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

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.

Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α‐Glycosidase and Cholinesterase Inhibitors

“…Clinically, it is known that diabetic patients are at higher risk of developing cognitive impairment [5] . Researchers have stated that diabetes in the central nervous system exacerbates depression, phobias, and anorexia [6–8] …”

Review of the Effect of Natural Compounds and Extracts on Neurodegeneration in Animal Models of Diabetes Mellitus

“…The expression of inflammatory TNF-α, and NF-κB genes are significantly reduced and other studies have also reported the role of grape seed extract in modulating AGEs/RAGE/NF-kappaB inflammatory pathway in the brain [114]. Urtica dioica leaves extract, rich in scopoletin, rutin, esculetin and quercetin, has also shown antioxidant and anti-inflamatory activities in the hippocampus from STZ-induced diabetic mice [115,116]. In addition, the number of astrocytes in the hippocampus from diabetic rats is reduced after treatment with Urtica dioica extract, supporting its anti-inflammatory role at different levels [117].…”

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“…Anti-inflammatory: U. dioica has been reported to increase total antioxidant capacity and reduce inflammatory stress 47 . The two most prevalent active chemical agents found in the Stinging Nettle are formic acid (methanoic acid) and histamine (1H-Imidazole-4-ethanamine; 2-(4-Imidazolyl ethylamine; 4-(2-Aminoethyl)-1H-imidazole) which function as an anti-inflammatory agent 7 .…”

“…carotenoid such as β-carotene, hydroxyl-β-carotene, lucoxanthin, lutein-epoxide and violaxanthin 30 Anti-diabetic, Anti-inflammatory, Antiapoptotic, Cytotoxic, Anticancerous 57 Seed Fatty acid-Palmitic, stearic, Oleic, Linoleic and Eicosenoic acid, Amino acid Aspartic acid, threonine, serine Essential oils-Carvacrol, carvone, napthelene, Phytol 19 Anti-diabetic, Antiinflammatory 47 Stinging hairs formic acid, histamine,serotonin 93 …”