Identification of Putative Toxicophores in Annona muricata Phytochemical and their Hepatotoxic Potential

Abstract BACKGROUND: Traditional herbal medicine is popular in Southeast and East Asia, particularly in the Philippines. Among the most widely utilized herbal remedies in this region is soursop or Annona muricata . Soursop is known for its numerous therapeutic properties, including anti-inflammatory, antiparasitic, antipyretic, antibacterial, and even anticancer activities. However, the wide availability and affordability of soursop, coupled with its promising medicinal properties, may lead to potential misuse or overuse, particularly among terminally ill patients. We hypothesize that the phytochemicals in the fruit pulp of A. muricata , which contain toxicophores, may contribute to its potential hepatotoxic effects. This study aims to explore whether A. muricata exhibits hepatotoxic properties. MATERIALS AND METHODS: A comprehensive literature search was conducted to identify the phytochemicals present in the fruit pulp of A. muricata . The potential toxicophores of these identified phytochemicals were then assessed through in silico analysis. Furthermore, molecular docking studies were performed to evaluate the binding affinity of each phytochemical with various hepatic enzymes. RESULTS: Our findings show that approximately half of the identified phytochemicals were predicted to possess hepatotoxic properties, potentially impairing liver function. Phytochemicals identified with toxic substructures include 2-methoxyphenol, 2,4,5-trimethoxybenzoic acid, chromocor, 2-isopropyl-3-phenyl, 4-oxide quinoxaline, 9-octadecen-12-ynoic acid methyl ester, 5-methyl-2 (3H)-furanone, tributyl aconitate, butyl citrate, tributyl acetyl citrate, 4-hydroxy-beta-ionone, and 1,2-diiodoethane. However, only six of these phytochemicals demonstrated high binding affinities with gamma-glutamyl transferase, CYP3A4, and CYP2D6, with most also showing high absorbability. CONCLUSION: These results suggest that the potential hepatotoxicity of soursop may be linked to altered drug metabolism and reduced glutathione biosynthesis. Consequently, the consumption of A. muricata should be regulated until further in vitro and in vivo studies provide conclusive evidence to the contrary.