https://orcid.org/0000-0003-1386-840X
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
Background 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.
Acknowledgment
This study was supported by funding from the National Natural Science Foundation of China (Grant No.81202678, 81302933) and a Science and Technology Commission Guidance Project of Shanghai (Grant No.14401931300, 17401934300).
These authors are regarded as co-first authors: Jingyu Xu, Zhenbiao Guan, and Xiaowei Wang.
Disclosure
Xuan Zhang reports grants from National Natural Science Foundation of China and Science and Technology Commission Guidance Project of Shanghai, during the conduct of the study. The authors declare that they have no other potential conflicts of interest for this work.