Salvianolic Acid A Has Anti-Osteoarthritis Effect In Vitro and In Vivo.

Yifan Wu,Zhanghong Wang,Zeng Lin,Kehe Yu,Jingdi Zhan,Xin Fu

doi:10.3389/fphar.2020.00682

Abstract

Osteoarthritis (OA) is a degenerative disease found in middle-aged and elderly people, which seriously affects their quality of life. The anti-inflammatory and anti-apoptosis pharmacological effects of salvianolic acid A (SAA) have been shown in many studies. In this study, we intended to explore the anti-inflammatory and anti-apoptotic effects of SAA in OA. We evaluated the expression of pro-inflammatory mediators and cartilage matrix catabolic enzymes in chondrocytes by ELISA, Griess reaction, immunofluorescence, and Western blot, which includes nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMPs (MMP-3, MMP-13), and ADAMTS-5. Bax, Bcl-2, and cleaved caspase-3 were also measured by Western blot methods. The results of this experiment in vitro showed that SAA not only inhibited the production of inflammatory mediators induced by IL-1β and the loss of cartilage matrix but also reduced the apoptosis of mouse chondrocytes induced by IL-1β. According to the results of immunofluorescence and Western blot, SAA inhibited the activation of the NF-κB pathway and MAPK pathway. The results of these in vitro experiments revealed for the first time that SAA down-regulated the production of inflammatory mediators and inhibited the apoptosis of mouse chondrocytes and the degradation of extracellular matrix (ECM), which may be attributed to the inhibition of the activation of NF-κB and MAPK signaling pathways. In the in vivo experiments, 45 mice were randomly divided among three groups (the sham group, OA group, and OA + SAA group). The results of animal experiments showed that SAA treatment for eight consecutive weeks inhibited further deterioration of OA. These results demonstrate that SAA plays an active therapeutic role in the development of OA.

Highlights

Osteoarthritis (OA) is a joint degenerative disease that seriously affects the quality of life of patients, leading to reduced function and even disability, which brings a huge economic burden to patients, families, and society (Kon et al, 2012; Johnson and Hunter, 2014)
Previous studies have shown that the activation of Jun N-terminal kinase (JNK) and p38-mitogen-activated protein kinase (MAPK) promoted inflammation and apoptosis, and the extracellular signalregulated kinase (ERK) signaling pathway was essential for cell survival (Iwayama et al, 2011)
Primary antibodies against collagenase type II, COX-2, inducible nitric oxide synthase (iNOS), matrix metalloproteinases (MMPs)-3, ADAMTS-5, Lamin B1, and GAPDH were purchased from Proteintech Group (WuHan, China) and JNK, p-JNK, ERK, p-ERK, p38, and p-p38 were obtained from CST (MA, USA)

Summary

Introduction

Osteoarthritis (OA) is a joint degenerative disease that seriously affects the quality of life of patients, leading to reduced function and even disability, which brings a huge economic burden to patients, families, and society (Kon et al, 2012; Johnson and Hunter, 2014). Normal articular cartilage contains many cartilage extracellular matrixes, which are mainly composed of collagen (mostly type II collagen) and proteoglycan. These are very important to the biomechanical properties of cartilage and provide key elastic supports for joint activities (Wieland et al, 2005; Sarin et al, 2019). The signal pathway of the mitogen-activated protein kinase (MAPK) family mainly includes extracellular signalregulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 (Geng et al, 1996; Johnson and Lapadat, 2002). Previous studies have shown that the activation of JNK and p38-MAPK promoted inflammation and apoptosis, and the ERK signaling pathway was essential for cell survival (Iwayama et al, 2011)

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Conclusion