In vitro antiplasmodial activity-directed investigation and UPLC-MS fingerprint of promising extracts and fractions from Terminalia ivorensis A. Chev. and Terminalia brownii Fresen.

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Medicinal plants from the Terminalia genus are widely used as remedies against many infectious diseases, including malaria. As such, Terminalia ivorensis A. Chev. and Terminalia brownii Fresen. are famous due to their usefulness in traditional medicines to treat malaria and yellow fever. However, further information is needed on the extent of anti-Plasmodium potency of extracts and fractions from these plants and their phytochemical profile. AIM OF THE STUDY: This study was designed to investigate the in vitro antiplasmodial activity and to determine the chemical profile of promising extracts and fractions from T. ivorensis and T. brownii stem bark. MATERIALS AND METHODS: Crude aqueous, ethanolic, methanolic, hydroethanolic and ethyl acetate extracts were prepared by maceration from the stem barks of T. brownii and T. ivorensis. They were subsequently tested against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum using the parasite lactate dehydrogenase (PfLDH) assay. Extracts showing very good activity on both plasmodial strains were further fractionated using column chromatography guided by evidence of antiplasmodial activity. All bioactive extracts and fractions were screened for their cytotoxicity on Vero and Raw cell lines using the resazurin-based assay and on erythrocytes using the hemolysis assay. The phytochemical profiles of selected potent extracts and fractions were determined by UPLC-QTOF-MS analysis. RESULTS: Of the ten extracts obtained from both plant species, nine showed inhibitory activity against both P. falciparum strains (Pf3D7 and PfDd2), with median inhibitory concentration (IC50) values ranging from 0.13 µg/ml to 10.59 µg/ml. Interestingly, the aqueous extract of T. ivorensis (TiW) and methanolic extract of T. brownii (TbM) displayed higher antiplasmodial activities against both strains (IC50 0.13-1.43 µg/ml) and high selectivity indices (SI > 100). Their fractionation led to two fractions from T. ivorensis and two from T. brownii that showed very promising antiplasmodial activity (IC50 0.15-1.73 µg/mL) and SI greater than 100. The hemolytic assay confirmed the safety of crude extracts and fractions on erythrocytes. UPLC-MS-based phytochemical analysis of the crude aqueous extract of T. ivorensis showed the presence of ellagic acid (1) and leucodelphidin (2), while analysis of the crude methanol extract of T. brownii showed the presence of ellagic acid (1), leucodelphinidin (2), papyriogenin D (3), dihydroactinidiolide (4) and miltiodiol (5). CONCLUSIONS: The extracts and fractions from T. ivorensis and T. brownii showed very good antiplasmodial activity, thus supporting the traditional use of the two plants in the treatment of malaria. Chemical profiling of the extracts and fractions led to the identification of chemical markers and the known antimalarial compound ellagic acid. Further isolation and testing of other pure compounds from the active fractions could lead to the identification of potent antiplasmodial compounds.

Urtica dioica-Derived Phytochemicals for Pharmacological and Therapeutic Applications.

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value.

Specific sub fractions from Terminalia mantaly (H. Perrier) extracts potently inhibit Plasmodium falciparum rings, merozoite egress and invasion.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia mantaly (H. Perrier) and Terminalia superba (Engl. & Diels) are sources of treatment for various diseases, including malaria and/or related symptoms in parts of Southwestern Cameroon. However, there is limited information on the extent of the antiplasmodial potential of their extracts. AIM OF THE STUDY: The present study was designed to investigate the antiplasmodial potential of chromatographic sub fractions (SFs) from promising fractions of Terminalia mantaly (Tm) [TmsbwChl, the chloroform fraction from water extract of Tm, IC50 (µg/mL) PfINDO: 0.56, Pf3D7: 1.12; SI > 357 (HEK/PfINDO) & 178 (HEK/Pf3D7)] and Terminalia superba (Ts) [TsrmEA, the ethyl acetate fraction from methanolic extract of Ts, IC50 (µg/mL) PfINDO: 1.82, Pf3D7: 1.65; SI > 109 (HEK/PfINDO) & 121 (HEK/Pf3D7)] obtained from previous studies. The SFs were tested against Plasmodium falciparum 3D7 (Pf3D7-chloroquine sensitive) and INDO (PfINDO-chloroquine resistant) strains in culture. Also, the phytochemical profile of potent SFs was determined and finally, the inhibition of the asexual blood stages of Plasmodium falciparum by the SFs with the highest promise was assessed. MATERIAL AND METHODS: Selected SFs were submitted to a second bio-guided fractionation using silica gel column chromatography. The partial phytochemical composition of potent antiplasmodial SFs was determined using gas chromatography coupled to mass spectrometry (GC-MS). The SYBR Green I-based fluorescence microtiter plate assay was used to monitor the growth of Plasmodium falciparum parasites in culture in the presence or absence of extracts. Microscopy and flow cytometry counting was used to assess the Plasmodium falciparum stage-specific inhibition and post-drug exposure growth suppression by highly potent extracts. RESULTS: Twenty-one of the 39 SFs afforded from TmsbwChl showed activity (IC50: 0.29-4.74 µg/mL) against both Pf3D7 and PfINDO strains. Of note, eight SFs namely, Tm25, Tm28-30, Tm34-36 and Tm38, exerted highly potent antiplasmodial activity (IC50 < 1 µg/mL) with IC50PfINDO: 0.41-0.84 µg/mL and IC50Pf3D7: 0.29-0.68 µg/mL. They also displayed very high selectivity (50 < SIPfINDO, SIPf3D7 > 344) on the two Plasmodial strains. On the other hand, 7 SFs (SFs Ts03, Ts04, Ts06, Ts09, Ts10, Ts12 and Ts13) from TsrmEA showed promising inhibitory potential against both parasite strains (IC50: 2.01-5.14 µg/mL). Sub fraction Tm36 (IC50PfINDO: 0.41 µg/mL, SIPfINDO > 243; IC50Pf3D7: 0.29 µg/mL, SIPf3D7 > 344) showed the highest promise. The GC-MS analysis of the 8 selected SFs led to the identification of 99 phytometabolites, with D-limonene (2), benzaldehyde (12), carvone (13), caryophyllene (35), hexadecanoic acid, methyl ester (74) and 9-octadecenoic acid, methyl ester (82) being the main constituents. Sub fractions Tm28, Tm29, Tm30, Tm36 and Tm38 inhibited all the three intraerythrocytic stages of P. falciparum, with strong potency against ring stage development, merozoite egress and invasion processes. CONCLUSIONS: This study has identified highly potent antiplasmodial SFs from Terminalia mantaly with significant activity on the intraerythrocytic development of Plasmodium falciparum. These SFs qualify as promising sources of novel antiplasmodial lead compounds. Further purification and characterization studies are expected to unravel molecular targets in rings and merozoites.

Anticancer properties of bromelain: State-of-the-art and recent trends.

Bromelain is a key enzyme found in pineapple (Ananas comosus (L.) Merr.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases.

Plant Natural Compounds in the Treatment of Adrenocortical Tumors.

Plant natural products are a plethora of diverse and complex molecules produced by the plant secondary metabolism. Among these, many can reserve beneficial or curative properties when employed to treat human diseases. Even in cancer, they can be successfully used and indeed numerous phytochemicals exert antineoplastic activity. The most common molecules derived from plants and used in the fight against cancer are polyphenols, i.e., quercetin, genistein, resveratrol, curcumin, etc. Despite valuable data especially in preclinical models on such compounds, few of them are currently used in the medical practice. Also, in adrenocortical tumors (ACT), phytochemicals are scarcely or not at all used. This work summarizes the available research on phytochemicals used against ACT and adrenocortical cancer, a very rare disease with poor prognosis and high metastatic potential, and wants to contribute to stimulate preclinical and clinical research to find new therapeutic strategies among the overabundance of biomolecules produced by the plant kingdom.

Naturally Occurring Bioactives as Antivirals: Emphasis on Coronavirus Infection.

The current coronavirus disease (COVID-19) outbreak is a significant threat to human health and the worldwide economy. Coronaviruses cause a variety of diseases, such as pneumonia-like upper respiratory tract illnesses, gastroenteritis, encephalitis, multiple organ failure involving lungs and kidneys which might cause death. Since the pandemic started there have been more than 107 million COVID-19 infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ∼2.4 million deaths globally. SARS-CoV-2 is easily transmitted from person-to-person and has spread quickly across all continents. With the continued increase in morbidity and mortality caused by COVID-19, and the damage to the global economy, there is an urgent need for effective prevention and treatment strategies. The advent of safe and effective vaccines has been a significant step forward in the battle against COVID-19, however treatment of the symptoms associated with the disease still requires new anti-viral and anti-inflammatory drug therapies. To this end, scientists have been investigating available natural products that may be effective against SARS-CoV-2, with some products showing promise in fighting several viral infections. Since many natural products are dietary components or are prepared as dietary supplements people tend to consider them safer than synthetic drugs. For example, Traditional Chinese Medicines have been effectively utilized to treat SARS-CoV-2 infected patients with promising results. In this review, we summarize the current knowledge of COVID-19 therapies and the therapeutic potential of medicinal plant extracts and natural compounds for the treatment of several viral infections, with special emphasis on SARS-CoV-2 infection. Realistic strategies that can be employed for the effective use of bioactive compounds for anti-SARS-CoV-2 research are also provided.

In vitro Anti-Mycobacterium ulcerans and cytotoxic activities of some selected medicinal plants and an indoloquinoline alkaloid.

Background: Buruli ulcer (BU) is a neglected tropical disease caused by the Mycobacterium ulcerans. BU is an endemic disease in many communities in sub-Saharan Africa where population have long history of using medicinal plants for treatment. Indeed, several medicinal plants have been documented against BU and related conditions. The present study was undertaken to prove the efficacy of seven medicinal plants documented for the treatment of mycobacterial infections and related symptoms in Ghana. Method: Antimycobacterial activity of the stem bark extracts and reference control drugs were conducted using the resazurin microtiter assay (REMA) assay method in clear round bottom 96-well microtiter plates. The extracts that showed anti-mycobacterium ulcerans activity were assessed for cytotoxicity using the Alamar blue assay. Results: Overall, The Cryptolepis sanguinolenta root aqueous extract exhibited the highest antimycobacterial activity (MIC=64 µg/mL) followed by Cleistopholis patens (MIC=256 µg/mL). Based on the marked activity of the Cryptolepis sanguinolenta extracts, pure cryptolepine, its major metabolite recorded a MIC value of 32 µg/mL. These extracts with considerable antimycobacterial activity showed 50% cytotoxic concentration (CC50) ranging from 94 to 384 µg/mL. Conclusions: Thus, Cleistopholis patens and Cryptolepis sanguinolenta are primed for further studies and could afford novel drugs for the mitigation of buruli ulcer disease.

In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei.

BACKGROUND: Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. OBJECTIVES: The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. MATERIALS AND METHODS: Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. RESULTS: Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 µg/mL to 5.886 µg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50 = 0.809 µg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. CONCLUSION: The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity.

Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases.

Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed.

Insights on the anticancer potential of plant-food bioactives: A key focus to prostate cancer.

Prostate cancer is an international health problem and represents one of the most encountered malignancies among men. In this complex and heterogeneous disease, androgens and their receptors play a crucial role in both progression and development. Although the search for its effective treatment is still ongoing, among other priorities it requires developing better anticancer agents with greater efficacy and fewer side effects. In this regard, herbal medicines, which have been used in cancer treatment, represent a large source of new and bioactive chemical entities for the development of chemotherapeutic agents, many of them exhibiting favorable side effect and toxicity profiles compared to conventional chemotherapeutic agents. In fact, more than 50% of the current anticancer drugs originate from natural sources. Thus, the present review aims to provide an overview of the past and recent trends in the research, the role of secondary metabolites in urogenital disorders, and phytochemical assays in prostate cancer management.

In vitro and in vivo anti-salmonella properties of hydroethanolic extract of Detarium microcarpum Guill. & Perr. (Leguminosae) root bark and LC-MS-based phytochemical analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Typhoid fever treatment remains a challenge in endemic countries. Detarium microcarpum is traditionally used to manage typhoid. AIM OF THE STUDY: The study aims to explore the efficacy of hydroethanolic extract of Detarium microcarpum root bark in rats infected with salmonella. MATERIAL AND METHODS: The phytochemical profile of the extract was obtained by UHPLC-MS analysis in an attempt of standardization. The in vitro antimicrobial activity was determined using broth dilution method. Salmonella infection was induced by oral administration of S. thyphimurium to immunosuppressed rats. Infected rats were then treated 2 h later with the extract (75, 150 and 300 mg/kg), distilled water (normal and salmonella control) and ciprofloxacin (8 mg/kg) for control. Body weight was monitored and stools were cultured to determine the number of colony-forming units. At the end of treatment, animals were sacrificed, blood and organs were collected for hematological, biochemical and histopathological analyses. RESULTS: Detarium microcarpum extract as well as the isolated compound (rhinocerotinoic acid) exhibited good antimicrobial activity in vitro with bacteriostatic effects. The plant extract significantly (p < 0.05) inhibited the bacterial development in infected animals with an effective dose (ED50) of 75 mg/kg. In addition, the extract prevented body weight loss, hematological, biochemical and histopathological damages in treated rats. CONCLUSION: Detarium microcarpum extract possesses antisalmonella properties justifying its traditional use for the typhoid fever management.

Antidiabetic Potential of Medicinal Plants and Their Active Components.

Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. Examples of medicinal plants with antidiabetic potential are described, with focuses on preclinical and clinical studies. The beneficial potential of each plant matrix is given by the combined and concerted action of their profile of biologically active compounds.

Athyrium plants - Review on phytopharmacy properties.

Athyrium plants consist of more than 230 species that are largely distributed in the Sino-Himalayan region and the Western Pacific islands. Athyrium species are being used in traditional medicine worldwide to treat various ailments such as cough, rheumatic pain, scorpion stings, sores, burns and scalds, intestinal fever, pain, specifically breast pain during child birth, to increase milk flow, as an antiparasitic, anthelmintic, and carminative. A deep look in the literature has revealed that Athyrium species have been poorly investigated for their food preservative applications and in vivo and in vitro biological and phytochemical studies. However, some Athyrium species have demonstrated antimicrobial, anti-inflammatory, antioxidant, antiproliferative and anti-HIV potential. Athyrium multidentatum (Doll.) Ching is the most investigated species and the biological activities of their extracts, such as they antioxidant properties, seem to be related to the sulfate contents of their polysaccharides. This review provides an update on the ethnopharmacology, phytochemistry and biological properties of Athyrium plants that might be useful for further research. Of course, well-designed clinical trials will be required for some species to be used as therapy.

Kaempferol: A Key Emphasis to Its Anticancer Potential.

A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective effect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling pathways. In this sense, this article reviews data from experimental studies that investigated the links between kaempferol and kaempferol-rich food intake and cancer prevention. Even though growing evidence supports the use of kaempferol for cancer prevention, further preclinical and clinical investigations using kaempferol or kaempferol-rich foods are of pivotal importance before any public health recommendation or formulation using kaempferol.

Anti-Plasmodium falciparum Activity of Extracts from 10 Cameroonian Medicinal Plants.

Background: In the midst of transient victories by way of insecticides against mosquitoes or drugs against malaria, the most serious form of malaria, caused by Plasmodium falciparum, continues to be a major public health problem. The emergence of drug-resistant malaria parasites facilitated by fake medications or the use of single drugs has worsened the situation, thereby emphasizing the need for a continued search for potent, safe, and affordable new antimalarial treatments. In line with this need, we have investigated the antiplasmodial activity of 66 different extracts prepared from 10 different medicinal plants that are native to Cameroon. Methods: Extracts were evaluated for their capacity to inhibit the growth of the chloroquine-sensitive (Pf3D7) and resistant (PfINDO) strains of P. falciparum using the SYBR green fluorescence method. The cytotoxicity of promising extracts against human embryonic kidney cells (HEK293T) mammalian cells was assessed by MTT assay. Results: The antiplasmodial activity (50% inhibitory concentration, IC50) of plant extracts ranged from 1.90 to >100 µg/mL against the two strains. Six extracts exhibited good activity against both Pf3D7 and PfINDO strains, including cold water, water decoction, and ethyl acetate extracts of leaves of Drypetes principum (Müll.Arg.) Hutch. (IC503D7/INDO = 4.91/6.64 µg/mL, 5.49/5.98 µg/mL, and 6.49/7.10 µg/mL respectively), water decoction extract of leaves of Terminalia catappa L. (IC503D7/INDO = 6.41/8.10 µg/mL), and water decoction extracts of leaves and bark of Terminalia mantaly H.Perrier (IC503D7/INDO = 2.49/1.90 µg/mL and 3.70/2.80 µg/mL respectively). These promising extracts showed no cytotoxicity against HEK293T up to 200 µg/mL, giving selectivity indices (SIs) in the range of >31.20⁻80.32. Conclusions: While providing credence to the use of D. principum, T. catappa, and T. mantaly in the traditional treatment of malaria, the results achieved set the stage for isolation and identification of active principles and ancillary molecules that may provide us with new drugs or drug combinations to fight against drug-resistant malaria.

Aloe Genus Plants: From Farm to Food Applications and Phytopharmacotherapy.

Aloe genus plants, distributed in Old World, are widely known and have been used for centuries as topical and oral therapeutic agents due to their health, beauty, medicinal, and skin care properties. Among the well-investigated Aloe species are A. arborescens, A. barbadensis, A. ferox, and A. vera. Today, they account among the most economically important medicinal plants and are commonly used in primary health treatment, where they play a pivotal role in the treatment of various types of diseases via the modulation of biochemical and molecular pathways, besides being a rich source of valuable phytochemicals. In the present review, we summarized the recent advances in botany, phytochemical composition, ethnobotanical uses, food preservation, and the preclinical and clinical efficacy of Aloe plants. These data will be helpful to provide future directions for the industrial and medicinal use of Aloe plants.

In Vitro Activity of Selected West African Medicinal Plants against Mycobacterium ulcerans Disease.

Buruli ulcer (BU) is the third most prevalent mycobacteriosis, after tuberculosis and leprosy. The currently recommended combination of rifampicin-streptomycin suffers from side effects and poor compliance, which leads to reliance on local herbal remedies. The objective of this study was to investigate the antimycobacterial properties and toxicity of selected medicinal plants. Sixty-five extracts from 27 plant species were screened against Mycobacterium ulcerans and Mycobacterium smegmatis, using the Resazurin Microtiter Assay (REMA). The cytotoxicity of promising extracts was assayed on normal Chang liver cells by an MTT assay. Twenty five extracts showed activity with minimal inhibitory concentration (MIC) values ranging from 16 µg/mL to 250 µg/mL against M. smegmatis, while 17 showed activity against M. ulcerans with MIC values ranging from 125 µg/mL to 250 µg/mL. In most of the cases, plant extracts with antimycobacterial activity showed no cytotoxicity on normal human liver cells. Exception were Carica papaya, Cleistopholis patens, and Polyalthia suaveolens with 50% cell cytotoxic concentrations (CC50) ranging from 3.8 to 223 µg/mL. These preliminary results support the use of some West African plants in the treatment of Buruli ulcer. Meanwhile, further studies are required to isolate and characterize the active ingredients in the extracts.

Antimycobacterial potency and cytotoxicity study of three medicinal plants.

OBJECTIVE/BACKGROUND: Mycobacterial infections including tuberculosis, leprosy, and buruli ulcer are among the most prevalent, debilitating, and deadly tropical diseases, especially in Sub-Saharan Africa. The development of drug resistance to the currently available drugs and the poor compliance emphasize the need for new chemotherapeutic agents. This study was designed to evaluate the in vitro activity of Cleistopholis patens, Annona reticulata, and Greenwayodendron suaveolens against Mycobacterium smegmatis. The safety on normal liver cells was also assessed. METHODS: The crude extracts, fractions, and subfractions were tested against M. smegmatis and for cell cytotoxicity on WRL-68, normal human hepatocyte using microdilution resazurin-based assays. The phytochemical screening was performed using standard methods. RESULTS: Most of the extracts, fractions, and subfractions inhibited the growth of M. smegmatis with minimum inhibitory concentration (MIC) values ranging from 6.25µg/mL to 125µg/mL. The subfractions P12 and P29 from G. suaveolens twig were more potent with MIC values of 6.25µg/mL and 25µg/mL, respectively. Fruit crude extract and root CH2Cl2 fraction from A. reticulata also showed activity with MIC values of 50µg/mL and 25µg/mL, respectively. Crude extracts from the twig and stem bark of C. patens displayed inhibition at MIC values of 125µg/mL and 100µg/mL, respectively. Majority of active extracts showed no cell cytotoxicity, except the extract from C. patens with IC50 ranging from 41.40µg/mL to 93.78µg/mL. The chemical investigation of the promising extracts revealed the presence of phenols, alkaloids, glycosides, triterpenes, and acetogenins. CONCLUSION: The results achieved from this preliminary antimycobacterial drug discovery study supported the traditional claims of C. patens, A. reticulata, and G. suaveolens in the treatment of mycobacterial infections. Meanwhile, further fractionation is required to characterize the active ingredients.

Antimycobacterial ingredients from plants used in traditional medicine to treat Buruli ulcer.

AIM AND OBJECTIVES: Buruli ulcer (BU) is a neglected tropical disease caused by a mycobacteria, Mycobacterium ulcerans. The WHO recommended Rifampicin-Streptomycin combination side effects and poor compliance, leaves rural populations with no choice than to patronise indigenous remedies. This study is aimed at validating medicinal plants used in traditional medicine to treat BU by investigating the in vitro efficacy and safety as well as their composition in active molecules. METHODS: A short report-based survey was used to identify medicinal plants used traditionally for BU treatment. Maceration of collected plant samples in methanol, hydroethanolic, ethanol, dichloromethane, and hexane, resulted in a total of 67 extracts assessed for antimycobacteria activity against Mycobacterium smegmatis and Mycobacterium ulcerans using the Resazurin Microtiter Assay. The cytotoxicity effect of promising extracts was assessed on normal human liver cells using the MTT assay. The bio-guided fractionation of the promising extracts led to the isolation of active compounds. RESULTS: Majority of plants prepared as infusion, decoction, poultice, and macerate were administered topically. Significant antimycobacterial activity with MIC values ranging from 16 to 250µg/mL was recorded against M. smegmatis (25 extracts) and M. ulcerans (17 extracts).1 Most of antimycobacterial extracts showed no significant cytotoxicity against normal human hepatocytes.1 The isolation guided by the biological activity revealed nine compounds with significant in vitro anti-M. ulcerans activity (MIC=16-128µg/mL). CONCLUSIONS: The results completed support the use these plants in the indigenous knowledge against BU. Further analyses of active principles might lead to new drug toe fight against BU.

Ethnopharmacological reports on anti-Buruli ulcer medicinal plants in three West African countries.

ETHNOPHARMACOLOGICAL RELEVANCE: Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control. MATERIAL AND METHODS: A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA, Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans. This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro. This review covered the available literature up to December 2014. RESULTS: The majority of reports originated from the three most affected West African countries (Cote d'Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the pharmacological studies were performed only on 54 species. To a lesser extent, ethnopharmacological knowledge was validated in vitro for only 13 species. Of those, seven species including Ricinus comminus, Cyperus cyperoides (cited as Mariscus alternifolius), Nicotiana tabacum, Mangifera indica, Solanum rugosum, Carica papaya, and Moringa oleifera demonstrated efficacy in hospitalised BU patients. Four isolated and characterized compounds were reported to have moderate bioactivity in vitro against M. ulcerans. CONCLUSIONS: This review compiles for the first time ethnopharmacologically useful plants against BU. The phamacological potential of 13 of them has been demonstrated in vitro and support BU evidence-based traditional medicines. In addition, 7 species showed activity in BU patients and have emerged as a promising source of the traditional medicine for treatment of BU. Yet, further safety and efficacy study should be initiated prior any approval as alternative therapy. Overall, a huge gap in knowledge appeared, suggesting further well-planned and detailed investigations of the in vitro, in vivo, and safety properties of the claimed anti-BU plants. Therefore, plants with medicinal potential should be scrutinized for biologically active compounds, using bioassay-guided fractionation approach to provide new insights to find novel therapeutics for BU control.