Nephroprotection of Garcinia mangostana Pericarp Extract and α-Mangostin Against Oxidative Stress in Renal Manifestation of Ulcerative Colitis in Mice

Abstract

Garcinia mangostana (GM) pericarp is an herbal medicine in the Thailand National Essential Drug List. GM pericarp and its major active constituent α-mangostin (MGS) exhibit several pharmacological properties, including anti-oxidative activity. Ulcerative colitis (UC) is the consequence of prolonged oxidative stress and inflammation in the large intestine and can result in extraintestinal manifestations (EIM) in other organs. This study evaluated the impact of GM pericarp extract and MGS on oxidant-antioxidant status in the kidneys of UC-induced mice. Six-week-old ICR mice were administered orally GM pericarp extract (40, 200, and 1,000 mg kg-1 ), MGS (30 mg kg-1 ), or sulfasalazine (100 mg kg-1 ) for 7 consecutive days. UC was induced by administering dextran sulfate sodium (40 kDa; 6 g kg-1) on days 4-7. Kidneys were collected to determine the activity and expression of the catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) antioxidant enzymes, lipid peroxidation levels, and glutathione stores. UC induction suppressed expression of Cat, CuZn-Sod, Mn-Sod, and Gpx mRNAs and reduced CAT, SOD, and GPx activities in the kidneys, which was followed by  an increase in lipid peroxidation. Total GSH and reduced GSH contents decreased, while oxidized GSSG content increased, reducing the GSH/GSSG ratio in the kidneys. GM and MGS improved the oxidative status of the kidneys similar to sulfasalazine by restoring the expression and activity of the antioxidant enzymes and balancing the glutathione stores. GM and MGS are promising nephroprotective antioxidant treatments and are worthy of development as alternative medicines for renal EIMs of UC.