Skip to main content
SpringerLink
Log in

Isoorientin exerts a urate-lowering effect through inhibition of xanthine oxidase and regulation of the TLR4-NLRP3 inflammasome signaling pathway

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

Isoorientin (ISO), a natural flavonoid compound, has been identified in several plants and its biological activity is determined and the study on lowering uric acid has not been reported. In view of the current status of treatment of hyperuricemia, we evaluated the hypouricemic effects of ISO in vivo and in vitro, and explored the underlying mechanisms. Yeast extract-induced hyperuricemia animal model as well as hypoxanthine and xanthine oxidase (XOD) co-induced high uric acid L-O2 cell model and enzymatic experiments in vitro were selected. The XOD activity and uric acid (UA) level were inhibited after the treatment of ISO in vitro and in vivo. Furthermore, serum creatinine (CRE) and blood urea nitrogen (BUN) levels were also significantly reduced and liver damage was recovered in pathological histology after the ISO administration in hyperuricemia animal model. The results of mechanism illustrated that protein expressions such as XOD, toll-like receptor 4 (TLR4), cathepsin B (CTSB), NLRP3, and its downstream caspase-1 as well as interleukin-18 (IL-18) were markedly downregulated by ISO intervention in vitro and in vivo. Our results suggest that ISO exerts a urate-lowering effect through inhibiting XOD activity and regulating TLR4-NLRP3 inflammasome signal pathway, thus representing a promising candidate therapeutic agent for hyperuricemia.

Graphic abstract

Both animal models and in vitro experiments suggested that ISO may effectively lower uric acid produce. The mechanism might be the inhibition of XOD activity and NLRP3 inflammasome of upregulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ISO:

Isoorientin

XOD:

Xanthine oxidase

UA:

Uric acid

CRE:

Creatinine

BUN:

Blood urea nitrogen

TLR 4:

Toll-like receptor 4

NF-κB:

Nuclear factor-κB

CTSB:

Cathepsin B

NLRP:

NOD-like receptor superfamily pyrin

PRRs:

Pattern recognition receptors

NLRC:

NOD-like receptor subfamily C

NAIP:

NLR family, apoptosis inhibitory protein

CARD:

Caspase activation and recruitment domain

PYHIN:

Pyrin and HIN domain-containing protein

URAT1:

Urate anion transporter 1

GLUT9:

Glucose transporter 9

OAT:

Organic cation transporter

ABCG2:

ATP-binding cassette transporter ABCG2/BCRP

ASC:

Apoptosis-associated speck-like protein

IL-1β:

Interleukin-1β

IL-18:

Interleukin-18

IR:

Insulin resistance

LPS:

Lipopolysaccharide

K:

Potassium

Ca:

Calcium

FDA:

Food and Drug Administration

BCA:

Bicinchoninic acid

SPF:

Specific pathogen free

PBS:

Phosphate-buffered saline

PMSF:

Phenylmethylsulfonyl fluoride

DMSO:

Dimethyl sulfoxide

FBS:

Fetal bovine serum

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

DMEM:

Dulbecco’s modified Eagle’s medium

ROS:

Reactive oxygen species

H&E:

Hematoxylin and eosin

TGF-β:

Transforming growth factor beta

RIPA:

Radioimmunoprecipitation

PVDF:

Polyvinylidene fluoride

References

  1. Chen C, Lu JM, Yao Q (2016) Hyperuricemia-related diseases and xanthine oxidoreductase (XOR) inhibitors: an overview. Med Sci Monit 22:2501–2512

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Wang H, Zhang H, Sun L, Guo W (2018) Roles of hyperuricemia in metabolic syndrome and cardiac-kidney-vascular system diseases. Am J Transl Res 10(9):2749–2763

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Ali N, Perveen R, Rahman S, Mahmood S, Rahman S, Islam S, Haque T, Sumon AH, Kathak RR, Molla NH, Islam F, Mohanto NC, Nurunnabi SM, Ahmed S, Rahman M (2018) Prevalence of hyperuricemia and the relationship between serum uric acid and obesity: a study on Bangladeshi adults. PLoS ONE 13(11):e0206850

    PubMed  PubMed Central  Google Scholar 

  4. Zhu Y, Pandya BJ, Choi HK (2011) Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheumatol 63(10):3136–3141

    Google Scholar 

  5. Kim Y, Kang J, Kim GT (2018) Prevalence of hyperuricemia and its associated factors in the general Korean population: an analysis of a population-based nationally representative sample. Clin Rheumatol 37(9):2529–2538

    Google Scholar 

  6. Liu R, Han C, Wu D, Xia X, Gu J, Guan H, Shan Z, Teng W (2015) Prevalence of hyperuricemia and gout in Mainland China from 2000 to 2014: a systematic review and meta-analysis. Biomed Res Int 2015:762820

    PubMed  PubMed Central  Google Scholar 

  7. Tan PK, Farrar JE, Gaucher EA, Miner JN (2016) Coevolution of URAT1 and uricase during primate evolution: implications for serum urate homeostasis and gout. Mol Biol Evol 33(9):2193–2200

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Tan PK, Ostertag TM, Miner JN (2016) Mechanism of high affinity inhibition of the human urate transporter URAT1. Sci Rep 6:34995

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang Z, Cui T, Ci X, Zhao F, Sun Y, Li Y, Liu R, Wu W, Yi X, Liu C (2019) The effect of polymorphism of uric acid transporters on uric acid transport. J Nephrol 32(2):177–187

    PubMed  Google Scholar 

  10. Fujita K, Ichida K (2018) ABCG2 as a therapeutic target candidate for gout. Expert Opin Ther Targets 22(2):123–129

    CAS  PubMed  Google Scholar 

  11. Desideri G, Castaldo G, Lombardi A, Mussap M, Testa A, Pontremoli R, Punzi L, Borghi C (2014) Is it time to revise the normal range of serum uric acid levels? Eur Rev Med Pharmacol Sci 18(9):1295–1306

    CAS  PubMed  Google Scholar 

  12. Ansari A, Aslam Z, De Sica A, Smith M, Gilshenan K, Fairbanks L, Marinaki A, Sanderson J, Duley J (2008) Influence of xanthine oxidase on thiopurine metabolism in Crohn’s disease. Aliment Pharmacol Ther 28(6):749–757

    CAS  PubMed  Google Scholar 

  13. Aranda R, Domenech E, Rus AD, Real JT, Sastre J, Vina J, Pallardo FV (2007) Age-related increase in xanthine oxidase activity in human plasma and rat tissues. Free Radic Res 41(11):1195–1200

    CAS  PubMed  Google Scholar 

  14. Alem MM, Alshehri AM, Cahusac PM, Walters MR (2018) Effect of xanthine oxidase inhibition on arterial stiffness in patients with chronic heart failure. Clin Med Insights Cardiol 12:1179546818779584

    PubMed  PubMed Central  Google Scholar 

  15. El-Bassossy HM, Watson ML (2015) Xanthine oxidase inhibition alleviates the cardiac complications of insulin resistance: effect on low grade inflammation and the angiotensin system. J Transl Med 13:82

    PubMed  PubMed Central  Google Scholar 

  16. Ives A, Nomura J, Martinon F, Roger T, LeRoy D, Miner JN, Simon G, Busso N, So A (2015) Xanthine oxidoreductase regulates macrophage IL1beta secretion upon NLRP3 inflammasome activation. Nat Commun 6:6555

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Bauernfeind F, Hornung V (2013) Of inflammasomes and pathogens–sensing of microbes by the inflammasome. EMBO Mol Med 5(6):814–826

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Amores-Iniesta J, Barbera-Cremades M, Martinez CM, Pons JA, Revilla-Nuin B, Martinez-Alarcon L, Di Virgilio F, Parrilla P, Baroja-Mazo A, Pelegrin P (2017) Extracellular ATP activates the NLRP3 inflammasome and is an early danger signal of skin allograft rejection. Cell Rep 21(12):3414–3426

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Bai H, Yang B, Yu W, Xiao Y, Yu D, Zhang Q (2018) Cathepsin B links oxidative stress to the activation of NLRP3 inflammasome. Exp Cell Res 362(1):180–187

    CAS  PubMed  Google Scholar 

  20. Amaral EP, Riteau N, Moayeri M, Maier N, Mayer-Barber KD, Pereira RM, Lage SL, Kubler A, Bishai WR, D’Imperio-Lima MR, Sher A, Andrade BB (2018) Lysosomal cathepsin release is required for NLRP3-inflammasome activation by Mycobacteriumtuberculosis in infected macrophages. Front Immunol 9:1427

    PubMed  PubMed Central  Google Scholar 

  21. Dalbeth N, Merriman TR, Stamp LK (2016) Gout. Lancet 388(10055):2039–2052

    CAS  PubMed  Google Scholar 

  22. Liu-Bryan R, Pritzker K, Firestein GS, Terkeltaub R (2005) TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation. J Immunol 174(8):5016–5023

    CAS  PubMed  Google Scholar 

  23. Ghaemi-Oskouie F, Shi Y (2011) The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep 13(2):160–166

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Grainger R, McLaughlin RJ, Harrison AA, Harper JL (2013) Hyperuricaemia elevates circulating CCL2 levels and primes monocyte trafficking in subjects with inter-critical gout. Rheumatology 52(6):1018–1021

    CAS  PubMed  Google Scholar 

  25. Crisan TO, Cleophas MC, Oosting M, Lemmers H, Toenhake-Dijkstra H, Netea MG, Jansen TL, Joosten LA (2016) Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra. Ann Rheum Dis 75(4):755–762

    CAS  PubMed  Google Scholar 

  26. Chen M, Lu X, Lu C, Shen N, Jiang Y, Chen M, Wu H (2018) Soluble uric acid increases PDZK1 and ABCG2 expression in human intestinal cell lines via the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway. Arthritis Res Ther 20(1):20

    PubMed  PubMed Central  Google Scholar 

  27. Bakan A, Oral A, Elcioglu OC, Takir M, Kostek O, Ozkok A, Basci S, Sumnu A, Ozturk S, Sipahioglu M, Turkmen A, Voroneanu L, Covic A, Kanbay M (2015) Hyperuricemia is associated with progression of IgA nephropathy. Int Urol Nephrol 47(4):673–678

    CAS  PubMed  Google Scholar 

  28. Gromadzinski L, Januszko-Giergielewicz B, Pruszczyk P (2015) Hyperuricemia is an independent predictive factor for left ventricular diastolic dysfunction in patients with chronic kidney disease. Adv Clin Exp Med 24(1):47–54

    PubMed  Google Scholar 

  29. Lin MS, Dai YS, Pwu RF, Chen YH, Chang NC (2005) Risk estimates for drugs suspected of being associated with Stevens-Johnson syndrome and toxic epidermal necrolysis: a case-control study. Intern Med J 35(3):188–190

    PubMed  Google Scholar 

  30. Zemmez Y, Hjira N (2018) Allopurinol-induced DRESS syndrome: drug reaction with eosynophilia and systemic symptoms (DRESS). Pan Afr Med J 30:120

    PubMed  PubMed Central  Google Scholar 

  31. Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, Sidoroff A, Schneck J, Roujeau JC, Flahault A (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Investig Dermatol 128(1):35–44

    CAS  PubMed  Google Scholar 

  32. Chohan S (2011) Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions. J Rheumatol 38(9):1957–1959

    CAS  PubMed  Google Scholar 

  33. Yu KH (2007) Febuxostat: a novel non-purine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in gout. Recent Pat Inflamm Allergy Drug Discov 1(1):69–75

    CAS  PubMed  Google Scholar 

  34. Bohm M, Vuppalanchi R, Chalasani N, Drug-Induced Liver Injury N (2016) Febuxostat-induced acute liver injury. Hepatology 63(3):1047–1049

    PubMed  PubMed Central  Google Scholar 

  35. Bruce SP (2006) Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout. Ann Pharmacother 40(12):2187–2194

    CAS  PubMed  Google Scholar 

  36. Lopez-Lazaro M (2009) Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 9(1):31–59

    CAS  PubMed  Google Scholar 

  37. Yan J, Zhang G, Hu Y, Ma Y (2013) Effect of luteolin on xanthine oxidase: inhibition kinetics and interaction mechanism merging with docking simulation. Food Chem 141(4):3766–3773

    CAS  PubMed  Google Scholar 

  38. Pauff JM, Hille R (2009) Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod 72(4):725–731

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Lin X, Wei J, Chen Y, He P, Lin J, Tan S, Nie J, Lu S, He M, Lu Z, Huang Q (2016) Isoorientin from Gypsophila elegans induces apoptosis in liver cancer cells via mitochondrial-mediated pathway. J Ethnopharmacol 187:187–194

    CAS  PubMed  Google Scholar 

  40. Yuan L, Wang J, Xiao H, Wu W, Wang Y, Liu X (2013) MAPK signaling pathways regulate mitochondrial-mediated apoptosis induced by isoorientin in human hepatoblastoma cancer cells. Food Chem Toxicol 53:62–68

    CAS  PubMed  Google Scholar 

  41. Yuan L, Wei S, Wang J, Liu X (2014) Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. J Agric Food Chem 62(23):5390–5400

    CAS  PubMed  Google Scholar 

  42. Yuan L, Wang Y, Wang J, Xiao H, Liu X (2014) Additive effect of zinc oxide nanoparticles and isoorientin on apoptosis in human hepatoma cell line. Toxicol Lett 225(2):294–304

    CAS  PubMed  Google Scholar 

  43. Da Silva MM, De Assis AM, Da Rocha RF, Gasparotto J, Gazola AC, Costa GM, Zucolotto SM, Castellanos LH, Ramos FA, Schenkel EP, Reginatto FH, Gelain DP, Moreira JC (2013) Passiflora manicata (Juss.) aqueous leaf extract protects against reactive oxygen species and protein glycation in vitro and ex vivo models. Food Chem Toxicol 60:45–51

    Google Scholar 

  44. Yuan L, Wang J, Wu W, Liu Q, Liu X (2016) Effect of isoorientin on intracellular antioxidant defence mechanisms in hepatoma and liver cell lines. Biomed Pharmacother 81:356–362

    CAS  PubMed  Google Scholar 

  45. Yuan L, Han X, Li W, Ren D, Yang X (2016) Isoorientin prevents hyperlipidemia and liver injury by regulating lipid metabolism, antioxidant capability, and inflammatory cytokine release in high-fructose-fed mice. J Agric Food Chem 64(13):2682–2689

    CAS  PubMed  Google Scholar 

  46. Yuan L, Wu Y, Ren X, Liu Q, Wang J, Liu X (2014) Isoorientin attenuates lipopolysaccharide-induced pro-inflammatory responses through down-regulation of ROS-related MAPK/NF-kappaB signaling pathway in BV-2 microglia. Mol Cell Biochem 386(1–2):153–165

    CAS  PubMed  Google Scholar 

  47. Lee W, Ku SK, Bae JS (2014) Vascular barrier protective effects of orientin and isoorientin in LPS-induced inflammation in vitro and in vivo. Vasc Pharmacol 62(1):13–14

    Google Scholar 

  48. Chen YX, Huang QF, Lin X, Wei JB (2013) Protective effect of isoorientin on alcohol-induced hepatic fibrosis in rats. Zhongguo Zhong Yao Za Zhi 38(21):3726–3730

    CAS  PubMed  Google Scholar 

  49. Lin X, Chen Y, Lv S, Tan S, Zhang S, Huang R, Zhuo L, Liang S, Lu Z, Huang Q (2015) Gypsophila elegans isoorientin attenuates CCl(4)-induced hepatic fibrosis in rats via modulation of NF-kappaB and TGF-beta1/Smad signaling pathways. Int Immunopharmacol 28(1):305–312

    CAS  PubMed  Google Scholar 

  50. Zhu SY, Zhou YD, Liu QS, Du GH (2007) Establishment and application of a high-throughput screening assay for xanthine oxidase inhibitor in vitro. Chin Pharm J 42(3):187–190

    CAS  Google Scholar 

  51. Chen GL, Sun XX, Wang QM, Zhang XM, Liu PH (2001) Study on hyperuricemia model in mice. Chin Pharm Bull 17(3):350–352

    CAS  Google Scholar 

  52. Niu YF, Liu K, Gao LH, Liu X, Li L (2015) Effects of 3,5,2’,4’-tetrahydroxychalcone on serum uric acid levels and the content of hepatic XOD/XDH in mice. Chin Pharm J 50(1):34–38

    CAS  Google Scholar 

  53. Xiong X, Ren Y, Cui Y, Li R, Wang C, Zhang Y (2017) Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation. Biomed Pharmacother 96:1292–1298

    CAS  PubMed  Google Scholar 

  54. Chen L, Li M, Wu JL, Li JX, Ma ZC (2019) Effect of lemon water soluble extract on hyperuricemia in a mouse model. Food Funct 10(9):6000–6008

    CAS  PubMed  Google Scholar 

  55. Hayyan M, Hashim MA, AlNashef IM (2016) Superoxide ion: generation and chemical implications. Chem Rev 116(5):3029–3085

    CAS  PubMed  Google Scholar 

  56. Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF (2000) Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc Natl Acad Sci USA 97(20):10723–10728

    CAS  PubMed  Google Scholar 

  57. Hou CW, Lee YC, Hung HF, Fu HW, Jeng KC (2012) Longan seed extract reduces hyperuricemia via modulating urate transporters and suppressing xanthine oxidase activity. Am J Chin Med 40(5):979–991

    PubMed  Google Scholar 

  58. Qin Z, Wang S, Lin Y, Zhao Y, Yang S, Song J, Xie T, Tian J, Wu S, Du G (2018) Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice. Acta Pharm Sin B 8(2):306–315

    PubMed  Google Scholar 

  59. Hongyan L, Suling W, Weina Z, Yajie Z, Jie R (2016) Antihyperuricemic effect of liquiritigenin in potassium oxonate-induced hyperuricemic rats. Biomed Pharmacother 84:1930–1936

    CAS  PubMed  Google Scholar 

  60. Shuyan Y, Mingsan M (2014) Interventional study of total flavone extract of lysimashia on hyperuricemia animal models. Henan University of Chinese Medicine, Zheng Zhou

    Google Scholar 

  61. Minami M, Ishiyama A, Takagi M, Omata M, Atarashi K (2005) Effects of allopurinol, a xanthine oxidase inhibitor, on renal injury in hypercholesterolemia-induced hypertensive rats. Blood Press 14(2):120–125

    CAS  PubMed  Google Scholar 

  62. Dubreuil M, Zhu Y, Zhang Y, Seeger JD, Lu N, Rho YH, Choi HK (2015) Allopurinol initiation and all-cause mortality in the general population. Ann Rheum Dis 74(7):1368–1372

    CAS  PubMed  Google Scholar 

  63. Ma L, Hu J, Li J, Yang Y, Zhang L, Zou L, Gao R, Peng C, Wang Y, Luo T, Xiang X, Qing H, Xiao X, Wu C, Wang Z, He JC, Li Q, Yang S (2018) Bisphenol A promotes hyperuricemia via activating xanthine oxidase. FASEB J 32(2):1007–1016

    CAS  PubMed  Google Scholar 

  64. Braga TT, Forni MF, Correa-Costa M, Ramos RN, Barbuto JA, Branco P, Castoldi A, Hiyane MI, Davanso MR, Latz E, Franklin BS, Kowaltowski AJ, Camara NO (2017) Soluble uric acid activates the NLRP3 inflammasome. Sci Rep 7:39884

    CAS  PubMed  PubMed Central  Google Scholar 

  65. He Y, Hara H, Nunez G (2016) Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 41(12):1012–1021

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Kim JJ, Jo EK (2013) NLRP3 inflammasome and host protection against bacterial infection. J Korean Med Sci 28(10):1415–1423

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Yunnan provincial key programs of Yunnan Eco-friendly Food International Cooperation Research Center project under Grant (2019ZG00904, 2019ZG00909), and the Science and Technology Plan Project of Yunnan Province (2018IA060).

Author information

Author notes

  1. Meng-Fei An and Ming-Yue Wang have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Pu-erh Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, 650224, People’s Republic of China

    Meng-Fei An, Ming-Yue Wang, Chang Shen, Ze-Rui Sun, Yun-Li Zhao, Xuan-Jun Wang & Jun Sheng

  2. College of Science, Yunnan Agricultural University, Kunming, 650224, People’s Republic of China

    Yun-Li Zhao, Xuan-Jun Wang & Jun Sheng

  3. College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650224, People’s Republic of China

    Meng-Fei An, Ming-Yue Wang, Chang Shen & Ze-Rui Sun

  4. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, People’s Republic of China

    Yun-Li Zhao

  5. State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming, 650224, People’s Republic of China

    Xuan-Jun Wang & Jun Sheng

Authors
  1. Meng-Fei An
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-Yue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chang Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ze-Rui Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun-Li Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xuan-Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Sheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yun-Li Zhao, Xuan-Jun Wang or Jun Sheng.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

An, MF., Wang, MY., Shen, C. et al. Isoorientin exerts a urate-lowering effect through inhibition of xanthine oxidase and regulation of the TLR4-NLRP3 inflammasome signaling pathway. J Nat Med 75, 129–141 (2021). https://doi.org/10.1007/s11418-020-01464-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-020-01464-z

Keywords

Search

Navigation