Proanthocyanidins combined with piperine improved depression and anxiety-like behavior of chronic stress mice through serotonin receptor pathway
LI Ru1, YU Wenpiao2, GUO Wei3, LOU Yongliang4
1.The Laboratory of Animal Central, Wenzhou Medical University, Wenzhou 325035, China; 2.The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou 325035, China; 3.State Key Laboratory of Optometry and Vision Science, Wenzhou Medical University, Wenzhou 325027, China; 4.School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China
LI Ru,YU Wenpiao,GUO Wei, et al. Proanthocyanidins combined with piperine improved depression and anxiety-like behavior of chronic stress mice through serotonin receptor pathway[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(7): 517-523.
Abstract：Objective: To investigate the anti-depressant and anti-anxiety effect of OPC combined with PIP on chronic unpredictable mild stress (CUMS) mice and to study the mechanism by analyzing the receptor of 5-HT1A in hippocampus, pre-frontal cortex and hypothalamus. Methods: The mice were divided into eight groups: Control group, CUMS group, CUMS+PIP 5 mg/kg+OPC (12.5, 25, 50 mg/kg) group, CUMS+PIP (5 mg/kg)+ OPC (50 mg/kg)+NAN-190 (0.1 mg/kg) group, CUMS+NAN-190 (0.1 mg/kg) group and CUMS+fluoxetine (10 mg/kg). After 21 days of chronic unpredicted mild stress, all mice were subjected to the forced swimming test, tail suspension test, novel food inhibition test and marble bury test to evaluate the depression- and anxiety-like behaviors. Then, we used high performance liquid chromatography method to detect the concentration of monoamine (5-HT, NE and DA) in the hippocampus, pre-frontal cortex and hypothalamus. Results: Compared with control group, the immobility time of forced swimming test and tail suspension test was significantly increased in CUMS group (P<0.01) and the latency to feed of CUMS in the novelty suppressed feeding also significantly increased (P<0.05). Meanwhile, the number of marbles buried of CUMS in the marble bury test obviously elevated (P<0.05, P<0.01). Given of OPC (25, 50 mg/kg) combined with PIP (5 mg/kg) improved the depression and anxiety behavior induced by CUMS (P<0.05, P<0.01). Using the HPLC method we found that OPC (25, 50 mg/kg) combined with PIP (5 mg/kg) significantly reversed the 5-HT level caused by CUMS in hippocampus, pre-frontal cortex and hypothalamus (P<0.05, P<0.01, P<0.001), however, there was no significant effect on NE and DA in the hippocampus, pre-frontal cortex and hypothalamus. Pretreatment with the 5-HT1A receptor antagonist NAN-190 prevented the improvement (P<0.05, P<0.01, P<0.001). Conclusion: OPC combined with PIP has improved the antidepressant- and anxiety-like behavior in CUMS mice probably by activating 5-HT1A receptor in the central nervous system.
