Modified Simiaowan prevents articular cartilage injury in experimental gouty arthritis by negative regulation of STAT3 pathway.

Abstract

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.

• Authors: Le Shi, Ziqiao Yuan, Jing Liu, Rui Cai, Muhammad Hasnat, Hui Yu, Jing Feng, Zhanglian Wang, Qianqian Zhao, Min Wu, Xinxin Huang, Fei Shen, Lian Yin, Yun Yu, Tao Liang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 270 Pg. 113825 (Apr 24 2021) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 33460754 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Drugs, Chinese Herbal
• Interleukin-1beta
• Protective Agents
• Proteoglycans
• STAT3 Transcription Factor
• STAT3 protein, human
• Stat3 protein, rat
• simiaowan
• Uric Acid

Topics

• Animals
• Arthritis, Gouty (chemically induced, drug therapy)
• Cell Line
• Chondrocytes (drug effects)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Edema (chemically induced, drug therapy)
• Humans
• Interleukin-1beta (toxicity)
• Male
• Protective Agents (pharmacology, therapeutic use)
• Proteoglycans (drug effects)
• Rabbits
• Rats, Sprague-Dawley
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Uric Acid (toxicity)
• Rats