Neuroprotective role of Tinospora cordifolia extract in streptozotocin induced neuropathic pain

Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.

摘要 糖尿病神经病变（Diabetic Neuropathy，DN）是糖尿病常见的微血管并发症之一，以神经病理性疼痛为典型临床表现。链脲佐菌素（Streptozotocin，STZ）诱导的大鼠糖尿病模型，已被广泛应用于痛性糖尿病神经病变的相关研究。STZ注射可引发外周神经毒性，进而在大鼠模型中诱发周围糖尿病神经病变。本研究旨在探究宽筋藤（Tinospora cordifolia）提取物对STZ诱导的神经毒性的保护作用，并解析其缓解神经病理性疼痛的潜在机制。研究人员在STZ注射前，以及以250 mg/kg、500 mg/kg剂量的宽筋藤提取物干预后，对痛觉过敏、触诱发痛及运动功能缺损等神经病理性疼痛标志物进行了评估；并在干预7周后，检测了坐骨神经中的氧化应激标志物与神经生长因子（Nerve growth factor，NGF）的表达水平。结果显示，经宽筋藤叶提取物干预7周后，通过提升抗氧化酶活性、降低脂质过氧化水平，并上调糖尿病大鼠坐骨神经中的NGF表达，可显著缓解热痛觉过敏与触诱发痛。本研究结果表明，口服宽筋藤提取物可有效减轻糖尿病性神经病理性疼痛，其作用机制可能与其强大的抗氧化活性及诱导坐骨神经内NGF mRNA表达密切相关。