Protective effects of ten oligostilbenes from Paeonia suffruticosa seeds on interleukin-1β-induced rabbit osteoarthritis chondrocytes

Abstract

Background: Paeonia suffruticosa is an important traditional Chinese herb used to treat osteoarthritis (OA) and oligostilbenes are the main active ingredient of the seeds of P. suffruticosa. The monomer trans-resveratrol of this species was demonstrated to have chondroprotective effects as a lead compound for the treatment of osteoarthritis, but it has not been applied due to its low efficacy. Methods: Oligostilbenes were isolated by chromatography and were identified by NMR and HPLC. A rabbit osteoarthritis chondrocyte model was induced by interleukin-1β and was treated with individual drugs to systematically evaluate their effects. Cell Counting Kit 8 was used to test their effects on cell viability, calculate EC50 and plot a dose- response curve.Their effects on apoptosis were analyzed by Annexin V and PI staining, and the expression of chondrocyte-specific genes COL2A1, MMP13 and SOX9 was evaluated by real-Time PCR. Results: Paeonia suffruticosa seed extract could promote the cell viability of rabbit OA chondrocytes at low concentration and then ten oligostilbenes were isolated from it. Trans-oligostilbenes were better than their cis-forms, trimers and dimers were better than monomers for promoting the cell viability of rabbit osteoarthritis chondrocytes. None of the oligostilbenes was more effective than seed extract at the appropriate concentration; 1 uM oligostilbenes all showed various anti-Apoptotic effects. Trans-gnetin H showed the best effect on proliferation and inhibition of MMP13 expression on OA chondrocytes, while trans-viniferin was most effective in promoting the expression of COL2A1 and SOX9. Conclusions: Ten oligostilbenes from P. suffruticosa seed all have certain protective effects on OA chondrocytes at low concentration. The trans-viniferin and some trimers have the potential to be further developed for the treatment of osteoarthritis because they were more effective than resveratrol and diacerein. The synergistic effect that may exist between oligostilbenes also warrants further research.