Baicalein Neutralizes Hypercholesterolemia-Induced Aggravation of Oxidative Injury in Rats

Hypercholesterolemia is a major risk factor for several cardiovascular and metabolic diseases as it triggers oxidative and pro-inflammatory cascades. Baicalein (BL) is a natural flavone with multiple therapeutic properties. The present study aimed to evaluate the potential protective effect of BL supplementation in hypercholesterolaemic rats. Rats were fed a high-cholesterol diet (HCD) for six weeks and then orally administered BL at two doses (25 and 50 mg/kg body weight/day) for four weeks. Serum lipids, liver enzymes, cardiac enzymes, renal markers, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), interleukin-10 (IL-10), caspase-3, nitric oxide (NO) and prostaglandin-2 (PGE-2) were measured. In renal, hepatic, and cardiac tissues, thiobarbituric acid-reactive (TBARS) substance, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. The altered levels of lipoproteins, aminotransferases, creatine kinases, and urea in hypercholesterolemic animals were significantly corrected by BL. Inflammatory and apoptotic biomarkers were also markedly attenuated in the HCD group following BL treatment. Hypercholesterolemia considerably induced the lipid peroxidation product, TBARS, and oxidative radicals in cardiac, hepatic, and renal tissues, which were attenuated by BL treatment, particularly, at the 50 mg/kg/day dose. BL enhanced the activities of superoxide dismutase, catalase, and glutathione peroxidase that were suppressed by HCD. Histological alterations induced by cholesterol overload in cardiac, hepatic, and renal tissues were ameliorated by BL supplementation. Our results show that the BL treatments (25 and 50 mg/kg/day) to HCD fed rats improved all the altered parameters. These results demonstrate that BL treatment improves cardiac, renal and hepatic dysfunctions in hypercholesterolaemic rats by activation of cellular antioxidant enzymes and/or suppression of inflammatory cytokines.