Yiqi Huoxue decoction protects against intervertebral disc herniation through autophagy

Abstract Backgrounds: Deficiency of autophagy causes alterations in articular cartilage that lead to intervertebral disc degeneration (IDD) and osteoarthritis. In China, conservative treatment with traditional Chinese medicine (TCM) is a reasonably preferred choice for ruptured lumbar disc herniation (LDH). It has been reported that autophagy was activated by Yiqi Huoxue decoction (YHD) treatment. However, the role of YHD-induced autophagy in the prevention and treatment of IDH remains to be clarified. Methods: The effect of YHD treatment on IDH rats was evaluated by hematoxylin and eosin staining. Western blot and immunohistofluorescence (IHF) assay were used to detect the relative expressions of the autophagy-related proteins, and the changes of VPS34 mRNA were detected by quantitative real-time PCR. Results: The YHD treatment significantly improved the resorption of interverbral disc along with the increased expression of autophagy related proteins, including VPS34, Beclin1 and LC3II/LC3I in IDH rats. Western blot and IHF analyses showed increased level of USP13 in YHD treatment groups. In contrast, inhibition of USP13 by autophagy inhibitor spautin-1 promoted the ubiquitination of Beclin1, decreased the expressions of VPS34, Beclin1 and LC3II/LC3I, which in turn blocked facilitative effect of YHD on discresorption. Conclusions: Our findings suggest that YHD activates autophagy by regulating the deubiquitination activity of USP13 to Beclin1, thereby promoting the resorption of interverbral disc.