Local knowledge, practices, challenges of ethnopharmacologically used medicinal plants in Benin and implications for brain illnesses.

Traditional medicine (TM) is a significant resource for primary healthcare management all over the world, and principally in Africa. Quality improvement activities that promote evidence-based practices and the integration of traditional medicine into primary healthcare systems can help improve the quality of patient care. In the Republic of Benin (West Africa), traditional medicine practitioners (TMPs) provide different treatments and ways of use, depending on the ailments and the medicinal plants used. The present study aimed at documenting the knowledge, attitudes and practices of Beninese TMPs regarding the use of medicinal plants and the challenges associated with their activities. A focus group survey was conducted using semi-structured interviews with a sample of 91 TMPs in 8 departments of the Republic of Benin. The respondents had an average age of 50 years old and belonged to various categories of TMPs. Medicinal plants are harvested depending on the season and time of the day, and are dried in the shade before being used as decoctions or infusions. Nevertheless, the majority of TMPs do not conduct the necessary tests for quality control, efficacy or toxicity of the proposed remedies, which raises several scientific interrogations, particularly for the treatment of mental and brain-related disorders. Among ~ 110 plants used in the treatment of several pathologies, 66 were revealed as threatened species. The challenges faced by TMPs are mainly material, financial and technical difficulties. The present study reports the importance of intervention to modernize TM practices in Benin. Quality improvement could enhance healthcare delivery and provide support for evidence-based interventions aimed at addressing behavioral, social, and environmental determinants of health.

Unleashing the Potential of Medicinal Plants in Benin: Assessing the Status of Research and the Need for Enhanced Practices.

Medicinal plants play a crucial role in the primary health care of the population in developing countries such as Benin. The national universities of Benin conduct research on the pharmacological, toxicological, and phytochemical properties of these plants, but the resulting knowledge often does not lead to the development of phytomedicines for the improvement of public health. This study aims to assess the current status of research on medicinal plants in Benin. A literature review was conducted using various search engines, and the collected data was analyzed. The results indicate that research on the biological properties of medicinal plants is still in its early stages, with limited and inadequate methodological approaches. These limitations highlight the urgent need to enhance research practices and facilitate the development of effective and safe phytomedicines.

Alterations in Bacterial Metabolism Contribute to the Lifespan Extension Exerted by Guarana in Caenorhabditis elegans.

Guarana (Paullinia cupana) is a widely consumed nutraceutical with various health benefits supported by scientific evidence. However, its indirect health impacts through the gut microbiota have not been studied. Caenorhabditis elegans is a useful model to study both the direct and indirect effects of nutraceuticals, as the intimate association of the worm with the metabolites produced by Escherichia coli is a prototypic simplified model of our gut microbiota. We prepared an ethanoic extract of guarana seeds and assessed its antioxidant capacity in vitro, with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and in vivo, utilizing C. elegans. Additionally, we studied the impact of this extract on C. elegans lifespan, utilizing both viable and non-viable E. coli, and assessed the impact of guarana on E. coli folate production. The extract showed high antioxidant capacity, and it extended worm lifespan. However, the antioxidant and life-extending effects did not correlate in terms of the extract concentration. The extract-induced life extension was also less significant when utilizing dead E. coli, which may indicate that the effects of guarana on the worms work partly through modifications on E. coli metabolism. Following this observation, guarana was found to decrease E. coli folate production, revealing one possible route for its beneficial effects.

Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers.

Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia-host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.

Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells.

Redox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of schisandrin, schisandrin B and schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production. In THP-1 cells, levels of intracellular reactive oxygen species (ROS) were elevated after 1 h exposure to schisandrin. Schisandrin B and schisandrin C decreased cellular glutathione pools, which is a phenotype previously reported to promote anti-inflammatory functions. Treatment of human primary monocytes with the lignans during their maturation to dendritic cells did not have any effect on the appearance of surface markers HLA-DR and CD86 but schisandrin B and schisandrin C suppressed the secretion of cytokines interleukin (IL)-6, IL-10 and IL-12 by the mature dendritic cells. Dendritic cells maturated in presence of schisandrin C were further cocultured with naïve CD4+ T cells, resulting in reduced IL-12 production. In THP-1 cells, schisandrin B and schisandrin C reduced the IL-6 and IL-12 production triggered by E. coli lipopolysaccharide and IL-12 production induced by an infection with Chlamydia pneumoniae. In conclusion, the studied lignans act as immunomodulatory agents by altering the cytokine secretion, but do not interfere with dendritic cell maturation. And the observed effects may be associated with the ability of the lignans to alter cellular redox status.

Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors.

Throughout its known history, the gram-negative bacterium Chlamydia pneumoniae has remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new approaches for targeting this ubiquitous human pathogen are urgently needed. In this review, we describe the strategies that have been successfully applied for the identification of nonconventional antichlamydial agents, including target-based and ligand-based virtual screening, ethnopharmacological approach and pharmacophore-based design of antimicrobial peptide-mimicking compounds. Among the antichlamydial agents identified via these strategies, most translational work has been carried out with plant phenolics. Thus, currently available data on their properties as antichlamydial agents are described, highlighting their potential mechanisms of action. In this context, the role of mitogen-activated protein kinase activation in the intracellular growth and survival of C. pneumoniae is discussed. Owing to the complex and often complementary pathways applied by C. pneumoniae in the different stages of its life cycle, multitargeted therapy approaches are expected to provide better tools for antichlamydial therapy than agents with a single molecular target.

Mint Flavorings from Candies Inhibit the Infectivity of Chlamydia pneumoniae.

The impact of solvent extracts from the distillation water (flavoring extracts) isolated from mint flavored candies on the infectivity of the intracellular bacterium Chlamydia pneumoniae was evaluated by an in vitro model of epithelial cell infections., The mint flavoring extracts were isolated from the candies by simultaneous hydrodistillation and their chemical composition, established by GC-MS, demonstrated menthol and limonene as the most abundant components. Results obtained by treating C. pneumoniae elementary bodies (EBs) with the flavoring extracts or pure reference compounds showed a significant decrease in EB infectivity, achieved with most of the extracts. This antichlamydial activity could be related to the relatively high menthol content of the extracts. Overall, the obtained data indicates that the flavorings present in the candies are able to target the metabolically quiet, non-replicating form of the bacterium and to suppress the spread of this respiratory pathogen from one cell to another.

The Lignan-containing Extract of Schisandra chinensis Berries Inhibits the Growth of Chlamydia pneumonia.

The purpose of this study was to investigate the effect and selectivity of an extract of Schisandra chinensis berries against Chlamydia pneumoniae and C. trachomatis. Among the ethnopharmacological uses of the extract from Schisandrae fructus are cough and pneumonia. Therefore we focused on respiratory pathogens. The extract completely inhibited the growth of C. pneumoniae strain CV6 at 250 µg/mL concentration. The inhibition of C. pneumoniae and C. trachomatis growth was dose dependent and established with three different strains. The extract inhibited C. pneumoniae production of infectious progeny in a dose dependent manner. Chlamydia selectivity was elucidated with growth inhibition measurements of three other respiratory bacterial species. A pure compound found in Schisandra chinensis berries, schisandrin B at 20.0 µg/mL concentration inhibited the growth of both C. pneumoniae and C. trachomatis. The extract was found to be non-toxic to the human host cells. These findings highlight the potential of the extract from Schisandra chinensis berries as a source for antichlamydial compounds.

Inhibitory activity of the isoflavone biochanin A on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.

Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.

How to translate a bioassay into a screening assay for natural products: general considerations and implementation of antimicrobial screens.

Natural product sources have been a valuable provider of molecular diversity in many drug discovery programs and several therapeutically important drugs have been isolated from these. However, the screening of such materials can be very complicated due to the fact that they contain a complex mixture of secondary metabolites, but also the purified natural compounds exert a challenge for bioactivity screening. Success in identifying new therapeutics using in vitro bioassays is largely dependent upon the proper design, validation, and implementation of the screening assay. In this review, we discuss some aspects which are of significant concern when screening natural products in a microtiter plate-based format, being partly applicable to other assay formats as well, such as validation parameters, layouts for assay protocols, and common interferences caused by natural products samples, as well as various troubleshooting strategies. Examples from the field of natural product drug discovery of antibacterial compounds are discussed, and contributions from the realm of academic screenings are highlighted.