Protective mechanisms of loquat leaf extract and ursolic acid against diabetic pro-inflammation

J Mol Med (Berl). 2022 Aug 13. doi: 10.1007/s00109-022-02243-x. Online ahead of print.ABSTRACTThe pharmacological effectiveness of loquat leaf extract (LE) and its important component, ursolic acid (UA), in the treatment of diabetes mellitus, has been well established in traditional medicine; however, the mechanism underlying their action is still unclear. We evaluated the protective effects of LE and UA against hyperglycemia-induced advanced glycation end product (AGE) formations and hepatic pro-inflammation. Oral administration of UA and LE at a dose of 50 mg/kg/day for 15 days yielded no significant hypoglycemic effect in diabetic db/db mice. UA and LE suppressed hepatic oxidative stress and AGE formation in diabetic mice, and this was followed by the downregulated mitogen-activated protein kinase signaling and nuclear factor κ B (NF-κB) activity. To identify the molecular target of LE and UA, a docking simulation was performed, and this predicted UA to bind to liver kinase B1 (LKB1), an upstream of AMP-activated protein kinase (AMPK)/transcription factor forkhead box O3 (FOXO3) axis. UA reversed the high-glucose-induced downregulation of LKB1-AMPK1-FOXO3 activation and antioxidant gene transcription. These findings demonstrated the antioxidant and anti-inflammatory effects of UA and LE against hyperglycemia-induced hepatic inflammation. Furthermore, we speculate that the LKB1/AMPK/FOXO3 pathway is a potential target responsible for these beneficial effects of LE and UA....
Source: Molecular Medicine - Category: Molecular Biology Authors: Source Type: research