Unravelling therapeutic potentials of Solanum anomalum fruits: antiplasmodial, hepatoprotective, and anti-oxidative stress activities, semi-purification, GC-MS, and in silico profiling.

Background: The high prevalence rate of malaria due to the proliferation of drug-resistant strains of Plasmodium falciparum could mitigate the realization of sustainable development goals in Nigeria, necessitating research on the discovery of novel chemotherapies against resistant strains of the parasite. However, Solanum anomalum with ethnopharmacological claims could foster this breakthrough, prompting an investigation on the antiplasmodial and hepatoprotective activities of the plant's fruit, semi-purification and characterization of its constituents, as well as in silico studies on its compounds.

Methods: Standard protocols were employed for the semi-purification and characterization; evaluation of antiplasmodial and hepatoprotective assays; retrieval of target proteins from PDB, ADMET, and docking studies. Column and thin layer chromatography and GC-MS aided the semi-purification and characterization of compounds; PKCSM and ADMET Lab 2 enhanced the evaluation of pharmacokinetic properties; AutoDock Vina and PyRx for docking analysis; and Biovia Discovery Studio and PyMol software for the visualization of interactions.

Results: The n-hexane extract (20 g) (with the best antiplasmodial therapeutic index) undergone chromatographic analyses and yielded bulked column fractions (A-H); fraction A (1459 mg) was further semi-purified to column sub-fractions A3 (18 mg), A4 (27 mg), and A9 (14 mg); their GC-MS analyses revealed 5-cyano-3-methyoxymethylene cholestane; morphinan-6,10-diol; phthalic acid; protocatechic acid, etc. In silico studies revealed the above lead compounds with better binding affinities to chloroquine, non-inhibition of mono-oxygenases, ease of excretion, non-carcinogenicity, as well as non-violation of Lipinski's criteria. Moreover, the mice's treatment caused increases in SOD, CAT, GPx, and GSH but decreased in MDA, ALT, AST, and ALP, total and conjugated bilirubin levels, with little pathological changes in the liver's histological section that contrasted the evidence in the negative control group.

Conclusion: The lead compounds were responsible for Solanum anomalum fruit's antiplasmodial, antioxidative stress, and hepatoprotective activities through the inhibition of DHFR, PfEMP-1, and plasmepsin X activities.