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

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.

Morin Suppresses Astrocyte Activation and Regulates Cytokine Release in Bone Cancer Pain Rat Models

“…) is sufficient to suppress neuro‐inflammation in bone cancer pain. A previous study showed that 30 mg/kg morin could attenuate the expression of pro‐inflammatory cytokines and relieve pain hypersensitivity in chronic constriction injury pain model (Komirishetty et al ., ). The present study extends to neuropathic pain model and demonstrates that morin shows therapeutic benefits.…”

Melatonin prevents mitochondrial dysfunction and promotes neuroprotection by inducing autophagy during oxaliplatin‐evoked peripheral neuropathy

“…The response of the rat was noted for 20 seconds, and the response was graded on a 4‐point scale: 0, no response; 1, quick withdrawal or flicking the paw; 2, prolonged withdrawal or repeated flicking; and 3, repeated flicking of the paw with licking of the paw. With a time gap of 5 minutes, acetone was applied thrice onto the hind paw and the individual scores noted in 20‐seconds intervals were added to obtain a single cumulative score with a minimal score of 0 and a maximum score of 9 …”

Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and neuroinflammation in experimental diabetic neuropathy

“…Lee et al proved that morin administration ameliorated oxidative stress, inflammation, and mitochondrial dysfunction in a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mice model of Parkinson's disease (PD) . Moreover through our previous studies, we have observed that morin exhibits potent anti oxidative and anti inflammatory effects against experimental chronic constriction injury (CCI)‐Induced peripheral neuropathy by reducing ROS . Being known for its role in ameliorating ROS generation, in this study we evaluated the neuroprotective properties of morin in STZ‐induced diabetic rats and high glucose‐induced metabolic stress in mouse neuroblastoma (N2A) cells.…”