Tannins from Terminalia chebula fruits attenuates GABA antagonist-induced anxiety-like behaviour via modulation of neurotransmitters

Abstract

Abstract Objectives This article investigates the anxiolytic activity of Terminalia chebula tannin-rich extract against picrotoxin (PTX; GABA antagonist)-induced anxiety in mice model. Methods Anxiolytic activity was studied by elevated plus maze (EPM), open field test (OFT), light/dark box test (LDT) and Vogel's conflict test (VCT). Electroencephalogram (EEG) was performed to know the changes in brain activity instigated by GABA antagonist. 5-hydroxytryptamine (5-HT), dopamine and norepinephrine levels in brain tissues were estimated by HPLC. The mRNA (CREB, BDNF, GABA, and 5-HT1A) and protein expression (CREB, p-CREB, BDNF, ERK ½, p-ERK ½, GABAARα1, 5-HT1A and GAPDH) levels in brain tissue were determined by RT-PCR and Western blot analysis, respectively. Key findings Terminalia chebula tannin-rich extract (TCHE) supplementation increased locomotion in mice towards open arm (EPM), time spent in illuminated area (LDT), rearing frequency (OFT) and number of shocks (VCT) compared to PTX (P < 0.05). Furthermore, TCHE down-regulated serum cortisol levels and showed increased levels of 5-HT, DA and NE. Gene expressions such as BDNF, CREB, GABAA and 5-HT1A were up-regulated by TCHE treatment compared to PTX. Conclusions Terminalia chebula tannin-rich extract showed significant anxiolytic activity against picrotoxin and could be used as natural therapy in neurodegenerative disorders.