Ethnopharmacology, ethnomedicine, and wildlife conservation.

ETHNOPHARMACOLOGICAL RELEVANCE: There are longstanding traditions of animal-derived products being employed as medicines, and they continue to be important in many traditional cultural healthcare practices. However, the populations of numerous so-used animals are known to be threatened with extirpation by such practices. Ethnopharmacological studies documenting these animal-derived drugs are not only interesting from an anthropological standpoint, but they are also relevant from a wildlife conservation perspective - especially since ethnopharmacologists are intermediaries between indigenous and scientific communities, placing them at the forefront of being able to ethically access information to address these issues. METHODS: Using the example of documenting culturally acceptable substitute materials for animal products (which ultimately also extends to flora), we explore the intersection of ethnopharmacology, biocultural resources, and wildlife conservation. RESULTS: Pharmacological efficacy and symbolism are factors influencing the utilization of traditional medicines. Achieving the integration of conservation aims with ethnopharmacology requires a nuanced understanding of both factors, along with fair adjudication when conservation and cultural aims diverge. Ethnopharmacology is suitably placed for making conservation-orientated recommendations - including investigating more sustainable substitutes for animal products in the context of medical efficacy, and for engaging ethically with local communities to facilitate information generation aimed at protecting the environment and their traditions. CONCLUSION: We suggest an integrative approach to ethnopharmacological studies investigating medicinal bioresource use. This approach is considerate of species' conservation profiles, the substitutability and pharmacological efficacy of biocultural resources, indigenous and cultural rights, and a collaborative ethos for stakeholder engagement.

Assessment of The Effect of Antidiarrheal Drugs and Plant Extracts on Drosophila melanogaster.

To study human gastrointestinal physiology, biomedical scientists have relied on the use of model organisms. Although many researchers have used mice as a model to study intestinal function, only a few reports have focused on Drosophila melanogaster (D. melanogaster). Compared to mice, fruit flies present many advantages, such as a short life cycle, cost-effective and simple maintenance, and no ethical issues. Furthermore, the mammalian gastrointestinal physiology, anatomy, and signaling pathways are highly conserved in D. melanogaster. Plant extracts have been used traditionally to treat diarrhea and constipation. For example, Psidium guajava (P. guajava) is one of the most known antidiarrheal agents in the tropics. However, no studies have evaluated the effect of antidiarrheal and laxative drugs and plant extracts in D. melanogaster, and it remains unknown if similar effects (e.g., smaller, more concentrated, and less abundant fecal deposits in the case of antidiarrheal drugs) can occur in the fruit flies compared to mammals. In this study, an antidiarrheal effect induced by P. guajava is demonstrated in a D. melanogaster strain that presents a diarrheic phenotype. Fecal sampling produced by flies is monitored using a dye-supplemented food. This protocol outlines the method used for preparing food with drugs, evaluating the fecal deposits of flies fed on these food preparations, and interpreting the data obtained.

Traditional medical practices for children in five islands from the Society archipelago (French Polynesia).

BACKGROUND: Traditional Polynesian medicine for children has been poorly documented, and few data are available on their efficacy and safety. In this context, the aim of this study was to identify traditional practices used for treating children and then assess the efficacy and safety of the most cited remedies by reviewing the literature. METHODS: In 2022, a semi-structured survey was carried out on five islands from the Society archipelago (Bora Bora, Huahine, Moorea, Raiatea, and Tahiti). A total of 86 participants were interviewed including 19 experts in herbalism. A thorough literature review was performed on the most cited plant species to gather the relevant ethnobotanical, pharmacological, and clinical data of each remedy. RESULTS: Participants mentioned using 469 remedies to treat 69 health disorders. The most represented health categories were digestive system, skin disorders, infectious diseases, and respiratory system. A total of 67 plant species (representing 731 use-reports) were mentioned and Annona muricata, Gardenia taitensis, and Hibiscus rosa-sinensis were the main plants reported. Regarding the safety of cited remedies, one plant (Microsorum grossum) showed high risk of toxicity, and its use should be avoided in infants and children. CONCLUSION: Our survey confirms the importance of traditional medical practices for children in the Society Islands. A lack of data in children for most cited remedies demonstrate the need for more pharmacological and toxicological research on Polynesian medicinal plants. Finally, the potential risk of toxicity for some cited plant species reported calls for a better information of traditional medicine users and healers.

Traditional medicine consumption in postpartum for HBV-infected women enrolled in the ANRS 12345 TA PROHM study in Cambodia.

In Cambodia, traditional medicine was commonly described as being used by pregnant women at two time points: one month before birth and during early postpartum. The present study aims to describe traditional medicine consumption during postpartum phase for women enrolled in the TA PROHM study and to investigate the possible association between traditional medicine consumption and acute liver toxicity. An ethnobotanical survey was conducted in 2 groups of HBV-infected pregnant women (with and without postpartum hepatocellular injury) enrolled in the study. Hepatocellular injury was defined by having Alanine Aminotransferase (ALT) > 2.5 times the Upper Limit of Normal (ULN = 40 U/L) at the 6th week postpartum visit. Interviews were done using a standardized questionnaire. Plant samples were collected and later identified by two traditional healers. Chi-square test was used to find the association between hepatocellular injury and traditional medicine consumption or a specific plant species. In total, 75 women were enrolled and 52 (69.3%) used at least one traditional remedy composed of 123 different plants and 12 alcoholic macerations of porcupine stomach. Orally consuming at least one remedy with alcohol was significantly associated with hepatocellular injury (33% vs 13%, p = 0.034). Among the 123 plants species identified, four were found to be associated with hepatocellular injury, namely Amphineurion marginatum (Roxb.) D.J.Middleton [Apocynaceae] (p = 0.022), Selaginella tamariscina (P.Beauv.) Spring [Selaginellaceae] (p = 0.048), Mitragyna speciosa Korth. [Rubiaceae] (p = 0.099) and Tetracera indica (Christm. & Panz.) Merr. [Dilleniaceae] (p = 0.079). Consumption of traditional medicine in postpartum is a common practice for women enrolled in the TA PROHM study. Alcohol-based remedies may exacerbate the risk of acute hepatocellular injury in HBV-infected women already exposed to immune restoration. The complex mixtures of herbs need to be further evaluated by in vitro and in vivo studies.

Anti-Salmonella activity of plant species in the Benin republic: Artemisia afra and Detarium senegalense with promising in vitro and in vivo activities.

Non-typhoidal invasive Salmonella (NTiS) diseases are one of the most important zoonoses in the world. This study explored the antipathogenic potential of twenty-four plants used in Benin folk medicine against NTiS diseases. The in vitro antibacterial and antibiofilm activities of ethanolic plant extracts were screened against clinical resistant isolates and ATCC reference strains of Salmonella. Salmonella enterica serovar Typhimurium-infected rat model was used to examine the in vivo antibacterial potential of plant extracts. Of the 24 plants, 18 plants exhibited antibacterial activity against Salmonella enterica strains with minimum inhibitory concentrations (MICs) ranging from 0.156 to 1.25 mg/mL. Anacardium occidentale, Artemisia afra, Detarium microcarpum, Detarium senegalense, and Leucaena leucocephala were the most active plant species. Extracts from A. afra, D. microcarpum, and D. senegalense showed biofilm inhibition greater than 50% against Salmonella clinical isolates. In the rat model of infection, A. afra and D. senegalense extracts were found to have an effective dose of less than 100 mg/kg and to stop the salmonellosis after 10 days of treatment. Additionally, these extracts did not produce any toxic effects in the treated animals. These results indicate clear evidence supporting the anti-Salmonella activity of A. afra and D. senegalense. Further studies are now needed to isolate bioactive compounds and to ensure the safety of these plant species.

Polynesian medicine used to treat diarrhea and ciguatera: An ethnobotanical survey in six islands from French Polynesia.

ETHNOPHARMACOLOGICAL RELEVANCE: In French Polynesia, many pathologies common or endemic to the territory cause diarrhea. This is the case for rotavirus gastroenteritis, salmonella food poisoning, ingestion of water contaminated by bacteria, and ciguatera. To treat these ailments, the population may employ traditional medicine for cultural reasons, geographical isolation, and poor health coverage. Polynesian remedies are often used without medical consultation and there is no data on their benefit-risk balance. A few ethnobotanical studies have been carried out in order to identify the traditional remedies used for various ailments, but few studies have focused on gastrointestinal pathologies. In this context, an ethnobotanical survey was carried out to identify treatments used for diarrhea and ciguatera, inventory the plants used, better understand the local representation of these remedies, and provide efficacy and safety data on these uses. MATERIALS AND METHODS: From February to April 2021, a semi-structured survey was conducted on six islands in French Polynesia, including one island in the Windward Islands archipelago (Tahiti), three islands in the Marquesas archipelago (Hiva Oa, Nuku Hiva, Tahuata), and two islands in the Leeward Islands archipelago (Raiatea, Tahaa). A total of 133 people was interviewed including 34 specialists (of which 29 experts in herbalism). RESULTS: These people mentioned the use of 27 plants for the treatment of diarrhea, and 24 for the treatment of ciguatera. Citrus aurantiifolia, Psidium guajava and Cordyline fruticosa were the three most cited plant species used for treating diarrhea, while Cocos nucifera, Punica granatum and Barringtonia asiatica were the most cited for ciguatera. A large majority of plants are widespread and introduced plants, which is congruent with the history of Polynesian people. While some plants are well known for similar uses (e.g. Psidium guajava for diarrhea, Heliotropium arboreum for ciguatera), others are less well known and may present toxicity risks (e.g. Barringtonia asiatica for ciguatera). CONCLUSION: Traditional Polynesian medicine is an integral part of the local culture so important to be preserved and valued. However, more pharmacological and toxicological studies are still needed to determine the benefit-risk balance of some of these remedies and to allow their official integration into the Polynesian health system.

Biofilm Production by Uropathogens in Postmenopausal Women with Recurrent and Isolated Urinary Tract Infection.

OBJECTIVES: The aims of this study were to assess the in vitro biofilm-producing capabilities of uropathogens grown from a postmenopausal urogynecologic population with isolated and recurrent urinary tract infection (UTI) and to determine whether the biofilm-producing bacterial phenotype was associated with recurrent infection. METHODS: This was an institutional review board-approved cross-sectional analysis within a large academic referral center. Uropathogens were cultured from postmenopausal women with either isolated or recurrent acute UTI and then screened for in vitro biofilm formation using crystal violet microtiter assays. Demographic and clinical variables, including pelvic floor symptoms and surgical history were collected and analyzed. A multivariate model was developed to determine whether recurrent UTI was independently associated with biofilm production. RESULTS: Eighty-nine women were included: 67.4% White, 25.8% Black, 3.4% Asian, and 1.1% Hispanic with a mean age of 72 ± 10.5 years. Ninety-five uropathogen strains were isolated. Most uropathogens produced biofilm (n = 53, 55.8%). Uropathogens from women with recurrent UTI were significantly more likely to produce biofilm (70%) than uropathogens collected from women with isolated UTI (38.6%, P = 0.0033). Adjusting for age, prior pelvic reconstructive surgery, and body mass index, recurrent UTI bacteria were more likely to produce biofilm, compared with isolated UTI (odds ratio, 5.37; 95% confidence interval, 2.0-14.4; P = 0.001). CONCLUSIONS: In this cohort of postmenopausal urogynecology patients, in vitro biofilm formation was more frequently observed in uropathogens isolated from women with recurrent UTI compared with women with isolated UTI. Further study is needed to assess the role of biofilms in recurrent UTIs in postmenopausal women.

Pharmacological validation of Solanum mammosum L. as an anti-infective agent: Role of solamargine.

ETHNOPHARMACOLOGICAL RELEVANCE: Fungal and bacterial infections remain a major problem worldwide, requiring the development of effective therapeutic strategies. Solanum mammosum L. (Solanaceae) ("teta de vaca") is used in traditional medicine in Peru to treat fungal infections and respiratory disorders via topical application. However, the mechanism of action remains unknown, particularly in light of its chemical composition. MATERIALS AND METHODS: The antifungal activity of TDV was determined against Trichophyton mentagrophytes and Candida albicans using bioautography-TLC-HRMS to rapidly identify the active compounds. Then, the minimum inhibitory concentration (MIC) of the fruit crude extract and the active compound was determined to precisely evaluate the antifungal activity. Additionally, the effects of the most active compound on the formation of Pseudomonas aeruginosa biofilms and pyocyanin production were evaluated. Finally, a LC-HRMS profile and a molecular network of TDV extract were created to characterize the metabolites in the fruits' ethanolic extract. RESULTS: Bioautography-TLC-HRMS followed by isolation and confirmation of the structure of the active compound by 1D and 2D NMR allowed the identification solamargine as the main compound responsible for the anti-Trichophyton mentagrophytes (MIC = 64 µg mL-1) and anti-Candida albicans (MIC = 64 µg mL-1) activities. In addition, solamargine led to a significant reduction of about 20% of the Pseudomonas aeruginosa biofilm formation. This effect was observed at a very low concentration (1.6 µg mL-1) and remained fairly consistent regardless of the concentration. In addition, solamargine reduced pyocyanin production by about 20% at concentrations of 12.5 and 50 µg mL-1. Furthermore, the LC-HRMS profiling of TDV allowed us to annotate seven known compounds that were analyzed through a molecular network. CONCLUSIONS: Solamargine has been shown to be the most active compound against T. mentoagrophytes and C. albicans in vitro. In addition, our data show that this compound affects significantly P. aeruginosa pyocyanin production and biofilm formation in our conditions. Altogether, these results might explain the traditional use of S. mammosum fruits to treat a variety of fungal infections and respiratory disorders.

Collection, Extraction, and In Vitro Antibacterial Evaluation of Plants Used in Traditional Medicine.

Medicinal plants are used to treat infectious and inflammatory diseases in various traditional medical systems, and thus could represent a promising source of antimicrobials. To establish the scientific basis for the therapeutic actions of traditional plant medicines, we provide a general workflow for evaluating the anti-infective properties of crude extracts from plants. We provide guidance starting from plant collections in the field and the creation of herbarium voucher specimens, moving to the processing of plants by drying, grinding, and extracting the plant parts collected, and finally ending with the antimicrobial investigation of these plant extracts. In this protocol, we provide a description of our workflow for the growth inhibitory evaluation of plant extracts against common human pathogenic bacteria.

Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery.

The crisis of antibiotic resistance necessitates creative and innovative approaches, from chemical identification and analysis to the assessment of bioactivity. Plant natural products (NPs) represent a promising source of antibacterial lead compounds that could help fill the drug discovery pipeline in response to the growing antibiotic resistance crisis. The major strength of plant NPs lies in their rich and unique chemodiversity, their worldwide distribution and ease of access, their various antibacterial modes of action, and the proven clinical effectiveness of plant extracts from which they are isolated. While many studies have tried to summarize NPs with antibacterial activities, a comprehensive review with rigorous selection criteria has never been performed. In this work, the literature from 2012 to 2019 was systematically reviewed to highlight plant-derived compounds with antibacterial activity by focusing on their growth inhibitory activity. A total of 459 compounds are included in this Review, of which 50.8% are phenolic derivatives, 26.6% are terpenoids, 5.7% are alkaloids, and 17% are classified as other metabolites. A selection of 183 compounds is further discussed regarding their antibacterial activity, biosynthesis, structure-activity relationship, mechanism of action, and potential as antibiotics. Emerging trends in the field of antibacterial drug discovery from plants are also discussed. This Review brings to the forefront key findings on the antibacterial potential of plant NPs for consideration in future antibiotic discovery and development efforts.

Antibacterial activity of plant species used for oral health against Porphyromonas gingivalis.

Porphyromonas gingivalis is the keystone pathogen of periodontitis, a chronic inflammatory disease which causes tooth loss and deterioration of gingiva. Medicinal plants have been traditionally used for oral hygiene and health and might play a role as antibacterial agents against oral pathogens. In this work, we aimed to evaluate the antibacterial activity of plants used for oral hygiene or symptoms of periodontitis against P. gingivalis. We first reviewed the literature to identify plant species used for oral hygiene or symptoms of periodontitis. Then, we cross-checked this species list with our in-house library of plant extracts to select extracts for testing. Antibacterial activity tests were then performed for each plant extract against P. gingivalis, and their cytotoxicity was assessed on HaCaT cells. The selectivity index (SI) was then calculated. A total of 416 plant species belonging to 110 families and 305 genera were documented through our literature search, and 158 plant species were noted as being used by North American Native peoples Once cross-checked with the extracts contained in our library of natural products, 30 matches were identified and 21 were defined as high priority. Of the 109 extracts from 21 plant species selected and tested, 21 extracts from 11 plants had higher than 90% inhibition on P. gingivalis at 64 µg/mL and were further selected for MIC (Minimum Inhibitory Concentration) assays. Out of 21 plant extracts, 13 extracts (7 plant species) had a SI > 10. Pistacia lentiscus fruits showed the best MIC with value of 8 µg/mL, followed by Zanthoxylum armatum fruits/seeds with a MIC of 16 µg/mL. P. lentiscus fruits also showed the highest SI of 256. Most of the extracts tested present promising antibacterial activity and low cytotoxicity. Further testing for biofilm eradication and examination of activity against other dental pathogens and oral commensals should be performed to confirm the potential of these extracts as antibacterial agents. Future work will focus on application of a bioassay-guided fractionation approach to isolating and identifying the most active natural products in the top performing extracts. This study can serve as a basis for their future development as ingredients for oral hygiene products.

Targeting ESKAPE pathogens with anti-infective medicinal plants from the Greater Mpigi region in Uganda.

Antibiotic resistance poses one of the greatest threats to global health today; conventional drug therapies are becoming increasingly inefficacious and limited. We identified 16 medicinal plant species used by traditional healers for the treatment of infectious and inflammatory diseases in the Greater Mpigi region of Uganda. Extracts were evaluated for their ability to inhibit growth of clinical isolates of multidrug-resistant ESKAPE pathogens. Extracts were also screened for quorum quenching activity against S. aureus, including direct protein output assessment (δ-toxin), and cytotoxicity against human keratinocytes (HaCaT). Putative matches of compounds were elucidated via LC-FTMS for the best-performing extracts. These were extracts of Zanthoxylum chalybeum (Staphylococcus aureus: MIC: 16 µg/mL; Enterococcus faecium: MIC: 32 µg/mL) and Harungana madagascariensis (S. aureus: MIC: 32 µg/mL; E. faecium: MIC: 32 µg/mL) stem bark. Extracts of Solanum aculeastrum root bark and Sesamum calycinum subsp. angustifolium leaves exhibited strong quorum sensing inhibition activity against all S. aureus accessory gene regulator (agr) alleles in absence of growth inhibition (IC50 values: 1-64 µg/mL). The study provided scientific evidence for the potential therapeutic efficacy of these medicinal plants in the Greater Mpigi region used for infections and wounds, with 13 out of 16 species tested being validated with in vitro studies.

Triterpenoid acids isolated from Schinus terebinthifolia fruits reduce Staphylococcus aureus virulence and abate dermonecrosis.

Staphylococcus aureus relies on quorum sensing to exert virulence to establish and maintain infection. Prior research demonstrated the potent quorum sensing inhibition effects of "430D-F5", a refined extract derived from the fruits of Schinus terebinthifolia, a medicinal plant used for the traditional treatment of skin and soft tissue infections. We report the isolation and identification of three compounds from 430D-F5 that reduce virulence and abate dermonecrosis: 3-oxo-olean-12-en-28-oic acid (1), 3-oxotirucalla-7,24Z-dien-26-oic acid (2) and 3α-hydroxytirucalla-7,24 Z-dien-27-oic acid (3). Each compound inhibits all S. aureus accessory gene regulator (agr) alleles (IC50 2-70 µM). Dose-dependent responses were also observed in agr-regulated reporters for leucocidin A (lukA, IC50 0.4-25 µM) and glycerol ester hydrolase or lipase (gehB, IC50 1.5-25 µM). Surprisingly, dose-dependent activity against the nuclease reporter (nuc), which is under the control of the sae two-component system, was also observed (IC50 0.4-12.5 µM). Compounds 1-3 exhibited little to no effect on the agr-independent mgrA P2 reporter (a constitutive promoter from the mgrA two-component system) and the esxA reporter (under control of mgrA). Compounds 1-3 inhibited δ-toxin production in vitro and reduced dermonecrosis in a murine in vivo model. This is the first report of triterpenoid acids with potent anti-virulence effects against S. aureus.

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective.

Background: Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Furthermore, the development of new antibiotics has slowed dramatically since the 1950s' golden age of discovery. Plants produce a variety of bioactive secondary metabolites that could be used to fuel the future discovery pipeline. While many studies have focused on specific aspects of plants and plant natural products with antibacterial properties, a comprehensive review of the antibacterial potential of plants has never before been attempted. Objectives: This systematic review aims to evaluate reports on plants with significant antibacterial activities. Methods: Following the PRISMA model, we searched three electronic databases: Web of Science, PubMed and SciFinder by using specific keywords: "plant," "antibacterial," "inhibitory concentration." Results: We identified a total of 6,083 articles published between 1946 and 2019 and then reviewed 66% of these (4,024) focusing on articles published between 2012 and 2019. A rigorous selection process was implemented using clear inclusion and exclusion criteria, yielding data on 958 plant species derived from 483 scientific articles. Antibacterial activity is found in 51 of 79 vascular plant orders throughout the phylogenetic tree. Most are reported within eudicots, with the bulk of species being asterids. Antibacterial activity is not prominent in monocotyledons. Phylogenetic distribution strongly supports the concept of chemical evolution across plant clades, especially in more derived eudicot families. The Lamiaceae, Fabaceae and Asteraceae were the most represented plant families, while Cinnamomum verum, Rosmarinus vulgaris and Thymus vulgaris were the most studied species. South Africa was the most represented site of plant collection. Crude extraction in methanol was the most represented type of extraction and leaves were the main plant tissue investigated. Finally, Staphylococcus aureus was the most targeted pathogenic bacteria in these studies. We closely examine 70 prominent medicinal plant species from the 15 families most studied in the literature. Conclusion: This review depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions.

Forest Fevers: traditional treatment of malaria in the southern lowlands of Laos.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is still a highly challenging public health issue in southern Lao PDR, with increasing cases of artemisinin resistance and Plasmodium vivax infections which are more complicated to treat. Traditional medicine has a long history of use in Laos, and is primarily practised by traditional village healers, who possess unique bodies of transmitted knowledge focused on herbal prescriptions, including those for the treatment of malaria. Villagers also use plants for healthcare in the home. The aim of the study is to document local fever concepts and use of herbal remedies, and examine whether they may have potential as complementary treatments against malaria. MATERIALS AND METHODS: The study took place in Champasak province in the far south of Laos, in primarily lowland areas. First, 35 traditional healers across the 10 districts of the province were interviewed to elicit details about knowledge and treatment of fevers. Second, a household survey was conducted in a village in a malaria-endemic area; 97 households were interviewed on fever incidence, differentiation, treatment-seeking behaviour and knowledge of plant-based remedies for fevers. Plants indicated by both healers and villagers were collected and voucher specimens deposited in the herbarium of the National University of Laos for identification. RESULTS: Malaria is a well-known pathology among the healers and villagers of lowland Champasak province; biomedical treatments are preferentially used, but traditional medicine is a popular complementary method, especially in chronic cases with additional symptoms. 30 different fever types were recorded, which were usually named symptomatically, and grouped into 12 categories. Some were described as forms of malaria, which was conceived as a dynamic, changing pathology affecting many body systems. Healers formulate treatments based on symptoms and the person's constitution, and with the intention of creating specific pharmacological actions associated with temperature or flavours. 11 of the healers gave prescriptions for malaria (27 in total), including 47 identified plant species. The most-used plants (4 or more use-reports) were also the most cited in the literature for use against malaria, demonstrating a correspondence between Lao healers and other traditional medical systems. Furthermore, some of these species show promising results for future research, especially Amorphophallus paeniifolius (Dennst.) Nicolson and Alocasia macrorrhizos (L.) G. Don. CONCLUSION: Traditional healers are important actors in the treatment of malaria in southern Laos, and herbal remedies should be evaluated further by the use of reverse treatment outcome trials, especially those which may be of use as complementary remedies in treating P. vivax. Initiatives on knowledge transmission, medicinal plant conservation and healthcare integration are also urgently needed.

Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach.

With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People's Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC50 = 1.96 ± 0.47 µg/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC50 = 1.318 ± 0.59 µg/mL) and corosolic acid (IC50 = 1.01 ± 0.06 µg/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products.

Validation of a 16th Century Traditional Chinese Medicine Use of Ginkgo biloba as a Topical Antimicrobial.

In the search for new therapeutic solutions to address an increasing number of multidrug-resistant bacterial pathogens, secondary metabolites from plants have proven to be a rich source of antimicrobial compounds. Ginkgo biloba, a tree native to China, has been spread around the world as an ornamental tree. Its seeds have been used as snacks and medical materials in Traditional Chinese Medicine (TCM), while over the last century its leaf extracts emerged as a source of rising pharmaceutical commerce related to brain health in Western medicine. Besides studies on the neuro-protective effects of Ginkgo, its antibacterial activities have gained more attention from researchers in the past decades, though its leaves were the main focus. We reviewed a 16th-century Chinese text, the Ben Cao Gang Mu by Li Shi-Zhen, to investigate the ancient prescription of Ginkgo seeds for skin infections. We performed antibacterial assays on various Ginkgo seed extracts against pathogens (Staphylococcus aureus, Cutibacterium acnes, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes) relevant to skin and soft tissue infections (SSTIs). We demonstrate here that Ginkgo seed coats and immature seeds exhibit antibacterial activity against Gram-positive skin pathogens (C. acnes, S. aureus, and S. pyogenes), and thus validated its use in TCM. We also identified one compound tied to the antibacterial activity observed, ginkgolic acid C15:1, and examine its toxicity to human keratinocytes. These results highlight the relevance of ancient medical texts as leads for the discovery of natural products with antimicrobial activities.

Herbal medicine for epilepsy seizures in Asia, Africa and Latin America: A systematic review.

RELEVANCE: More than 70 million people suffer epilepsy worldwide. Low availability of anti-epileptic drugs, side-effects and drug-resistant epilepsy affect the quality of life of persons with epilepsy in countries with a poorly developed health system. Herbal medicine is frequently used for this neurological condition. OBJECTIVES: The main objective was to provide a detailed analysis of Herbal Medicine used for neurological conditions related with epilepsy in Asia, Africa and Latin America. More broadly, this study aims to highlight species with assessed efficacy (cross-cultural use, pharmacological effects on models of epileptic seizures) and safety (toxicological data in laboratory) information, in order to point out species of interest for further studies. A critical assessment of models used in pharmacological evaluations was done. MATERIALS AND METHODS: The systematic search for Herbal Medicine treatments for epilepsy was performed considering all the articles published until February 2017 through three scientific databases. It was made with MeSH terms and free text defining the epilepsy seizures and plant species. We included studies carried out in Asia, Africa and Latin America. All articles reporting the use of Herbal Medicine to treat epilepsy seizures and/or their pharmacological evaluation were retained for further analysis. RESULTS: The search yielded 1886 articles, from 30 countries. Hundred and six articles published between 1982 and 2017 were included, corresponding to a total of 497 use reports for 351 plant species belonging to 106 families. Three hundred and seventy seven use reports corresponding to 264 species in ethnopharmacological surveys and 120 evaluation reports corresponding to 107 species were noted. Twenty-nine reports, for 29 species, combined both ethnopharmacological and pharmacological evaluation. Fifty eight studies originated from Africa, 35 studies from Asia and 18 from Latin America. Highest use report was noted for rhizomes of Acorus calamus L. (12 use report in 1 country) and leaves of Bacopa monnieri (L.) Wettst. (8 use report in 2 countries). Therefore these species display the highest use convergence. Regarding pharmacological evaluation most studied species were: Leonotis leonurus (L.) R.Br. (4 evaluation reports in 1 country), Uncaria rhynchophylla (Miq.) Miq. ex Havil. (3 evaluation reports in 2 countries) and Calotropis gigantea (L.) Dryand. (3 evaluation reports in 1 country). In vivo models of chronic epilepsy were more relevant than in vitro models or chemical models inducing acute seizures for pharmacological assessment. CONCLUSION: Species with the highest use report were not those with pharmacological evaluation. It will be pertinent to assess the pharmacological effects and safety of medicinal plants used mostly by traditional healers on predictive models of seizures.

A Seven-Year Retrospective Study on the Surveillance of Hepatitis B in Laos.

OBJECTIVE: Lao PDR is one of the most highly endemic countries for hepatitis B in Asia and the second country for liver cancer incidence. Therefore, the follow-up of infected individuals through predictive serological markers is of utmost importance to monitor the progression of the pathology and take the decision on treatment. METHODS: A retrospective-descriptive cohort study was conducted on 3,857 HBV-infected patients. Information about infection status (viral load, VL), liver function (aminotransferases), and treatments was recorded. RESULTS: M/F sex ratio was 1.77 for a median age of 37. Patients under 37 displayed higher VL than older ones and men had higher VL than women. Initial VL ranged from <50 IU/mL to 2.5 1013 IU/mL. Median aminotransferase values were 45.5 U/L for ALAT and 44 U/L for ASAT, ranging from <8 to >2,000 U/L. Men had higher aminotransferase than women. Globally 20% of patients received treatment (mainly immunostimulant and reverse-transcriptase inhibitors); 11% had high levels of VL and liver enzymes, but only 2% of them were treated. CONCLUSION: Public health decisions should be taken urgently to rationalise vaccination and provide fair access to early diagnosis and treatment; otherwise the burden of HBV-associated diseases will be overwhelming for Laos in the near future.

A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases.

Liver cancer is a major health burden in Southeast Asia, and most patients turn towards the use of medicinal plants to alleviate their symptoms. The aim of this work was to apply to Southeast Asian plants traditionally used to treat liver disorders, a successive ranking strategy based on a comprehensive review of the literature and metabolomic data in order to relate ethnopharmacological relevance to chemical entities of interest. We analyzed 45 publications resulting in a list of 378 plant species, and our point system based on the frequency of citation in the literature allowed the selection of 10 top ranked species for further collection and extraction. Extracts of these plants were tested for their in vitro anti-proliferative activities on HepG2 cells. Ethanolic extracts of Andrographis paniculata, Oroxylum indicum, Orthosiphon aristatus and Willughbeia edulis showed the highest anti-proliferative effects (IC50 = 195.9, 64.1, 71.3 and 66.7 µg/ml, respectively). A metabolomic ranking model was performed to annotate compounds responsible for the anti-proliferative properties of A. paniculata (andrographolactone and dehydroandrographolide), O. indicum (baicalein, chrysin, oroxylin A and scutellarein), O. aristatus (5-desmethylsinensetin) and W. edulis (parabaroside C and procyanidin). Overall, our dereplicative approach combined with a bibliographic scoring system allowed us to rapidly decipher the molecular basis of traditionally used medicinal plants.