In silico analysis of antihypertensive and hepatotoxicity potential of the n-butanol fraction of the methanol extract of of cantaloupe (Cucumis melo var. cantalupensis)

Abstract Background: Hypertension is a major cardiovascular disease risk factor. Indonesian people tend to consume herbal medicine to maintain hypertension therapy, i.e cantaloupe (Cucumis melo var. cantalupensis). However, the mechanism of action of cantaloupe in lowering blood pressure and toxicity potential for long term consumption is unclear. The study aimed to analyze the antihypertensive mechanism of cantaloupe and its toxic potential through the in silico. Methods: The dried cantaloupe powder was macerated using absolute methanol, then fractionated using n-butanol. The phytochemical test was done by LC-MS method, then the bioactive compounds were traced to their SMILES in the PubChem. The QSAR analysis of the antihypertensive potential was done using the PASS server. The toxicity class and hepatotoxicity potential were analyzed using ProTox-II, followed by networking analysis using STITCH and STRINGdb. Results: At least 434 types of compounds were shown in the n-butanol fraction of the methanol extract of cantaloupe (BFMEC). Based on the networking analysis, BFMEC may work in lowering blood pressure through the action mechanism of the amlodipine compound-like, which stabilizes voltage-gated L-type calcium channels in an inactive conformation, thus, prevents calcium-dependent myocyte contraction and vasoconstriction. BFMEC presumably has hepatotoxic through the action mechanism of itraconazole compound-like inhibited cytochrome P450-dependent enzymes, affecting the impairment of ergosterol synthesis, and efavirenz which has neurotoxic effects. The inhibition of cytochrome P450 may cause drug toxicity and liver damage. Conclusion: BFMEC may work in lowering blood pressure through the action mechanism which stabilizes voltage-gated L-type calcium channels in an inactive conformation