Drug Design, Development and Therapy (Jan 2021)
Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity
Abstract
Jingyu Xu,1,* Zhenbiao Guan,2,* Xiaowei Wang,1,* Dazhi Sun,1 Yongjin Li,1 Bei Pei,1 Ye Lu,1 Liangxi Yuan,3 Xuan Zhang1 1Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, People’s Republic of China; 2Department of Respiration, Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China; 3Department of Vascular Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liangxi YuanDepartment of Vascular Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, People’s Republic of ChinaEmail [email protected] ZhangDepartment of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, People’s Republic of ChinaEmail [email protected] and Objective: 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 Astragali Radix, 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: network pharmacology, astragaloside IV, oxaliplatin neurotoxicity, neuroinflammation, oxidative stress
