Metabolic Activation of Myristicin and Its Role in Cellular Toxicity

• DOI: 10.1021/acs.jafc.9b00893
• Publication Date: 2019-03-26T09:38:18Z
• Authors: Xu Zhu; Yi-Kun Wang; Xiao-Nan Yang; Xue-Rong Xiao; Ting Zhang; Xiu-Wei Yang; Hong-Bo Qin; Fei Li
• Keywords: Male; 0303 health sciences; Cell Survival; Allylbenzene Derivatives; Dioxolanes; Pyrogallol; Acetylcysteine; 3. Good health; Activation, Metabolic; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Benzyl Compounds; Cytochrome P-450 CYP1A1; Hepatocytes; Animals; Humans; Cells, Cultured

Myristicin is widely distributed in spices and medicinal plants. The aim of this study was to explore the role metabolic activation myristicin its potential toxicity through a metabolomic approach. myristicin–N-acetylcysteine adduct identified by comparing maps 1′-hydroxymyristicin. supplement N-acetylcysteine could protect against cytotoxicity 1′-hydroxymyristicin primary mouse hepatocytes. When depletion intracellular pretreated with diethyl maleate hepatocytes, induced deteriorated. It suggested that resulting from bioactivation closely associated toxicity. Screening human recombinant cytochrome P450s (CYPs) treatment CYP inhibitors revealed CYP1A1 mainly involved formation Collectively, provided global view metabolism bioactivation, which be used for understanding mechanism