CRCAM Journal

Plant family	herbals	Model	Functions	Mechanisms	Ref.
Asteraceae	Atractylodes Lancea (Thunb.) DC.	SPF SD rats RAW264.7 macrophages	Anti-inflammatory	IL-1β↓; IL-6↓; TNF-α↓; PTGS2↓	[44]
	Atractylodes macrocephala Koidz.	Male SD rats	Anti-inflammatory Anti-hyperuricemia Improve renal injury	IL-1β↓; TNF-a↓; XOD↓	[45]
	Cichorium intybus L.	Male SD rats macrophages	Anti-inflammatory	NLRP3↓;IL-1β↓; NF-κB p65↓	[46]
	Siegesbeckia orientalis L.	Male Wistar rats	Anti-inflammatory Anti-hyperuricemia Inhibit uric acid production	XOD↓	[47]
	Helianthus annuus Head	Male BALB/c mice	Anti-inflammatory Anti-hyperuricemia	IL-10↓; MCP-1↓;XOD↓	[48]
Dioscoreaceae	Dioscorea collettii	THP‑1 cell	Anti-inflammatory	NLRP3↓;IL-1β↓; IL-18↓; TNF-α↓;	[49]
	Discorea nipponica Makino	Male SD rats	Anti-inflammatory	glutathione metabolism, glycerol phospholipid metabolism, inositol phosphate metabolism, galactose metabolism p38 MAPK, SDF-1/CXCR-4	[50,51]
Liliaceae	Smilax glabra Roxb	Male SD rats Male BALB/c mice	Anti-inflammatory Anti-hyperuricemia Promote uric acid excretion Improve kidney injury Inhibit uric acid production	IL-1β↓; IL-6↓; IL-12↓; TNF-α↓; TGF-β1↓; ABCG2↑; OAT1↑; OCT2↑; OCTN2↑ mURAT1↓; XOD↓	[52-55]
	Smilax china L.	Male ICR mice	Anti-hyperuricemia	XOD↓	[56]
Cornaceae	Cornus officinalis Sieb.	Male ICR mice	Anti-hyperuricemia	XOD↓	[57]
Lamiaceae	Saluia plebeia R. Br.	Male ICR mice	Anti-hyperuricemia	XOD↓	[58]
Araceae	Alocasia longiloba Miq.	Male SD rats	Anti-hyperuricemia	XOD↓	[59]
Oleaceae	Olea europaea L. leaf	Male SD rats	Anti-hyperuricemia	XOD↓	[60]
Theaceae	Camellia japonica L.	Male SD rats	Anti-hyperuricemia	XOD↓	[61]
Magnoliaceae	Liriodendron chinense (Hemsl.) Sarg.	Male C57BL/6 mice	Anti-inflammatory Anti-hyperuricemia Improve kidney injury Promote uric acid excretion	TNF-α↓; NF-κB p65↓ OAT1↓; OAT3↓; ABCG2↓	[62]
Polygonaceae	Polygonum capitatum Buch. Ham. ex D. Don	Male Kunming mice	Anti-inflammatory Anti-hyperuricemia Promote uric acid excretion Improve kidney injury Inhibit uric acid production	IL-1β↓; IL-6↓; TNF-α↓; GLUT9↓; URAT1↓; OAT1↓; XOD↓	[63]
Moraceae	Mori Ramulus	Male Kunming mice	Anti-hyperuricemia Promote uric acid excretion	GLUT9↓; URAT1↓; OAT1↓; mOCT1↑; mOCT2↑; mOCTN1↑; mOCTN2↑	[64]
Urticaceae	Urtica hyperborea Jacq.	Human renal tubular epithelial HK2 cells Male Kunming mice	Anti-hyperuricemia Promote uric acid excretion Inhibit uric acid production	URAT1↓; OAT1↓; XOD↓	[65]
Phyllanthaeae	Phyllanthus emblica L.	SPF Male SD rats	Anti-inflammatory	NLRP3↓; caspase-1↓; MMP13↓; IL-1β↓; IL-10↓; TNF-α↓;	[66]
Apiaceae	Apium graveolens L. seed	Male BalB/c mice	Anti-inflammatory Antioxidant stress	IL-1β↓; IL-10↓; ROS↓	[67]
Ranunculaceae	Aconitum carmichaelii Debeaux	Male SD rats THP-1 cells	Anti-inflammatory	IL-1β↓; IL-18↓; TNF-α↓; MAPK14↓; MMP9↓; PTGS2↓;	[68]
Lauraceae	Cinnamomum cassia Presl	Bone marrow-derived macrophages Male C57BL/6 mice	Anti-inflammatory	NLRP3↓; IL-1β↓	[69]
Ginkgoaceae	Ginkgo biloba L. leaves	Male SD rats	Anti-inflammatory	L-1β↓	[70]
Simaroubaceae	Eurycoma longifolia Jack.	Adult Wistar albino rats	Anti-inflammatory	Toll-like receptor, MAPK, chemokine, NOD-like receptor, T cell receptor signaling pathway	[71]
Lardizabalaceae	Stauntonia brachyantherand-Mazz		Anti-inflammatory	MAPK, PI3K-Akt, Toll-like Receptor, NOD-like receptor signaling pathway	[72]

Table 1: Summary of Single herbs for gout

Therapeutic Effects of Natural Compounds from TCM for Gout

Polysaccharides

Polysaccharides isolated from herbal medicines have important pharmacological properties, including anti-inflammatory, anticancer, antioxidant, antidiabetic, antiviral, hypolipidemic, and immune regulation properties [73,74]. Isatidis Radix is a biennial herb of the Brassicaceae family. In TCM, Isatidis Radix plays an important role in heat clearance and detoxification [75]. As reported in modern pharmacological research, Isatidis Radix contains many important components, including polysaccharides, alkaloids, and organic acids [76].

Isatidis Radix polysaccharide (IRP) extracted from Isatidis Radix could inhibit the activation of multiple inflammasomes and alleviate gouty arthritis, as seen both in vivo and in vitro experiments. Under in vitro conditions, IRP can inhibit caspase-1 cleavage and IL-1β secretion by blocking NLRP3 inflammasome activation. Under in vivo conditions, IRP can alleviate joint swelling caused by MSU crystals in mice and reduce the secretion of MPO, IL-6, IL-18, and IL-1β in the swollen joints [77].

Plantaginis semen polysaccharide (PSP) can alleviate gout and renal damage. Oral administration of PSP (0.27 g/kg body weight, daily for 20 days) can significantly reduce serum uric acid and urine protein levels. PSP can also inhibit the expression of TNF-α, TGF-β, and IL-6 and downregulate the expression of caspase-1, ASC, and NLRP3 proteins. To sum up, PSP can alleviate gout by reducing uric acid levels, and PSP can alleviate gout nephropathy by reducing urinary protein levels and inhibiting the release of inflammatory factors by reducing the expression of caspase-1, ASC, and NLRP3 proteins [78].

Lonicera japonica polysaccharide (i.p., 0.1, 0.2, and 0.3 g/kg body weight) exerted anti-hyperuricemic effects in rats by inhibiting XOD activity. It also decreased the flares of gouty arthritis and alleviated ankle swelling in mice by downregulating the expression of IL-1β, IL-6, TNF-α, and COX-2–related inflammatory factors in murine serum [79]. (Table 2).

Table 2: Summary of Polysaccharides for gout

Alkaloids

Alkaloids are an important kind of natural products widely existing in various plant species. Most alkaloids have significant biological potential, such as alleviating gouty arthritis, anti–human immunodeficiency virus activity, lowering blood pressure, and antiparasitic activity. Phellodendri chinensis cortexis a TCM for treating gout and hyperuricemia in China, which is mainly used for clearing heat dampness and purging fire detoxification [80]. Berberine is the main component of Phellodendron chinense cortex and has anti-hyperuricemic and anti-gout effects [81]. Berberrubine (BRB) is the biologically active metabolite of berberine in the body. Lin et al. reported that oral administration of BRB (6.25, 12.5, and 25.0 mg/kg body weight) reduced serum uric acid levels in a hyperuricemic mouse model induced by potassium oxazinate, and the mechanism involved reduction of XOD activity in the liver and inhibition of the expression of GLUT9 and URAT1. Additionally, ABCG2 and BRB activate the expression of OAT1/3 [82].

Dihydroberberine (DHB) is a derivative of berberine. Xu et al. investigated the effects of DHB on the reduction of uric acid levels and renal protection in hyperuricemic mice. Oral DHB (25 and 50 mg/kg body weight) decreased the uric acid level triggered by potassium oxazinate and hypoxanthine in a dosedependent manner. DHB significantly inhibits XOD activity, thereby decreasing uric acid production. DHB can also promote uric acid excretion by downregulating the expression of URAT1 and GLUT9. Additionally, DHB inhibits the mRNA expression of NLRP3, ASC, caspase-1, and IL-1β in the kidney to protect renal function [83].

Palmatine (PAL) is the main active ingredient in Corydalis yanhusuo. Juanjuan et al. demonstrated that PAL has the potential as an effective therapeutic candidate for gouty arthritis because of its anti-inflammatory activities. PAL treatment at doses of 20, 40, and 80 µm alleviated MSU-induced gouty arthritis in a rat model. PAL treatment dose-dependently inhibits the mRNA expression of IL-1β, IL-6, IL-18, and TNF-α. Additionally, it can promote the production of superoxide dismutase and glutathione (GSH) and reduce the production of malondialdehyde (MDA). Western blotting has shown that PAL can effectively inhibit the NF-κB/ NLRP3 signaling pathway by inhibiting the expression of NLRP3, ASC, IL-1β, and Caspase-1, while enhancing the expression of the antioxidant proteins Nrf2 and HO-1. Moreover, PAL further reduces the infiltration of neutrophils into synovitis [84]. Tetrahydropalmatine (THP), another effective compound from Corydalis yanhusuo, can attenuate MSU-induced gouty arthritis. Oral THP (10, 20, and 40 mg/kg body weight) dose-dependently reduced MSU-induced plantar swelling, and when compared with the model group, the levels of inflammatory factors in the treatment group decreased and the infiltration of inflammatory cells weakened, both of which are attributed to the role of THP in inhibiting NLRP3 inflammasome activation and caspase-1 formation. THP also reduces ROS production induced by MSU crystal deposition by increasing the activity of antioxidant enzymes under both in vivo and in vitro conditions. It is worth noting that the impact of a high dose is equivalent to that of a positive drug [85].

Coptisine, the main effective component of Coptis chinensis, can significantly inhibit the secretion of mature IL-1β from RAW264.7 macrophages stimulated by LPS together with MSU, ATP, and nigericin, by inhibiting caspase-1 activation. Moreover, it blocks the NF-κB signaling pathway to inhibit NLRP3 expression, thereby preventing the priming of inflammasome. Under in vivo conditions, oral administration of coptisine reduced the degree of foot swelling in mice of the treatment group. The aforementioned findings suggest that coptisine can be used to treat gouty arthritis caused by NLRP3 inflammasomes [86]. (Table 3).

Table 3: Summary of Alkaloids for gout

Phenolic Compounds

Phenolic compounds exert a wide range of pharmacological activities, including antioxidation, anti-gout, mprovement of vascular endothelial function, anti-atherosclerosis, and inhibition of platelet aggregation [87].

Caffeic acid can effectively reduce serum uric acid levels in hyperuricemic mice triggered by potassium oxazinate, and it acts by inhibiting XOD activity in the liver [88,89].

Chlorogenic acid alleviates mouse foot swelling induced by MSU crystals by blocking the expression of IL-6, IL-1β, and TNF-α. Moreover, chlorogenic acid alleviates gouty arthritis [90]. With regard to the mechanism of chlorogenic acid in relieving gouty arthritis, its action may show an association with the regulation of mitogen-activated protein kinase (MAPK), PI3KAkt, and NF-κB signaling pathways and the intervention of TLRs, affecting the release of cellular inflammatory factors [91].

Vanillin, a phenolic compound, is an effective component in Amomum villosum Lour. Under in vitro conditions, vanillic acid inhibits XOD activity [92], but its effect on uric acid has not been investigated. Based on previous experimental results, we speculate that vanillic acid may have a beneficial effect on gouty arthritis by reducing serum uric acid levels.

Paeonol is an effective component of Moutan Cortex. Chen et al. reported that paeonol can attenuate gouty arthritis induced by MSU crystals. Specifically, oral paeonol reduced foot swelling induced by MSU crystals in rats; reduced the expression of TNF-α, IL-1β, and IL-6; upregulated the protein expression of P65 in the nucleus; and significantly inhibited NF-κB DNA binding activity. The aforementioned results indicate that paeonol may play an antiinflammatory role and hinder the expression of proinflammatory cytokines and NF-κB [93].

6-Shogaol is an active ingredient extracted from Zingiber officinale Roscoe. that can effectively reduce serum uric acid levels by inhibiting XOD activity. Moreover, 6-shogaol can also reduce the production of inflammatory cytokines such as IL-1β and TNF-α [94] (Table 4).

Table 4: Summary of Phenolic compounds for gout

Flavonoids

Most Chinese herbal medicines contain flavonoids. They have a wide range of pharmacological activities, including antiinflammatory, antioxidant, immune enhancement, anticancer, and other effects [95].

Kaempferol, the main effective component of Cudrania tricuspidata leaf ,can decrease serum uric acid levels in hyperuricemic mice by hindering XOD activity, the therapeutic effect of kaempferol is equivalent to that of allopurinol [96], it is a promising drug as an alternative to allopurinol in the treatment of hyperuricemia and gout.

Icariin is the main active ingredient in Epimedium. Cao et al. confirmed the therapeutic effect of icariin against gouty arthritis and reported that icariin (20, 40, and 80 mg/kg body weight) inhibits the expression of IL-1β, IL-6, PGE₂, and TNF-α in the synovial tissue, alleviates the infiltration of inflammatory factors, and weakens ankle joint swelling in rats. Moreover, icariin can reduce the expression of the NALP3 inflammasome by inhibiting the nuclear transcription of proteins participating in the NF-κB pathway. In vitro studies showed that icariin reduced the activity of chondrocytes and inhibited the levels of the inflammasome and glycosaminogly [97].

Luteolin and luteolin-4′-O-glucoside, effective components extracted from Gnaphalium affine D. Don., can inhibit the protein expression of URAT1 and the activity of XOD to reduce uric acid production and increase uric acid excretion, thereby alleviating hyperuricemia symptoms. It can also reduce foot swelling induced by MSU crystals and the production of inflammatory cytokines such as IL-1, IL-β, and TNF-α [98]. Other studies have obtained consistent results, that is, luteolin-4′-O-glucoside and luteolin-4′O-glucoside can alleviate hyperuricemia and gouty arthritis [99].

Chrysin, a flavonoid compound extracted from Oroxylum indicum (L.) (Bignoniaceae) has the effect of anti-inflammation, anti-oxidation and anti-hyperuricemia. Chang et al. reported that oral administration of chrysin (50, 100, and 150 mg/kg body weight, daily for 28 days) lowered serum uric acid levels in hyperuricemia induced by high-fructose syrup in a dose-dependent manner. Moreover, chrysin can inhibit XOD activity; western blotting analysis demonstrated that the protein expression of URAT1 and GLUT9 showed an evident decrease, whereas that of OAT1 and human ABCG2 protein was increased. Chrysin can significantly reduce IL-1β levels in the kidney and serum of rats and MDA levels, suggesting that chrysin has significant antioxidant and antiinflammatory activities. It is worth noting whether such a high dose (50mg/kg body weight) will produce toxic and side effects in experimental animals [100].

Quercetin, a flavonoid compound widely dispersed throughout the plant kingdom has the effect of anticancer, antioxidant and anti-gouty arthritis. Feng et al. predicted 72 potential targets of quercetin for gout using network pharmacology analysis and constructed an interaction network between quercetin and gout. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the IL-17, TNF-α, MAPK, and PI3K signaling pathways were the main involved pathways. Quercetin administration to mice with MSU-induced gouty arthritis, relative to the model group and the control group, significantly reduced ankle joint swelling, hindered the expression of IL-6/17A/F in the IL-17 signaling pathway, and reduced the expression of retinoic acid–related orphan receptor, TNF-α, and TGF-β, all of which are in line with those obtained previously [101].

(-)-Epicatechin (EC) is the main active component in some medicinal plants and food, with anti-inflammatory and anti-oxidant effects. Chen et al. conducted in-depth research on its role and mechanism in gouty arthritis treatment. First, in vitro experiments showed that EC could increase the activity of THP-1 cells treated with MSU; reduce the levels of IL-6, IL-18, IL-1β, and TNF-α in the supernatant of THP-1 cells; and significantly increase the expression of ASC, NLRP3, and caspace-1 induced by MSU administration. Nuclear P65 expression was found to be reduced, suggesting that EC restricted P65 from entering the nucleus. The same results were obtained during the in vivo experiments either [102].

Baeckein E (BF-2) is an active compound isolated from Baeckea frutescens L. BF-2 evidently blocks IL-1β secretion, inhibits the thermophilicity of macrophages, and alleviates ankle swelling. BF-2 also alleviates oxidative stress by inhibiting the combination of pre-Caspase 1 and ASC, thereby inhibiting the assembly of the NLRP3 inflammasome. More interestingly, BF-2 can block the activation of the NLRP3 inflammasome by inhibiting the MAPK/NF-κB signaling pathway [103] (Table 5).

Monomers	Sources	Model	Functions	Mechanisms	Ref.
Kaempferol	Cudrania tricuspidata Leaf (Moraceae)	male ICR mice	Anti-hyperuricemia	XOD↓	[96]
Icariin	Epimedium brevicornu Maxim (Berberidaceae)	Male SD rats chondrocytes	Anti-inflammatory	NLRP3↓;IL-1β↓; IL- 6↓; TNF-α↓; PGE2↓;	[97]
Luteolin	Gnaphalium affine D. Don. (Asteraceae)	male Kun-Ming mice male ICR mice	Anti-inflammatory Anti-hyperuricemia Improve kidney injury Inhibit uric acid production Promote uric acid excretion	IL-1β↓; TNF-α↓; URAT1↓; GLUT9↓; XOD↓	[98,99]
Luteolin-4′-O-glucoside
Chrysin	Many plants	Male SD rats	Anti-inflammatory Anti-hyperuricemia Antioxidant stress reaction Inhibit uric acid production Promote uric acid excretion	IL-1β↓; ROS↓; URAT1↓; GLUT9↓; OAT1↑; ABCG2↑	[100]
Quercetin	Many plants	Male SD rats	Anti-inflammatory	IL-1β↓; IL-6↓; IL-17A↓; IL-17F↓; TNF-α↓	[101]
(-)-Epicatechin (EC)	Many plants	Male C57BL/6 mice THP-1 cells	Anti-inflammatory	NLRP3↓;IL-1β↓; IL6↓; IL-18↓; TNF-α↓;	[102]
Baeckein E	Baeckea frutescens L. (Myrtaceae)	J774A.1 macrophages male C57BL/6 mice	Anti-inflammatory Antioxidant stress reaction	NLRP3↓;IL-1β↓; ROS↓	[103]

Table 5: Summary of Flavonoids for gout

Quinones

Rhein, a active components of Rheum tanguticum Maxim. ex Regel, can significantly inhibit the production of IL-1β and TNF-α by macrophages and caspase-1 protein. The rate of inhibition of IL-1β by rhein at a concentration of 2.5 µg/mL is 47%, and rhein (5 µg/mL) can significantly reduce ASC content and inhibit NLRP3 expression. To sum up, rhein alleviates gouty arthritis by inhibiting the activation of the NLRP3 inflammasome and macrophages [104].

Polydatin , a quinone compound isolated from Reynoutria japonica Houtt., has a wide range of pharmacological effects, including its efficacy in preventing and treating diabetes, atherosclerosis, hyperlipidemia, and gout [105]. Oral administration of polydatin (20 and 50 mg/kg body weight) to hyperuricemic rats induced by potassium oxazinate reduced the levels of uric acid and creatinine in blood and urine respectively and achieved the same effect as that of the positive drug allopurinol. It can also restore TNF-α, IL-1, IL-β, and IL-6 levels in the serum and kidney of the rats in the model group to the original level. Polydatin blocked NF-κB protein expression and significantly lowered IκBα phosphorylation. Additionally, western blotting showed that the expression of ASC, Caspase-1, and NLRP3 was inhibited. Furthermore, polydatin upregulated the expression of p-AMPK and SIRT1 proteins in the kidney. It is speculated that polydatin may inhibit the production of NF-κB and NLRP3 inflammasome in the kidney by regulating the AMPK/SIRT1 signaling pathway in gout treatment [106] (Table 6).

Monomers	Sources	Model	Functions	Mechanisms	Ref.
Rhein	Rheum tanguticum Maxim. ex Regel (Polygonaceae)	THP-1 cells	Anti-inflammatory	IL-1β↓; TNF-α↓; caspase-1↓	[104]
Polydatin	Reynoutria japonica Houtt. (Polygonaceae)	Male SD rats	Anti-inflammatory Anti-hyperuricemia Improve kidney injury	IL-1β↓; IL-6↓; TNF-α↓; NF-κB p65↓	[106]

Table 6: Summary of Quinones for gout

Saponins

Saponin is an effective active component of many Chinese herbal medicines. Modern pharmacology has demonstrated that saponin has diverse biological activities, including anti-inflammatory, anticancer, hypoglycemic, and other effects [107].

Smilaxchinoside A and Smilaxchinoside C are steroidal saponins isolated from the ethanolic extract of Smilax riparia. Wu et al. reported that these two compounds inhibit uric acid production and stimulate uric acid excretion by inhibiting mURAT1 expression in the kidney and XOD activity. Smilaxchinoside A and Smilaxchinoside C are, therefore, potential clinical drugs for gout treatment [108]. Riparoside B and timosaponin J, which are also extracted from Smilax riparia, have the same effect as that of Smilaxchinoside A and Smilaxchinoside C and promote uric acid excretion by inhibiting URAT1 expression [109] (Table 7).

Monomers	Sources	Model	Functions	Mechanisms	Ref.
Smilaxchinoside A	Smilax riparia . (Liliaceae)	Male Kunming mice	Anti-hyperuricemia Inhibit uric acid production Promote uric acid excretion	mURAT1↓; mGLUT9↓; XOD↓; OAT1↑	[108]
Smilaxchinoside C
Riparoside B	Smilax riparia (Liliaceae)	Male Kunming mice	Anti-hyperuricemia Inhibit uric acid production Promote uric acid excretion	mURAT1↓; XOD↓	[109]
Timosaponin J

Table 7: Summary of Saponins for gout

Terpenoids

Terpenoids are widely present in many plants and have extensive pharmacological and biological activities [110].

Andrographolide (AND), the main component of Andrographis paniculata (Burm. f.) Nees, can inhibit IL-1β production by bone marrow macrophages in mice with gout induced by MSU crystals and infiltration of monocytes. AND interacts with the IKK/NF-κB signaling pathway and inhibits the activation of the NLRP3 inflammasome (endotoxin induced), leading to the downregulation of NLRP3 and Pro-IL-1β protein expression. AND also inhibits HO-1 protein expression and reduces ROS production. It is worth noting that AND reduces the combination of ASC and NLRP3. AND alleviates gouty arthritis by inhibiting ROS-induced NLRP3 inflammasome assembly and IL-1β release by increasing HO-1 expression [111].

Cucurbitacin B (CUB) is a terpenoid compound isolated from plants belonging to Cucurbitaceae. Xue et al. confirmed that CUB could significantly reduce IL-1β secretion by blocking the formation of NLRP3 inflammasome and inhibiting the key enzymes of macrophage glycolysis. Through histopathological analysis, the authors also showed that CUB improved foot swelling and inflammatory cell infiltration in gouty arthritis mice [112].

Tanshinones is a class of effective biological components in Salvia miltiorrhiza Bge. Yue et al. identified 15 tanshinones that can inhibit NLRP3 inflammasome activation, among which tanshinone IIA, isocryptotanshinone, and dihydrotanshinone I can reduce the production of oxygen free radicals in macrophages. Tanshinone protects mitochondria by promoting autophagic protein kinase and AMP-activated protein kinase, suggesting that tanshinone is effective for treating gouty arthritis [113].

Budlein A is a metabolite in the biosynthesis of sesquiterpene lactones in Asteraceae plants. Budlein A can alleviate knee joint swelling, reduce neutrophil aggregation, inhibit neutrophil phagocytosis due to the deposition of MSU crystals, and block the mRNA expression of IL-1β and TNF-α in the knee joint tissue homogenate. It is worth noting that inhibition of NF-κB activation may reduce TNF-α production. The aforementioned results suggest that Budlein A alleviates gouty arthritis by activating NF-κB and promoting the assembly of inflammatory factors [114].

Tripterine pentacyclic triterpene compound isolated from Tripterygium wilfordii Hook., can alleviate gouty arthritis. Specifically, it can reduce the swelling degree in MSU-induced joint swelling in mice. A high dose of tripterine (1 mg/kg body weight) can reduce the swelling degree by 83.9%, and a low dose can reduce the swelling degree by 72.4%. Hematoxylineosin staining analysis has shown that tripterine can reduce the infiltration of inflammatory cells. Additionally, enzyme-linked immunosorbent assay has demonstrated that tripterine inhibited the secretion of IL-1β. The protein expression of Caspase-1 was also downregulated [115] (Table 8).

Monomers	Sources	Model	Functions	Mechanisms	Ref.
Andrographolide	Andrographis paniculata (Burm. f.) Nees (Acanthaceae)	male C57BL/6J mice Bone marrow-derived macrophages	Anti-inflammatory Antioxidant stress	NLRP3↓;IL-1β↓; caspase-1↓; HO-1↓; ROS↓	[111]
Cucurbitacin B	Cucurbitaceae plants	Male C57BL/6 mice Bone marrow-derived macrophages	Anti-inflammatory	IL-1β↓; IL-18↓; HK1↓; HK2↓; PKM2↓; LDHA↓; PDH↓;	[112]
Tanshinone IIA	Salvia miltiorrhiza Bge. (Lamiaceae)	Male C57BL/6 mice J774A.1 macrophages	Anti-inflammatory Antioxidant stress	IL-1β↓; ROS↓	[113]
Isocryptotanshinone
Dihydrotanshinone I
Budlein A	Asteraceae plants	Male C57BL/6 mice Bone marrow-derived macrophages	Anti-inflammatory	IL-1β↓; TNF-α↓; NF-κB p65↓	[114]
Tripterine	Tripterygium wilfordii Hook. f. (Celastraceae)	male WT C57BL/6J mice HEK293T cells THP-1 cells Bone marrow-derived macrophages	Anti-inflammatory Improve liver injury	NLRP3↓; IL-1β↓;	[115]

Table 8: Summary of Terpenoids for gout

Glycosides

Gentiopicroside (GPS) is an iridoid glycoside isolated from Gentiana Macrophylla Pall. GPS can reduce foot swelling caused by MSU crystals; block the secretion of inflammatory factors, namely, IL-1β, IL-6, IL-18, and TNF-α; and significantly inhibit neutrophil infiltration. Immunosuppression analysis has demonstrated that GPS significantly restored the expression of NLRP3, ASC, and Caspase-1 proteins in the model group. GPS can inhibit the activation of NLRP3 inflammasomes in macrophages under in vitro conditions. GPS can be used to treat gouty arthritis by hindering the activation of the NLRP3 inflammasome [116].

Kinsenoside is the main effective ingredient in Anoectochilus roxburghii (Wall.) Lindl. in the treatment of gouty joints. Kinsenoside can negatively regulate the NF-κB/MAPK signaling pathway, thereby reducing the expression of inflammatory cytokines present downstream of NF-κB and inhibiting the biological activity of vascular endothelial cells. Kinsenoside can also inhibit the expression of NALP3 and TLR2 and the uptake of CD14 mediated by MSU crystals in macrophages. Under in vivo conditions, kinsenoside can significantly reduce inflammatory cell infiltration and endothelial damage and alleviate ankle swelling [117].

Total glucosides of paeony，the main components of Paeoniae Radix Alba, regulates the interaction among MALAT1, MIMR8765p, and NLRP3 proteins, blocks the TLR4/MYD88/NF-κB signaling pathway, and inhibits the THP-1 macrophage inflammation induced by MSU crystals, thus producing a therapeutic effect on gouty arthritis [118] (Table 9).

Monomer s	Sources	Model	Functions	Mechanisms	Ref.
Gentiopicroside	Gentiana Macrophylla Pall. (Gentianaceae)	Male C57BL/6 mice RAW264.7 macrophage cell	Antiinflammatory	NLRP3↓; IL-1β↓; IL-6↓; IL18↓;	[116]
Kinsenoside	Anoectochilus roxburghii (Wall.) Lindl. (Orchidaceae)	human umbilical vein endothelial cell Male SD rats	Antiinflammatory	IL-1β↓; IL-6↓; TNF-α↓; COX-2↓; NF-κB p65↓; PGE2↓;	[117]
Total glucosides of paeony	Paeonia lactiflora Pall. (Paeoniaceae)	THP-1 cells	Antiinflammatory	NLRP3↓; Caspase-1↓; IL-1β↓; MALAT1/miR-876-5p/NLRP3 axis TLR4/MyD88/NF-κB	[118]

Table 9: Summary of Glycosides for gout

TCM Prescription for Gout

Ermiao Pill is made up of phellodendron chinense Schneid. (Rutaceae) and Atractylodes lancea (Thunb.) DC. (Asteraceae), and it was introduced in “Dan Xi Xin Fa” by Zhu Danxi during the Yuan Dynasty in China. Used in the treatment of gouty arthritis, rheumatoid arthritis, and arthralgia [119,120]. The mechanism of the uric acid lowering effect of Ermiao Pill was linked to the regulation of purine metabolism, taurine metabolism, hypotaurine metabolism, glyceride metabolism, amino acid metabolism, and primary bile acid metabolism [121]. By inhibiting the expression of the proinflammatory factor IL-6, it can also reduce ankle swelling in gouty arthritis rats. Ermiao Wan can be used to treat gouty arthritis by lowering uric acid levels and inhibiting inflammatory reactions; however, its effective components and mechanism need to be investigated further [122].

Sanmiao Pill is a Chinese medicinal compound derived from the Ming Dynasty medical book “Yi Xue Zheng Zhuan”, which consists of three components, Phellodendron chinense Schneid. (Rutaceae ), Atractylodes lancea (Thunb.) DC. (Asteraceae), and Achyranthes bidentata Blume ( Amaranthaceae). Due to dampheat in the lower energizer, it is primarily used in the clinical treatment of gout [123]. Zhu et al. demonstrated that Sanmiao Pill could treat gout by inhibiting cartilage matrix degradation. The cartilage matrix is primarily made up of proteoglycan and collagen. In particular, when compared to the model group, the treatment group’s oral administration of Sanmiao Pill significantly reduced glycosaminoglycan expression while increasing proteoglycan levels. Notably, Sanmiao Pill significantly inhibited MMP-3 and aggrecanase-4 expression while increasing TIMP-1 and TIMP-3 expression [124]. Furthermore, Sanmiao pill reduced joint swelling in a gouty arthritis mouse model induced by MSU crystals and inhibited the production of IL-1β, TNF-α, and MPO. Surprisingly, the alcoholic extract of Sanmiao pill has a stronger anti-inflammatory effect than the aqueous extract [125].

Simiao Pill was derived from China’s “Cheng Fang Bian Du” in the Qing Dynasty, which comprises four individual herbs, namelyPhellodendron chinense Schneid. (Rutaceae),Atractylodes lancea (Thunb.) DC. (Asteraceae), Achyranthes bidentata Blume (Amaranthaceae), Coix lacryma-jobi L.var.mayuen( Roman.) Stapf (Poaceae). It is clinically used to treat damp-heat pouring downward gout [126]. Cao et al. found that by promoting PI3K/Akt activation and M2 polarization in macrophages, Simiao Pill (1 and 10 mg/ kg body weight) could significantly inhibit IL-6 and IL-1β levels and alleviate the inflammatory response caused by MSU crystals [127]. Simiao Pill can also reduce serum inflammatory factors like MIP-1α, MIP-1β, interferon-γ, and IL-9, downregulate NLRP3 expression, reduce intestinal cell apoptosis, and improve intestinal microflora to treat gouty arthritis [128]. Network pharmacology has discovered that Simiao Pill can also inhibit IL-17 and TNF-α [129]. Simiao Pill has been shown to lower serum uric acid levels in other studies. Simiao Pill, in particular, inhibited XOD activity and promoted uric acid excretion by inhibiting the expression of OAT1, URAT1, and GLUT9 transporters in the kidney [130,131]. Furthermore, modified Simiao pill can reduce joint swelling in rats with gouty arthritis caused by MSU crystals and can inhibit the expression of inflammatory factors like IL-6, IL-1β, and TNF-α. The p-STAT3 and MMP3 proteins were upregulated in C28/I2 cells in cartilage tissue, but the tissue inhibitor of metalloproteinase (TIMP)-3 protein was downregulated [132-134].

The Quzhuo-Tongbi decoction (QTD) is a TCM empirical prescription used clinically to treat acute gouty arthritis that consists of nine different Chinese herbal medicines (Table 10). Oral administration of QTD (0.5 g/kg body weight) inhibited the expression of NLRP3, reduced the production of IL-1β and TNF-α, and alleviated ankle swelling in rats with gouty arthritis caused by MSU crystals [135]. Other research has found that QTD can treat gout by regulating intestinal flora. QTD specifically improves intestinal barrier function by increasing the abundance of butyrate-producing bacteria and encouraging the production of SCFAs. Notably, a lack of SCFAs was linked to increased glycolysis. Furthermore, QTD can lower serum uric acid levels, and its mechanism may be linked to increased ABCG2 expression [136,137].

Zisheng-Shenqi decoction (ZSD), derived from “the Golden mirror of medicine” in China’s Qing dynasty, is made up of ten Chinese herbal medicines (Table 10) and has the function of tonifying the kidneys and removing dampness. It is used to treat gout in clinical settings. According to network pharmacology, ZSD can inhibit inflammatory reactions, resist oxidative stress, and relieve pain by regulating the ATP-P2X7R and NLR signaling pathways, thereby treating gout [138]. Another study found comparable results. ZSD can effectively treat gouty arthritis in vivo due to its anti-inflammatory and antioxidant properties. Oral ZSD (400 mg/10 g body weight) administration could inhibit the expression of inflammatory factors TNF-α and IL-1β, as well as the activation of NF-κB. Furthermore, glutathione peroxidase and superoxide dismutase activated the antioxidant stress effects. This study’s findings provided sufficient evidence for its use in gout treatment [139].

Guizhi-Shaoyao-Zhimu decoction (GSZD) is a classical prescription in China, which is derived from “Outline of the Golden Chamber”. It is a combination of nine Chinese herbal medicines

(Table 10) that is clinically used to treat gout and osteoarthritis [140]. By blocking the NLRP3/NF-κB signaling pathway, Zhou et al. demonstrated that GSZD could inhibit the expression of IL-1β, IL-6 inflammatory factor, and MCP-1 levels. Therefore, an antiinflammatory effect is produced. Furthermore, GSZD can lower serum uric acid levels [141,142].

The Shuang-Qi gout capsule (SQGC) is made up of six different herbs:Phragmites australis (Cav.) Trin. ex Steud. (Poaceae), Berchemia floribunda (Wall.) Brongn. (Rhamnaceae), Mallotus apelta (Lour.) Muell. Arg. (Euphorbiaceae), Schefflera arboricola Hay. (Araliaceae), Cinnamomum camphora (L.) presl (Lauraceae), Panax notoginseng (Burkill) F. H. Chen ( Araliaceae). It is used in the treatment of gouty arthritis. SQGC (57, 113, and 225 mg/kg body weight) reduced ankle joint swelling in a dose-dependent manner while also significantly inhibiting the expression of IL-1β and TNF-α. It is worth noting that the high-dose Shuang-qi gout capsule followed the same pattern as the positive drug [143]. Furthermore, SQGC can increase uric acid excretion. The mechanism is to inhibit URAT1 and GLUT9 expression while increasing the expression of OCT1, OCT2, and OAT1 [144].

Huzhen-Tongfeng formula (HTF) is an empirical prescription developed by Jinan University based on clinical experience with gouty arthritis.polygonum cuspidatum Sieb. et Zucc. (Polygonaceae),ligustri Lucidi Fructus (Oleaceae),plantago asiatica L. (Plantaginaceae), and polistes olivaceus (DeGeer) (Vespidae) are included in the prescription. Deng et al. revealed the mechanism of HTF for the first time in the treatment of gouty arthritis. Network pharmacology analysis predicted that the arachidonic acid metabolic pathway was most closely related to its anti-inflammatory action. In vivo studies revealed that oral administration of HTF reduced ankle swelling and inflammatory cell infiltration in rabbits with gouty arthritis. In vitro, HTF inhibited the expression of COX-1, COX-2, and 5-lipoxygenase [145]. Furthermore, HTF can be used to treat gouty arthritis by inhibiting the release of proinflammatory factors such as IL-1, IL6, TNF-α, and ASC oligomerization [146].

Jiangsuan-Chubi formula (JCF) was a traditional Chinese medicine prescription obtained through clustering analysis and frequency of use, consisting of 12 Chinese herbal medicines (Table 10) and used clinically to treat gouty arthritis. JCF has been shown in studies to inhibit the secretion of the inflammatory factor IL-1β by inhibiting the expression of the NRLP3 protein, resulting in an anti-gouty arthritis effect [147]. Qingre-Lishi decoction (QLD) is made up of 12 Chinese herbal medicines (Table 10) and is used to promote blood circulation, remove blood stasis, and relieve pain. It is used in the treatment of gout. Yu et al. confirmed that QLD could treat gouty arthritis by inhibiting NRLP3 protein expression and inflammatory factor IL-1β secretion [148]. Huzhang-Guizhi formula (HGF) is a traditional Chinese medicine derived from “Taiping Shenghui Fang,” which contains polygonum cuspidatum Sieb.et Zucc. (Polygonaceae) and cassia Twig ( Lauraceae). HGF, according to research, can inhibit the production of TNF-α and IL-1β in synovial fluid and the expression of the NF-KB p65 protein in synovial tissue, resulting in anti-gouty arthritis effects [149]. The ingredients in Shaoyao-Gancao decoction (SGD) are

Paeonia lactiflora Pall. (Paeoniaceae) and Glycyrrhiza uralensis Fisch. (Fabaceae). SGD significantly reduced PGE2 production in vitro by inhibiting the release of inflammatory factors COX2, IL-1β, and IL-6, thereby exerting an anti-gouty arthritis effect [150]. Tongfengding capsule is a traditional prescription that has been approved by the China Pharmacopoeia Committee (2020). It contains eight Chinese herbal medicines (Table 10). The medication is clinically used to treat gout and rheumatoid arthritis. Tongfengding capsule has been shown in studies to have an anti-gouty arthritis effect by inhibiting the secretion of the inflammatory factors TNF-α and IL-6. Furthermore, its mechanism may be linked to the inhibition of the arachidonic acid signaling pathway [151]. Xiaofeng granule is made from a new formula that has been improved from modified simiaowan and has heatclearing and dampness-drying properties. Shi et al. discovered that Xiaofeng granules can help with gout by inhibiting cartilage matrix degradation [152].

Shenling-Baizhu San (SBS) is a well-known prescription that is derived from “Prescriptions of the Bureau of Taiping People’s Welfare” and contains ten Chinese herbal medicines. Used in the treatment of gout and hyperuricemia. According to studies, SBS lowers serum uric acid levels by increasing uric acid excretion. Furthermore, it has been shown to inhibit the expression of p-PPARγSer273 in renal tubular epithelial cells [153]. Erding Formula (EF) is a traditional Chinese medicine prescription included in the China Pharmacopoeia, and it consists of viola philippica (Violaceae),taraxacum mongolicum Hand.-Mazz. (Asteraceae),lobelia chinensis Lour. (Campanulaceae) and isatis indigotica Fortune (Brassicaceae). According to pharmacological studies, EF can promote uric acid excretion by inhibiting URAT1 expression and increasing OAT3 expression [154]. Tongbixiao Pills (TBX) were a Chinese medicinal prescription developed by the Gout TCM Research Cooperation Group of Jingzhou Hospital of Traditional Chinese Medicine for the clinical treatment of gout. TBX has been shown in studies to have anti-gouty arthritis properties. Furthermore, it can lower serum uric acid levels by increasing uric acid excretion [155]. Tongfengtai granules (TFT) are a combination of seven Chinese herbal medicines that are clinically used to treat gouty nephropathy and rheumatism. Studies have shown that TFT can reduce serum uric acid levels by inhibiting XOD activity [156]. (Table 10).

Prescription	Composition of prescription	Model	Effect	Action mechanism	Ref
Er Miao pill	Phellodendron chinense Schneid. (Rutaceae)Atractylodes lancea (Thunb.) DC. (Asteraceae)	Male SD rats	Antiinflammation Antihyperuricemia Promote uric acid excretion	IL-6↓	[121,122]
Sanmiao pill	Phellodendron chinense Schneid. (Rutaceae) Atractylodes lancea (Thunb.) DC. (Asteraceae) Achyranthes bidentata Blume (Amaranthaceae)	Male SD rats chondrocyte	Antiinflammation Lowering uric acid level Inhibit cartilage matrix degradation	IL-1β↓; TNF-α↓; IL-6↓ MMPs-3↓; ADAMTS-4↓ TIMPs-1↑; TIMPs -3↑	[124,125]
Simiao pill	Phellodendron chinense Schneid. (Rutaceae) Atractylodes lancea (Thunb.) DC. (Asteraceae) Achyranthes bidentata Blume (Amaranthaceae) Coix lacryma-jobi L.var.mayuen (Roman.)Stapf （Poaceae）	THP-1 cells; Male C57BL/6 mice Male Kun- Ming strain of mice	Antiinflammation Antihyperuricemia Regulating intestinal flora Lowering uric acid level Promote uric acid excretion	NLRP3↓; IL6↓; IL-1β↓; TNF-α↓; p-Akt↑; MPO↓; XOD↓; ADA↓; mURAT1↓; mGLUT9↓; mOAT1↑; mOCT2↑	[127-131]
Modified Simiao pill	Phellodendron chinense Schneid. (Rutaceae) Atractylodes lancea (Thunb.) DC. (Asteraceae) Achyranthes bidentata Blume (Amaranthaceae) Coix lacryma-jobi L.var.mayuen (Roman.)Stapf ）Poaceae） Smilax glabra Roxb. (Liliaceae) Lonicerajaponica Thunb (Caprifoliaceae)	Male SD rats C28/I2 cell THP-1 cell	Antiinflammation Antihyperuricemia	IL-1β↓; TNF-α↓; IL-6↓; MMP-3↓; TIMP-3↑	[132-134]
Quzhuo-tongbi decoction	Smilax glabra Roxb. (Liliaceae) Dioscorea septemloba Thunb (Dioscoreaceae) Zea mays L. ( Poaceae) Coix lacryma-jobi L.var.mayuen (Roman.)Stapf ）Poaceae） Siegesbeckia orientalis L. (Asteraceae) Curcuma longa L . (Zingiberaceae) Taxillus sutchuenensis (Lecomte) Danser (Loranthaceae) Corydalisyanhusuo W.T.Wang (Papaveraceae) CitrusmedicaLvar.sarcodac-tylis Swingle (Rutaceae)	Male SD rats male C57BL/6 mice	Antiinflammation Antihyperuricemia Regulating intestinal flora	NLRP3↓; IL-1β↓; TNF-α↓; ABCG2↑; SCFAs↑	[135-137]

Zisheng-shenqi decoction	Rehmannia glutinosa (Gaert.) Libosch. (Scrophulariaceae) Cornus officinalis Sieb. (Cornaceae) Poria cocos(Schw.)Wolf (Polyporaceae) Cortex moutan ( Paeoniaceae) Dioscorea polystachya Turczaninow (Dioscoreaceae) Alisma orientalis (Sam.) Juzep. (Alismataceae) Amomum villosum Lour. (Zingiberaceae)	male Wistar rats	Antiinflammation Antioxidant stress	IL-1β↓; TNF-α↓; NF-κB↓ SOD↓; GSH-Px↓	[138,139]
Guizhi-Shaoyao- Zhimu decoction	Cinnamomum cassia Presl (Lauraceae) Atractylodes macrocephala Koidz. (Asteraceae) Glycyrrhiza uralensis Fisch. (Fabaceae) Ephedra sinica Stapf (Ephedraceae) Zingiber officinale Roscoe (Zingiberaceae) Atractylodes macrocephala Koidz. (Asteraceae) Anemarrhena asphodeloides Bunge (Liliaceae) Saposhnikovia divaricata ( Trucz.) Schischk. (Apiaceae) Aconitum carmichaelii Debx (Ranunculaceae)	Male C57BL/6J mice	Antiinflammation Antihyperuricemia	NLRP3↓; IL-1β↓; IL-6↓; MCP-1↓; IKKβ↓; p65↓	[140-142]
Shuang-Qi gout capsule	Phragmites australis (Cav.) Trin. ex Steud. (Poaceae) Berchemia floribunda (Wall.) Brongn. (Rhamnaceae) Mallotus apelta (Lour.) Muell. Arg. ( Euphorbiaceae) Schefflera arboricola Hay. (Araliaceae) Cinnamomum camphora (L.) presl (Lauraceae) Panax notoginseng (Burkill) F. H. Chen ( Araliaceae)	Male ICR mice Male SD rats HUVE cells	Antiinflammation Antihyperuricemia Promote uric acid excretion	IL-1β↓; TNF-α↓; mURAT1↓; mABCG2↑ mOAT1↑; mOCT1↑; mOCT2↑ mGLUT9↓	[143,144]
Huzhen-Tongfeng formula	Polygonum cuspidatum Sieb.et Zucc. (Polygonaceae) Ligustri Lucidi Fructus (Oleaceae) Plantago asiatica L. (Plantaginaceae) Polistes olivaceus (DeGeer) (Vespidae)	Male SD rats RAW264.7 cells THP-1 cell Male Japanese big ear white rabbits	Antiinflammation Antioxidant stress	IL-1β↓; IL-6↓; TNF-α↓; PGES2↓; COX-1↓; COX-2↓;	[145,146]
Jiang-Suan-Chu-Bi formula	Smilax glabra Roxb. (Liliaceae) Paeonia lactiflora Pall. (Paeoniaceae) Polygonum cuspidatum Sieb.et Zucc. (Polygonaceae) Iphigenia indica Kunth (Liliaceae) Rheum officinale Baill. (Polygonaceae) Clematis chinensis Osbeck (Ranunculaceae)Heracleum hemsleyanum Diels ( Apiaceae) Phellodendron chinense Schneid. (Rutaceae) Atractylodes lancea( Thunb.) DC. (Asteraceae) Glycyrrhiza uralensis Fisch. (Fabaceae) Salvia miltiorrhiza Bge. (Labiatae) Angelica sinensis (Oliv.) Diels (Apiaceae)	THP-1 cells	Antiinflammation	NLRP3↓; IL- 1β↓; ACS↓; caspase-1↓	[147]

heat-clearing and diuresis-promoting prescription	Tulipa gesneriana L. (Liliaceae) Lysimachia christiniae Hance (Primulaceae) Atractylodes Lancea (Thunb.) DC. (Asteraceae) Clematis chinensis Osbeck (Ranunculaceae) Smilax glabra Roxb. ( Liliaceae) Achyranthes bidentata Bl. (Amaranthaceae) Coix lacryma-jobi L.var.mayuen(Roman.)Stapf (Poaceae) Phellodendron chinense Schneid. (Rutaceae) Lycopus lucidus Turcz.vat.hirtus Regel (Labiatae) Anemarrhena asphodeloides Bunge (Liliaceae) Dioscorea polystachya Turczaninow (Dioscoreaceae) Polygonum cuspidatum Sieb.et Zucc. (Polygonaceae)	Clinical patient	Antiinflammation Antihyperuricemia	NLRP3↓; IL1β↓	[148]
Huzhang-Guizhi herb pair	Polygonum cuspidatum Sieb.et Zucc. (Polygonaceae) CassiaTwig (Lauraceae)	male SD rats	Antiinflammation	IL-1β↓; TNF-α↓ p65↓	[149]
Shaoyao-gancao decoction	Paeonia lactiflora Pall. (Paeoniaceae)Glycyrrhiza uralensis Fisch. ( Fabaceae)	Male ICR mice RAW264.7 cells	Antiinflammation	IL-1β↓; IL-6↓; TNF-α↓; COX-2↓; PGES2↓	[150]
Tongfengding capsule	Gentiana macrophμlla Pall. (Gentianaceae) Phellodendron chinense Schneid. (Rutaceae) Corydalis yanhusuo W. T. Wang (Papaveraceae) Paeonia lactiflora Pall. (Paeoniaceae) Cyathula officinalis Kuan (Amaranthaceae) Alisma plantago-aquatica Linn. (Alismataceae) Plantago asiatica L. (Plantaginaceae) Smilax glabra Roxb. (Liliaceae)	Male SD rats THP-1 cells	Antiinflammation	TNF-α↓; IL-6↓; PGES2↓	[151]
Xiaofeng Granules	Atractylodes lancea( Thunb.)DC. (Asteraceae) Phellodendron chinense Schneid. (Rutaceae) Coix lacryma-jobi L.var.mayuen(Roman.)Stapf (Poaceae) Achyranthes bidentata Bl. (Amaranthaceae) Smilax glabra Roxb. (Liliaceae) Lonicera japonica Thunb. (Caprifoliaceae)	Male SD rats chondrocyte	Antiinflammation Inhibit cartilage matrix degradation	L-1β↓; IL-6↓; TNF-α↓ MMPs/TIMP- 1↓; ADAMTS-4/ TIMP-3↓	[152]
Shenling Baizhu San	Panax ginseng C.A.Mey. (Araliaceae) Poria cocos (Schw.) Wolf (Polyporaceae) Atractylodes macrocephala Koidz. (Compositae) Dioscorea opposita Thunb. (Dioscoreaceae) Dolichos lablab L. (Leguminosae) Nelumbo nucifera Gaertn. (Nelumbonaceae) Coix lacryma-jobi. var. ma-yuen. (Rom.Caill.) Stapf (Poaceae) Amomum villosum Lour. (Zingiberaceae) Platycodon grandiflorus (Jacq.) A. DC. (Campanulaceae) Glycyrrhiza uralensis Fisch. (Leguminosae)	male quails	Antihyperuricemia	p-PPARγ↓	[153]
Erding Formula	Viola philippica (Violaceae) Taraxacum mongolicum Hand.-Mazz. (Asteraceae) Lobelia chinensis Lour. (Campanulaceae) Isatis indigotica Fortune (Brassicaceae)	Male Kunming mice	Antihyperuricemia Antiinflammation relieve pain	mOAT3↑; mURAT1↓	[154]
Tongbixiao Pills	Rehmannia glutinosa (Gaetn.) Libosch. (Scrophulariaceae) Cynanchum otophyllum Schneid. (Asclepiadaceae) Gentiana macrophylla (Gentianaceae) Achyranthes bidentata Blume (Amaranthaceae) Homalomena occulta (Araceae) Cervus nippon Temminck (Cervidae) Carica papaya L. (Caricaceae) Coix lacryma-jobi L.var.mayuen(Roman.)Stapf (Poaceae) Poria cocos(Schw.)Wolf (Polyporaceae) Citrus reticulata Blanco (Rutaceae) Cynanchum atratum Bunge. (Asclepiadaceae) Phellodendron chinense Schneid. (Rutaceae) Atractylodes lancea (Thunb.) DC. (Asteraceae) Lonicera japonica Thunb. (Caprifoliaceae) Tetrapanax papyrifer (Hook.) K. Koch (Araliaceae)Plantago depressa Willd. ( Plantaginaceae) Taraxacum mongolicum Hand.-Mazz. (Asteraceae) Clematis chinensis Osbeck (Ranunculaceae) Aristolochia mollissima Hance (Aristolochiaceae) Caulis Sinomenii (Menispermaceae) Dioscorea septemloba Thunbt (Dioscoreaceae) Areca catechu L. (Arecaceae)	Male SD rats	Antihyperuricemia Antiinflammation	serum creatinine levels↓; serum urea nitrogen levels↓	[155]
TongFengTangSan	Tinospora sagittata (Oliv.) Gagnep. (Menispermaceae) Terminalia chebula Retz. (Combretaceae) Faeces Trogopterpri	Male SD rats	Antihyperuricemia	XOD↓	[156]

Table 10: Summary of antigout TCM prescriptions