A Study on Toxicity and Antimalarial Efficacy of Ocimum Gratissimum, Influence on Lung Antioxidant Defense and Nrf2 Expression in Plasmodium Berghei (Nk65) Infected Mice

Malaria chemotherapy, the mainstay of treatment is currently failing due to the emergence and spread of resistance of the causative parasites to conventional drugs endangering public health. The most severe complication of malaria is pulmonary involvement which occurs in 3-10% of the infection with about 70% mortality. So, discovery of antimalarial therapeutic agent with the capacity to combat associated lung complications is imperative. In Nigeria, herbs, like Ocimum gratissimum are used to treat malaria and associated fevers. Hence, this study evaluated the qualitative phytochemical constituents, toxicity, and antimalarial properties of O. gratissimum with its capacity to resolve the malarial-induced disturbances in lungs. The curative murine models and standard methods were adopted for the study. Results indicates that Plasmodium berghei (NK65) malarial parasite induced biochemical derangement in lungs of experimental adult male BALB/c mice, traceable to free radical-elicited lipid peroxidation of lung’s membrane, occasioned by the down regulation of the tissue’s Nuclear Factor Erythroid 2 Related Factor (Nrf2) as evidenced by its immunohistochemical expression. However, the ethanol extract of O. gratissimum (EEOg) was observed to be non-toxic with rich medicinal antimalarial phytochemicals capable of curing malaria and combating the associated lung complications by stimulating the expression of Nrf2 in lung tissue which enhanced the level of reduced glutathione (GSH) and activities of superoxide dismutase (SOD) and catalase antioxidants in the lungs of malarial infected mice treated with EEOg (125, 250, 500 mg/kg) and standard drug Artemether-lumefantrine (LDS). Our computational study identified eugenol as the most active compound with drug-likeness property which strongly inhibited Plasmodium falciparum lactate dehydrogenase (PfLDH), and modulated Keap1-Nrf2/p62 pathway. These properties indicate that eugenol is a potential antimalarial and antioxidant compound which could be optimized for enhanced performance as potent antimalarial agent, capable of resolving the associated lung impairments and oxidative stress.