ABSTRACT
The present review expounds the advancements in the application and mechanisms of flavonoids in gouty arthritis, highlighting their significance in managing the disease. Gouty arthritis is among the most common and severe inflammatory diseases, caused by hyperuricemia and the deposition of sodium urate crystals in the joints and surrounding tissues, posing a serious threat to human life and health. Flavonoids, extracted from various herbs, have attracted significant attention due to their efficacy in improving gouty arthritis. The present study systematically reviews the in vivo studies and in vitro animal studies on flavonoids from herbal medicines for the treatment of gouty arthritis that have been previously published in the PubMed, ScienceDirect, Google Scholar and China National Knowledge Infrastructure databases between 2000 and 2023. The review of the literature indicated that flavonoids can improve gouty arthritis through multiple mechanisms. These include lowering xanthine oxidase activity, inhibiting uric acid (UA) synthesis, regulating UA transporters to promote UA excretion, reducing the inflammatory response and improving oxidative stress. These mechanisms predominantly involve regulating the NODlike receptor 3 inflammasome, the Tolllike receptor 4/myeloid differentiation factor 88/nuclear factorκB signaling pathway, and the levels of UA transporter proteins, namely recombinant urate transporter 1, glucose transporter 9, organic anion transporter (OAT)1 and OAT3. Various flavonoids used in traditional Chinese medicine hold therapeutic promise for gouty arthritis and are anticipated to pave the way for novel pharmaceuticals and clinical applications.
Subject(s)
Arthritis, Gouty , Flavonoids , Uric Acid , Arthritis, Gouty/drug therapy , Arthritis, Gouty/metabolism , Humans , Flavonoids/therapeutic use , Flavonoids/pharmacology , Flavonoids/chemistry , Animals , Uric Acid/metabolism , Signal Transduction/drug effects , Xanthine Oxidase/metabolism , Xanthine Oxidase/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oxidative Stress/drug effects , Hyperuricemia/drug therapy , Hyperuricemia/metabolismABSTRACT
Yajieshaba (YJSB), a traditional Dai medicine formula containing botanical drugs, is commonly employed in Yunnan due to its significant therapeutic effects on liver protection. Consequently, to determine the efficacy of YJSB and the mechanism of action of Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway against liver fibrosis. We wanted to see if YJSB could treat CCl4-induced liver fibrosis by regulating the Keap1-Nrf2 signaling pathway. YJSB significantly improved liver function biochemical indices, liver fibrosis quadruple, hydroxyproline (Hyp), and transforming growth factor-ß1 (TGF-ß1) levels. The staining results demonstrated that the degree of liver fibrosis was significantly reduced. YJSB reduced the content of malondialdehyde (MDA) and elevated the content of superoxide dismutase (SOD) in the liver, exhibiting antioxidant effects; meanwhile, it regulated the expression of Keap1-Nrf2 pathway protein, increased the expression of NAD(P)H: Quinone oxidoreductase (NQO1), Heme Oxygenase 1 (HO-1), Glutamate cysteine ligase modifier subunit (GCLM), and Glutamate cysteine ligase catalytic subunit (GCLC) expression in the liver decreased while Nrf2 expression increased. Fluorescence immunoassay studies demonstrated that YJSB promoted the trans-nuclearization of Nrf2. YJSB possesses anti-liver fibrosis pharmacological effects that improve liver function and effectively counteract CCl4-induced liver fibrosis damage. The mechanism of action might be related to the regulation of protein expression of the Keap1-Nrf2 pathway, increasing the ability of the body to resist oxidative stress and reduce oxidative stress injury.
