Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, People's Republic of China.
Department of Respiration, Changhai Hospital, Naval Medical University, Shanghai 200433, People's Republic of China.
Drug Des Devel Ther. 2021 Jan 12;15:99-110. doi: 10.2147/DDDT.S262818. eCollection 2021.
Neurotoxicity is a common side effect of oxaliplatin; the effect of current drugs such as methylcobalamin and gabapentine is not obvious. Astragaloside IV (AS-IV) is an important active ingredient of , which can protect the nervous system and inhibit tumor growth to a certain extent. However, whether AS-IV can reduce oxaliplatin neurotoxicity and its molecular mechanism remain unclear.
The network pharmacology method was used to determine the collective targets of AS-IV and oxaliplatin neurotoxicity. The model of neurotoxicity was established by intraperitoneal injection of oxaliplatin in rats. Bodyweight, mechanical withdrawal threshold (MWT), cold allodynia, and nerve conduction velocity (NCV) were examined, pathological changes were observed by hematoxylin-eosin staining, number of Nissl bodies were assessed by Nissl staining, the key collective targets were measured by spectrophotometry and immunohistochemistry.
Through network pharmacological analysis, 25 collective targets of AS-IV and oxaliplatin neurotoxicity were identified, mainly related to inflammation and oxidative stress. AS-IV could increase body weight, elevate MWT, and reduce cold allodynia of model rats, it also raised NCV. Neuropathology was improved and the number of Nissl bodies was increased by AS-IV administration. It reduced TNF-α, IL-6, and IL-1β in the spinal cord of model rats to inhibit inflammation; it also decreased MDA, raised SOD, CAT, and GSH-Px in the spinal cord of model rats to block oxidative stress.
AS-IV improves oxaliplatin neurotoxicity by regulating neuroinflammation and oxidative stress; the results can provide a new perspective for the potential treatment strategy of oxaliplatin neurotoxicity.
神经毒性是奥沙利铂的常见副作用；目前药物如甲钴胺和加巴喷丁的效果并不明显。黄芪甲苷（AS-IV）是 的重要活性成分，能在一定程度上保护神经系统和抑制肿瘤生长。然而，AS-IV 是否能减轻奥沙利铂的神经毒性及其分子机制尚不清楚。
采用网络药理学方法确定 AS-IV 和奥沙利铂神经毒性的共同靶点。通过腹腔注射奥沙利铂建立神经毒性模型。检测大鼠体重、机械撤回避痛阈值（MWT）、冷感觉异常和神经传导速度（NCV），通过苏木精-伊红染色观察病理学变化，尼氏染色评估尼氏体数量，分光光度法和免疫组织化学法检测关键共同靶点。
通过网络药理学分析，确定了 25 个 AS-IV 和奥沙利铂神经毒性的共同靶点，主要与炎症和氧化应激有关。AS-IV 可增加模型大鼠的体重，提高 MWT，减轻冷感觉异常，提高 NCV。AS-IV 可改善神经病理学，增加模型大鼠脊髓尼氏体数量。它降低了模型大鼠脊髓中 TNF-α、IL-6 和 IL-1β 的水平，从而抑制炎症；它还降低了 MDA，提高了 SOD、CAT 和 GSH-Px 的水平，从而阻断氧化应激。
AS-IV 通过调节神经炎症和氧化应激改善奥沙利铂神经毒性；结果可为奥沙利铂神经毒性的潜在治疗策略提供新视角。
