NEUROPROTECTIVE POTENTIAL OF AZADIRACHTA INDICA LEAVES IN DIABETIC RATS


Nidhi Srivastva, Naveen Kumar Gupta, Sanjeev Puri, Veena Puri

Abstract


Objective: Azadirachta indica is a treasure of multiple pharmacological properties and presently leaves of this plant have been explored to evaluate the neuroprotective potential in diabetic rats.

Methods: Male Sprague-Dawley rats were injected with single intra peritoneal dose of streptozotocin (60mg/ Kg body weight (BW.) to develop animal model of diabetes. Post twenty one days of streptozotocin induction, animals were treated with aqueous Azadirachta indica Leaf Extract (ALE, 600mg/Kg BW.) for seven consecutive days. Followed this, all animals were evaluated for the levels of blood glucose, lipid peroxidation (LPO), C Reactive Proteins (CRP), pro oxidant biomarkers and histological changes.

Results: Streptozotocin treated rats exhibited elevated levels of blood glucose, LPO, CRP and altered pro oxidant biomarkers in comparison to control rats. Additionally, histological alterations/damage was evidenced as fragmentation, vacuolization, inflammation etc. However, ALE treatment to these rats significantly decreased blood glucose levels, LPO, CRP levels and restored pro-oxidants status. Light microscopic and ultra microscopic analysis also indicated less damage, tissue architectural changes in comparison to untreated diabetic rats. Further decrease in hyperalgesia and inflammation levels; along with protective and restorative changes following ALE treatment suggested the neuroprotective potential of Azadirachta indica leaves in diabetic rats.

Conclusion: The oral administration of ALE to streptozotocin induced diabetic animals resulted in neuro-protection against degenerative oxidative stress associated with metabolic and histopathological damage in the brain.

Key words:  Azadirachta indica, Antioxidants, Hyperalgesia, Neuroprotection

 

 


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References


Yadav SK, Nagori BP, Desai PK. Pharmacological characterization of different fractions of Calotropis procera (Asclepiadaceae) in streptozotocin induced experimental model of diabetic neuropathy. J Ethnopharmacol 2014;152(2):349-57.

Deli G, Bosnyak E, Pusch G, Komoly S, Feher G. Diabetic neuropathies: Diagnosis and management. Neuroendocrinology 2014;98(4):267-80.

Gupta A, Gupta Y. Diabetic neuropathy: Part. J Pak Med Assoc 2014;64:714-21.

Pandhare RB, Sangameswaran B, Mohite PB, Khanage SG. Attenuating effect of seeds of Adenanthera pavonina aqueous extract in neuropathic pain in streptozotocin-induced diabetic rats: An evidence of neuroprotective effects. Rev Bras Farmacogn 2012;22(2):428-35.

Prabhakar PK. Pathophysiology of secondary complications of diabetes mellitus. Asian J Pharm Clin Res 2016;9(1):32-6.

Pandey RK, Singh SN, Shahnawaz K. Comparative study of aegle marmelos, Azadirachta indica and glimepride on blood sugar in experimentally induced hyperglycemia in albino rats. J Evol Med Dent Sci 2015;4:3815-22.

Yang H, Fan S, Song D, Wang Z, Ma S, Li S, et al. Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress. Mol Med Rep 2013;7(2):431-40.

Vojtková J, Čiljaková M, Bánovčin P. Diabetic microangiopathy etiopathogenesis, new possibilities in diagnostics and management in Microangiopathy. In: Microangiopathy. 1st ed. Europe, Rijeka, Croatia: In Tech; 2012. p. 37-66.

Hama AT, Plum AW, Sagen J. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain. Pharmacol Biochem Behav 2010;97(1):249-55.

Zenker J, Ziegler D, Chrast R. Novel pathogenic pathways in diabetic neuropathy. Trends Neurosci 2013;36(8):439-49.

Dong Q, Wright JR. Expression of C-reactive protein by alveolar macrophages. J Immunol 1996;156(12):4815-20.

Sreenivasan V, Kandasamy CS, Kumar MG, Prabhu KG, Arulraj P, Johnson JS, et al. Review on different natural herbals associated with the anti-diabetic activity. World J Pharm Pharmsci 2015;4(8):581-95.

World Health Organization. WHO traditional medicine strategy 2002-2005 glucose metabolism to neurodegeneration. J Diabetes Res 2003;4:303-12.

Nduka SO, Daniel AL, Ilodigwe EE, Adimorah U, Mbagwu SI. Pharmacodynamic herb-drug interactions: The effects of Azadirachta indica leaf extracts on two commonly used second generation sulfonylureas. World J Pharm Pharm Sci 2015;4(7):1702-11.

Raphael E. Phytochemical constituents of some leaves extract of Aloe vera and Azadirachta indica plant species. Glob Adv Res J Environ Sci Toxicol 2012;1(2):14-7.

Pandey G, Verma KK, Singh M. Evaluation of phytochemical, antibacterial and free radical scavenging properties of Azadirachta indica (neem) leaves. Int J Pharm Pharm Sci 2014;6(2):444-7.

Hussein HE. Reversal of diabetic retinopathy in streptozotocin induced diabetic rats using traditional Indian anti-diabetic plant, Azadirachta indica (L.). Indian J Clin Biochem 2002;17(2):115-23.

Gupta NK, Srivastva N, Bubber P, Puri S. The Antioxidant prtential of Azadirachta indica ameliorates cardioprotection following diabetic mellitus induced microangiopathy. Pharmacogn Mag 2016;12(3):371-8.19. Verma VK, Sarwa KK, Zaman KM. Antihyperglycemic activity of Swertia chirayita and Andrographis paniculata plant extracts in streptozotocin induced diabetic rats. Int J Pharm Pharm Sci 2013;5(3):305-11.

Luck H. Catalase. In: Bergmeyer HU, editor. Methods of Enzymatic Analysis. 2nd ed. Weinheim, New York: Verlag Chemie and Academic Press; 1963. p. 885-8.

Carlberg IN, Mannervik BE. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem 1975;250(14):5475-80.

Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol 1984;105:114-21.

Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 1978;186(1):189-95.

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82(1):70-7.

Wills ED. Mechanisms of lipid peroxide formation in animal tissues. Biochem J 1966;99(3):667-76.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193(1):265-75.

Woolfe G, MacDonald AD. The evaluation of the analgesic action of pethidine hydrochloride (demerol). J Pharmacol Exp Ther 1944;80(3):300-7.

Ben-Bassat J, Peretz E, Sulman FG. Analgesimetry and ranking of analgesic drugs by the receptacle method. Arch Int Pharmacodyn Ther 1959;122:434-47.

Sima AA, Zhang WX, Tze WJ, Tai J, Nathaniel V. Diabetic neuropathy in STZ-induced diabetic rat and effect of allogeneic islet cell transplantation: Morphometric analysis. Diabetes 1988;37(8):1129-36.

Hussein JI, El-Matty D, El-Khayat ZA, Abdel-Latif YA. Brain neurotransmitters in diabetic rats treated with CO enzyme Q10. Int J Pharm Pharm Sci 2012;4:554-6.

Inzucchi SE, Sherwin RS. Type 1 diabetes mellitus. Cecil Medicine. 24th ed. Philadelphia, PA: Saunders, Elsevier; 2011. p. 78-81.

Chattopadhyay RR. Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf extract. Part IV. Gen Pharmacol 1996;27(3):431-4.

Gupta R, Bajpai KG, Johri S, Saxena AM. An overview of Indian novel traditional medicinal plants with antidiabetic potentials. Afr J Trad Complement Altern Med 2008;5(1):1-17.

Chatterjea MN, Shinde R. Textbook of Medical Biochemistry. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2011. p. 380-5.

Roy S, Mondru AK, Dontamalla SK, Vaddepalli RP, Sannigrahi S, Veerareddy PR. Methoxy VO-salen stimulates pancreatic β cell survival by upregulation of eNOS and downregulation of apoptosis in STZ-induced diabetic rats. Biol Trace Elem Res 2011;144(1-3):1095-11.

Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A. Neuroinflammation and oxidative stress in diabetic neuropathy: Futuristic strategies based on these targets. Int J Endocrinol 2014;2014:1-10.

Hashmat I, Azad H, Ahmed A. Neem (Azadirachta indica A. Juss) - A nature’s drugstore: An overview. Int Res J Biol Sci 2012;1(1):76-9.

Reed TT. Lipid peroxidation and neurodegenerative disease. Free Radic Biol Med 2011;51(7):1302-19.

Hassler SN, Johnson KM, Hulsebosch CE. Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats. J Neurochem 2014;131(4):413-7.

Kuhad A, Chopra K. Tocotrienol attenuates oxidative-nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy. Neuropharmacology 2009;57(4):456-62.

Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and β-cell loss in Type 1 diabetes. Nat Rev Endocrinol 2009;5(4):219-26.

Spranger J, Kroke A, Möhlig M, Hoffmann K, Bergmann MM, Ristow M, et al. Inflammatory cytokines and the risk to develop Type 2 diabetes results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 2003;52(3):812-7.

Dandona P, Aljada A, Bandyopadhyay A. Inflammation: The link between insulin resistance, obesity and diabetes. Trends Immunol 2004;25(1):4-7.

Mahmoud MF, Hassan NA, El Bassossy HM, Fahmy A. Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: Effect on low grade inflammation. PloS One 2013;8(5):e63784.

Schumacher M, Cerella C, Reuter S, Dicato M, Diederich M. Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway. Genes Nutr 2011;6(2):149-60.

Bharati S, Rishi P, Koul A. Azadirachta indica exhibits chemopreventive action against hepatic cancer: Studies on associated histopathological and ultrastructural changes. Microsc Res Tech 2012;75(5):586-95.

Mishra J, Dash AK, Dash DK. Nature’s drug store: The free tree of India. World J Pharm Pharm Sci 2013;2(6):4778-98.

Sharma S, Kulkarni SK, Agrewala JN, Chopra K. Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain. Eur J Pharmacol 2006;536(3):256-61.

Ohsawa M, Kamei J. Possible involvement of spinal protein kinase C in thermal allodynia and hyperalgesia in diabetic mice. Eur J Pharmacol 1999;372(3):221-8.

Lee-Kubli CA, Mixcoatl-Zecuatl T, Jolivalt CG, Calcutt NA. Animal models of diabetes-induced neuropathic pain. Behavioral Neurobiology of Chronic Pain. Berlin, Heidelberg: Springer; 2014. p. 147-70.

Zychowska M, Rojewska E, Przewlocka B, Mika J. Mechanisms and pharmacology of diabetic neuropathy-experimental and clinical studies. Pharmacol Rep 2013;65(6):1601-10.

Janes K, Neumann WL, Salvemini D. Anti-superoxide and anti-peroxynitrite strategies in pain suppression. Biochim Biophys Acta 2012;1822(5):815-21.

Hidmark A, Fleming T, Vittas S, Mendler M, Deshpande D, Groener JB, et al. A new paradigm to understand and treat diabetic neuropathy. Exp Clin Endocrinol Diabetes 2014;122(4):201-7.

Skundric DS, Lisak RP. Role of neuropoietic cytokines in development and progression of diabetic polyneuropathy: From glucose metabolism to neurodegeneration. J Diabesity Res 2003;4(4):303-12.




About this article

Title

NEUROPROTECTIVE POTENTIAL OF AZADIRACHTA INDICA LEAVES IN DIABETIC RATS

DOI

10.22159/ajpcr.2017.v10i4.16657

Date

01-04-2017

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 10 Issue 4 April 2017 Page: 243-248

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

125 Views | 82 Downloads

Authors & Affiliations

Nidhi Srivastva

Naveen Kumar Gupta

Sanjeev Puri

Veena Puri


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