The fibroblast-like synoviocytes (FLSs) are highly specialized mesenchymal cells found in the synovial membrane. The synovium is considered to be a structure of connective soft-tissue membrane located in the joint cavity and the fibrocartilage, around arthrosis to provide nutrition and lubrication ( Jay et al., 2000). There is an urgent need to continuously develop new anti-RA drugs. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) show therapeutic effects for RA, but there are some individual differences because of different genetic backgrounds and environmental stimuli ( Lampropoulos et al., 2015), and they do not cure the disease ( Yamada, 2023). In addition, there are also problems of high expense and gastrointestinal adverse effects for DMARDs ( Zhang et al., 2019). DMARDs such as methotrexate (MTX), while suppressing inflammation and joint destruction, might cause nausea, anorexia, stomatitis, alopecia, myelosuppression, and even liver and pulmonary toxicity in severe cases, which requires careful monitoring. With the use of NSAIDs, the risk of cardiovascular disease might occur as well as gastrointestinal side effects, so a comprehensive evaluation is needed ( O'Shea et al., 2013). Currently, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) (synthetic or biologic agents), and glucocorticoids ( Lampropoulos et al., 2015 Zhang et al., 2022) are popular in the treatment of RA. A lot of attention is paid to the treatment of RA because it has high morbidity, might lead to disability, and has poor prognosis ( Davis et al., 2012 Almutairi et al., 2021). It shows the clinical presentation of joint pain, thickening of the synovial membrane, pannus formation, and infiltration of various inflammatory cells in the joint space, leading to the damage of the cartilage as well as bone tissue, even remarkably joint deformity and dysfunction ( Smolen et al., 2018). Among the multiple factors, genetic and autoimmune along with environmental factors might be the primary causes. RA might affect 0.5%–1% of the global population ( Zhang et al., 2022). It often occurs in women and the elderly. Rheumatoid arthritis (RA) is a type of autoimmune joint disease. There is an urgent need to unremittingly develop new agents for RA.
#PRO CSGO STATS TRIAL#
Meanwhile, most natural products are currently in the experimental stage, not the clinical trial stage, such as triptolide. A small number of synthetic small molecule compounds have entered the clinic to treat RA and are often used in combination with other drugs. Compared with MAPK and NF-κB signaling pathways, the JAK/STAT signaling pathway has great potential for research as targets. In the end, there were some views for further action. Based on this, we summed up the pathological mechanism of RA-FLS and reviewed the recent progress of small molecule drugs, including the synthetic small molecule compounds and natural products targeting RA-FLS. Evidently, it is a highly promising way to target the pathological function of FLS for new anti-RA drugs. In RA, FLS exhibits a uniquely aggressive phenotype, leading to synovial hyperplasia, destruction of the cartilage and bone, and a pro-inflammatory environment in the synovial tissue for perpetuation and progression. In the pathological process of RA, the alteration of fibroblast-like synoviocyte (FLS) and its related factors is the main influence in the clinic and fundamental research. Rheumatoid arthritis (RA) is a type of chronic autoimmune and inflammatory disease. 3School of Chinese Medicine, The University of Hong Kong, Shatin, Hong Kong SAR, China.2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.1Chengdu Second People’s Hospital, Chengdu, Sichuan, China.Yitong Tong 1 † Xinyu Li 2 † Qichuan Deng 2 Jianyou Shi 2* Yibin Feng 3* Lan Bai 2*
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