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Biofactors. 2018 Mar;44(2):109-122. doi: 10.1002/biof.1397. Epub 2017 Nov 28.

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

Author information

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

Abstract

Morin, a bioflavonoid with diverse pharmacological effects against various diseases; in most cases morin protective effects were attributed to its detoxifying effect against reactive oxygen species (ROS). Diabetic neuropathy (DN) is a chronic, debilitating neuronal pain associated with intense generation of free radicals and proinflammatory cytokine accumulation in peripheral neurons. We investigated the pharmacological effect of morin against metabolic excess mediated mitochondrial ROS generation and corresponding effect on Nrf2, NF-κB pathways in Streptozotocin (STZ)-induced diabetic rats and in high glucose insulted Mouse neuroblastoma cell line, Neuro 2A (N2A). Animals were evaluated for nerve function parameters, motor and sensory nerve conduction velocities (MNCV and SNCV) and nerve blood flow (NBF) followed by TUNEL and immunoblot analysis. Mitochondrial function was evaluated by performing JC-1 and MitoSOX assays in high glucose (30 mM) incubated N2A cells. Diabetic animals showed significant impairment in MNCV, SNCV, and NBF as well as increased pain hypersensitivity. However, oral administration of morin at 50 and 100 mg/kg improved SNCV, MNCV, and NBF and reduced sensorimotor alterations (hyperalgesia and allodynia) in diabetic animals. Studies in N2A cells have revealed that morin ameliorated the high glucose-induced mitochondrial superoxide production, membrane depolarization, and total ROS generation. Morin effectively counteracted NF-κB-mediated neuroinflammation by reducing ROS mediated IKK activation and increased Nrf2-mediated antioxidant defenses in high glucose-induced N2A cells. The results of our study suggest that morin has exquisite role in offering neuroprotection in experimental DN and further clinical investigation may reward in finding better alternative for the management of DN.

KEYWORDS:

NF-κB; Nrf2; SOD2; diabetic neuropathy; mitochondrial dysfunction

PMID:
29193444
DOI:
10.1002/biof.1397
[Indexed for MEDLINE]

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