Gout is a kind of hyperuricemia caused by the increased synthesis or decreased excretion of uric acid due to the disorder of purine metabolism (Hutton et al. 2018). When the level of uric acid in blood is too high, uric acid is deposited in joints, soft tissues, cartilages and kidneys in the form of sodium salts, causing inflammatory reaction of tissues (Vazquezmellado et al. 2018).
In recent years, more and more attention has been paid to the use of traditional Chinese medicine and natural medicine in the treatment of gout, which has the advantages of definite efficacy, safety and less adverse reactions (Chow et al. 2019). It is believed that damp-heat, phlegm turbidity, blood stasis and insufficiency of liver, spleen and kidney are the main causes and pathogenesis of gout (Tomioka et al. 2016). Damp-heat gathering, stasis-heat accumulation, Phlegm-turbidity block and liver-kidney Yin deficiency are the basic syndromes of gout (Liang et al. 2017; Wu et al. 2014). DH and SG are Chinese medicine pairs that are often used for gout treatment (Xie et al. 2017). It has been found that 70% ethanol extract of DH can raise the expression of organic anion transporter 1 (OAT1), organic anion transporter 2 (OAT2) genes and proteins in animal kidneys, and transfer to a lower expression of urate transporter 1 (URAT1) genes and proteins (Pernthaler 2017; Nałęcz 2017). Total saponins of DH can decrease serum uric acid level in a dose-dependent manner, increase uric acid concentration and uric acid secretion, creatinine secretion, uric acid excretion fraction, glomerular filtration uric acid secretion (Wang et al. 2017; Njoum & Kyriacou 2017). The water extract of DH can down-regulate the gene expression of monocyte chemoattractant protein-1 (MCP-1) in serum and tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in kidney of rats with hyperuricemia and improve the anti-inflammatory effect of the body (Wu et al. 2019; Mahmoud et al. 2017). SG can inhibit xanthione oxidase (XOD) to reduce uric acid, alleviate oxidative stress induced by hyperuricemia, play an anti-inflammatory role, and protect kidney function (Xie et al. 2017; He et al. 2016).
Clinical studies have confirmed that IL-1β is an inflammatory factor in synovial tissue of articular cavity during the pathological process of gouty arthritis (Claude-Taupin et al. 2018; Jesus & Goldbach-Mansky 2014). The activation of NLRP3 inflammatory bodies and the release of IL-1β plays a major part in the progress of gout (He et al. 2012). MSU plays an important role in the regulation of NLRP3 gene and its expression (Yan et al. 2013; Haneklaus et al. 2013). MSU crystals can be recognized by NLRP3, which can increase the number of monocyte macrophages to phagocytize MSU crystals, destroy cell lysosomes and other organelles, release histamine and chemokines, cause local vascular dilation, leukocyte aggregation and other inflammatory reactions, and lead to acute gouty arthritis (Lee et al. 2016; Orlowski et al. 2016). NLRP3 can also form highly ordered oligomers of NLRP3 protein through ATP polymerization, and recruit Caspase 1 (CASP1) to form inflammatory bodies of NLRP3 to produce activated CASP1 (Wang et al. 2017; Duncan et al. 2018). Activated CASP1 can cleave the inactive precursor of IL-1β at 116 aspartic acid sites, and form activated mature IL-1β secreted to the outside of the cell, resulting in inflammation and immune response (Feng et al. 2017; Clipman et al. 2018; Afonina et al. 2017). P2RX7 gene plays an important role in monocytes and innate immunity, including Toll-like receptor-mediated Nuclear factor-kappa B (NF-κB) pathway and NALP3 inflammatory body pathway (Kim et al. 2018; Notomi et al. 2011). P2RX7 may be associated with the risk of primary gout in Chinese Han male population (Ying et al. 2017). When extracellular ATP concentration changes dramatically, P2X7 receptors are activated and opened, resulting in K+ outflow and Na+ and Ca2+ influx, which further leads to the release and activation of NLRP3 inflammatory bodies leading to acute gout attacks (Giacovazzo et al. 2018; Di Virgilio et al. 2017; Paredes et al. 2018). Some studies have pointed out that STS can inhibit MSU crystal–induced interleukin (IL) -1β secretion in primary human macrophages (Karmegam and Shetty 2017; Zhang et al. 2017; Henry et al. 2014). Also, STS decreases IL-1β in supernatants upon absent in melanoma 2 (AIM2) activation (Barnes 2018). IRF6 regulates NLRP3 inflammatory bodies, induces degradation of extracellular matrix of chondrocytes, and plays a considerable part in cartilage destruction of gouty arthritis diseases (Kumari et al. 2018). NADPH oxidase activates ROS1 to produce enhanced trigger redox sensitive pathways (Joo & Rhie 2017). Hyperuricemia increases ROS1 production through activation of NADPH oxidase and xanthine oxidase (Roskoski 2017). ATP8A2 promotes the chemotaxis of inflammatory cells by recognizing CX3C chemokine receptor 1 (CX3CR1) and acts a momentous part in the pathological process of inflammatory reaction including ROS1 aggregation and adhesion (Wang et al. 2018; Coleman et al. 2012). EPHB2 is involved in the regulation of T cell migration and monocyte activation (Alapin et al. 2020). Some studies have shown that EPHB2 has some effects on the proliferation of vascular smooth muscle cells and the secretion of ROS1 to emerge redox sensitive pathways (Pozniak et al. 2016; Min et al. 2016; Gaitanos et al. 2016). Activated PRKAA1 can enhance inhibitor of NF-κB, α isoform (IKBα) expression from cytoplasm to nucleus and regulate the activity of NF-κB pathway to act on NLRP3 inflammatory bodies (Krishan et al. 2014). SLC22A12 is a uric acid anion exchanger of uric acid-converting protein gene in kidney, which can regulate the concentration of uric acid in human blood (Vázquez-Mellado et al. 2017; Shima et al. 2006; Kuriyama 2020). Experiments showed that the reabsorption of uric acid by kidneys of mice knocked out SLC22A12 gene by gene knockout test was significantly reduced (Arakawa et al. 2020).