TABLE 3.
Active ingredients on lowering serum uric acid based on in vivo and in vitro studies.
| Type | Model | Active ingredients | Inducer | Animal/cell | Major findings | References |
|---|---|---|---|---|---|---|
| In vivo | HUA | Bergenin | Yeast, PO | Mice | SLC2A9, ABCG2, PPAR-γ, IL-6, IL-1β, TNF-α | Chen et al. (2020a) |
| In vivo | HUA | Phloretin | Adenine and PO | Mice | α-SMA, TGF-β, IL-1β, NLRP3, caspase-1, IL-18, XOD, URAT1, GLUT9 | Cui et al. (2020) |
| In vivo | HUA | Polydatin | PO | SD rats | N/A | Han et al. (2020) |
| In vivo | HUA | Total glucosides of herbaceous peony (Paeonia lactiflora Pall.) flower | Adenine, ethambutol | Rats | XOD, URAT1, OAT1, GLUT9 | Kang et al. (2020) |
| In vivo | HUA and hyperlipidemia | Total flavonoids of Mori Cortex | High fat diet, adenine, ethylamine butanol | SD rats | URAT1, IL-6, TNF-α, OAT1 | Dang et al. (2019) |
| In vivo | Gouty arthritis | Pulchinenoside b4 | MSU | SD rats | N/A | Lyu et al. (2019) |
| In vivo | Hyperuricemic nephropathy | Pterostilbene | Adenine and PO | Mice | Fibronectin, collagen I, α-SMA, TGF-β1, Smad3, Src, STAT3 | Pan et al. (2019) |
| In vivo and in vitro | HUA | Liquiritigenin | PO, xanthine | Mice, MDCK-hOAT4, HEK293-hURAT1 | OAT4, URAT1 | Wang et al. (2019e) |
| In vivo | Nonalcoholic fatty liver disease and HUA | Resveratrol | PO and yeast | Rats | FOXO3a, SIRT1, NF-κB | Xu et al. (2019) |
| In vivo | Diabetic nephropathy | Total flavonoids from Oxytropis falcata Bunge | High-fat diet | Mice | MCP-1, NF-κB, IL-6, TGF-β1, JAK 1, STAT3, STAT 4, SOCS-1, SOCS-3 | Yang et al. (2019b) |
| In vivo | Intestinal injury | Ganoderma atrum polysaccharide | Acrylamide | SD rats | MDA, catalase, SOD, glutathione, IL-2, IL-1β, TNF-α, IL-4, IL-10, ALP, endothelin-1 | Yang et al. (2019d) |
| In vivo | HUA and acute gouty arthritis | Luteolin | PO and MSU | Mice | XO, URAT1, GLUT9, IL-1β, TNF-α | Lin et al. (2018) |
| In vivo | HUA and acute gouty arthritis | Luteolin-4′-O-glucoside | PO and MSU | Mice | XO | Lin et al. (2018) |
| In vivo | HUA and gouty arthritis | Hirudin | Hypoxanthine, sodium uric | Mice, wistar rats | XOD, GLUT9 | Liu et al. (2018) |
| In vivo | HUA | Arctiin | Adenine and ethambutanol | Rats | XOD, MCP-1, TNF-α | Louxin et al. (2018) |
| In vivo | HUA | Mangiferin aglycon derivative J99745 | PO | Mice | XO, URAT1, GLUT9, OAT1, ABCG2 | Qin et al. (2018) |
| In vivo | HUA and gouty arthritis | [6]—shogaol | PO, MSU and hypoxanthine | SD rats | IL-1β, TNF-α | Wang et al. (2018) |
| In vivo and in vitro | HUA | Dioscin | PO | Mice, HCT116 cells | URAT1, GLUT9 | Zhang et al. (2018b) |
| In vivo | HUA | Epigallocatechin-3-gallate | PO and yeast | Mice | URAT1, GLUT9, XO | Zhu et al. (2018) |
| In vivo and in vitro | HUA | Taxifolin | Mice: GMP and IMP, cells: Guanosine and inosine | Mice, AML12 cells | XO | Adachi et al. (2017) |
| In vivo | HUA | Vaticaffinol | PO | Mice | XDH, XO, GLUT9, URAT1, OAT1, OCT1, OCT2, OCTN1, NLRP3 | Chen et al. (2017b) |
| In vivo | HUA | Caffeoylquinic acid | PO | Mice | XO, GLUT9, OAT1, URAT1, IL-1β, TNF-α | Jiang et al. (2017) |
| In vivo and in vitro | Gout | Procyanidins | Mice: MSU, cells: LPS and MSU | Mice, raw 264.7 cells | NLRP3, IL-1β, caspase-1, ROS, NR 1, p38, ERK | Liu et al. (2017) |
| In vivo | HUA | Gypenosides | Lipid emulsion | Rats | ADA, XDH, URAT1, GLUT9, OAT1 | Pang et al. (2017) |
| In vivo | Gouty arthritis | Total saponin fraction from dioscorea nipponica makino | MSU | Rats | TLR2, TLR4, IRAK1, TRAF6, NF-κB, IκBα, IKKα, TAK1, IL-1β, IL-6, TNF-α | Zhou et al. (2017) |
| In vivo | HUA | Saponins extracted from dioscorea collettii | Adenine and ethambutol | SD rats | URAT1, GLUT9, OAT1, OAT3 | Zhu et al. (2017) |
| In vivo | HUA | Total saponins from dioscorea septemloba thunb | Adenine | SD rats | OATP1A1 | Chen et al. (2016b) |
| In vivo | HUA with renal dysfunction | Emodinol | PO | Mice | XOD, GLUT9, URAT1, ABCG2, OAT1, OCT1, OCT2, OCTN1, OCTN2, OIT3 | Hui et al. (2016) |
| In vivo and in vitro | HUA | Pallidifloside D | PO | Mice, PC12 | PRPS, HGPRT, PRPPAT | Li et al. (2016) |
| In vivo | HUA | Mangiferin | PO | Mice | XOD | Niu et al. (2016) |
| In vivo | HUA | Salvianolic acid C | PO | Mice | XOD | Tang et al. (2016) |
| In vivo | HUA | Green tea polyphenols | PO | Mice | XO, URAT1, OAT1, OAT3 | Chen et al. (2015a) |
| In vivo | HUA | Flavonoids and phenylethanoid glycosides from Lippia nodiflora | PO and hypoxanthine | SD rats | XO | Cheng et al. (2015) |
| In vivo | HUA | Pallidifloside D | PO | Mice | XO, URAT1, GLUT9, OAT1 | Hou et al. (2015) |
| In vivo | Gout | Lemnalol | MSU | Rats | TGF-β1, MMP-9, cathepsin K, TRAP | Lee et al. (2015) |
| In vivo | HUA and nephropathy | Rhein | Adenine and ethambutol | Mice | IL-1β, TNF-α, PGE2 | Meng et al. (2015) |
| In vivo | HUA | Nuciferine | PO | Mice | URAT1, GLUT9, ABCG2, OAT1, OCT1, OCTN1, OCTN2, IL-1β, TLR2, TLR4, NF-κB, NLRP3, ASC, caspase1 | Wang et al. (2015) |
| In vivo | HUA | Anthocyanins from purple sweet potato | PO | Mice | XO, URAT1, GLUT9, OAT1, OCTN2 | Zhang et al. (2015) |
| In vivo | HUA | Total saponin of dioscorea | PO, ethambutol | SD rats | N/A | Chen et al. (2014b) |
| In vivo | HUA | Chrysanthemum flower oil | PO | Rats | XO | Honda et al. (2014) |
| In vivo | HUA | Exopolysaccharide produced by Cordyceps militaris | PO | Mice | XO | Ma et al. (2014) |
| In vivo | HUA | Dioscin | PO | Mice | OAT1, URAT1, OCT2, XO | Su et al. (2014) |
| In vivo | HUA | Pallidifloside D | PO | Mice | URAT1, GLUT9, OAT1 | Wu et al. (2014a) |
| In vivo | HUA | Smilaxchinoside A, Smilaxchinoside C | PO | Mice | URAT1, GLUT9, OAT1 | Wu et al. (2014b) |
| In vivo | HUA | Riparoside B, timosaponin J | PO | Mice | XO, URAT1, GLUT9, OTA1 | Wu et al. (2014d) |
| In vivo and in vitro | HUA | Total saponins from Discorea nipponica | Mice: PO, cells: IL-1β | Mice, synovial cells | URAT1, GLUT9, OAT1, OAT3 | Zhou et al. (2014) |
| In vivo | Uric acid nephropathy | Quercetin | Adenine and ethambutol | SD rats | NLRP3, ASC, Caspase-1, TLR2, TLR4 | Hu et al. (2013a) |
| In vivo | HUA | Aspalathin | IMP | Mice | XO | Kondo et al. (2013) |
| In vivo | Gouty arthritis | Quercetin | MSU | SD rats | IL–1β, TNF–α, COX-2, PGE2, NO, MDA, SOD, glutathione peroxidase | Huang et al. (2012) |
| In vivo | HUA | Mangiferin | PO | Mice | XDH, XOD | Niu et al. (2012) |
| In vivo | Hyperuricemic nephropathy | Tanshinone IIA | Adenine | SD rats | NF-κB, MCP-1, IL-10 | Wu et al. (2012a) |
| In vivo | Uric acid nephropathy | Tanshinone IIA | Adenine | SD rats | NF-κB, MCP-1, IL-10 | Wu et al. (2012b) |
| In vivo | HUA | Curcumin | Fructose | SD rats | NO, GLUT9, RST, OAT1, MRP4, OCT1, JAK2, STAT3, SOCS3, TGF-β1 | Zhang et al. (2012) |
| In vivo | HUA | Iridoid glycosides of Paederia scandens | PO and adenine | SD rats | MCP-1, α-SMA, NF-κB | Zhu et al. (2012) |
| In vivo | HUA | Mulberroside a | PO | Mice | GLUT9, URAT1, OAT1, OCT1, OCT2, OCTN1, OCTN2 | Wang et al. (2011) |
| In vivo | HUA | Morin | PO | Mice | URAT1, GLUT9, OAT1, OAT3, OCT1, OCT2, OCTN1, OCTN2, | Wang et al. (2010a) |
HUA, hyperuricemia; PO, potassium oxonate; MSU, monosodium urate; SLC2A9, solute carrier family 2, facilitated glucose transporter member; PPAR-γ, peroxisome proliferator-activated receptor γ; IL, interleukin; TNF-α, tumor necrosis factor; α-SMA, alpha-smooth muscle actin; TGF-β, transforming growth factor beta-1; NLRP3, the NOD-like receptor P3 inflammasome; XO/XOD, xanthine oxidase; URAT1, urate transporter one; GLUT9, glucose transporter nine; OAT1/3, organic anion transporter one and three; Smad3, mothers against decapentaplegic homolog three; Src, proto-oncogene tyrosine-protein kinase Src; STAT3, signal transducer and activator of transcription three; FOXO3α, forkhead box O3 alpha; SIRT1, silent information regulator one; NF-κB, nuclear factor-kappa B; MCP-1, monocyte chemoattractant protein-1; JAK2, Janus kinase two; SOCS-1/3, suppressor of cytokine signaling 1/3; MDA, malondialdehyde; SOD, superoxide dismutase; ABCG2, adenosine triphosphate (ATP)-binding cassette transporter two; XDH, xanthine dehydrogenase; OCT1/2, organic cation transporter; ALP: alkaline phosphatase; OCTN1/2, organic cation/carnitine transporter one and two; ROS, reactive oxygen species; NR-1, N-methyl-D-aspartic acid receptor one; p38, phosphorylated p38 mitogen-activated protein kinase; ERK, phosphorylated extracellular regulated protein kinase; ADA, adenosine deaminase; TLRs, toll-like receptors; IRAK, IL-1R-associated kinase; TRAF6, TNF receptor associated factor 6; IκB, inhibitor of NF-κB; IKKα, inhibitor of nuclear factor kappa-B kinase; TAK1, transforming growth factor beta-activated kinase one; OATP1A1, organic anion transporting polypeptide 1A1; OIT3, oncoprotein-induced transcript 3; PRPS, phosphoribosyl pyrophosphate synthetase; HGPRT, hypoxanthine-guanine phosphoribosyl transferase; PRPPAT, phosphoribosyl pyrophosphate amino-transferase; MMP-9, matrix metalloproteinase nine; TRAP, tartrate-resistant acid phosphatase; COX-2, cyclooxygenase-2; PGE2, prostaglandin E2; NO, nitric oxide; ASC, the apoptosis-associated speck-like protein containing a caspase recruitment domain; RST, renal-specific transporter; MRP4, multidrug resistance protein 4. N/A, not available.