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Excessive inflammation contributes greatly to the pathogenesis and development of rheumatoid arthritis (RA). Oroxylin A (OA) is a natural anti-inflammatory flavonoid compound. In this study, we investigated the effects of OA on collagen-induced arthritis (CIA) and human RA fibroblast-like synoviocytes (FLS). CIA was induced in DBA/1 mice and mice were intraperitoneally treated with OA (10 mg/kg) for 10 days. Arthritis severity was evaluated every day and the histopathologic examination of joints was done. Serum levels of anti-collagen II antibodies (anti-CII Abs) and cytokines were determined by ELISA. Frequency of regulatory T cells (Tregs) and Th17 cells in draining inguinal lymph nodes (ILN) was quantified by flow cytometry. FLS from patients with active RA were treated with varying doses of oroxylin A, followed by stimulation with tumor necrosis factor (TNF)-α (10 ng/mL). The production of cytokines was measured by ELISA. Signal transduction proteins were examined by western blot. OA significantly diminished the arthritis and histological damage. Serum anti-CII Abs, IL-1β, IL-6, TNFα, and IL-17 were significantly diminished by OA treatment. Analysis of CD4 + T cell populations in OA-treated mice showed an increase in Tregs and reduction in Th17 cells in the ILN. In vitro, OA decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA FLS in a dose-dependent manner. TNFα-induced p38 MAPK, ERK1/2 and NF-κB signaling pathways were suppressed by OA. Our results indicate that OA exerts an anti-inflammatory activity and may have therapeutic potential for human RA. [ABSTRACT FROM AUTHOR]

The imbalance between glucose metabolism and cancer cell growth in tumor microenvironment (TME), which are closely related with the occurrence and progression of cancer. Accumulating evidence has demonstrated that flavonoids exert many biological properties, including antioxidant and anticarcinogenic activities. Recently, the roles and applications of flavonoids, particularly in relation to glucose metabolism in cancers, have been highlighted. Thus, the identification of flavonoids targeting alternative glucose metabolism pathways in TME may represent an attractive approach to the more effective therapeutic strategies for cancer. In this review, we will focus on the roles of flavonoids in regulating glucose metabolism and cancer cell growth in TME, such as proliferation advantage, cell mobility, and chemoresistance to cancer, as well as modifiers of thermal sensitivity. Not only have such large-scale endeavors been useful in providing fundamental insights into natural and synthesized flavonoids that can prevent and treat cancer, but also have led to the discovery of potential targets for cancer therapy. [ABSTRACT FROM PUBLISHER]