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Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy.

Abstract

Diabetes mellitus is a serious debilitating epidemic affecting all social strata in developing as well as developed countries. Diabetic neuropathy is most common of secondary complications associated with diabetes mellitus and is characterized by slowing of nerve conduction velocity, elevated pain, sensory loss and nerve fiber degeneration. The aim of the present investigation was to evaluate the neuroprotective effect of naringin against streptozotocin (STZ) induced diabetic neuropathic pain in laboratory rats. Four weeks after intraperitoneal injection of STZ resulted in significant decrease in mechano-tactile allodynia, mechanical hyperalgesia, thermal hyperalgesia and motor nerve conduction velocity. Activity of endogenous antioxidant like superoxide dismutase as well as membrane bound inorganic phosphate enzyme was also found to be significantly decreased. It not only caused neural cell apoptosis but also enhanced lipid peroxide, nitrite, and inflammatory mediators' (TNF-α) level. Chronic treatment with naringin (40 and 80mg/kg) for 4 weeks significantly and dose dependently attenuated the decrease in level of nociceptive threshold, endogenous antioxidant and membrane bound inorganic phosphate enzyme. It also decreased the elevated levels of oxidative-nitrosative stress, inflammatory mediators as well as apoptosis in neural cells significantly and dose dependently. The important finding of the study is that, the naringin-insulin combination not only attenuated the diabetic condition but also reversed the neuropathic pain, whereas insulin or naringin alone only improved hyperglycemia but partially reversed the pain response in diabetic rats. Thus, naringin is a potential flavonone bearing antioxidant, antiapoptotic and disease modifying property acting via modulation of endogenous biomarker to inhibit diabetes induced neuropathic pain.

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  • Authors+Show Affiliations

    ,

    Centre of Advance Research in Pharmaceutical Sciences, Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, 411038, India

    , , ,

    Source

    Fitoterapia 83:4 2012 Jun pg 650-9

    MeSH

    Animals
    Antioxidants
    Apoptosis
    Biomarkers
    Diabetes Mellitus, Experimental
    Diabetic Neuropathies
    Dose-Response Relationship, Drug
    Flavanones
    Hyperglycemia
    Inflammation Mediators
    Insulin
    Male
    Neuralgia
    Neurons
    Neuroprotective Agents
    Nitrosation
    Oxidative Stress
    Phytotherapy
    Plant Extracts
    Rats
    Rats, Wistar
    Tumor Necrosis Factor-alpha

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22343014

    Citation

    Kandhare, Amit D., et al. "Neuroprotective Effect of Naringin By Modulation of Endogenous Biomarkers in Streptozotocin Induced Painful Diabetic Neuropathy." Fitoterapia, vol. 83, no. 4, 2012, pp. 650-9.
    Kandhare AD, Raygude KS, Ghosh P, et al. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia. 2012;83(4):650-9.
    Kandhare, A. D., Raygude, K. S., Ghosh, P., Ghule, A. E., & Bodhankar, S. L. (2012). Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia, 83(4), pp. 650-9. doi:10.1016/j.fitote.2012.01.010.
    Kandhare AD, et al. Neuroprotective Effect of Naringin By Modulation of Endogenous Biomarkers in Streptozotocin Induced Painful Diabetic Neuropathy. Fitoterapia. 2012;83(4):650-9. PubMed PMID: 22343014.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. AU - Kandhare,Amit D, AU - Raygude,Kiran S, AU - Ghosh,Pinaki, AU - Ghule,Arvindkumar E, AU - Bodhankar,Subhash L, Y1 - 2012/02/09/ PY - 2011/11/06/received PY - 2012/01/25/revised PY - 2012/01/31/accepted PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2012/9/28/medline SP - 650 EP - 9 JF - Fitoterapia JO - Fitoterapia VL - 83 IS - 4 N2 - Diabetes mellitus is a serious debilitating epidemic affecting all social strata in developing as well as developed countries. Diabetic neuropathy is most common of secondary complications associated with diabetes mellitus and is characterized by slowing of nerve conduction velocity, elevated pain, sensory loss and nerve fiber degeneration. The aim of the present investigation was to evaluate the neuroprotective effect of naringin against streptozotocin (STZ) induced diabetic neuropathic pain in laboratory rats. Four weeks after intraperitoneal injection of STZ resulted in significant decrease in mechano-tactile allodynia, mechanical hyperalgesia, thermal hyperalgesia and motor nerve conduction velocity. Activity of endogenous antioxidant like superoxide dismutase as well as membrane bound inorganic phosphate enzyme was also found to be significantly decreased. It not only caused neural cell apoptosis but also enhanced lipid peroxide, nitrite, and inflammatory mediators' (TNF-α) level. Chronic treatment with naringin (40 and 80mg/kg) for 4 weeks significantly and dose dependently attenuated the decrease in level of nociceptive threshold, endogenous antioxidant and membrane bound inorganic phosphate enzyme. It also decreased the elevated levels of oxidative-nitrosative stress, inflammatory mediators as well as apoptosis in neural cells significantly and dose dependently. The important finding of the study is that, the naringin-insulin combination not only attenuated the diabetic condition but also reversed the neuropathic pain, whereas insulin or naringin alone only improved hyperglycemia but partially reversed the pain response in diabetic rats. Thus, naringin is a potential flavonone bearing antioxidant, antiapoptotic and disease modifying property acting via modulation of endogenous biomarker to inhibit diabetes induced neuropathic pain. SN - 1873-6971 UR - https://www.unboundmedicine.com/medline/citation/22343014/Neuroprotective_effect_of_naringin_by_modulation_of_endogenous_biomarkers_in_streptozotocin_induced_painful_diabetic_neuropathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0367-326X(12)00037-8 DB - PRIME DP - Unbound Medicine ER -