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ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neuropharmacology
Volume 18 - 2024 |
doi: 10.3389/fnins.2024.1464477
This article is part of the Research Topic Pain and Pain-Related Neuropsychiatric Disorders: From Mechanistic Insights to Innovative Therapeutic Strategies View all 12 articles
Analgesic effect of Dahuangfuzi Decoction in Neuropathic pain through Inhibiting TNF-α and PI3K-AKT Signaling
Provisionally accepted- 1 Guizhou University of Traditional Chinese Medicine, Guiyang, China
- 2 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
- 3 Southwestern Medical University, Luzhou, China
- 4 Guangzhou Medical University, Guangzhou, Guangdong Province, China
Neuropathic pain (NeP) presents considerable challenges in terms of effective management and significantly impacts the quality of life for affected patients. The current treatment options for NeP are limited, highlighting the need for alternative therapeutic approaches. Dahuang Fuzi Decoction (DF), a formula from traditional Chinese medicine, has shown potential in relieving pain symptoms associated with various types of NeP. However, the mechanisms through which DF exerts its effects remain largely unknown.. In this study, we utilized ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) to analyze DF's ingredients, tentatively identifying 24 compounds. Using a chronic sciatic nerve compression injury (CCI) rat model, we evaluated DF's analgesic efficacy for NeP and observed notable effects, as indicated by increases in mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Network pharmacology analysis revealed that DF potentially modulated TNF-α and PI3K-AKT signaling pathways. Additionally, DF treatment led to lower levels of IL-1β, IL-6, and TNF-α in the spinal cord tissues of CCI rats, suggesting an inhibitory impact on neuroinflammation related to NeP. Western blot analysis showed that DF treatment reduced the expressions of TNF-α, TNFR1, and phosphorylated forms of PI3K, AKT, IKKα/β, IKBα, and NF-κB in the spinal cord of CCI rats. Futhernore, immunofluorescence results indicated significant reductions in TNF-α and TNFR1 expression, as well as in AKT and NF-κB phosphorylation within astrocytes following DF administration in CCI rats. Collectively, our findings characterize DF's constituents and elucidates its underlying mechanism for NeP relief, involving the inhibition of TNF-α and PI3K-AKT signaling pathways.
Keywords: Dahuangfuzi Decoction, neuropathic pain, TNF signaling pathway, Network Pharmacology, PI3K-Akt signaling
Received: 14 Jul 2024; Accepted: 19 Nov 2024.
Copyright: © 2024 Qu, Gong, He, Peng, Chen, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Peng Chen, Guizhou University of Traditional Chinese Medicine, Guiyang, China
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