The role of Indonesianin-5 in HMG CoA reductase and sterol regulatory element binding protein-2 expressions of hypercholesterolemic rat

Increased cholesterol level increases the risk of heart disease and stroke. Sterol Regulatory Element Binding Protein-2 (SREBP-2) is a transcription factor for the synthesis of cholesterol genes. SREBP-2 can induce the expression of HMG CoA Reductase (HMGR). HMGR is a key cholesterol synthesis enzyme. Indonesianin-5, derived from Mahogany seeds (Swietenia macrophylla K), is a flavonoid. Indonesianin-5 is known to have a hypocholesterolemic effect. This study aimed to analyze the mechanism of Indonesianin-5 to decrease LDL and cholesterol levels and the expression of hepatic SREBP-2 and HMGR. Rattus norvegicus were grouped into 5 groups: normal group (N), Hypercholesterolemia group (HC), Hypercholesterolemic groups given simvastatin (HC+Sim), 10 mg of Indonesianin-5 (HC+ 10 Ind-5) and 90 mg of Indonesianin-5 (HC+ 90 Ind-5). In silico analysis was used to determine the effects of Indonesianin-5. The expressions of SREBP-2 and HMGR were analyzed by the RT-PCR method. Indonesianin-5 inhibited the activity of the HMGR enzyme. Expression of SREBP-2 was high after induction of Indonesianin-5 (p<0.05). The expression of HMGR was high after induction of Indonesianin-5 (p<0.05). Indonesianis-5 inhibits HMG CoA reductase and increases gene expression of SREBP-2 and HMG CoA reductase.