Research on the Mechanism of Duhuo in Treating Intervertebral Disc Degeneration based on Bioinformatics and Network Pharmacology

Fei Liu, Zhiwei Xu, Chengqi Zhang,Yang Lü, Zhifa Li,Xiaofei Wu, Chao Jiang,Zongchao Liu,Feng Chen, Qi Yan

Research Square (Research Square)(2023)

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摘要
Abstract Background Intervertebral disc degeneration (IVDD) is a common orthopedic disease in middle-aged and elderly people, and the low back pain caused by it brings a heavy burden on the economy and life of patients. The study found that the apoptosis and autophagy of nucleus pulposus cells mediated by BCL2, CASP3, CASP8, CASP9, etc. are closely related to IVDD. In addition, studies have found that Duhuo has the effect of anti-inflammation and improving intervertebral disc degeneration, but the specific molecular mechanism is still unclear. Methods In this study, we used bioinformatics methods to discover the apoptosis and autophagy molecular mechanisms of IVDD, and further discovered the apoptosis and autophagy mechanisms of Duhuo in treating intervertebral disc degeneration through network pharmacology. Results Through bioinformatics analysis, we found that NLRP3, IL6, A KT1, M MP9 and other inflammatory factors are highly expressed in patients with IVDD. The main cellular processes involved are senescence, apoptosis, autophagy, and ferroptosis. The key signaling pathways are HIF − 1, FoXo, PI3k-Ak and other signaling pathways, the key immune cells are T cells and Th 17 cells. Network pharmacology found that Ammidin, isoimperatorin, beta-sitosterol, O- acetylcolumbianetin, and Angelol D, the main active ingredients of Duhuo, may play an important role. There are 23 potential targets for the treatment of IVDD by living alone, among which BCL, CASP3, CASP8, CASP9, ERR1 and PTGS1 may play an important role. Enrichment analysis showed that Duhuo mainly improves intervertebral disc degeneration by regulating apoptosis, autophagy, HIF − 1, and PI3k -Akt signaling pathways. Molecular docking results showed that beta-sitosterol, the main active ingredient of Duhuo, can interact with key targets. Effective combination further confirms our results. Conclusion In summary, we have revealed the molecular mechanism of intervertebral disc degeneration, and further discovered the intrinsic mechanism by which Duhuo regulates nucleus pulposus cell apoptosis and autophagy to improve IVDD.
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关键词
intervertebral disc degeneration,duhuo,pharmacology,bioinformatics
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