Protective effects of tetrahydropalmatine against ketamine-induced learning and memory injury via antioxidative, anti-inflammatory and anti-apoptotic mechanisms in mice.

Summary

Tetrahydropalmatine, a compound with known analgesic and other pharmacological effects, protected against ketamine-induced learning and memory impairment in mice. In the Morris water maze and open field tests, tetrahydropalmatine treatment reduced escape latency and increased platform site crossings. It also lowered oxidative stress, inflammation, and acetylcholinesterase activity, and decreased acetylcholine levels. The treatment suppressed iNOS, caspase-3, caspase-9, nuclear factor-κB, glial fibrillary acidic protein, cytochrome c, and phospholipase C-γ1 protein expression, while increasing glial cell-derived neurotrophic factor. These findings suggest tetrahydropalmatine may counteract ketamine's cognitive side effects through antioxidative, anti-inflammatory, and anti-apoptotic mechanisms.

Study at a glance

Abstract

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 ketamine‑induced 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, caspease‑3 and caspase‑9, iNOS, glial fibrillary acidic protein (GFAP), glial cell‑derived neurotrophic factor (GDNF), cytochrome c and phospholipase C (PLC)‑γ1 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 ketamine‑induced mice. In addition, tetrahydropalmatine significantly inhibited oxidative stress, inflammation and acetylcholinesterase activity, and decreased acetylcholine levels in ketamine‑induced mice. Tetrahydropalmatine also suppressed iNOS protein expression, weakened caspase‑3 and caspase‑9 activation, inhibited nuclear factor‑κB, glial fibrillary acidic protein, cytochrome c and phospholipase C‑γ1 protein expression, and induced glial cell‑derived neurotrophic factor protein expression in ketamine‑induced mice. Taken together, these results indicated that tetrahydropalmatine may protect against ketamine‑induced learning and memory impairment in mice via antioxidative, anti‑inflammatory and anti‑apoptotic 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.