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Shang Gao,1 Chenmoji Wang,1 Lijie Qi,2 Songlin Liang,1 Xintian Qu,1 Wei Liu,3,* Nianhu Li4,* 1The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 4Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nianhu Li; Wei Liu, Email tigerlee073@126.com; weiliu800109@163.comBackground: The method of action of Bushen Formula (BSHXF) in the treatment of intervertebral disc degeneration (IVDD) was uncovered in this work using in vivo and in vitro tests. To clarify the mechanism of action of BSHXF, we validated the rat intervertebral disc degeneration model and the nucleus pulposus cell degeneration model.Methods: In an in vivo model of IVDD the study explores the impact of BSHXF on mitochondrial function, pro-inflammatory cytokines, pro-apoptotic factors, and matrix metalloproteinases. Additionally, it evaluates the induced degeneration of nucleus pulposus (NP) cells in an in vitro model stimulated by interleukin-1 β (IL-1β). The study measures the effects of BSHXF on both the inflammatory response and mitochondrial function.Results: The MRI results showed that BSHXF reduced intervertebral disc volume reduction and degradation of NP tissue. HE, SO-FG and immunofluorescence further confirmed the protective effect of BSHXF on degenerative intervertebral discs. BSHXF reduced the inflammatory levels of IL-6 IL-1β and TNF-α in degenerative intervertebral disc tissue. Meanwhile, JC-1, mPTP and ROS detection revealed that BSHXF can restore mitochondrial function by regulating the expression of antioxidant proteins, playing a