Abstract:
Millions of people have been negatively affected by the Covid-19 (SARS-CoV-2) pandemic worldwide. Multiple stages characterize Covid-19 infection, initial stages include common symptoms that are milder in nature (fever, dry coughs, fatigue) with later stages being characterized by more severe symptoms such as pneumonia, acute respiratory stress disorder (ARDS), inflammation, coagulation, potentially multiple organ failure and death. This study aimed to evaluate the ethanolic extracts of twenty-three medicinal plants for their cytotoxic effects and their anticoagulant and anti-inflammatory activities. Furthermore, bioactive extracts were evaluated for potential interactions with Cytochrome P450 enzymes, which play a role in drug metabolism. Ten plants, namely, Aspalathus linearis, Bulbine frutescens, Clausena anisata, Capparis tomentosa, Foeniculum vulgare, Myrsine africana, Podocarpus latifolius, Polygala virgata, Rhoicissus tridentata and Tylosema esculentum exhibited no cytotoxicity on human lung fibroblast cells (MRC-5) and were subsequently tested for anticoagulant activity. Four plants, namely, F. vulgare, M. africana, P. latifolius and R. tridentata showed anticoagulant activity and were further tested for drug-herb interactions. Interactions with CYP 1A2, CYP 2C9, CYP 2C19, CYP 2D6 and CYP 3A4 showed that 10 µg/ml of M. africana and R. tridentata increased the activity of all enzymes. F. vulgare exhibited a significant increase in activity of all CYP P450 enzymes tested except for CYP 2C9, while P. latifolius showed significant inhibition of both CYP 2C9 and CYP 2C19 and significant increases in CYP 1A2, CYP 2D6 and CYP 3A4 activity. The given herb-drug interactions suggest caution and further investigation as both inhibition and induction of CYP P450 enzymes may lead to adverse effects in drug interactions through bioaccumulation of the drug to toxic amounts or increased clearance. During the evaluation of anti-inflammatory activity of F. vulgare, M. africana, P. latifolius and R. tridentata ethanolic extracts, it was found that F. vulgare inhibited the production of IL-8, IL-12p70 and IL-6 at 100 µg/ml. The extract of M. africana inhibited IL-12p70, IL-8, TNF-α and IL-6 cytokines at 100 µg/ml. Both P. latifolius and R. tridentata showed inhibition of IL-12p70, IL-6 and IL-8 at 100 µg/ml. It can be concluded that F. vulgare, M. africana, P. latifolius and R. tridentata have been identified as possible leads against the selected targets associated with Covid-19 infection and should be investigated further for pre-clinical studies.
