Anti-inflammatory, Antimicrobial, Antidiarrhea and Toxic Effects of the Aqueous and Methanolic Leaf and Fruit Extracts of Cucumis Dipsaceus in Winstar Rats and New Zealand White Rabbits

Abstract

Inflammation, diarrhea, and microbial infections produce high morbidity and mortality globally, contributing to a high burden of disease in developing countries. Despite the utilisation of conventional drugs to treat inflammation, diarrhea, and microbial infections, their inaccessibility, unaffordability and their side effects hinder the successful treatment and alleviation of disease. The emergence of antimicrobial-resistant bacteria and fungi strains have compromised the efficiency of antimicrobial chemotherapy, which leads to undesirable sequalae. There is an urgent need to search for alternative therapies, which are efficacious, affordable, accessible and safe in order to alleviate human suffering and promote the quality of life. Medicinal plants present a feasible alternative source of potent pharmacological molecules, which are affordable, easily accessible and safe due to the many biologically active phytochemicals they have. Although medicinal plants have been used by humans for ages as medicines and food, only a few have been empirically investigated. Cucumis dipsaceus has a long history of ethnomedicinal usage in treating inflammation, diarrhea, and microbial infections, in Kenya and other countries. However, there is scanty empirical data to validate its efficacy and safety. The anti-inflammatory antidiarrhea, antimicrobial, and toxic effects of methanolic and aqueous leaf and fruit (methanolic and aqueous leaf and fruit) extracts of C. dipsaceus were investigated. The in vivo anti-inflammatory activities of the methanolic and aqueous leaf and fruit extracts of C. dipsaceus were studied using the formalin-induced paw oedema technique in Wistar rats. The castor oil-induced diarrhea method was used to determine the antidiarrhea activity of the methanolic and aqueous leaf and fruit extracts of the studied plant in Wistar rats. Isolated rabbit ileum was used to determine the effects of the C. dipsaceus extracts on the gastrointestinal motility. Antimicrobial activity of the methanolic and aqueous leaf and fruit extracts was determined using the disk diffusion and broth microdilution techniques described previously. The acute oral and dermal toxicity effects of the methanolic and aqueous leaf and fruit extracts of C. dipsaceus were studied in rabbits and rats, respectively, using appropriate guidelines. Data was analysed using GraphPad Prism statistical software version 9.1. The results indicated significant reductions in formalin-induced paw oedema in the Wistar rats by methanolic and aqueous leaf and fruit extracts of C. dipsaceus, in a dose- and time-dependent manner (P<0.05), with percentage inhibition of between 1.56% and 97.59%. Methanolic and aqueous leaf and fruit extracts of C. dipsaceus significantly (P<0.05) inhibited diarrhea and intestinal motility in Wistar rats and rabbits respectively, in a dose-dependent manner, thereby depicting their antidiarrhea effects. Furthermore, the methanolic and aqueous leaf and fruit extracts of C. dipsaceus significantly inhibited the growth of P. aeruginosa, S. enteriditis, E. coli, C. albicans, and B. subtilis in varying degrees as depicted by the different growth inhibition zones of between 6 mm and 20 mm and the Minimum Inhibitory Concentrations of 3.125 μg/ml. The observed anti-inflammatory, antidiarrhea, and antimicrobial activities of the plant extracts were attributed to various phytochemicals extractable by water and methanol, which exerted pharmacological efficacy via various mechanisms. Moreover, aqueous and the methanolic and aqueous leaf and fruit extracts of C. dipsaceus showed no observable acute dermal toxicity effects on the abraded and intact skins of New Zealand White rabbits. Similarly, the methanolic and aqueous leaf and fruit extracts of C. dipsaceus showed no observable acute oral toxicity during the 14-day experimental period. In conclusion, the extracts were considered safe according to the OECD Guidelines. Further pharmacological and toxicological investigations of the tested plant extracts using more advanced techniques should be done in order to elucidate and optimise bioactive molecules for treating inflammation, diarrhea, and microbial infections.