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.

Plant responses to metals stress: microRNAs in focus.

Metal toxicity can largely affect the growth and yield of numerous plant species. Plants have developed specific mechanisms to withstand the varying amounts of metals. One approach involves utilization of microRNAs (miRNAs) that are known for cleaving transcripts or inhibiting translation to mediate post-transcriptional control. Use of transcription factors (TFs) or gene regulation in metal detoxification largely depends on metal-responsive miRNAs. Moreover, systemic signals and physiological processes for plants response to metal toxicities are likewise controlled by miRNAs. Therefore, it is necessary to understand miRNAs and their regulatory networks in relation to metal stress. The miRNA-based approach can be important to produce metal-tolerant plant species. Here, we have reviewed the importance of plant miRNAs and their role in mitigating metal toxicities. The current review also discusses the specific advances that have occurred as a result of the identification and validation of several metal stress-responsive miRNAs.

Non-compartmental toxicokinetic studies of the Nigerian Naja nigricollis venom.

Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria Naja nigricollis venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We found that N. nigricollis venom contained sixteen venom protein families following a mass spectrometric analysis of the whole venom. Most of these proteins belong to the three-finger toxins family (3FTx) and venom phospholipase A2 (PLA2) with molecular weight ranging from 3 to 16 kDa. Other venom protein families were in small proportions with higher molecular weights. The N. nigricollis venom was rapidly absorbed at 0.5 h, increased after 1 h and continued to decrease until the 16th hour (Tmax), where maximum concentration (Cmax) was observed. This was followed by a decrease in concentration at the 32nd hour. The venom of N. nigricollis was found to have high volume of distribution (1250 ± 245 mL) and low clearance (29.0 ± 2.5 mL/h) with an elimination half-life of 29 h. The area under the curve (AUC) showed that the venom remaining in the plasma over 32 h was 0.0392 ± 0.0025 mg h.L-1, and the mean residence time was 43.17 ± 8.04 h. The pharmacometrics simulation suggests that the venom toxins were instantly and rapidly absorbed into the extravascular compartment and slowly moved into the central compartment. Our study demonstrates that Nigerian N. nigricollis venom contains low molecular weight toxins that are well absorbed into the blood and deep tissues. The venom could be detected in rabbit blood 48 h after intramuscular envenoming.

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.