Saikosaponin A inhibits IL-1β-induced inflammatory mediators in human osteoarthritis chondrocytes by activating LXRα

Hang Gao,Wei Feng,Dongsong Li,Yanyan Song,Jianguo Liu

doi:10.18632/oncotarget.21495

Abstract

Saikosaponin a (SSa), one of the main active components of Bupleurum falcatum, has been reported to have anti-inflammatory effect. In the present study, we investigated the anti-inflammatory effect of SSa on IL-1β-stimulated human osteoarthritis chondrocytes. The cells were pretreated with SSa 12 h before IL-1β treatment. The production of PGE2 and NO were detected by ELISA and Griess method. The levels of MMP1, MMP3, and MMP13 were measured by ELISA and qRT-PCR. The expression of NF-κB and LXRα were tested by western blot analysis. The results showed that SSa inhibited IL-1β-induced PGE2 and NO production in a concentration-dependent manner. SSa also suppressed IL-1β-induced MMP1, MMP3, and MMP13 production. Furthermore, SSa significantly attenuated IL-1β-induced phosphorylation levels of NF-κB p65 and IκBα. SSa also up-regulated the expression of LXRα. The inhibition of SSa on PGE2, NO, MMP1, MMP3, and MMP13 production were reversed by LXRα siRNA or GGPP, the inhibitor of LXRα. In conclusion, our results demonstrated that SSa inhibited inflammatory responses in human chondrocytes in vitro. SSa might be a potential therapeutic drug for osteoarthritis.

Highlights

Osteoarthritis (OA), a common form of arthritis, is characterized by degradation and destruction of cartilage matrix and inflammatory responses in chondrocytes [1]
SSa did not affect the viability of human osteoarthritis chondrocytes
We firstly detected the effects of SSa on the viability of human osteoarthritis chondrocytes

Summary

Introduction

Osteoarthritis (OA), a common form of arthritis, is characterized by degradation and destruction of cartilage matrix and inflammatory responses in chondrocytes [1]. Accumulating evidence suggested that inflammation played a critical role in the development of OA [2, 3]. IL-1β could induce the activation of NF-κB signaling pathway, which leads to the release of inflammatory mediators [5]. These inflammatory mediators, such as PGE2, NO, and MMP, lead to articular cartilage damage [6]. Non-steroidal anti-inflammatory drugs were often used in the treatment of OA [7]. Due to the numerous side effects, the development of effective and safe drugs to treat OA is urgently needed

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