Adaptogenic potential of ginsenosides against domoic acid-induced toxicity by regulating neuronal stress and kinate receptors: Ex vivo and in silico studies.

This study is focused on potential effects of ginsenosides from Panax ginseng (PG) against amnesic shell fish poison, that is, domoic acid-induced excitotoxicity. Mice received PG at two different dosages by oral feeding for a period of 28 days (50 and 100 mg kg-1 bwt.-1 ). Domoic acid was injected to the mice to induce excitotoxicity (DA; 3 mg kg-1  bwt.-1 ) and piracetam-injected animals (PIR; 100 mg kg-1  bwt.-1 ) were treated as positive control. DA-induced cognitive impairment was reverted by PG supplementation, which was observed in Morris water maze and novel object task. Moreover, PG supplementation restored levels of GABA and antioxidant enzymes. Our results further elucidated ameliorative effects of PG supplementation on DA-induced changes in the expression of synaptic plasticity (BDNF), inflammation (NFkB), and apoptotic (Bcl2, Bax, and Caspase 3) markers. Hence, this study elucidates potential nootropic effects of ginsenosides from P. ginseng extract against DA-induced neuronal impairments via, modulation of behavioral and biochemical mechanisms involved in excitotoxicity, oxidative stress, neuro-inflammation, and apoptosis. PRACTICAL APPLICATIONS: This study highlights potential effects of ginsenosides from Panax ginseng against amnesic shell fish poison, that is, domoic acid-induced excitotoxicity for the first time. This study confirms that ginsenosides have the beneficial effects against amelioration of DA-induced toxicity. This study elucidates the potential nootropic effects of P. ginseng extract against DA-induced neuronal impairments via, modulation of synaptic plasticity markers and oxido-inflammatory responses leading to apoptosis. This study will be helpful in offering various mechanisms involved in pharmacological applications of P. ginseng in the management of DA-induced excitotoxicity.

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

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, GABAA Rα1, 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.