title: Urtica dioica leaves modulates hippocampal smoothened-glioma associated oncogene-1 pathway and cognitive dysfunction in chronically stressed mice.
abstract: 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 (25-30g) were divided into six groups, viz. group-I received 0.3% carboxymethyl cellulose and served as control (CTRL), group II was exposed to CUS (21days) and received vehicle (CUS), group III was subjected to CUS and received Hypericum perforatum extract (350mg/kg, p.o.) (CUS+HYP), group IV received Hypericum perforatum extract (350mg/kg, p.o.) (CTRL+HYP); group V was subjected to CUS and received UD extract (50mg/kg, p.o.) (CUS+UD), group VI received UD extract (50mg/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.
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, 173234, Himachal Pradesh, India.
authors.forename: Sita Sharan
authors.initials: SS
authors.lastname: Patel
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, 173234, Himachal Pradesh, India; School of Pharmaceutical Sciences, Shoolini University, Solan, 173229, Himachal Pradesh, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Mahindroo
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, 173234, Himachal Pradesh, India. Electronic address: m_udayabanu@rediffmail.com.
authors.forename: Malairaman
authors.initials: M
authors.lastname: Udayabanu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D060825:Cognitive Dysfunction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects; D015538:Nitrosation; D018384:Oxidative Stress / Q000187:drug effects; D064209:Phytochemicals / Q000032:analysis / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry*; D012015:Reference Standards; D015398:Signal Transduction / Q000187:drug effects; D000072086:Smoothened Receptor / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D026982:Urtica dioica / Q000737:chemistry*; D015431:Weight Loss / Q000187:drug effects; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism*
chemical_list: C498520:Gli1 protein, mouse; D064209:Phytochemicals; D010936:Plant Extracts; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1
keywords: Chronic stress; Cognition; Hypericum perforatum; Sonic hedgehog; Urtica dioica