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Mechanism of Qufeng Huoxue decoction in treating paclitaxel-induced peripheral neuropathy based on network
Geriletu Ao1, Danni Shu1, Lingli Xu2
1Department of Pulmonary and Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang Province, 324000, China.
Background And Purpose:
Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse reaction in cancer patients, affecting 30-50% of patients' quality of life. Qufeng Huoxue Decoction (QHD), has been used for many years as an adjunctive treatment for CIPN in China. However, the underlying mechanism of the role of Qufeng Huoxue Decoction in PIPN remains elusive.
Methods:
We analyzed the potential molecular mechanisms and targets of QHD for PIPN using network pharmacology and molecular docking techniques, respectively. Subsequently, the effects of QHD treatment on Paw withdrawal threshold (PWT) and cold escape behavior were evaluated in the PIPN mouse model. HE staining and LFB staining were observed for spinal cord injury. Inflammatory factors, oxidative stress, and activation of astrocytes and microglia in the spinal cord and neurons were measured by RT-PCR/Elisa/immunofluorescence.
Results:
97 genes were obtained by analyzing the interaction genes between QHD and PIPN. The core targets with top ten degree values were acquired. Biological processes mainly involve exogenous stimuli, oxidative stress, and apoptosis. The signaling pathways mainly included TNF, IL-17, PI3K-Akt, and MAPK pathways. Molecular docking and experimental validation indicated that amentoflavone and QHD are equally critical compounds for alleviating paclitaxel-induced pain and ameliorating spinal cord injury, inflammatory response, oxidative stress, and immune cell activation.
Conclusion:
Our study identified that QHD modulated neuronal responses to alleviate paclitaxel-induced pain, inhibiting inflammatory activation and inflammatory/ chemokine secretion. And we propose that amentoflavone is probably the most critical core component.
