Preclinical Evaluation of Neuroprotective Effects of Terpenes Terpenoids and Stilbenoids in Ischemia Disease

Abstract

Cerebral ischemia is one of the major concerns of the 21st century. Post-ischemic disability is a burden to society. New leads with neuroprotective activity could provide a beneficial role during post-ischemic conditions. Further, new leads with plant origin could play an important role in this path because of their fewer side effects and availability in nature. Studies have demonstrated many molecular targets for cerebral ischemia. JNK3 is a neural-specific kinase with a distressing role in cerebral ischemia. Targeting this enzyme could be beneficial in cerebral ischemia with lower non-CNS effect due to its neuronal specificity. During our study, we observed that piceatannol, which is a stilbenoid, significantly inhibited JNK3 enzyme and produced neuroprotective activity and improved the pathological condition of cerebral ischemia both in in-vitro and in-vivo. Kinases have long been a target for neuroprotection, and due to its neural specificity, we have targeted c-jun N-terminal kinase 3 (JNK3). Previous studies have shown that inhibition of JNK3 could potentiate the neuroprotective effect in ischemic diseases. The objective of the present study was the development of a lead that could probably provide neuroprotection after an ischemic insult. Plant sources have been exploited for many years for therapeutic purposes due to their lesser side-effects and availability in nature. Terpenoids and stilbenoids are naturally occurring organic compounds that have been explored for their traditional and therapeutic uses. Many terpenoids and stilbenoids have also shown neuroprotective activity in in-vitro and in-vivo. In the present study, we have virtually screened a library od terpenoids and stilbenoids against JNK3. This suggests that piceatannol treatment could potentiate the production of eNOS and at the same time, inhibit the activity of iNOS after an ischemic insult. Hence study can be concluded that piceatannol produces neuroprotection by preventing phosphorylation of JNK3 and interfering with the mitochondrial apoptosis pathway.