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Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation

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Abstract

Neuropathic pain is initiated or caused due to the primary lesion or dysfunction in the nervous system and is proposed to be linked to a cascade of events including excitotoxicity, oxidative stress, neuroinflammation and apoptosis. Oxidative/nitrosative stress aggravates the neuroinflammation and neurodegeneration through poly (ADP) ribose polymerase (PARP) overactivation. Hence, the present study investigated the antioxidant and anti-inflammatory effects of the phytoconstituent; morin in chronic constriction injury (CCI) induced neuropathy. Neuropathic pain was induced by chronic constriction of the left sciatic nerve in rats, and the effect of morin (15 and 30 mg/kg, p.o.) was evaluated by measuring behavioural and biochemical changes. Mechanical, chemical and thermal stimuli confirmed the CCI-induced neuropathic pain and treatment with morin significantly improved these behavioural deficits and improved the sciatic functional index by the 14th day after CCI induction. After 14 days of CCI induction, oxidative/nitrosative stress and inflammatory markers were elevated in rat lumbar spinal cord. Oxidative stress induced PARP overactivation resulted in depleted levels of ATP and elevated levels of poly (ADP) ribose (PAR). Treatment with morin reduced the levels of nitrites, restored glutathione levels and abrogated the oxidant induced DNA damage. It also mitigated the increased levels of TNF-α and IL-6. Protein expression studies confirmed the PARP inhibition and anti-inflammatory activity of morin. Findings of this study suggest that morin, by virtue of its antioxidant properties, limited PARP overactivation and neuroinflammation and protected against CCI induced functional, behavioural and biochemical deficits.

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Acknowledgments

Authors would like to acknowledge Department of Pharmaceuticals, Ministry of Chemical and Fertilizers and NIPER-Hyderabad for their support to carry out the study.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, Hyderabad, Telangana State, 500037, India

    Prashanth Komirishetty, Aparna Areti & Ashutosh Kumar

  2. Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad, India

    Ramakrishna Sistla

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  1. Prashanth Komirishetty
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Correspondence to Ashutosh Kumar.

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Komirishetty, P., Areti, A., Sistla, R. et al. Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation. Neurochem Res 41, 2029–2042 (2016). https://doi.org/10.1007/s11064-016-1914-0

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