Garcinia mangostana and α-Mangostin Revive Ulcerative Colitis-Modified Hepatic Cytochrome P450 Profiles in Mice

Naroeporn Nopwinyoowong, Waranya Chatuphonprasert, Nitima Tatiya-aphiradee and Kanokwan Jarukamjorn

Background and Objective: Ulcerative colitis (UC) is inflammation of the large intestine with ulceration but can also cause extraintestinal manifestations (EIM) by damaging surrounding organs such as the liver. Garcinia mangostana (GM) pericarp and α-mangostin (MGS) have been reported to have anti-inflammatory activity. This study evaluated the effects of GM pericarp extract and MGS on the expression of hepatic cytochrome P450 (CYP) enzymes as an EIM of UC. Materials and Methods: Male ICR mice were orally administered GM pericarp extract (40, 200 and 1000 mg/kg/day), MGS (30 mg/kg/day) or sulfasalazine (SUL) (100 mg/kg/day) daily for 7 days. On days 4-7, UC was induced by dextran sulfate sodium (DSS 40 kDa, 6 g/kg/day). Profiles of CYP mRNA expression were determined by RT/qPCR. Alkoxyresorufin O-dealkylation (including ethoxy-, methoxy-, pentoxy- and benzyloxy-resorufin), aniline hydroxylation and erythromycin N-demethylation CYP responsive activities were also examined. Results: The DSS-induced UC mice showed suppressed expression of Cyp1a1, Cyp1a2, Cyp2b9/10, Cyp2e1, Cyp2c29, Cyp2d9, Cyp3a11 and Cyp3a13 mRNAs. The GM pericarp extract and MGS restored expression of all investigated CYPs and their responsive enzyme activities in DSS-induced UC mice to levels comparable to the control and parallel to the effects of the anti-inflammatory control SUL. Conclusion: The GM is a promising therapy to restore UC-modified hepatic CYP profiles.

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