Modified Simiaowan prevents articular cartilage injury in experimental gouty arthritis by negative regulation of STAT3 pathway
- J Ethnopharmacol. 2021 Apr 24;270:113825. doi: 10.1016/j.jep.2021.113825.
- 1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 2. China Pharmaceutical University, Nanjing, 210009, China. Electronic address: [email protected].
- 3. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 4. Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, 210029, China. Electronic address: [email protected].
- 5. Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Outfall Road, Lahore, 54600, Pakistan.
- 6. Nanjing Xinbai Pharmaceutical Co., Ltd, Nanjing, 210023, China. Electronic address: [email protected].
- 7. Nanjing Xinbai Pharmaceutical Co., Ltd, Nanjing, 210023, China. Electronic address: [email protected].
- 8. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 9. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 10. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 11. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 12. Nanjing Xinbai Pharmaceutical Co., Ltd, Nanjing, 210023, China. Electronic address: [email protected].
- 13. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 14. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
- 15. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: [email protected].
Ethnopharmacological relevance: Modified Simiaowan (MSW) is a traditional Chinese medicine formula that is composed of six herbs. It has been widely used in the treatment of gouty arthritis.
Aim of the study: This study was designed to investigate the effect of MSW on gouty arthritis and explore the possible mechanisms.
Material and methods: The rat gouty arthritis model was established by intra-articular injection of Monosodium Urate (MSU) crystal, and then treated with MSW for 5 days. The perimeter of the knee joints was measured in a time-dependent manner and serum samples were collected for the detection of TNF-α, IL-1β, and IL-6 protein levels by ELISA. The protein expressions of MMP-3, TIMP-3, STAT3, and p-STAT3 in cartilage tissues and C28/I2 cells were detected by Western blot, and the levels of proteoglycan in primary chondrocytes and cartilage tissues were determined by toluidine blue staining. In addition, AG490 and IL-6 were used in vitro to explore the function of IL-6/STAT3 pathway in the protective effect of MSU.
Results: MSW reduced the joint swelling rate in gouty arthritis model and inhibited MSU induced up-regulation of IL-1β, TNF-α, and IL-6 protein levels in serum and synovial fluid. IL-1β induced an increase in p-STAT3 and MMP-3 protein expression in C28/I2 cells, as well as a decrease in TIMP-3. MSW serum inhibited the protein expression changes induced by IL-1β in vitro. Furthermore, inhibition of STAT3 signaling negated the effect of MSW serum on p-STAT3, MMP-3, and TIMP-3 protein levels in C28/I2 cells. MSW also increased the content of proteoglycan significantly both in vivo and in vitro.
Conclusion: Our data indicated that MSW protected rats from MSU-induced experimental gouty arthritis and IL-1β/IL-6/STAT3 pathway played an essential role in the protective effect of MSU against GA.