Zhang_2018_Mol.Med.Rep_17_6873

Tetrahydropalmatine exerts numerous pharmacological activities, including analgesic and narcotic effects; anti-arrhythmic, blood pressure lowering and cardioprotective effects; protective effects against cerebral ischemia-reperfusion injury; inhibition of platelet aggregation; prevention of ulcerative diseases and inhibition of gastric acid secretion; antitumor effects; and beneficial effects on the withdrawal symptoms associated with drug addiction. The present study aimed to investigate the protective effects of tetrahydropalmatine against ketamineinduced learning and memory impairment in mice. The Morris water maze test and open field test were used to analyzed learning and memory impairment in mice. ELISA kits and western blotting were used to analyze oxidative stress, inflammation factors, caspease3 and caspase9, iNOS, glial fibrillary acidic protein (GFAP), glial cellderived neurotrophic factor (GDNF), cytochrome c and phospholipase C (PLC)gamma1 protein expression. The results demonstrated that tetrahydropalmatine treatment significantly decreased escape latency in the learning phase and increased the number of platform site crossings in ketamineinduced mice. In addition, tetrahydropalmatine significantly inhibited oxidative stress, inflammation and acetylcholinesterase activity, and decreased acetylcholine levels in ketamineinduced mice. Tetrahydropalmatine also suppressed iNOS protein expression, weakened caspase3 and caspase9 activation, inhibited nuclear factorkappaB, glial fibrillary acidic protein, cytochrome c and phospholipase Cgamma1 protein expression, and induced glial cellderived neurotrophic factor protein expression in ketamineinduced mice. Taken together, these results indicated that tetrahydropalmatine may protect against ketamineinduced learning and memory impairment in mice via antioxidative, antiinflammatory and antiapoptotic mechanisms. The present study provided an experimental basis for the clinical application of tetrahydropalmatine to reduce the severe side effects associated with ketamine therapy in future studies.