Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation
Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation
复制标题
DOI：
10.1007/s11064-016-1914-0
复制
发表时间：
2016-08-01
影响因子：
4.4
通讯作者：
Kumar, Ashutosh
中科院分区：
文献类型：
--
作者：
Komirishetty, Prashanth;Areti, Aparna;Kumar, Ashutosh
神经性疼痛是由于神经系统中的原发性病变或功能障碍而引发或引起的，并且被认为与包括兴奋性毒性、氧化应激、神经炎症和细胞凋亡的级联事件有关。氧化/亚硝化应激通过多聚腺苷二磷酸核糖聚合酶（PARP）的过度激活而加重神经炎症和神经退行性变。因此，本研究调查的抗氧化剂和抗炎作用的植物成分，桑色素在慢性压迫性损伤（CCI）引起的神经病变。通过大鼠左侧坐骨神经的慢性收缩诱导神经病理性疼痛，并且桑色素（15和30 mg/kg，p.o.）通过测量行为和生化变化进行评估。机械，化学和热刺激证实了CCI诱导的神经性疼痛和桑色素治疗显着改善这些行为缺陷，并改善了CCI诱导后第14天的坐骨神经功能指数。CCI诱导14天后，大鼠腰髓中的氧化/亚硝化应激和炎症标志物升高。氧化应激诱导的PARP过度激活导致ATP水平耗尽和聚（ADP）核糖（PAR）水平升高。桑色素处理降低了亚硝酸盐的水平，恢复谷胱甘肽水平，并消除了氧化剂诱导的DNA损伤。它还减轻了TNF-α和IL-6水平的升高。蛋白质表达研究证实了桑色素的PARP抑制作用和抗炎活性。这项研究的结果表明，桑色素，凭借其抗氧化性能，限制PARP过度激活和神经炎症，并防止CCI诱导的功能，行为和生化缺陷。
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-alpha 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.