Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity
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, Changh...
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doaj-13adc092fa1a4a5fa8a707ce6971fb002021-01-12T22:45:01ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-01-01Volume 159911061104Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin NeurotoxicityXu JGuan ZWang XSun DLi YPei BLu YYuan LZhang XJingyu 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 yuanlx116@163.comXuan ZhangDepartment of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, People’s Republic of ChinaEmail zhangx@smmu.edu.cnBackground 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 stresshttps://www.dovepress.com/network-pharmacology-and-experimental-evidence-identify-the-mechanism--peer-reviewed-article-DDDTnetwork pharmacologyastragaloside ivoxaliplatin neurotoxicityneuroinflammationoxidative stress |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xu J Guan Z Wang X Sun D Li Y Pei B Lu Y Yuan L Zhang X |
spellingShingle |
Xu J Guan Z Wang X Sun D Li Y Pei B Lu Y Yuan L Zhang X Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity Drug Design, Development and Therapy network pharmacology astragaloside iv oxaliplatin neurotoxicity neuroinflammation oxidative stress |
author_facet |
Xu J Guan Z Wang X Sun D Li Y Pei B Lu Y Yuan L Zhang X |
author_sort |
Xu J |
title |
Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity |
title_short |
Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity |
title_full |
Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity |
title_fullStr |
Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity |
title_full_unstemmed |
Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV in Oxaliplatin Neurotoxicity |
title_sort |
network pharmacology and experimental evidence identify the mechanism of astragaloside iv in oxaliplatin neurotoxicity |
publisher |
Dove Medical Press |
series |
Drug Design, Development and Therapy |
issn |
1177-8881 |
publishDate |
2021-01-01 |
description |
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 yuanlx116@163.comXuan ZhangDepartment of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, People’s Republic of ChinaEmail zhangx@smmu.edu.cnBackground 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 |
topic |
network pharmacology astragaloside iv oxaliplatin neurotoxicity neuroinflammation oxidative stress |
url |
https://www.dovepress.com/network-pharmacology-and-experimental-evidence-identify-the-mechanism--peer-reviewed-article-DDDT |
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