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Effect of Urtica Dioica on Memory Dysfunction and Hypoalgesia in an Experimental Model of Diabetic Neuropathy

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Effect of Urtica Dioica on Memory Dysfunction and Hypoalgesia in an Experimental Model of Diabetic Neuropathy See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/255690725 Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy Article in Neuroscience Letters · July 2013 DOI: 10.1016/j.neulet.2013.07.029 · Source: PubMed CITATIONS READS 14 118 2 authors: Sita Sharan Patel Udayabanu Malairaman Sagar Institute of Research and Technology Jaypee University of Information Technology 26 PUBLICATIONS 311 CITATIONS 28 PUBLICATIONS 221 CITATIONS SEE PROFILE SEE PROFILE Some of the authors of this publication are also working on these related projects: Investigation of the effect of scopoletin on neurological alterations during streptozotocin induced chronic diabetes View project Computational approach for investigation of genes and proteins associated to Alzheimer's Disease for early diagnosis of the disease. View project All content following this page was uploaded by Sita Sharan Patel on 06 August 2015. The user has requested enhancement of the downloaded file. This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier’s archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/authorsrights Author's personal copy Neuroscience Letters 552 (2013) 114–119 Contents lists available at ScienceDirect Neuroscience Letters jou rnal homepage: www.elsevier.com/locate/neulet Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy a,b,1 a,∗,1 Sita Sharan Patel , M. Udayabanu a Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India b Lakshmi Narain College of Pharmacy, Bhopal, Madhya Pradesh, India h i g h l i g h t s • We investigated the effect of Urtica dioica against diabetic neuropathy. • Long standing diabetes resulted in hypoalgesia and cognitive deficit. • Urtica dioica showed results comparable to rosiglitazone. a r t i c l e i n f o a b s t r a c t Article history: Diabetic neuropathy is considered as a disease of the peripheral nervous system, but recent evidences Received 12 April 2013 suggest the involvement of central nervous system as well. In this study we evaluated the effect of Urtica Received in revised form 13 July 2013 dioica (UD) extract against memory dysfunction and hypoalgesia on a mouse model of streptozotocin Accepted 21 July 2013 (STZ) induced diabetic neuropathy. STZ (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes, followed by treatment with the UD extract (50 mg/kg, oral) and rosiglitazone (5 mg/kg, oral) for Keywords: 8 weeks. Cognitive functions were evaluated using Morris water maze and passive avoidance step through Diabetic neuropathy task. Pain thresholds were measured using thermal, mechanical and chemical induced hyperalgesia. We Hypoalgesia Memory observed that chronic diabetes resulted in a decline in circulating insulin level, elevated blood glucose, Rosiglitazone reduced body weight, increased water intake, cognitive impairment and hypoalgesia. UD significantly Morris water maze reduced the blood glucose and polydypsia, as well as improved the body weight, insulin level, cognition Cognitive impairment and insensate neuropathy. In conclusion, UD showed results comparable to rosiglitazone in reversing the long standing diabetes induced complications such as central and peripheral neuronal dysfunction. © 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction population [26]. Currently, there are only two FDA approved drugs, viz., duloxetine and pregabalin for diabetic neuropathy specifically Diabetic neuropathy is a neuronal disorder resulting from for painful neuropathy. Moreover, they have serious side effects long standing diabetes mellitus. Peripheral diabetic neuropathy such as allergic reactions, suicidal thoughts, swelling of legs, sleepi- is a progressive and irreversible serious complication of diabetes ness, etc. mellitus which is associated with demyelination and degenera- Urtica L. Stinging nettle (Urticaceae) is an annual and peren- tion of neuronal fibers, loss of sensory fibers, alterations in the nial herbs, distinguished with stinging hairs. Among Urtica microvasculature, etc. [15]. It is the most common complication species, Urtica dioica (UD) and Urtica urens have already of long-standing diabetes mellitus which frequently results in clin- been known and consumed for a long time as medicinal ically significant morbidities, e.g. pain, foot ulcers and amputations plants globally. UD has shown a protective effect against [27]. The central nervous system is not spared. Depression, phobias, hepatic ischemic reperfusion [13], hyperglycemia [5], hyper- anorexia [17], loss of memory and reduction in complex reason- cholesterolemia [23], arthritic pain [28], etc. The constituents ing skills are more prevalent in diabetic patients than the general of UD are p-hydroxybenzaldehyde, homovanillyl alcohol, ␤- sitosterol, stigmasterol, scopoletin, campesterol, daucosterol, 5-hydroxy tryptamine (5-HT), acetylcholine, cholineacetyltrans- ferase, syringic acid, gallic acid, ferulic acid, ␤-carotene, lutein, Abbreviations: 5-HT, 5-hydroxy tryptamine; NMDA, N-methyl-d-aspartate; STL, myricetin, quercetin, kaempferol, carvacrol, etc. [8,22,24,36]. Car- step through latency; UD, Urtica dioica. ∗ vacrol shows a neuroprotective effect against focal cerebral Corresponding author. Tel.: +91 1792 239387, fax: +91 1792 245362. ischemia/reperfusion injury [37], and modulates dopamine and E-mail address: m [email protected] (M. Udayabanu). 1 Both authors contributed equally to the work. serotonin levels in the prefrontal cortex and hippocampus [40]. 0304-3940/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2013.07.029 Author's personal copy S.S. Patel, M. Udayabanu / Neuroscience Letters 552 (2013) 114–119 115 Scopoletin is known to potentiate acetylcholine release from dark (10 cm × 10 cm × 16 cm) compartments. The light compart- synaptosomes, amplifies hippocampal long-term potentiation and ment was illuminated with 60 W bulb, positioned 70 cm above ameliorate memory impairment [12]. It increases the gene expres- the apparatus. Initially, all mice were given one habituation trial sion of peroxisome proliferator-activated receptor ␥ (PPAR-␥) and to explore both chambers for 120 s. On day 1 of acquisition trial ameliorates insulin resistance in HepG2 cells [38]. Recent studies the mice were allowed to explore the light chamber for 5 s. The suggest that rosiglitazone improves learning and memory in both guillotine door was opened and time taken by the mouse to enter human and animal models [25] and alleviates neuropathic pain in the dark chamber was recorded as step-through latency. Each ani- experimental animals [7]. PPARs are known to regulate angiogene- mal received an inescapable electric shock for 2 s on a grid floor in sis [4] and Schwann cell differentiation, which plays an important the dark chamber. On day 2 of acquisition, memory retention was role in peripheral nerve injury and regeneration [6]. UD is a rich tested for each animal in the same manner, but the shock was not source of 5-HT [8], which is known for its association with insulin delivered [33]. secretion [1] and memory functions [19,20]. All these facts make Spatial memory was assessed using Morris water maze, which UD an ideal candidate for the treatment of diabetes and its asso- consisted of a white circular pool of 1 m diameter, filled with water ◦ ciated complications such as memory impairment and peripheral (24–25 C) and has a submerged transparent escape platform kept neuropathy, which has not been investigated yet. The present study 2 cm below the water level. The pool was made opaque with a was aimed to investigate the effect of UD on streptozotocin (STZ) nontoxic water-soluble white paint. The pool was divided into induced diabetic neuropathy and its associated complications such four hypothetical quadrants. Each mice from all the groups were as memory impairment and hypoalgesia. allowed to swim freely (habituation trial) in the water maze for 5 min (without platform). During training trial the platform was 2. Materials and methods positioned in the center of quadrant and each mouse was released facing toward the wall of the pool in the randomly selected quad- UD was collected from the North Western Himalayan region rant. The mice were allowed to search the platform spontaneously and authenticated from the Department of Forest Product, Dr. within 60 s. If the mice failed to find the platform within 60 s it was Y.S. Parmar University of Horticulture & Forestry, India. UD leaves gently moved toward the platform by the experimenter and left on were shade-dried and subjected to hydro-alcoholic extraction with the platform for 5 s (learning trial). Each mouse received three to methanol and water (1:1). The extract was evaporated under four learning sessions per day with 10 min interval between each reduced
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