticosa Forssk. (Euphorbiaceae) and Salvadora persica L. (Salvadoraceae). In regard to medicinal plants used for ethnoveterinary purposes, eleven species were identified while seven species were reported as being important for obtaining natural products or concoctions used for stored grain preservation especially against weevils. The data obtained revealed that there were new records of priority medicinal plants which had not been documented as priority species in the past. Results on conservation status of these plants showed that more than 80% of the respondents were unaware that wild medicinal plants were declining, and, consequently, few of them have any domesticated species. Some of the species that have been conserved on farm or deliberately allowed to persist when wild habitats are converted into agricultural lands include: Croton megalocarpus Hutch., Aloe secundiflora, Azadirachta indica A. Juss., Warburgia ugandensis Sprague, Ricinus communis L. and Terminalia brownie Fresen. A small proportion of the respondents however, were aware of the threats facing medicnal plants. Some of the plants reported as declining include, Solanum renschii Vatke (Solanaceae), Populus ilicifolia (Engl.) Rouleau (Salicaceae), Strychnos henningsii Gilg (Loganiaceae) and Rumex usambarensis (Dammer) Dammer (Polygonaceae). Considering the low level of understanding of conservation concerns for these species, there is need therefore, to build capacity among the local communities in this area particularly in regard to sustainable use of natural resources, conservation methods as well as domestication processes.     

Phenolic production and antioxidant properties of some Macedonian medicinal plants

Investigations have been made to study the production of phenolic compounds (total phenolics, flavonoids and phenylpropanoids) and total antioxidant capacity in 27 Macedonian traditional medicinal plants to improve its potential as a source of natural antioxidants. Antioxidant potential of plant extracts was analyzed by five different assays: cupric reducing antioxidant capacity (CUPRAC), phosphomolybdenum method (PM), reducing power (RP), 2,2-diphenyl-1-picrylhydrazyl (DPPH^·) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS^·+) radical scavenging activity. Origanum vulgare extract consistently exhibited the highest content of phenolic compounds and the strongest antioxidant capacity based on the tests performed, and can be proposed as a promising source of natural antioxidants. Melissa officinalis and Salvia ringens were also identified as valuable sources of antioxidant compounds. A positive linear correlation between antioxidant activity and total phenolics, flavonoids and phenylpropanoids indicates that these compounds are likely to be the main antioxidants contributing to the observed activities of evaluated plants. These findings suggest that the medicinal plants studied in this paper are good sources of bioactive compounds for the food and pharmaceutical industries.     

In vitro antioxidant,antimicrobial and antiproliferative studies of four different extracts of Orthosiphon stamineus,Gynura procumbens and Ficus deltoidea

BackgroundMedicinal plants are important source of drugs with pharmacological activities. Therefore, there is always rising demands to discover more therapeutic agents from various species. Orthosiphon stamineus, Gynura procumbens and Ficus deltoidea are high valued medicinal plants of Malaysia contain rich source of phenolic and flavonoid compounds. The aims of the present study were to evaluate anti-oxidant, antimicrobial and anti-proliferative effects on A549, HePG2 and MCF7 cell lines of four different extracts of Orthosiphon stamineus, Gynura procumbens and Ficus deltoidea.MethodologyThe leaves of all selected plants were extracted with methanol, chloroform, ethyl acetate and butanol separately with simple cold maceration. Antioxidant activity of all crude extracts were quantitatively measured against DPPH and Ferric Reducing Assay. Antimicrobial evaluation was done by Microdilution and MTT assay and antipoliferative activity of all extracts of selected plant were evaluated against A549, HePG2 and MCF7 cell lines.ResultsResults showed that methanol extract exhibited highest percentage free radical scavenging activity of almost all extracts of selected plants. Antimicrobials results showed chloroform and methanol extracts of O. stamineus extract were the two most active extracts against resistant MRSA but not S. aureus. Only methanol extract of G. procumbens showed antimicrobial activity against the tested pathogens. Chloroform and methanol extracts of F. deltoidea elicited antimicrobial activity against S. aureus but not MRSA. Antiproliferative activity against three tested cell lines results showed that ethyl acetate extract of O. stamineus showed good effect whereas methanol extract of F. deltoidea and G. procumbens exhibited good antiproliferative activity.ConclusionsThe results of the present investigation demonstrated significant variations in the antioxidant, antimicrobial and antiproliferative effects of different solvent extracts. These data could be helpful in isolation of pure potent compounds with good biological activities from the extracts of plants.