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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Neuropathic pain (NP) is a type of chronic pain resulting from injury or dysfunction of the nerves or spinal cord. Previous studies have shown that the combination of ligustrazine (LGZ) and sinomenine (SIN) exerts a synergistic antinociceptive effect in peripheral and central NP models. On this basis, a comprehensive analgesic evaluation was performed in a chronic constriction injury (CCI)-induced NP model in rats. Sciatic nerve histopathological changes were observed, and 22 cytokines and chemokines levels were analyzed. We also combined network pharmacology and metabolomics to explore their molecular mechanisms. Results showed that the combination of LGZ and SIN significantly alleviated the pain-like behaviors in CCI rats in a time- and dose-dependent manner, demonstrating superior therapeutic effects compared to LGZ or SIN alone. It also improved pathological damage to sciatic nerves and regulated inflammatory cytokine levels. Network pharmacology identified shared and distinct pain-related targets for LGZ and SIN, while metabolomics revealed 54 differential metabolites in plasma, and 17 differential metabolites in CSF were associated with the combined intervention of LGZ and SIN. Finally, through an integrated analysis of the core targets and differential metabolites, tyrosine metabolism, phenylalanine metabolism, and arginine and proline metabolism were identified as potential key metabolic pathways underlying the therapeutic effects of LGZ and SIN in CCI treatment. In conclusion, our study provides evidence to support the clinical application of LGZ and SIN in the treatment of NP.

Details

Title
Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats
Author
Yuan, Zhaoyue 1 ; Zhao, Xiaoliang 1 ; Zhang, Yan 2 ; Jiao, Yue 1 ; Liu, Yang 1 ; Gao, Chang 1 ; Zhang, Jidan 1 ; Ma, Yanyan 1 ; Wang, Zhiguo 1 ; Li, Tao 3 

 Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; [email protected] (Z.Y.); [email protected] (X.Z.); 
 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; [email protected] 
 Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; [email protected] (Z.Y.); [email protected] (X.Z.); ; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; [email protected] 
First page
2604
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3181486458
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.