title: Effect of crude extract of Eugenia jambolana Lam. on human cytochrome P450 enzymes.
abstract: The fruit of Eugenia jambolana Lam. is very popular for its anti-diabetic property. Previous studies on the crude extract of E. jambolana (EJE) have successfully explored the scientific basis for some of its traditional medicinal uses. Considering its wide use and consumption as a seasonal fruit, the present study investigates the ability of E. jambolana to interact with cytochrome P450 enzymes. The standardized EJE was incubated with pooled human liver microsomes to assess the CYP2C9-, CYP2D6-, and CYP3A4-mediated metabolism of diclofenac, dextromethorphan, and testosterone, respectively. The metabolites formed after the enzymatic reactions were quantified by high performance liquid chromatography. EJE showed differential effect on cytochrome P450 activities with an order of inhibitory potential as CYP2C9 > CYP3A4 > CYP2D6 having IC50 of 76.69, 359.02, and 493.05 µg/mL, respectively. The selectivity of EJE for CYP2C9 rather than CYP3A4 and CYP2D6 led to perform the enzyme kinetics to explicate the mechanism underlying the inhibition of CYP2C9-mediated diclofenac 4'-hydroxylation. EJE was notably potent in inhibiting the reaction in a non-competitive manner with Ki of 84.85 ± 5.27 µg/mL. The results revealed the CYP2C9 inhibitory potential of EJE with lower Ki value suggesting that EJE should be examined for its potential pharmacokinetic and pharmacodynamic interactions when concomitantly administered with other drugs.
authors.affiliation: Department of Pharmacology, JSS College of Pharmacy, Udhagamandalam, Tamil Nadu, India.
authors.forename: Santhivardhan
authors.initials: S
authors.lastname: Chinni
authors.forename: Anil
authors.initials: A
authors.lastname: Dubala
authors.forename: Jayasankar
authors.initials: J
authors.lastname: Kosaraju
authors.forename: Rizwan Basha
authors.initials: RB
authors.lastname: Khatwal
authors.forename: M N
authors.initials: MN
authors.lastname: Satish Kumar
authors.forename: Elango
authors.initials: E
authors.lastname: Kannan
mesh_terms: D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004610:Ellagic Acid / Q000032:analysis; D005638:Fruit / Q000737:chemistry; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000032:analysis; D027842:Syzygium / Q000737:chemistry*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D059808:Polyphenols; D004610:Ellagic Acid; D003577:Cytochrome P-450 Enzyme System
keywords: Eugenia jambolana; Syzygium cumini; cytochrome P450; enzyme kinetics; herb-drug interactions; human liver microsomes