Emerging evidences have suggested that gout caused by monosodium urate deposition is related to disorders of purine metabolism and reduced uric acid excretion, so it is classified as a metabolic rheumatism. However, in recent studies it has been found that the pathogenesis is closely related to the mechanism of “metabolism-inflammation-immunity” . TCM treatment for gout, especially the formulas from Synopsis of Golden Chamber could interfere the mechanism of “metabolism-inflammation-immunity” .
The pharmacological mechanism of Simiao Powder and it’s modification in the treatment of gout
Simiao Powder is composed of Cortex Phellodendri Amurensis, Semen Coicis, Radix Achyranthis Bidentatae and Rhizoma Atractylodis Lanceae. All the herbs in the Simiao Powder are also the major ingredients in the Jiawei Simiao Powder, Tongfeng Decoction and Danxi Tongfeng Decoction. According to TCM theory, Cortex Phellodendri Amurensis is bitter in flavor and has curative effects on the kidneys, bladder and large intestine. The main medicinal components of Cortex Phellodendri Amurensis are alkaloids such as berberine, lipoid and sterol , with the function of anti-inflammation, bacteriostasis, cellular immune regulation, anti-gout and inhibiting the apoptosis of articular chondrocytes . Rhizoma Atractylodis Lanceae is pungent and bitter in flavor, and usually works on the kidneys, bladder and large intestine. It has the function of anti-bacterium, anti-inflammation, reducing blood glucose level and suppressing central nervous system . Satoh et al.  found that Rhizoma Atractylodis Lanceae could inhibit the activity of sodium–potassium-ATPase, prevent the absorption of water and sodium ions, and thus to promote urination and excretion.
Radix Achyranthis Bidentatae is sweet in flavor, has the function of reinforcing liver and kidneys, strengthening muscles and bones, and promoting urination, and usually works on the liver and kidneys. It is reported that Radix Achyranthis Bidentatae could promote the excretion of uric acid, improve the cellular and humeral immunity as well as the non-specific immune function .
The combination of Cortex Phellodendri Amurensis, Radix Achyranthis Bidentatae and Rhizoma Atractylodis Lanceae can reduce the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in synovial tissue. Having the function of anti-inflammatory and inhibiting cyclooxygenase-2 (COX-2), Semen Coicis Albais could works on regulating purine metabolism and reducing uric acid formation . After Semen Coicis Albais is added, this combination of four herbs becomes Simiao Powder, which has good effect on the patient with gout of dampness-heat type . Wang et al.  suggested that modified Sanmiao Powder could inhibit the content of inflammatory factors in the joint fluid of rats with acute gout arthritis.
Although Jiawei Simiao Powder, Tongfeng Decoction and Danxi Tongfeng Decoction are all invented based on Simiao Powder, the pharmacological mechanisms of these TCM formulas are different. Oral administration of Jiawei Simiao Powder and combined with external application of Jinhuang Cream could relieve the inflammation by reducing the levels of ESR, CRP and IL-8 . Tongfeng Decoction could effectively reduce SUA, inhibit inflammatory response, halt the progression of the disease, and have the function of reducing uric acid . Danxi Tongfeng Decoction could reduce ESR and SUA levels, and has a good analgesic effect .
The pharmacological mechanism of Wuwei Xiaodu Decoction in the treatment of gout
Wuwei Xiaodu Decoction, composed of Flos Lonicerae, Flos Dendranthematis Indici, Herba Taraxaci Mongolici, Herba Violae Philippicae and Nudicaulous Grounsel Herb, is firstly recorded in Golden Mirror of the Medical Tradition. It is recorded that Flos Lonicerae, Flos Dendranthematis Indici and Nudicaulous Grounsel Herb have the function of anti-inflammation and immunomodulation [46,47,48]. Some researchers find that Herba Taraxaci Mongolici has the function of anti-bacteria, anti-oxidation, anti-inflammation, diuresis, anti-allergy, promoting immunity, and is beneficial for the stomach . Because of its strong effect of anti-pathogenic microorganisms, Herba Violae Philippicae is often used in the treatment of ulcers and carbuncle with symptoms like swelling and pain . It is believed that Wuwei Xiaodu Decoction can enhance the immunity of diseased mice and reduce the IL-10 to the normal level . Besides, another report also illustrates that Wuwei Xiaodu Decoction could increase the phagocyte index and phagocyte rate of macrophages, adjust the balance of flora and thus enhance the immune function .
The pharmacological mechanism of Zhuye Shigao Decoction in the treatment of gout
Zhuye Shigao Decoction is composed of Folium Phyllostachydis Henonis, Gypsum Fibrosum, Rhizoma Pinelliae Praeparatum, Radix Ginseng, Radix Ophiopogonis, Oryza Sativa L., Radix Ophiopogonis Japonicir and Radix et Rhizoma Glycyrrhizae. Wang et al.  held that gout was caused by dampness accumulation and heat blocking the meridians and collaterals, so he adopted the methods of clearing heat and resolving dampness, unblocking the collaterals and relieving pain, and applied Zhuye Shigao Decoction for the treatment. Chen et al.  found that after being treated with modified Zhuye Shigao Decoction, serum levels of IL-1β and caspase-1 were reduced, and the expression levels of pro-IL-1 and pro-caspase-1 were down-regulated, suggesting that the modified Zhuye Shigao Decoction could inhibit the inflammation induced by sodium urate crystals, which may be related to the intervention of IL-1 signaling pathway.
The pharmacological mechanism of Qingre Chubi Decoction in the treatment of gout
There are two formulas named as Qingre Chubi Decoction which are of different compositions and similar effects. In one Qingre Chubi Decoction, the ingredients include Herba Aristolochiae Mollissimae, Caulis Sinomenii, Radix Cudraniae Cochinchinensi, Rhizoma Atractylodis Lanceae, and Rhizoma Anemarrhenae. Another Qingre Chubi Decoction is composed of Caulis Sinomenii, Caulis Piperis Kadsura, Ramulus Mori, Radix Stephaniae Tetrandrae Herba Lycopi Hirtiaa, Radix et Rhizoma Clematidis, Rhizoma Smilacis Glabrae and Lumbricus. Wang et al.  confirmed that the first Qingre Chubi Decoction could relieve the symptoms of patients such as feverish sensation, joint swelling and pain, and reduce the inflammatory indicators such as ESR and CRP. Some studies suggested that Qingre Chubi Decoction might inhibit the release of IL-1β and TNF-α to ameliorate the acute inflammatory response of gout . Additionally, Qingre Chubi Decoction inhibited the proliferation of THP-1 cells stimulated by MSU crystals. The inhibition of monocyte activity and IL-1β may be one of the anti-inflammatory mechanisms of Qingre Chubi Decoction .
The pharmacological mechanism of Tongfengshu Capsule in the treatment of gout
Tongfengshu Capsule, composed of Radix et Rhizoma Rhei Palmati, Semen Plantaginis, Rhizoma Alismatis, Radix Achyranthis Bidentatae and Radix Stephaniae Tetrandrae, is a Chinese patent medicine. Rheum emodin, one chemical component from Radix et Rhizoma Rhei Palmati, could inhibit the expression of NOD-like receptor family pyrin domain-containing 3 (NLRP3) and IL-1 mRNAs  and inhibit the activation of extra cellular signal–regulated kinases 1 and 2 (ERK1/2) and p38 nitrogen-activated protein kinases (p38 MAPK) signaling pathways by inhibiting the expression of ERK1/2 nucleus and p38MAPK, thereby reducing the release of inflammatory factors . Semen Plantaginis and Rhizoma Alismatis could promote urination, and reduce swelling and pain. Among them, Semen Plantaginis, rich in mullein glycolic anhydride, could promote uric acid secretion, reduce the creatinine level, scavenge reactive oxygen species (ROS) and improve renal function . In addition, it is reported that the ethanol extract of Rhizoma Alismatis could reduce SUA level without damaging renal function . Radix Stephaniae Tetrandrae has the function of dispelling wind, relieving pain and inducing diuresis to alleviate edema. Tetrandrine, the active ingredient of Radix Stephaniae Tetrandrae could inhibit the inflammatory response of cells, and this anti-inflammation mechanism may be related to inhibiting nuclear factors such as NF-κB, reducing IL-6 and TNF-α levels, and promoting the expression of anti-inflammatory cytokines such as IL-10 . It is also reported that Radix Achyranthis Bidentatae could increase superoxide dismutase (SOD) activity, reduce serum lipid peroxide level, and regulate immunity and metabolism of the body . Based on the previous study, the anti-inflammation mechanism of Tongfengshu Capsule may be related to inhibiting the synthesis or release of prostaglandin E2 (PGE2), reducing the production of inflammatory cytokines like TNF-α and resisting lipid peroxidation . It was also found that Tongfengshu capsule could significantly relieve symptoms of joints in rats with acute gout arthritis, suggesting the mechanism might be related to reducing IL-1β and TNF-α levels, inhibiting the expression of malonic dialdehyde (MDA) and nitrogen oxide (NO), and promoting the release of SOD . Besides, some researchers proposed that the therapeutic mechanism of Tongfengshu Capsule in the treatment of gout arthritis was related to the down-regulation of serum levels of high mobility group protein 1 (HMGB l) and receptor for advanced glycosylation end-products (RAGE) in patients with gout .
The pharmacological mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gout
Guizhi Shaoyao Zhimu Decoction, firstly recorded in the TCM classics, Synopsis of the Golden Chamber, is composed of Herba Ephedrae Sinicae, Ramulus Cinnamomi, Radix Saposhnikoviae, Largehead Atractylodes Rhizome, Radix Aconiti Lateralis Praeparata, Rhizoma Anemarrhenae, Radix Paeoniae Alba, Radix et Rhizoma Glycyrrhizae and Rhizoma Zingiberis Recens. Herba Ephedrae Sinicae, could scavenge ROS and had significant antioxidant effects . In addition to anti-bacterium, anti-virus and anti-inflammation effects [66, 67], Ramulus Cinnamomi and Radix Saposhnikoviae can also stimulate the secretion of saliva and gastric juice and stimulate sweat glands to dissipate heat . Largehead Atractylodes Rhizome and Radix Aconiti Lateralis Praeparata have the function of warming channels to dispel coldness. It is recorded that Rhizoma Anemarrhenae and Radix Paeoniae Alba could nourish yin and clear heat. It took the researchers 5 years to find that Guizhi Shaoyao Zhimu Decoction has the function of relieving pain, anti-inflammation and healing bone injury. Besides, it also could induce apoptosis of synovial cell, regulate immunity, and promote uric acid excretion, and protect renal function to treat gout arthritis . Some researchers proposed that the mechanism underlying the Guizhi Shaoyao Zhimu Decoction in the treatment of gout arthritis was related to reducing the expression of Toll-like receptor (TRL)-2, TRL-4, NLRP3 receptor, myeloid differentiation factor (MyD)88 and apoptosis-associated speck-like protein (ASC), increasing the expression of peroxisome proliferator-activated receptor (PPAR)-γ and inhibitor-κB (IκB)-α, inhibiting the differentiation and maturation of IL-1β and the activation of NF-κB .
The pharmacological mechanism of Tongfengan Mixture in the treatment of gout
Tongfengan Mixture, composed of Herba Lysimachiae, Semen Sinapis, Thallus Ulvae Fasciata, Spora Lygodii, Rhizoma Smilacis Glabrae, Flos Carthami, Radix Paeoniae Rubra, Pseudobullbus Cremastrae, Rhizoma Alismatis and Rhizoma Corydalis, has the function of softening hardness and dissipating mass. It is found that in the rat models, Tongfengan Mixture can relieve the swelling, reduce the level of MSU crystals in the ankle joints, and reduce the inflammatory reaction, which may be achieved by reducing the inflammatory reaction in the blood . Liu et al.  suggested that Tongfeng Mixture could inhibit the secretion of inflammatory factors like IL-1β, TNF-α and NF-κB in the synovial tissue of the ankle joint of rats by clearing away urate crystals, and reducing the inflammation.
The pharmacological mechanism of Quzhuo Tongbi Decoction in the treatment of gout
There are two formulas name as Quzhuo Tongbi Decoction which are of different compositions and similar effects. In one Quzhuo Tongbi Decoction, the ingredients include Rhizoma Smilacis Glabrae, Rhizoma Dioscoreae, Stigma Maydis, Semen Coicis, Rhizoma Curcumae Longae, Herba Taxilli Chinensis, Rhizoma Corydalis, Folium Pyrrosiae and Semen Plantaginis. Another Quzhuo Tongbi Decoction is composed of Radix Aconiti, Rhizoma Smilacis Glabrae, Radix Bupleuri Chinensi, Largehead Atractylodes Rhizome, Radix Astragali, Caulis Lonicerae and Radix Paeoniae Rubra. It has been documented that some intestinal bacteria could cause abnormal uric acid metabolism . Zhu et al.  found that the medium and high dosage of the first Quzhuo Tongbi Decoction can reduce the level of uric acid, serum creatinine and xanthine oxidase (XOD). Besides, it could also relieve inflammation symptoms, inhibit the production of PGE2, relieve pain sensation by blocking the sensation of peripheral nerves to pain stimuli .
The pharmacological mechanism of Peiyuan Huazhuo Decoction in the treatment of gout
Peiyuan Huazhuo Decoction is composed of Rhizoma Polygonatum Sibirici, Semen Cuscutae, Radix Astragali, Rhizoma Smilacis Glabrae, Semen Coicis and Rhizoma Corydalis. Yang et al.  found that Radix Astragali could increase the glomerular filtration rate. It was also found that Rhizoma Polygonatum Sibirici not only had a good effect of lowering SUA levels, but also reduced blood lipid and glucose . The herbs in this formula work together to treat lipid metabolism disorders, inhibit inflammatory reactions, prevent gout attack, and prevent renal damage in patients with gout.