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Volume 26
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10.3390/ijms26062604
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Open AccessArticle
by Zhaoyue Yuan SciProfiles Scilit Preprints.org Google Scholar Xiaoliang Zhao SciProfiles Scilit Preprints.org Google Scholar Yan Zhang SciProfiles Scilit Preprints.org Google Scholar Yue Jiao SciProfiles Scilit Preprints.org Google Scholar Yang Liu SciProfiles Scilit Preprints.org Google Scholar Chang Gao SciProfiles Scilit Preprints.org Google Scholar Jidan Zhang SciProfiles Scilit Preprints.org Google Scholar Yanyan Ma SciProfiles Scilit Preprints.org Google Scholar Zhiguo Wang SciProfiles Scilit Preprints.org Google Scholar Tao Li SciProfiles Scilit Preprints.org Google Scholar 
Zhaoyue YuanXiaoliang ZhaoYan ZhangYue JiaoYang LiuChang GaoJidan ZhangYanyan MaZhiguo WangTao Li
1
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
2
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(6), 2604; https://doi.org/10.3390/ijms26062604
Submission received: 22 January 2025 / Revised: 7 March 2025 / Accepted: 10 March 2025 / Published: 13 March 2025
(This article belongs to the Special Issue Natural Products in Drug Discovery and Development)
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.
Keywords: neuropathic pain; ligustrazine; sinomenine; tyrosine metabolism; phenylalanine metabolism
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MDPI and ACS Style
Yuan, Z.; Zhao, X.; Zhang, Y.; Jiao, Y.; Liu, Y.; Gao, C.; Zhang, J.; Ma, Y.; Wang, Z.; Li, T. Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats. Int. J. Mol. Sci. 2025, 26, 2604. https://doi.org/10.3390/ijms26062604
AMA Style
Yuan Z, Zhao X, Zhang Y, Jiao Y, Liu Y, Gao C, Zhang J, Ma Y, Wang Z, Li T. Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats. International Journal of Molecular Sciences. 2025; 26(6):2604. https://doi.org/10.3390/ijms26062604
Chicago/Turabian Style
Yuan, Zhaoyue, Xiaoliang Zhao, Yan Zhang, Yue Jiao, Yang Liu, Chang Gao, Jidan Zhang, Yanyan Ma, Zhiguo Wang, and Tao Li. 2025. "Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats" International Journal of Molecular Sciences 26, no. 6: 2604. https://doi.org/10.3390/ijms26062604
APA Style
Yuan, Z., Zhao, X., Zhang, Y., Jiao, Y., Liu, Y., Gao, C., Zhang, J., Ma, Y., Wang, Z., & Li, T. (2025). Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats. International Journal of Molecular Sciences, 26(6), 2604. https://doi.org/10.3390/ijms26062604
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
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MDPI and ACS Style
Yuan, Z.; Zhao, X.; Zhang, Y.; Jiao, Y.; Liu, Y.; Gao, C.; Zhang, J.; Ma, Y.; Wang, Z.; Li, T. Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats. Int. J. Mol. Sci. 2025, 26, 2604. https://doi.org/10.3390/ijms26062604
AMA Style
Yuan Z, Zhao X, Zhang Y, Jiao Y, Liu Y, Gao C, Zhang J, Ma Y, Wang Z, Li T. Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats. International Journal of Molecular Sciences. 2025; 26(6):2604. https://doi.org/10.3390/ijms26062604
Chicago/Turabian Style
Yuan, Zhaoyue, Xiaoliang Zhao, Yan Zhang, Yue Jiao, Yang Liu, Chang Gao, Jidan Zhang, Yanyan Ma, Zhiguo Wang, and Tao Li. 2025. "Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats" International Journal of Molecular Sciences 26, no. 6: 2604. https://doi.org/10.3390/ijms26062604
APA Style
Yuan, Z., Zhao, X., Zhang, Y., Jiao, Y., Liu, Y., Gao, C., Zhang, J., Ma, Y., Wang, Z., & Li, T. (2025). Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats. International Journal of Molecular Sciences, 26(6), 2604. https://doi.org/10.3390/ijms26062604
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
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