Genipin protects against cerebral ischemia-reperfusion injury. - GreenMedInfo Summary
Genipin protects against cerebral ischemia-reperfusion injury by regulating the UCP2-SIRT3 signaling pathway.
Eur J Pharmacol. 2019 Feb 15 ;845:56-64. Epub 2018 Dec 21. PMID: 30582911
Cerebral ischemia-reperfusion injury is a thorny issue in the treatment of stroke. Energy depletion and oxidative stress are the core mechanisms underlying cerebral ischemia-reperfusion injury. Mitochondrial function is involved in energy production and oxidative stress. It has been reported that mitochondrial uncoupling protein 2 (UCP2) may be involved in the regulation of cerebral ischemia-reperfusion injury. We hypothesized that UCP2 can regulate cerebral ischemia-reperfusion injury by regulating energy supply and oxidative stress. To test this hypothesis, we used a middle cerebral artery occlusion model in male C57BL/6 mice with/without genipin--an UCP2-specific inhibitor. We measured the expression and/or activity of UCP2, SIRT3, the level of ATP, and antioxidant-related molecules in the cerebral cortex and the LDH in serum after ischemia-reperfusion, the level of apoptosis was reflected by the level of cleaved-caspase3 and tunel staining. The results showed an increase in the expression of UCP2, coinciding with an increase in the level of apoptosis, NAD/NADH ratio, SIRT3 activity, LDH release and a decrease in the level of ATP and antioxidant-related molecules after 1 h of ischemia and 24 h of reperfusion. These findings suggest that UCP2 may regulate energy supply and oxidative stress in ischemia-reperfusion injury. Interestinly, above changes can be reserved by administration of genipin with the brain damage level going down. In conclusion, the UCP2-SIRT3signaling pathway is involved in the regulation of cerebral ischemia-reperfusion injury as a bridge between energy metabolism and oxidative stress. Genipin protects against cerebral ischemia-reperfusion injury by inhibiting UCP2.