Research Article
Volume 9 Issue 3 - 2021
Amelioration of Neurobehavioral and Biochemical Changes by Withania somnifera Root Extract During Type 2 Diabetes Mellitus Induced Cognitive Deficit in Rats
Anshul Tanwar1, Kavita Gulati1* and Arunabha Ray2*
1Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
2Department of Pharmacology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, Delhi, India
*Corresponding Author: Kavita Gulati, Professor, Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
Received: January 31, 2021; Published: February 27, 2021




Abstract

Objective: To investigate the effects of Withania somnifera root extract (WS) on type 2 diabetes mellitus induced cognitive deficit.

Methods: Type 2 diabetes mellitus (T2DM) was induced in rats by feeding them with high fat diet (HFD) for 8 weeks followed by intraperitoneal administration of Streptozotocin (STZ; 35 mg/kg). After four weeks, the fasting blood glucose, serum triglycerides, serum cholesterol and serum insulin levels were analyzed. After the confirmation of diabetes, WS was administered (two doses) for 8 weeks to the diabetic rats. After completion of the treatment animals were tested for memory deficits by Morris water maze (MWM) test and blood sample were collected for biochemical analysis. Glucose tolerance was determined by oral glucose tolerance test (OGTT) and insulin resistance by HOMA-IR models and all the results were compared with standard drug Pioglitazone (PZ).

Results: Significant elevation in fasting blood glucose, triglyceride, cholesterol and insulin levels were observed in HFD-STZ induced diabetic rats as compared to control animals and treatment with WS for 8 weeks significantly lowered these levels. In MWM test, diabetic rats spent significantly less time in target quadrant (TSTQ), an indicator of cognitive deficit for spatial learning, as compared to control animals. The animals treated with WS spent significantly more time in TSTQ when compared with diabetic group.

Conclusion: The data suggested that 8 weeks of treatment with Withania somnifera lowered the metabolic parameters of type 2 diabetes when compared with diabetic group. The reversal of biochemical markers was accompanied with significant improvement in memory retention and reduction in insulin resistance in rats with T2DM induced cognitive deficit. Thus, it can be concluded that Withania somnifera has therapeutic potential and can be explored in the management of T2DM induced Alzheimer’s disease.

Keywords: Metabolic Syndrome; Type 2 Diabetes; Insulin Resistance; Cognition; Neurobehavioral Studies; High-fat Diet; Withania somnifera

References

    1. Guo XX., et al. “Stability of a type 2 diabetes rat model induced by high-fat diet feeding with low dose streptozotocin injection”. Journal of Zhejiang University Science B 19 (2018): 559-569.
    2. Berbudi A., et al. “Type 2 diabetes and its impact on the immune system”. Current Diabetes Reviews 16 (2020): 442-449.
    3. Bilotta F., et al. “Insulin and the brain: A sweet relationship with intensive care”. Journal of Intensive Care Medicine 32 (2017): 48-58.
    4. Kim B and Feldman EL. “Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome”. Experimental and Molecular Medicine 47 (2015): e149.
    5. Park H., et al. “Exercise alleviates cognitive functions by enhancing hippocampal insulin signalling and neuroplasticity in high-fat diet-induced obesity”. Nutrients 11 (2019): 1603.
    6. Neth BJ and Craft S. “Insulin resistance and Alzheimer’s disease: Bioenergetic linkages”. Frontiers in Aging Neuroscience 9 (2017).
    7. Ma L., et al. “Rosiglitazone improves learning and memory ability in rats with type 2 diabetes through the insulin signaling pathway”. The American Journal of Medical Sciences 350 (2015): 121-128.
    8. Jash K., et al. “Cognitive dysfunction: A growing link between diabetes and Alzheimer’s disease”. Drug Development Research 81 (2020): 144-164.
    9. Diehl T., et al. “Insulin resistance in Alzheimer’s disease”. Translational Research 183 (2017): 26-40.
    10. Bhattacharya SK and Muruganandam AV. “Adaptogenic activity of Withania somnifera: An experimental study using a rat model of chronic stress”. Pharmacology, Biochemistry and Behavior 75 (2003): 547-555.
    11. Baliga MS., et al. “The health benefits of Indian traditional ayurvedic rasayana (Anti-aging) drugs: A review”. in: Watson R.R. (Ed.), Foods and dietary suppliments in the prevention and treatment of disease in older adults. Academic Press (2015): 151-161.
    12. Rayees S and Malik F. “Withania Somnifera: From Traditional Use to Evidence Based Medicinal Prominence” in: Kaul S.C., Wadhwa R. (Ed.), Science of Ashwagandha: Preventice and Therapeutic Potentials. Springer International Publishing AG (2017): 81-103.
    13. Srinivasan K., et al. “Combination of high fat diet fed and low dose streptozotocin treated rat: A model for type 2 diabetes and pharmacological screening”. Pharmacological Research 52 (2005): 313-320.
    14. Zhang T., et al. “Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of β-secretase activation and β-amyloid generation in rat brains”. Neuroscience 161 (2009): 1045-1056.
    15. Antony PJ., et al. “Myoinositol ameliorates high fat diet and streptozotocin induced diabetes in rats through promoting insulin receptor signalling”. Biomedicine and Pharmacotherapy 88 (2017): 1098-1113.
    16. Singh N., et al. “An overview on Ashwagandha: A rasayana (rejuvenator) of ayurveda”. African Journal of Traditional Complimentary and Alternative Medicines 8 (2011): 208-213.
    17. Kojah EY and Hafez DA. “Evaluation of Ashwagandha (Withania Somnifera) and its extract to protecting the liver from damage”. International Journal of Engineering Research and Technology 9 (2020): 52-60.
    18. Matthews JNS. “Analysis of serial measurements in medical research”. British Medical Journal 300 (1990): 230-235.
    19. Ishrat T., et al. “Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type”. Brain Research 1281 (2009): 117-127.
    20. Tanwar A., et al. “Anti-amnesic effect of Crataeva nurvala stem bark in scopolamine induced amnesia”. Journal of Applied Pharmaceutical Science 4 (2014): 66-72.
    21. Answer T., et al. “Effect of Withania somnifera on insulin sensitivity in non-insulin dependent diabetes mellitus rats”. Basic and Clinical Pharmacology and Toxicology 102 (2008): 498-503.
    22. Noshahr ZS. “Protective effects of Withania sonmifera root on inflammatory markers and insulin resistance in fructose-fed rats”. Reports of Biochemistry and Molecular Biology 3 (2015): 62-67.
    23. Li X., et al. “Link between type 2 diabetes and Alzheimer’s disease: from epidemiology to mechanism and treatment”. Clinical Interventions in Aging 10 (2015): 549-560.
    24. Craft S. “Insulin resistance and Alzheimer’s disease pathogenesis: Potential mechanisms and implications for treatment”. Current Alzheimer Research 4 (2007): 147-152.
    25. Lee SH., et al. “Insulin in the nervous system and the mind: Functions in metabolism, memory and mood”. Molecular Metabolism 5 (2016): 589-601.
    26. De Felice FG and Ferreira ST. “Inflammation, defective insulin signaling and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer’s disease”. Diabetes 63 (2014): 2262-2272.
    27. Upadhyay P., et al. “Effect of a novel polyherbal formulation on diabetes induced memory deficits in rats”. Clinical and Experimental Pharmacology 5 (2015): 194.
    28. Banu MR., et al. “Ameliorative effect of Withaferin A on ageing mediated impairment in the dopamine system and its associated behaviour of wistar albino rat”. Pharmacology 103 (2019): 114-119.
    29. Dar NJ. “Pharmacologic overview of Withania somnifera, the Indian Ginseng”. Cellular and Molecular Life Sciences 72 (2015): 4445-4460.
    30. Topuz RD., et al. “Effects of hippocampal histone acetylation and HDAC inhibition on spatial learning and memory in the Morris water maze in rats”. Fundamental and Clinical Pharmacology 34 (2020): 222-228.
    31. Baarendse PJJ., et al. “Differential involvement of the dorsal hippocampus in passive avoidance in C57BL/6J and DBA/2J mice”. Hippocampus 18 (2008): 11-19.
    32. Ogren SO and Stiedl O. “Passive avoidance”. in: Stolerman, I.P. (Ed.), Encyclopedia of psychopharmacology volume 2. Springer-Verlag Berlin Heidelberg (2010): 960-967.
    33. Yang S., et al. “Pioglitazone ameliorates Aβ 42 deposition in rats with diet induced insulin resistance associated with AKT/GSK3β activation”. Molecular Medicine Reports 15 (2017): 2588-2594.
    34. Nampoothiri M., “Effect of insulin on spatial memory in aluminium chloride-induced dementia in rats”. Cellular, Molecular and Developmental Neuroscience 28 (2017): 540-544.
    35. Sancheti H., et al. “Age-dependent modulation of synaptic plasticity and insulin mimetic effect of Lipoic acid on a mouse model of Alzheimer’s disease”. PLoS ONE 8 (2013): e69830.
    36. Yarchoan M., et al. “Abnormal serine phosphorylation of insulin receptor substrate 1 is associated with tau pathology in Alzheimer’s disease and taupathies”. Acta Neuropathologica 128 (2014): 679-689.
Citation: Kavita Gulati., et al. “Amelioration of Neurobehavioral and Biochemical Changes by Withania somnifera Root Extract During Type 2 Diabetes Mellitus Induced Cognitive Deficit in Rats”. EC Pharmacology and Toxicology 9.3 (2021): 45-58.

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