Background: Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis. Object: To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level. Methods: We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts. Results: In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling. Conclusions: Quercetin’s action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status.

A metal-free three-component protocol for quinoline synthesis is developed by using alkyl lactates, anilines and α-keto acids. In vitro experiments disclose the attractive anti-inflammatory activity of these quinoline compounds.

Rheumatoid arthritis (RA) is a complex autoimmune joint disease characterized by persistent synovial inflammation and hyperplasia. The TNF-α/NF-κB signaling pathway is one of the most important inflammatory pathways involved in the onset and progression of RA. In addition, impaired lymphatic drainage plays a critical role in disease exacerbation. Iguratimod (IGU), a novel disease-modifying antirheumatic drug, has been shown to exert immunomodulatory effects. However, the precise mechanisms underlying its anti-inflammatory function remain unclear. Furthermore, whether IGU could restore lymphatic reflux function in inflammatory arthritis has yet to be determined. Therefore, the study aimed to elucidate the mechanisms underlying the therapeutic effects of IGU in RA. The therapeutic efficacy of IGU was evaluated in a collagen-induced arthritis (CIA) mouse model, with methotrexate used as a positive control. Histopathological analyses of footpad and ankle tissues were performed to asses of disease onset and progression. Levels of inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-4, and IL-6) and IgG autoantibody (such as anti-CCP antibody) were determined using ELISA. Lymphangiogenic markers, including VEGF-C, VEGFR-3, and LYVE-1, were assessed in ankle joint tissues. The protein and mRNA expression levels of TNF-α and NF-κB in joint tissues were also evaluated. In addition, an in vitro tube formation assay was performed to examine the direct effects of IGU on lymphangiogenesis. IGU treatment significantly alleviated arthritis severity in CIA mice by reducing joint inflammation, minimizing tissue damage, and preserving bone integrity. Beyond its established anti-inflammatory properties, IGU could enhance lymphangiogenesis in inflamed joints. Mechanistically, IGU suppressed the TNF-α/NF-κB signaling pathway, thereby attenuating immune responses and inflammatory cytokine production. Furthermore, IGU directly promoted lymphatic vessel formation by upregulating LYVE-1, Prox-1, VEGF-C, and VEGFR-3 in lymphatic endothelial cells. The effect might contribute to the restoration of lymphatic drainage function. The study suggests that IGU exerts a dual therapeutic action by modulating inflammation and promoting lymphatic vessel formation, which might facilitate the restoration of lymphatic drainage and contribute to improved outcomes in RA.