4. Discussion
cancer, vasculitis, pain, RA synovitis, morning stiffness, Synovitis, pannus, joints, RA
INS, CANCER, VASCULITIS, DISEASE, NEOVASCULARIZATION, SYNOVITIS, PANNUS, PATHOLOGY
The clinical drugs used for the treatment of RA can be broadly classified into 2 categories according to their mode of action: those for the improvement of symptoms and those for the improvement of cartilage metabolism. However, symptom improvement drugs cannot fundamentally reverse the development of RA pathology. With the development of Chinese medicine extraction technology, the application of Chinese medicine preparation extracts for the treatment of RA has been increasingly reported and supported by relevant basic experimental studies. JSQS can effectively protect chondrocytes and maintain the integrity of cartilage, reduce the level of inflammatory cytokines, and play a certain therapeutic role in RA.In this study, 141 chiropteran capsule targets were mapped to 4791 RA target genes, 118 anti-RA key targets of JSQS were obtained, and a JSQS-key target-RA composite target network map was constructed. The quercetin in Quercetin has an anti-inflammatory effect on RA by reducing the ratio of MMP-13/TIMP-1, promoting the inhibition of cartilage extracellular matrix degradation, and protecting articular cartilage.The results of KEGG enrichment analysis showed that JSQS were mainly used to treat RA through the pathways in cancer, phosphatidylinositol-3-kinaseRAC–serine/threonine-protein kinase signaling pathway, MAPK signaling pathway, and aryl hydrocarbon receptor nuclear translocator signaling pathway, among others. The topological analysis of this study showed that TP53, INS, IL6, VEGFA, MYC, CASP3, ESR1, EGF, CCND1, PPARG, ERBB2, NFKBIA, TLR4, RELA, and CASP8 are the core key targets. Molecular docking was performed according to the corresponding active chemical components, suggesting binding fractions of >70 between PPARG and VEGFA and 3,5-dimethyl-4-hydroxybenzaldehyde, protocatechuic-aldehyde, vanillic acid, which had good binding energy. It indicated that these active chemical components might play an important role in RA treatment. However, further in vivo and in vitro studies are needed to confirm the possible existence of a therapeutic axis.PPAR, a member of the nuclear receptor superfamily that regulates lipid, glucose, and amino acid metabolism,Synovitis and vasculitis of joints are the basic pathological factors of RA. Neovascularization is considered to be one of the main factors in the formation and maintenance of pannus in RA, and some studies have shown that VEGF can increase vascular permeability and play a very critical role in the formation and development of pannus in RA synovitis.This study identified the possible material basis and molecular mechanism of JSQS in RA treatment. Thus, our team conducted a controlled clinical trial to verify the therapeutic effect of JSQS in RA treatment. The results showed that the capsules could effectively improve morning stiffness, joint pain, VAS score, other indicators of RA, clinical symptoms, and patient quality of life. The results of laboratory tests, such as ESR, CRP, RF, and anti-CCP, also indicated effective disease control, reduced levels of inflammation-related factors, such as TNF-α, IL-6, and IL-17, and significantly improved Th17/Treg balance. In conclusion, the multicomponent, multipathway, and multitarget synergistic interventions of JSQS can significantly improve clinical symptoms and quality of life of RA patients and delay the progression of the disease. Insufficient sample size is a regret of this study due to time and financial constraints. After obtaining the preliminary results, we will carry out a multicenter study, and at the same time, we will optimize the design of the study protocol on the line, in order to provide a theoretical basis and guidance for the clinical application of Chinese medicine.