4.7 Article

Asiatic acid protects articular cartilage through promoting chondrogenesis and inhibiting inflammation and hypertrophy in osteoarthritis

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 907, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ejphar.2021.174265

Keywords

Osteoarthritis; Chondrocytes; NF-kappa B signaling pathway; Inflammation; Asiatic acid

Funding

  1. National Natural Science Foundation of China [81772322, 81874000]
  2. Hong Kong Government Research Grant Council, General Research Fund [14120118, C7030-18G, T13-402/17-N]
  3. Hong Kong Medical Research Funds [16170951, 17180831]
  4. Natural Science Foundation of Guangdong Science and Technology Department [2019A1515110724, 2018A030313374]
  5. Guangdong Traditional Chinese Medicine Bureau Fund [20191184]
  6. Hong Kong Innovation Technology Commission Funds [PRP/050/19FX]
  7. SMART program, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong

Ask authors/readers for more resources

The study showed that asiatic acid (AA) can effectively inhibit inflammation, promote chondrocyte formation, and protect cartilage from degeneration and destruction by inhibiting NF-kappa B signaling activity, providing a new therapeutic strategy for treating osteoarthritis.
Natural small molecules have become attractive in osteoarthritis (OA) treatment. This study aims to investigate the effect of asiatic acid (AA) on OA development in vitro and in vivo. Chondrocytes were pretreated with AA at optimized concentrations and subsequently treated with interleukin-1 beta (IL-1 beta). Inflammatory mediator nitric oxide (NO) was measured by Griess method. The mRNA expression level of inflammatory markers nitric oxide synthase (iNOS) and cyclooxygenase 2 (Cox2), as well as chondrogenic or hypertrophic markers including SRYbox transcription factor 9 (Sox9), Aggrecan, Collagen 2a1 (Col II), and Matrix metalloproteinase-13 (Mmp13) were measured by using real-time PCR analysis. The nuclear factor-kappa B (NF-kappa B) signaling activity was determined by dual luciferase assay and Western blot analysis. Surgery-induced OA animal model was constructed, and AA was administrated to study its effect on OA pathogenesis. AA induced a dose-dependent inhibitory effect up to -67.4% on NO production. AA could repress iNOS and Cox2 protein expression levels (-77.2% and -73.4%, respectively) in IL-1 beta induced chondrocytes. AA increased the formation of cartilage extracellular matrix components including glycosaminoglycans (GAGs) and collagen type II. AA also mRNA expression of chondrogenesis marker including Aggrecan, Sox9, Col II and Fibronectin (402.87%, 151.04%, 314.15% and 187.76%, respectively) as well as hypertrophic marker Mmp13 (-67.8%). AA repressed the chondrocyte inflammation by directly inhibiting NF-kappa B signaling activity, which was revealed by the inhibition effect of AA on I kappa B alpha phosphorylation (-105.4%) and NF-kappa B/p65 translocation (-60.9%) induced by IL-1 beta. Furthermore, In vivo OA study indicated the protective effect of AA on OA progression by preventing articular cartilage from degeneration and destruction. AA treatment could significantly reduce OA score (16.125 vs 5.25) and repress mRNA expression level of Mmp13 and Col X (23.5, vs 2.375 and 18.125 vs 94.5). Taken together, our findings suggest that AA could effectively rescue IL-1 beta induced chondrocytes and protected cartilage in OA progression, which shed light on a potential novel therapeutic strategy of OA treatment.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available