Chondro-Protective Effects of Shikimic Acid on Osteoarthritis via Restoring Impaired Autophagy and Suppressing the MAPK/NF-κB Signaling Pathway.

Hongbo You,Qiyong Pan,Rui Zhang,Zekai Mao,Lingying Wang,Xiaojian Huang

doi:10.3389/fphar.2021.634822

Abstract

Osteoarthritis (OA) is a major cause of cartilage pain and limited mobility in middle-aged and elderly individuals. The degeneration of cartilage induced by inflammation and cartilage anabolic and catabolic disorder plays a key role in OA. Shikimic acid (SA), a natural ingredient extracted from Illicium verum, has been shown to exert notable anti-inflammatory effects in previous studies, suggesting its potential effects in the treatment of OA. In this study, we revealed that the pretreatment of SW1353 human chondrocytes with SA before interleukin 1β (IL-1β) stimulation effectively decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, matrix metalloproteinases (MMPs; MMP3 and MMP13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, type X collagen, and p62; increased the expression of type II collagen, ATG7, Beclin-1, and LC3; and increased the autophagic flux. Mechanistically, we found that SA suppressed the IL-1β-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. Furthermore, the results of safranin O staining and toluidine blue staining of primary rat cartilage chondrocytes and a trauma-induced rat model of OA showed that SA alleviated progression of OA in vivo. Collectively, our research enhances understanding of the mechanism of protective effect of SA against the progression of OA, which involves amelioration of cartilage degeneration, thereby providing new evidence for the use of SA as a therapy to prevent the development of OA.

Highlights

Osteoarthritis (OA) is a degenerative disease which is common in elderly individuals and is characterized by an inflammatory response and cartilage degeneration (Wieland et al, 2005; Martel-Pelletier et al, 2016)
Cells were exposed to 10 ng/ml interleukin 1β (IL-1β) with or without Shikimic acid (SA), and the Cell Counting kit-8 (CCK-8) results showed that 10 ng/ml IL-1β with or without SA (0.1, 1, and 10 mM) had no effect on cell viability (Figure 1C)
SW1353 cells pretreated with or without SA for 1 h were stimulated with IL-1β (10 ng/ml) for 24 h and harvested for sample extraction and evaluation of the effects of SA on the IL-1βinduced increasing of MMP3 and MMP13

Summary

Introduction

Osteoarthritis (OA) is a degenerative disease which is common in elderly individuals and is characterized by an inflammatory response and cartilage degeneration (Wieland et al, 2005; Martel-Pelletier et al, 2016). The number of people with OA has doubled in the past 60 years, the current treatment strategy for OA includes mainly nonpharmacological interventions with small to moderate therapeutic effects (McAlindon et al, 2014). Shikimic Acid Role in Osteoarthritis arthroplasty, but statistics show that approximately 82% of total knee replacements (TKRs) last for only 25 years and require subsequent replacement revision, which is associated with additional risks (GBD 2016 DALYs and HALE Collaborators, 2017; Evans et al, 2019). Studies have shown the potential effects of antiinflammatory components derived from plants, such as artemisinin and salicin (Zhong et al, 2018; Gao and Zhang, 2019), in protecting against cartilage degeneration, suggesting that there are alternative strategies for OA treatment

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Conclusion