4.7 Article

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

Journal

FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.00682

Keywords

salvianolic acid A; chondrocytes; osteoarthritis; inflammatory; apoptosis; MAPK; NF-kappa B

Funding

  1. Zhejiang Province Science and Technology Department Public Welfare Technology Research Program/Experimental Animal Project [LGD19H060001]
  2. Zhejiang Province Chinese Medicine Science and Technology Project [2013ZQ024]
  3. Zhejiang Province Health Department Project [2019RC052]

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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-alpha), 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 experimentin vitroshowed that SAA not only inhibited the production of inflammatory mediators induced by IL-1 beta and the loss of cartilage matrix but also reduced the apoptosis of mouse chondrocytes induced by IL-1 beta. According to the results of immunofluorescence and Western blot, SAA inhibited the activation of the NF-kappa B pathway and MAPK pathway. The results of thesein vitroexperiments 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-kappa B and MAPK signaling pathways. In thein vivoexperiments, 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.

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