ENTADA PHASEOLOIDES ATTENUATES SCOPOLAMINE INDUCED MEMORY IMPAIRMENT, NEURO-INFLAMMATION AND NEURO-DEGENERATION VIA BDNF/TRKB/NFΚB P65 PATHWAY IN RADIAL ARM MAZE

Objective: The present study investigates the protective effects of crude extract from seeds of Entada phaseoloides and isolated compounds in enhancing cognition in Scopolamine induced learning and memory impairments in the radial arm maze model.Methods: Two doses (100 and 200 mg/kg) of the crude methanolic extract of Entada phaseoloides (MEEP) were evaluated for amnesic activity by Radial Arm Maze memory model. Scopolamine (0.4 mg/kg i. p.), an amnestic drug was used for impairing memory. Tacrine (3 mg/kg, i. p.) was used as the standard drug. Animals were sacrificed to evaluate biochemical parameters viz. lipid peroxidase (LPO), nitrite oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), cytokine levels by ELISA, Catecholamine levels by high performance liquid chromatography (HPLC), Caspase-3 activity by Fluorogenic assay, Gene (BDNF, TrkB, NF-κB p65, BAX) expression studies by Western Blotting and AChE, α7nAchR, Caspase-3, Nrf2 and HO-1 by Reverse Transcriptase Polymerase Chain Reaction.Results: Treatment with MEEP significantly decreases escape latency and reference memory error (RME). MEEP treatment reversed the Scopolamine-induced hyperactivation of Acetylcholinesterase activity and overexpression of proteins NF-κB p65 BAX and also Caspase-3 activity in the hippocampus of rats. The level of BDNF, TrkB and α7nAchR were significantly up-regulated and AChE, Caspase-3, Nrf2, HO-1 were down-regulated in the MEEP treated rat. The extract increased the activity of SOD, GSH, Catalase, 5-HT, NE, Dopamine and decreased the levels of LPO and NO in rat hippocampus. Different active components of the seeds have been isolated.Conclusion: These results indicated that seeds of Entada phaseoloides might become a promising therapeutic agent for the treatment of cognitive dysfunction in addition to its already established medicinal properties

Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like behaviours in mice by modulating neuroinflammation and monoamine neurotransmitters in the hippocampus

Context: Depression is an inflammatory, commonly occurring and lethal psychiatric disorder having high lifetime prevalence. Zanthoxylum alatum Roxb. (Rutaceae), commonly called Timur, has high medicinal value and is used ethnomedicinally for the treatment of various diseases. Objective: To evaluate the effect of hexane extract of Z. alatum seeds (ZAHE) on lipopolysaccharide (LPS)-induced depression-like behaviour in Swiss albino mice. Materials and methods: Mice were treated with ZAHE (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) for 14 days. On 14th day of the treatment, depression-like behaviour was induced by LPS (0.83 mg/kg injected i.p.) and after 24 h of LPS administration, it was assessed by measuring behavioural parameters and biochemical estimations. Results: Behavioural tests, including the open field test, forced swimming test, tail suspension test and sucrose preference test revealed that ZAHE (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) alleviated the depression symptoms of LPS-induced mice. Moreover, ZAHE treatments reversed the LPS-induced alterations in the concentrations of norepinephrine and serotonin (5-HT) and inhibited the expression of brain-derived neurotrophic factor, pro-inflammatory cytokines and oxido-nitrosative stress in the mice. Acute toxicity was calculated to be LD50 > 2500 mg/kg. Discussion and conclusions: This study showed that LPS-induced depression in mice was significantly prevented by ZAHE at both the dosages. In conclusion, ZAHE exhibited an antidepressant activity by altering monoaminergic neurotransmitters in the brain combined with its anti-inflammatory potential. Thus, it could be an effective therapeutic against inflammation-induced depression and other brain disorders