Computational and experimental analysis of oleanolic acid as an allosteric activator of SIRT1

Sirtuin 1 (SIRT1) is a member of the sirtuin protein family and the biological effects of SIRT1 encompass various areas such as the ageing process, metabolism regulation, and cellular stress response. SIRT1 activators are compounds that enhance the activity of SIRT1 enzyme. These activators can be natural or synthetic compounds and have the potential to provide health benefits by augmenting the biological effects of SIRT1. Oleanolic acid (OA) is a triterpenoid compound that has antiinflammatory, antioxidant, and glucose and lipid metabolism-regulating properties naturally found in many plants. The aim of the present study was to investigate the effect of OA on SIRT1 activation and its underlying mechanism. SIRT1 activity was determined by ELISA in rat serum and liver and kidney tissue. SIRT1 activity was significantly higher in the OA-treated rats compared to the control group. Moreover, through the use of computational methods, the study examined the potential of OA as an allosteric compound for SIRT1. The findings revealed that OA demonstrated a greater affinity for the allosteric site than resveratrol did and may lead to a similar increase in SIRT1 activity. The findings of both experimental and computational studies were complementary, which led to the conclusion that OA serves as a positive regulator of SIRT1 activity.