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Urtica dioica leaves modulates muscarinic cholinergic system in the hippocampus of streptozotocin-induced diabetic mice

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Abstract

Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.

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Acknowledgments

Authors would like to thank Council of Scientific & Industrial Research (India) for financial assistance as Senior Research Fellowship (09/957/0002/2012/EMR-I).

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The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, 173234, Himachal Pradesh, India

    Sita Sharan Patel, Arun Parashar & Malairaman Udayabanu

  2. Department of Pharmacology, Lakshmi Narain College of Pharmacy, Bhopal, 462021, Madhya Pradesh, India

    Sita Sharan Patel

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  1. Sita Sharan Patel
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  2. Arun Parashar
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Correspondence to Malairaman Udayabanu.

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Suppl. 1

Effect of Urtica dioica extract on streptozotocin-induced alteration in fasting blood glucose level. Data were mean ± SEM values. Significant difference: *CTRL vs STZ, αSTZ vs UD50, βSTZ vs ROSI. *p < 0.05, ***p < 0.001. Reprinted from (Patel and Udayabanu 2013), Copyright © 2014, with permission from Elsevier. (PPTX 71 kb)

Suppl. 2

Effect of hydroalcoholic extract of Urtica dioica on streptozotocin induced memory dysfunction in Morris water maze learning trial (a), probe trial (b) and Passive avoidance step through task (c). Data were mean ± SEM values. Significant differences: *CTRL vs STZ, αSTZ vs UD50, βSTZ vs ROSI. *p < 0.05, **p < 0.01, ***p < 0.001. Reprinted from (Patel and Udayabanu 2013), Copyright © 2014, with permission from Elsevier. (PPTX 89 kb)

Suppl. 3

Effect of UD extract on diabetes mediated alterations in the relative OD of (M1) AchR mRNA in striatum (a) and (M4) AchR mRNA expression in hippocampus (b). Data were mean ± SEM values (n = 5). (PPTX 93 kb)

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Patel, S.S., Parashar, A. & Udayabanu, M. Urtica dioica leaves modulates muscarinic cholinergic system in the hippocampus of streptozotocin-induced diabetic mice. Metab Brain Dis 30, 803–811 (2015). https://doi.org/10.1007/s11011-014-9646-9

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