Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways

Rui Lu; Zhenni Wei; Zhenggang Wang; Shimeng Xu; Kai Sun; Peng Cheng; Xiaojian Huang; Hongbo You; Fengjing Guo; Shuang Liang; An-Min Chen

doi:10.1016/j.isci.2023.105936

Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways

iScience. 2023 Jan 5;26(2):105936. doi: 10.1016/j.isci.2023.105936. eCollection 2023 Feb 17.

Authors

Rui Lu¹, Zhenni Wei², Zhenggang Wang^{1

3}, Shimeng Xu¹, Kai Sun¹, Peng Cheng¹, Xiaojian Huang¹, Hongbo You¹, Fengjing Guo¹, Shuang Liang¹, An-Min Chen¹

Affiliations

¹ Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
² Wuhan Institute of Biological Products, Co. Ltd, Wuhan 430207, China.
³ Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden.

Abstract

Osteoarthritis (OA) is a trauma-/age-related degenerative disease characterized by chronic inflammation as one of its pathogenic mechanisms. Mulberroside A (MA), a natural bioactive withanolide, demonstrates anti-inflammatory properties in various diseases; however, little is known about the effect of MA on OA. We aim to examine the role of MA on OA and to identify the potential mechanisms through which it protects articular cartilage. In vitro, MA improved inflammatory response, anabolism, and catabolism in IL-1β-induced OA chondrocytes. The chondroprotective effects of MA were attributed to suppressing the MAPK, NF-κB, and PI3K-AKT-mTOR signaling pathways, as well as promoting the autophagy process. In vivo, intra-articular injection of MA reduced the cartilage destruction and reversed the change of anabolic and catabolic-related proteins in destabilized medial meniscus (DMM)-induced OA models. Thus, the study indicates that MA exhibits a chondroprotective effect and might be a promising agent for OA treatment.

Keywords: Biomolecules; Disease; Immune response.