Urtica dioica leaves modulates hippocampal smoothened-glioma associated oncogene-1 pathway and cognitive dysfunction in chronically stressed mice

The present study was aimed to evaluate the effect of Urtica dioica (UD) extract against chronic unpredictable stress (CUS)-induced associative memory dysfunction and attempted to explore the possible mechanism. Male Swiss albino mice (25-30 g) were divided into six groups, viz. group-I received 0.3% carboxymethyl cellulose and served as control (CTRL), group II was exposed to CUS (21 days) and received vehicle (CUS), group III was subjected to CUS and received Hypericum perforatum extract (350 mg/kg, p.o.) (CUS + HYP), group IV received Hypericum perforatum extract (350 mg/kg, p.o.) (CTRL + HYP); group V was subjected to CUS and received UD extract (50 mg/kg, p.o.) (CUS + UD), group VI received UD extract (50 mg/kg, p.o.) (CTRL + UD). CUS significantly induced body weight loss (p < 0.05) and associative memory impairment in step down task (p < 0.05) as compared to control mice. CUS significantly downregulated Smo (p < 0.05), Gli1 (p < 0.01), cyclin D1 (p < 0.05), BDNF (p < 0.01), TrKB (p < 0.01) and MAPK1 (p < 0.01) mRNA expression in hippocampus as compared to control mice. CUS significantly increased the levels of TBARS (p < 0.01) and nitric oxide (p < 0.001), and decreased catalase (p < 0.001) and total thiol (p < 0.01) in plasma resulting in oxidative stress and inflammation. Chronic UD administration significantly reverted CUS mediated body weight loss (p < 0.05) and cognitive impairment (p < 0.05). UD administration significantly decreased the levels of TBARS (p < 0.01) and nitric oxide (p < 0.05), and increased the levels of catalase (p < 0.01) and total thiol (p < 0.05) in plasma. Chronic UD administration significantly upregulated hippocampal Smo (p < 0.05), Gli1 (p < 0.001), cyclin D1 (p < 0.05), BDNF (p < 0.05), TrKB (p < 0.05) and MAPK1 (p < 0.05) in stressed mice. Further, UD extract did not reverse cyclopamine induced downregulation of Gli1 and Ptch1 mRNA in hippocampal slices. UD modulated Smo-Gli1 pathway in the hippocampus as well as exerted anti-inflammatory and antioxidant effects. UD extract might prove to be effective for stress mediated neurological disorders. (C) 2016 Elsevier Masson SAS. All rights reserved.