Abstract

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.

Details

Title
A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
Author
Chen, Ying-Jie 1 ; Yu-Xi, Liu 2 ; Jia-Ying, Wu 2 ; Chun-Yu, Li 3 ; Min-Min, Tang 3 ; Lu, Bai 3 ; Fu Xiu-Qiong 2 ; Jun-Kui, Li 2 ; Ji-Yao, Chou 2 ; Cheng-Le, Yin 2 ; Wang, Ya-Ping 2 ; Jing-Xuan, Bai 2 ; Wu, Ying 2 ; Xiao-Qi, Wang 2 ; Zhi-Ling, Yu 4 

 HKBU Shenzhen Research Institute and Continuing Education, Research and Development Centre for Natural Health Products, Shenzhen, China; Hong Kong Baptist University, Centre for Cancer and Inflammation Research, School of Chinese Medicine, Kowloon Tong, China (GRID:grid.221309.b) (ISNI:0000 0004 1764 5980) 
 HKBU Shenzhen Research Institute and Continuing Education, Research and Development Centre for Natural Health Products, Shenzhen, China (GRID:grid.221309.b); Hong Kong Baptist University, Centre for Cancer and Inflammation Research, School of Chinese Medicine, Kowloon Tong, China (GRID:grid.221309.b) (ISNI:0000 0004 1764 5980) 
 Hong Kong Baptist University, Centre for Cancer and Inflammation Research, School of Chinese Medicine, Kowloon Tong, China (GRID:grid.221309.b) (ISNI:0000 0004 1764 5980) 
 HKBU Shenzhen Research Institute and Continuing Education, Research and Development Centre for Natural Health Products, Shenzhen, China (GRID:grid.221309.b); Hong Kong Baptist University, Centre for Cancer and Inflammation Research, School of Chinese Medicine, Kowloon Tong, China (GRID:grid.221309.b) (ISNI:0000 0004 1764 5980); Hong Kong Baptist University, Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Kowloon Tong, China (GRID:grid.221309.b) (ISNI:0000 0004 1764 5980) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2489907331
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.