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  4. Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats

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 · DOI: 10.3390/ijms26062604 · Published: March 13, 2025

PharmacologyPain ManagementBioinformatics

Simple Explanation

Neuropathic pain (NP) is a chronic pain condition resulting from nerve or spinal cord damage. This study investigates the combined effects of ligustrazine (LGZ) and sinomenine (SIN) in alleviating NP symptoms in rats with chronic constriction injury (CCI). The researchers used network pharmacology to predict drug targets and metabolomics to identify key metabolites. By integrating these approaches, they aimed to understand the molecular mechanisms underlying the therapeutic effects of LGZ and SIN in treating NP. The study found that the combination of LGZ and SIN effectively reduced pain-like behaviors in CCI rats, improved nerve damage, and regulated inflammatory cytokine levels. Key metabolic pathways, such as tyrosine and phenylalanine metabolism, were identified as potential targets for the therapeutic effects of LGZ and SIN.

Study Duration
Not specified
Participants
42 Sprague Dawley rats
Evidence Level
Level 2: Experimental study in rats

Key Findings

  • 1
    The combination of LGZ and SIN significantly alleviated pain-like behaviors in CCI rats in a time- and dose-dependent manner, demonstrating superior therapeutic effects compared to LGZ or SIN alone.
  • 2
    Network pharmacology identified shared and distinct pain-related targets for LGZ and SIN, including six key targets: CA2, MPO, HTR6, MAOA, GSK3B, and BDKRB2.
  • 3
    Metabolomics revealed that 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.

Research Summary

This study aimed to elucidate the molecular mechanisms underlying the combined use of LGZ and SIN in treating NP using network pharmacology and metabolomics. The combination of LGZ and SIN demonstrated superior therapeutic effects in CCI rats by alleviating pain-like behaviors, improving nerve damage, and regulating inflammatory cytokine levels. Integrated analysis identified tyrosine metabolism, phenylalanine metabolism, and arginine and proline metabolism as potential key metabolic pathways underlying the therapeutic effects of LGZ and SIN in CCI treatment.

Practical Implications

Clinical Application

The study provides evidence to support the clinical application of LGZ and SIN in the treatment of NP, offering a potential combination therapy option.

Drug Target Identification

Identified key targets (CA2, MPO, HTR6, MAOA, GSK3B, BDKRB2) can serve as potential drug targets for developing more effective NP treatments.

Metabolic Pathway Modulation

Modulating tyrosine, phenylalanine, and arginine/proline metabolism pathways may offer new therapeutic strategies for managing neuropathic pain.

Study Limitations

  • 1
    Relatively short treatment duration
  • 2
    Lack of in-depth studies at the cytokine level
  • 3
    The study focused solely on male rats, which may not fully represent the effects in females

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