Pre-clinical efficacy of African medicinal plants used in the treatment of snakebite envenoming: A systematic review.

The World Health Organization has listed Snakebite Envenoming (SBE) as a priority neglected tropical disease, with a worldwide annual snakebite affecting 5.4 million people and injuring 2.7 million lives. In many parts of rural areas of Africa and Asia, medicinal plants have been used as alternatives to conventional antisnake venom (ASV) due in part to inaccessibility to hospitals. Systemic reviews (SR) of laboratory-based preclinical studies play an essential role in drug discovery. We conducted an SR to evaluate the relationship between interventional medicinal plants and their observed effects on venom-induced experiments. This SR was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Modified collaborative approach to meta-analysis and review of animal data from experimental studies (CAMARADES) and SYRCLE's risk of bias tools were used to appraise the included studies. Data were searched online in Medline via PubMed, Embase via OVID, and Scopus. Studies reporting in vivo and in vitro pharmacological activities of African medicinal plants/extracts/constituents against venom-induced pathologies were identified and included for screening. Data from the included studies were extracted and synthesized. Ten studies reported statistically significant percentage protection (40-100%) of animals against venom-induced lethality compared with control groups that received no medicinal plant intervention. Sixteen studies reported significant effects (p ≤ 0.05) against venom-induced pathologies compared with the control group; these include hemolytic, histopathologic, necrotic, and anti-enzymatic effects. The plant family Fabaceae has the highest number of studies reporting its efficacy, followed by Annonaceae, Malvaceae, Combretaceae, Sterculiaceae, and Olacaceae. Some African medicinal plants are preclinically effective against venom-induced lethality, hematotoxicity, and cytotoxicity. The evidence was extracted from three in vitro studies, nine in vivo studies, and five studies that combined both in vivo and in vitro models. The effective plants belong to the Fabaceae family, followed by Malvaceae, and Annonaceae.

Acacia sieberiana (Fabaceae) attenuates paracetamol and Bile Duct Ligation-Induced hepatotoxicity via modulation of biochemical and oxidative stress biomarkers.

Background: The plant Acacia sieberiana (Fabaceae) is traditionally used to manage hepatitis. This research work aims to investigate the hepatoprotective effectiveness of root bark extract of Acacia sieberiana (ASE) against paracetamol (PCM) and bile duct ligation (BDL)-induced hepatotoxicity. The phytochemical and median lethal dose (LD50) investigations were conducted. The rats were pre-treated with the ASE (250, 750, and 1,500 mg/kg) once daily via oral route for 7 consecutive days. On the 8th day, liver injury was initiated by PCM administration (2 g/kg). Similarly, in the BDL-induced liver injury, the animals were administered ASE (125, 250, and 380 mg/kg) intraperitoneally for 7 consecutive days. After 24 h, blood samples and hepatic tissues were obtained for biochemical and histopathological investigations. Results: Phytocomponents determination revealed glycosides, triterpenes, glycosides, saponins, tannins, flavonoids and alkaloids. The oral and intraperitoneal LD50 values of the ASE were >5,000 and 1,300 mg/kg, respectively. The ASE efficiently (p < 0.05) decreased the alanine transaminase (ALT) and aspartate transaminase (AST) levels and elevated the albumin and total protein (TP) levels. The direct bilirubin effectively (p < 0.05) decreased at 750 mg/kg. Besides, the extract efficiently elevated the glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in relation to the PCM hepatotoxic group. Also, the malondialdehyde (MDA) concentration was reduced by the ASE. Meanwhile, in the BDL-induced liver injury, the ASE remarkably (p < 0.05) declined the AST, ALP, bilirubin,and MDA. Besides, there was effective (p < 0.05) elevation in SOD, GPx and CAT in the ASE-treated groups. The morphology of liver tissue was preserved at 125 and 250 mg/kg ASE groups from BDL-induced necrosis and vascular congestion. Conclusion: The study shows that the ASE has hepatoprotective actions against liver damage by possible modulation of biochemical and oxidative stress biomarkers.

Preclinical efficacy of African medicinal plants used in the treatment of snakebite envenoming: a systematic review protocol.

BACKGROUND: Snakebite envenoming (SBE) is a high-priority, neglected, tropical disease that affects millions of people in developing countries annually. The only available standard drug used for the treatment of SBE is antisnake venom (ASV) which consists of immunoglobulins that have been purified from the plasma of animals hyper-immunized against snake venoms. The use of plants as alternatives for treatment of poisonous bites particularly snakebites is important in remote areas where there might be limited, or no access to hospitals and storage facilities for antivenom. The pharmacological activity of some of the medicinal plants used traditionally in the treatment of SBE have also been scientifically validated. METHOD: A systematic review will be conducted according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies checklist for study quality in animal/in vivo studies. The tool will be modified and validated to assess in vitro models and studies that combine in vivo and in vitro studies. The systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. English published articles on African medicinal plants used in the treatment of snakebite envenoming will be searched in Medline, Embase, and Scopus from 2000 to 2021. DISSEMINATION: The findings of the study will be communicated through publication in peer-reviewed journal and presentation at scientific conferences. Medicinal plants have been important sources for the development of many effective drugs currently available in orthodox medicine. Botanically derived medicines have played a major role in human societies throughout history. Plants components used in traditional medicine gained much attention by many toxinologists as a tool for designing potent antidotes against snake envenoming. Our systematic review will provide a synthesis of the literature on the efficacy of these medicinal plants. We will also appraise the prospects of African medicinal plants with pharmacologically demonstrated activity against snakebite and envenoming.

Data on the mechanisms of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum Diels (Combretaceae): Involvement of opioidergic and (α1 and ß)-adrenergic pathways.

This article describes the dataset for the elucidation of the possible mechanisms of antidiarrhoeal actions of methanol leaves extract of Combretum hypopilinum (Diels) Combretaceae in mice. The plant has been used in traditional medicine to treat diarrhoea in Nigeria and other African countries. We introduce the data for the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum at 1,000 mg/kg investigated using charcoal meal test in mice with loperamide (5 mg/kg) as the standard antidiarrhoeal agent. To elucidate the possible mechanisms of its antidiarrhoeal action, naloxone (2 mg/kg), prazosin (1 mg/kg), yohimbine (2 mg/kg), propranolol (1 mg/kg), pilocarpine (1 mg/kg) and isosorbide dinitrate (150 mg/kg) were separately administered to different groups of mice 30 minutes before administration of the extract. Each mouse was dissected using dissecting set, and the small intestine was immediately removed from pylorus to caecum, placed lengthwise on moist filter paper and measured the distance travelled by charcoal relative to the length of the intestine using a calibrated ruler in centimetre. Besides, the peristaltic index and inhibition of charcoal movement of each animal were calculated and recorded. The methods for the data collection is similar to the one used to investigate the possible pathways involved in the antidiarrhoeal action of Combretum hypopilinum in mice in the research article by Ahmad et al. (2020) "Mechanisms of Antidiarrhoeal Activity of Methanol Leaf Extract of Combretum hypopilinum Diels (Combretaceae): Involvement of Opioidergic and (α1 and ß)-Adrenergic Pathways" (https://doi.org/10.1016/j.jep.2020.113750) [1]. Therefore, this datasets could form a basis for in-depth research to elucidate further the pharmacological properties of the plant Combretum hypopilinum and its bioactive compounds to develop standardized herbal product and novel compound for management of diarrhoea. It could also be instrumental for evaluating the plant's pharmacological potentials using other computational-based and artificial intelligence approaches, including predictive modelling and simulation.

Mechanisms of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum diels (combretaceae): Involvement of opioidergic and (α1 and ß)-adrenergic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Combretum hypopilinum Diels (Combretaceae) is used in traditional medicine for the treatment of diarrhoea and other diseases in Africa. Previously, the antidiarrhoeal activity of its methanol leaf extract was reported. However, the mechanism(s) responsible for this activity is yet to be evaluated. AIM OF THE STUDY: This study aimed to elucidate the possible mechanism(s) of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum (MECH) in mice. MATERIALS AND METHODS: Phytochemical screening and acute toxicity study were conducted according to standard methods. Adult mice were orally (p.o) administered distilled water (10 ml/kg), MECH (1000 mg/kg) and loperamide (5 mg/kg). The probable mechanisms of antidiarrhoeal activity of MECH were investigated following pretreatment with naloxone (2 mg/kg, subcutaneously), prazosin (1 mg/kg, s.c), yohimbine (2 mg/kg, intraperitoneally), propranolol (1 mg/kg, i.p), pilocarpine (1 mg/kg, s.c) and isosorbide dinitrate (150 mg/kg, p.o) 30 min before administration of MECH (1000 mg/kg). The mice were then subjected to castor oil-induced intestinal motility test. RESULTS: The oral median lethal dose (LD50) of MECH was found to be higher than 5000 mg/kg. There were significant (p < 0.05) decrease in the charcoal movement in the mice treated with the MECH (1000 mg/kg) and loperamide (5 mg/kg). The pretreatment of the mice with naloxone, prazosin and propranolol each significantly (p<0.05) reversed the antidiarrhoeal activity produced by MECH. CONCLUSION: The results obtained in this study suggest the probable involvement of opioidergic and (α1 and ß)-adrenergic systems in the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum.