Mechanism of flavonoids in the treatment of gouty arthritis (Review)

Liu,Feifan; Bai,Yuanmei; Wan,Yan; He,Jinglin; Li,Qiongchao; Xie,Yuhuan; Guo,Peixin

doi:10.3892/mmr.2024.13256

Mechanism of flavonoids in the treatment of gouty arthritis (Review)

Authors:
- Feifan Liu
- Yuanmei Bai
- Yan Wan
- Jinglin He
- Qiongchao Li
- Yuhuan Xie
- Peixin Guo
View Affiliations

Affiliations: College of Ethnic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China, College of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, P.R. China
Published online on: May 28, 2024 https://doi.org/10.3892/mmr.2024.13256
Article Number: 132
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present review expounds the advancements in the application and mechanisms of flavonoids in gouty arthritis, highlighting their significance in managing the disease. Gouty arthritis is among the most common and severe inflammatory diseases, caused by hyperuricemia and the deposition of sodium urate crystals in the joints and surrounding tissues, posing a serious threat to human life and health. Flavonoids, extracted from various herbs, have attracted significant attention due to their efficacy in improving gouty arthritis. The present study systematically reviews the in vivo studies and in vitro animal studies on flavonoids from herbal medicines for the treatment of gouty arthritis that have been previously published in the PubMed, ScienceDirect, Google Scholar and China National Knowledge Infrastructure databases between 2000 and 2023. The review of the literature indicated that flavonoids can improve gouty arthritis through multiple mechanisms. These include lowering xanthine oxidase activity, inhibiting uric acid (UA) synthesis, regulating UA transporters to promote UA excretion, reducing the inflammatory response and improving oxidative stress. These mechanisms predominantly involve regulating the NOD‑like receptor 3 inflammasome, the Toll‑like receptor 4/myeloid differentiation factor 88/nuclear factor‑κB signaling pathway, and the levels of UA transporter proteins, namely recombinant urate transporter 1, glucose transporter 9, organic anion transporter (OAT)1 and OAT3. Various flavonoids used in traditional Chinese medicine hold therapeutic promise for gouty arthritis and are anticipated to pave the way for novel pharmaceuticals and clinical applications.

View Figures

View References

1	Cleophas MCP, Crişan TO, Klück V, Hoogerbrugge N, Netea-Maier RT, Dinarello CA, Netea MG and Joosten LAB: Romidepsin suppresses monosodium urate crystal-induced cytokine production through upregulation of suppressor of cytokine signaling 1 expression. Arthritis Res Ther. 21:502019. View Article : Google Scholar : PubMed/NCBI
2	Roddy E and Choi HK: Epidemiology of gout. Rheum Dis Clin North Am. 40:155–175. 2014. View Article : Google Scholar : PubMed/NCBI
3	Mbuyi N and Hood C: An update on gout diagnosis and management for the primary care provider. Nurse Pract. 45:16–25. 2020. View Article : Google Scholar : PubMed/NCBI
4	Ragab G, Elshahaly M and Bardin T. Gout: An old disease in new perspective-a review. J Adv Res. 8:495–511. 2017. View Article : Google Scholar : PubMed/NCBI
5	Dewulf JP, Marie S and Nassogne MC: Disorders of purine biosynthesis metabolism. Mol Genet Metab. 136:190–198. 2022. View Article : Google Scholar : PubMed/NCBI
6	Liu YR, Wang JQ and Li J: Role of NLRP3 in the pathogenesis and treatment of gout arthritis. Front Immunol. 14:11378222023. View Article : Google Scholar : PubMed/NCBI
7	Zhang J, Sun W, Gao F, Lu J, Li K, Xu Y, Li Y, Li C and Chen Y: Changes of serum uric acid level during acute gout flare and related factors. Front Endocrinol (Lausanne). 14:10770592023. View Article : Google Scholar : PubMed/NCBI
8	Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castaneda J, Coyfish M, Guillo S, Jansen T, Janssens H, et al: 2018 updated European league against rheumatism evidence-based recommendations for the diagnosis of gout. Ann Rheum Dis. 79:31–38. 2020. View Article : Google Scholar : PubMed/NCBI
9	Hu AM and Brown JN: Comparative effect of allopurinol and febuxostat on long-term renal outcomes in patients with hyperuricemia and chronic kidney disease: A systematic review. Clin Rheumatol. 39:3287–3294. 2020. View Article : Google Scholar : PubMed/NCBI
10	Rasheed Kayani R, Shamim R, Sultana Munir S, Sultana M, Nazir SUR, Riaz H, Nazir T, Maaz Ali M and Islam A: Medicinal plants and nonsteroidal anti-inflammatory drugs (NSAIDs) in treatment of arthritis: A literature review. Altern Ther Health Med. 28:58–64. 2022.PubMed/NCBI
11	Hainer BL, Matheson E and Wilkes RT: Diagnosis, treatment, and prevention of gout. Am Fam Physician. 90:831–836. 2014.PubMed/NCBI
12	Lucas G and Droney L: Severe adverse drug reaction to allopurinol. Aust Prescr. 45:130–131. 2022. View Article : Google Scholar : PubMed/NCBI
13	Febuxostat, . Updated advice suggests caution in patients with a history of cardiovascular disease. React Wkly 1960. 52023.
14	Ali S, Drendel AL, Rosychuk RJ, May SL, McGrath P, Carleton B and Johnson WD: LO049: Ibuprofen or oxycodone? An observational cohort study of post-emergency department discharge management of children's fracture pain. CJEM. 18 (Suppl 1):S472016. View Article : Google Scholar
15	Keller SF and Mandell BF: Management and cure of gouty arthritis. Rheum Dis Clin North Am. 48:479–492. 2022. View Article : Google Scholar : PubMed/NCBI
16	Atrahimovich D, Avni D and Khatib S: Flavonoids-macromolecules interactions in human diseases with focus on Alzheimer, atherosclerosis and cancer. Antioxidants (Basel). 10:4232021. View Article : Google Scholar : PubMed/NCBI
17	Li G, Ding K, Qiao Y and Zhang L, Zheng L, Pan T and Zhang L: Flavonoids regulate inflammation and oxidative stress in cancer. Molecules. 25:56282020. View Article : Google Scholar : PubMed/NCBI
18	Chagas MDSS, Behrens MD, Moragas-Tellis CJ, Penedo GXM, Silva AR and Gonçalves-de-Albuquerque CF: Flavonols and flavones as potential anti-inflammatory, antioxidant, and antibacterial compounds. Oxid Med Cell Longev. 2022:99667502022. View Article : Google Scholar : PubMed/NCBI
19	Zhang W, Sun C, Zhou S, Zhao W, Wang L, Sheng L, Yi J, Liu T, Yan J, Ma X and Fang B: Recent advances in chemistry and bioactivity of Sargentodoxa cuneata. J Ethnopharmacol. 270:1138402021. View Article : Google Scholar : PubMed/NCBI
20	Dhanasekar C and Rasool M: Morin, a dietary bioflavonol suppresses monosodium urate crystal-induced inflammation in an animal model of acute gouty arthritis with reference to NLRP3 inflammasome, hypo-xanthine phospho-ribosyl transferase, and inflammatory mediators. Eur J Pharmacol. 786:116–127. 2016. View Article : Google Scholar : PubMed/NCBI
21	Zhang C, Zhao M, Jiang B, Yu J, Hao Q, Liu W, Hu Z, Zhang Y and Song C: Extraction optimization, structural characterization and potential alleviation of hyperuricemia by flavone glycosides from celery seeds. Food Funct. 13:9832–9846. 2022. View Article : Google Scholar : PubMed/NCBI
22	Feng S, Wu S, Xie F, Yang CS and Shao P: Natural compounds lower uric acid levels and hyperuricemia: Molecular mechanisms and prospective. Trends Food Sci Tech. 123:87–102. 2022. View Article : Google Scholar
23	Altunayar-Unsalan C and Unsalan O: Molecular structure, antioxidant potential, and pharmacokinetic properties of plant flavonoid blumeatin and investigating its inhibition mechanism on xanthine oxidase for hyperuricemia by molecular modeling. ACS Omega. 9:13284–13297. 2024.PubMed/NCBI
24	Li J, Li S, Song Q, Ma E and Aimaijiang M: Mechanism of total flavonoids from Ampelopsis grossedentata against gouty arthritis based on multi-level interactive network and in vivo experimental validation. Zhongguo Zhong Yao Za Zhi. 47:4733–4743. 2022.(In Chinese). PubMed/NCBI
25	Huang J, Song Y, Zhao P, Feng Y and Liu Y: Experimental Study of Rutin in the Treatment of Acute Gouty Arthritis. Mil Med Joint Logist. 27:533–535+539. 2013.
26	Wu H, Wang Y, Huang J, Li Y, Lin Z and Zhang B: Rutin ameliorates gout via reducing XOD activity, inhibiting ROS production and NLRP3 inflammasome activation in quail. Biomed Pharmacother. 158:1141752023. View Article : Google Scholar : PubMed/NCBI
27	Huang J, Zhu M, Tao Y, Wang S, Chen J, Sun W and Li S: Therapeutic properties of quercetin on monosodium urate crystal-induced inflammation in rat. J Pharm Pharmacol. 64:1119–1127. 2012. View Article : Google Scholar : PubMed/NCBI
28	Qian X and Jiang Y, Luo Y and Jiang Y: The anti-hyperuricemia and anti-inflammatory effects of atractylodes macrocephala in hyperuricemia and gouty arthritis rat models. Comb Chem High Throughput Screen. 26:950–964. 2023. View Article : Google Scholar : PubMed/NCBI
29	Sato VH, Chewchinda S, Parichatikanond W and Vongsak B: In vitro and in vivo evidence of hypouricemic and anti-inflammatory activities of Maclura cochinchinensis (Lour.) Corner heartwood extract. J Tradit Complement Med. 10:85–94. 2019. View Article : Google Scholar : PubMed/NCBI
30	Nematbakhsh M, Hajhashemi V, Ghannadi A, Talebi A and Nikahd M: Protective effects of the Morus alba L. leaf extracts on cisplatin-induced nephrotoxicity in rat. Res Pharm Sci. 8:71–77. 2013.PubMed/NCBI
31	Lin Y, Liu PG, Liang WQ, Hu YJ, Xu P, Zhou J, Pu JB and Zhang HJ: Luteolin-4′-O-glucoside and its aglycone, two major flavones of Gnaphalium affine D. Don, resist hyperuricemia and acute gouty arthritis activity in animal models. Phytomedicine. 41:54–61. 2018. View Article : Google Scholar : PubMed/NCBI
32	Wang AH, Jin Y, Wu Y, Cheng XF, Tian QH, Xie Q and Liu W: Research progress on treatment of gout by xanthine oxidase inhibitor in traditional Chinese medicine. Tianjin J Tradit Chin Med. 36:1241–1245. 2019.
33	Mudgal R and Singh S: Xanthine oxidoreductase in the pathogenesis of endothelial dysfunction: An update. Curr Hypertens Rev. Feb 2–2024.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
34	Bardin T and Richette P: Novel uricosurics. Rheumatology (Oxford). 57 (Suppl 1):i42–i46. 2018. View Article : Google Scholar : PubMed/NCBI
35	Hu QH, Zhu JX, Ning LI and Miao MX: Effect of jasminoidin on potassium oxonate-induced hyperuricemia in mice and its mechanism. Cent S Pharm. 11:721–725. 2013.
36	Cheng Y and Li F: Current status of research on uric acid transporter proteins. J Hubei Univ Med. 36:470–473+486. 2017.
37	George RL and Keenan RT: Genetics of hyperuricemia and gout: Implications for the present and future. Curr Rheumatol Rep. 15:3092013. View Article : Google Scholar : PubMed/NCBI
38	Anzai N, Ichida K, Jutabha P, Kimura T, Babu E, Jin CJ, Srivastava S, Kitamura K, Hisatome I, Endou H and Sakurai H: Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans. J Biol Chem. 283:26834–26838. 2008. View Article : Google Scholar : PubMed/NCBI
39	So A and Thorens B: Uric acid transport and disease. J Clin Invest. 120:1791–1799. 2010. View Article : Google Scholar : PubMed/NCBI
40	Johnson RJ, Sanchez-Lozada LG and Nakagawa T: The effect of fructose on renal biology and disease. J Am Soc Nephrol. 21:2036–2039. 2010. View Article : Google Scholar : PubMed/NCBI
41	Wikoff WR, Nagle MA, Kouznetsova VL, Tsigelny IF and Nigam SK: Untargeted metabolomics identifies enterobiome metabolites and putative uremic toxins as substrates of organic anion transporter 1 (Oat1). J Proteome Res. 10:2842–2851. 2011. View Article : Google Scholar : PubMed/NCBI
42	Bush KT, Wu W, Lun C and Nigam SK: The drug transporter OAT3 (SLC22A8) and endogenous metabolite communication via the gut-liver-kidney axis. J Biol Chem. 292:15789–15803. 2017. View Article : Google Scholar : PubMed/NCBI
43	Nigam SK and Bhatnagar V: The systems biology of uric acid transporters: The role of remote sensing and signaling. Curr Opin Nephrol Hypertens. 27:305–313. 2018. View Article : Google Scholar : PubMed/NCBI
44	Woodward OM, Köttgen A, Coresh J, Boerwinkle E, Guggino WB and Köttgen M: Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci USA. 106:10338–10342. 2009. View Article : Google Scholar : PubMed/NCBI
45	Luo S, Cui X and Li X: Uric acid transporter in the kidney. Prog Physiol Sci. 50:231–235. 2019.
46	Zhang HJ, Li LN, Zhou J, Yang QQ, Liu PG, Xu P, Liang WQ, Cheng L, Zhang YQ, Pu JB, et al: Effects of Gnaphalium affine D. Don on hyperuricemia and acute gouty arthritis. J Ethnopharmacol. 203:304–311. 2017. View Article : Google Scholar : PubMed/NCBI
47	Caporali S, De Stefano A, Calabrese C, Giovannelli A, Pieri M, Savini I, Tesauro M, Bernardini S, Minieri M and Terrinoni A: Anti-inflammatory and active biological properties of the plant-derived bioactive compounds luteolin and luteolin 7-glucoside. Nutrients. 14:11552022. View Article : Google Scholar : PubMed/NCBI
48	Jiang Y, Lin Y, Hu YJ, Song XJ, Pan HH and Zhang HJ: Caffeoylquinic acid derivatives rich extract from Gnaphalium pensylvanicum willd. Ameliorates hyperuricemia and acute gouty arthritis in animal model. BMC Complement Altern Med. 17:3202017. View Article : Google Scholar : PubMed/NCBI
49	Li P, Ren G, Sun Y, Jiang D and Liu C: Extraction optimization, preliminary identification, and bioactivities in corn silk. Evid Based Complement Alternat Med. 2023:56851742023. View Article : Google Scholar : PubMed/NCBI
50	Xv G: Determination on the contents of the flavonoids and the nutritive components in different parts of three corns. J Henan Univ Technol (Natural Science Edition). 82–84. 2001.
51	Li P, Song J, Li Q, Zhang Q, Cui H, Guan B, Zhao Y and Song Z: Curative effect analysis of flavone extract from Stigma Maydis on rats of modified acute gouty arthritis model. China Mod Med. 25:8–11. 2018.
52	Chi X, Ye H, Ma C, Yue H, Guo J, Lin Z, Sun J, Ye D, Huang X and Lu G: Effect of total flavonoids in corn stigma on uric acid uptake and related gene expression in HK-2 cells. Pharmacol Clini Chin Mater Med. 36:95–100. 2020.(In Chinese).
53	Niu Y, Li Q, Tu C, Li N, Gao L, Lin H, Wang Z, Zhou Z and Li L: Hypouricemic actions of the pericarp of mangosteen in vitro and in vivo. J Nat Prod. 86:24–33. 2023. View Article : Google Scholar : PubMed/NCBI
54	Hu QH, Zhang X, Wang Y and Kong LD: Mangiferin promotes uric acid excretion and kidney function improvement and modulates related renal transporters in hyperuricemic mice. Yao Xue Xue Bao. 45:1239–1246. 2010.(In Chinese). PubMed/NCBI
55	Cobo I, Cheng A, Murillo-Saich J, Coras R, Torres A, Abe Y, Lana AJ, Schlachetzki J, Liu-Bryan R, Terkeltaub R, et al: Monosodium urate crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response. Cell Rep. 38:1104892022. View Article : Google Scholar : PubMed/NCBI
56	Lee YM, Cho SN, Son E, Song CH and Kim DS: Apamin from bee venom suppresses inflammation in a murine model of gouty arthritis. J Ethnopharmacol. 257:1128602020. View Article : Google Scholar : PubMed/NCBI
57	Cui R, Li M, Tuerxun G, Li Y and Xie S: Research on the role of toll-like receptor 2 and toll-like receptor 4 and its signal pathway in the pathogenesis of primary gout arthritis. Matrix Sci Pharma. 4:12020. View Article : Google Scholar
58	Jeong JH, Hong S, Kwon OC, Ghang B, Hwang I, Kim YG, Lee CK and Yoo B: CD14⁺ cells with the phenotype of infiltrated monocytes consist of distinct populations characterized by anti-inflammatory as well as pro-inflammatory activity in gouty arthritis. Front Immunol. 8:12602017. View Article : Google Scholar : PubMed/NCBI
59	Akahoshi T: Pathological mechanisms of gouty arthritis. Nihon Rinsho. 66:705–710. 2008.(In Japanese). PubMed/NCBI
60	Cronstein BN and Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 19:19–29. 2013. View Article : Google Scholar : PubMed/NCBI
61	Luo H, Tan J, Wei G, Huang L and JL: Advances in the pathogenesis, diagnosis and treatment of gout. Intern Med. 14:47–50. 2019.
62	Dai X, Fang X, Xia Y, Li M and Li X, Wang Y, Tao J and Li X: ATP-activated P2X7R promote the attack of acute gouty arthritis in rats through activating NLRP3 inflammasome and inflammatory cytokine production. J Inflamm. 15:1237–1248. 2022. View Article : Google Scholar : PubMed/NCBI
63	Xue Y, Li R, Fang P, Ye ZQ, Zhao Y, Zhou Y, Zhang KQ and Li L: NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice. J Mol Endocrinol. 67:27–40. 2021. View Article : Google Scholar : PubMed/NCBI
64	Han J, Shi G, Li W, Xie Y, Li F and Jiang D: Preventive effect of dioscin against monosodium urate-mediated gouty arthritis through inhibiting inflammasome NLRP3 and TLR4/NF-κB signaling pathway activation: An in vivo and in vitro study. J Nat Med. 75:37–47. 2021. View Article : Google Scholar : PubMed/NCBI
65	Ou X, Ding T, Yang H, et al: Research progress of signal pathway related to pathogenesis of gouty arthritis. Pharmacol Clin Chin Mater Med. 37:234–240. 2021.
66	Kelley N, Jeltema D, Duan Y and He Y: The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int J Mol Sci. 20:33282019. View Article : Google Scholar : PubMed/NCBI
67	Hulse J and Bhaskar K: Crosstalk between the NLRP3 inflammasome/ASC speck and amyloid protein aggregates drives disease progression in Alzheimer's and Parkinson's disease. Front Mol Neurosci. 15:8051692022. View Article : Google Scholar : PubMed/NCBI
68	Wang M, Zhu Y, Zhao H and Zhao HF: Moxibustion intervention improves synovitis by down-regulating NLRP3/Caspase-1/IL-1β signaling of synovial tissue in rats with adjuvant arthritis. Zhen Ci Yan Jiu. 48:1111–1116. 2023.(In English, Chinese). PubMed/NCBI
69	Li X and Yang N: Exosome miR-223-3p in the bone marrow-derived mesenchymal stem cells alleviates the inflammation and airway remodeling through NLRP3-induced ASC/Caspase-1/GSDMD signaling pathway. Int Immunopharmacol. 123:1107462023. View Article : Google Scholar : PubMed/NCBI
70	Li Z, Guo J and Bi L: Role of the NLRP3 inflammasome in autoimmune diseases. Biomed Pharmacother. 130:1105422020. View Article : Google Scholar : PubMed/NCBI
71	Zhang X, Liu Y, Deng G, Huang B, Kai G, Chen K and Li J: A purified biflavonoid extract from selaginella moellendorffii alleviates gout arthritis via NLRP3/ASC/Caspase-1 axis suppression. Front Pharmacol. 12:6762972021. View Article : Google Scholar : PubMed/NCBI
72	Rong S, Wan D, Fan Y, Liu S, Sun K, Huo J, Zhang P, Li X, Xie X, Wang F and Sun T: Amentoflavone affects epileptogenesis and exerts neuroprotective effects by inhibiting NLRP3 inflammasome. Front Pharmacol. 10:8562019. View Article : Google Scholar : PubMed/NCBI
73	Çevik D, Erdogan S, Serttas R, Kan Y and Kırmızıbekmez H: Cytotoxic and antimigratory activity of retrochalcones from Glycyrrhiza echinata L. on human cancer cells. Chem Biodivers. 20:e2022005892023. View Article : Google Scholar : PubMed/NCBI
74	Staurengo-Ferrari L, Ruiz-Miyazawa KW, Pinho-Ribeiro FA, Fattori V, Zaninelli TH, Badaro-Garcia S, Borghi SM, Carvalho TT, Alves-Filho JC, Cunha TM, et al: Trans-chalcone attenuates pain and inflammation in experimental acute gout arthritis in mice. Front Pharmacol. 9:11232018. View Article : Google Scholar : PubMed/NCBI
75	Sun X, Li P, Qu X and Liu W: Isovitexin alleviates acute gouty arthritis in rats by inhibiting inflammation via the TLR4/MyD88/NF-κB pathway. Pharm Biol. 59:1326–1333. 2021. View Article : Google Scholar : PubMed/NCBI
76	Hu N, Wang C, Dai X, Zhou M, Gong L, Yu L, Peng C and Li Y: Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4/MyD88/NF-κB signaling pathway. J Ethnopharmacol. 248:1123612020. View Article : Google Scholar : PubMed/NCBI
77	Takeda K and Akira S: Toll-like receptors. Curr Protoc Immunol. 109:14.12.1–14.12.10. 2015. View Article : Google Scholar : PubMed/NCBI
78	Zaninelli TH, Fattori V, Saraiva-Santos T, Badaro-Garcia S, Staurengo-Ferrari L, Andrade KC, Artero NA, Ferraz CR, Bertozzi MM, Rasquel-Oliveira F, et al: RvD1 disrupts nociceptor neuron and macrophage activation and neuroimmune communication, reducing pain and inflammation in gouty arthritis in mice. Br J Pharmacol. 179:4500–4515. 2022. View Article : Google Scholar : PubMed/NCBI
79	Tian J, Zhou D, Xiang L, Xie B, Wang B, Li Y and Liu X: Calycosin represses AIM2 inflammasome-mediated inflammation and pyroptosis to attenuate monosodium urate-induced gouty arthritis through NF-κB and p62-Keap1 pathways. Drug Dev Res. 83:1654–1672. 2022. View Article : Google Scholar : PubMed/NCBI
80	Wang F, Cao J, Li Y, Ren F, Bai J, Dong Q and Guo J: Study of quality markers of antiuric acid formula by grey relational analysis. SN Appl Sci. 3:6612021. View Article : Google Scholar
81	Xiong W, Zhang H, Wen L, Wang X, Zhong G, Shi Y, Du X and Zhu J: Effect of Lagotis brachystachys Maxim extract on xanthine oxidase and renal urate transporters in hyperuricemia mice. Chin J New Drugs. 27:1538–1543. 2018.
82	Shan J, Ouyang X, Yang H, Wei R, Liu Y, Zhong G, Liu H and Zhu J: Study on the effective parts of Lagotis brachystachys Maxim against acute gouty arthritis in rats. Tradit Chin Drug Res Clin Pharmacol. 32:492–498. 2021.(In Chinese).
83	Shi Y, Li X, Wen L, Zeng J, Zhong G, Yao X, Mu Z, Wang X and Zhu J: Anti-acute alcoholic liver injure effects and mechanism of Lagotis brachystachy and lagotis brevituba. Tradit Chin Drug Res Clin Pharmacol. 28:600–605. 2017.(In Chinese).
84	Wang L, Zhang H, Shi Y, Li M, Mu Z, Zhong G, Zhu J and Wang H: Chemical constituents from Lagotis brachystachy. Chin Tradit Patent Med. 42:2926–2930. 2020.(In Chinese).
85	Nishitani Y, Yamamoto K, Yoshida M, Azuma T, Kanazawa K, Hashimoto T and Mizuno M: Intestinal anti-inflammatory activity of luteolin: role of the aglycone in NF-κB inactivation in macrophages co-cultured with intestinal epithelial cells. Biofactors. 39:522–533. 2013. View Article : Google Scholar : PubMed/NCBI
86	Luan RL, Meng XX and Jiang W: Protective effects of apigenin against paraquat-induced acute lung injury in mice. Inflammation. 39:752–758. 2016. View Article : Google Scholar : PubMed/NCBI
87	Li Q, Tian Z, Wang M, Kou J, Wang C, Rong X, Li J, Xie X and Pang X: Luteoloside attenuates neuroinflammation in focal cerebral ischemia in rats via regulation of the PPARγ/Nrf2/NF-κB signaling pathway. Int Immunopharmacol. 66:309–316. 2019. View Article : Google Scholar : PubMed/NCBI
88	Ouyang X, Li NZ, Guo MX, Zhang MM, Cheng J, Yi LT and Zhu JX: Active flavonoids from Lagotis brachystachya attenuate monosodium urate-induced gouty arthritis via inhibiting TLR4/MyD88/NF-κB pathway and NLRP3 expression. Front Pharmacol. 12:7603312021. View Article : Google Scholar : PubMed/NCBI
89	Shen R, Ma L and Zheng Y: Anti-inflammatory effects of luteolin on acute gouty arthritis rats via TLR/MyD88/NF-κB pathway. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 45:115–122. 2020.(In English, Chinese). PubMed/NCBI
90	Lee MN, Lee Y, Wu D and Pae M: Luteolin inhibits NLRP3 inflammasome activation via blocking ASC oligomerization. J Nutr Biochem. 92:1086142021. View Article : Google Scholar : PubMed/NCBI
91	Wang Z, Chen W, Li Y, Zhang S, Lou H, Lu X and Fan X: Reduning injection and its effective constituent luteoloside protect against sepsis partly via inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways. J Ethnopharmacol. 270:1137832021. View Article : Google Scholar : PubMed/NCBI
92	Zhao F, Dang Y, Zhang R, Jing G, Liang W, Xie L and Li Z: Apigenin attenuates acrylonitrile-induced neuro-inflammation in rats: Involved of inactivation of the TLR4/NF-κB signaling pathway. Int Immunopharmacol. 75:1056972019. View Article : Google Scholar : PubMed/NCBI
93	Zhu JX, Yang HY, Hu WQ, Cheng J, Liu Y, Yi LT and Cheng HY: Active components from Lagotis brachystachya maintain uric acid homeostasis by inhibiting renal TLR4-NLRP3 signaling in hyperuricemic mice. Inflammopharmacology. 29:1187–1200. 2021. View Article : Google Scholar : PubMed/NCBI
94	Newsholme P, Cruzat VF, Keane KN, Carlessi R and de Bittencourt PIH Jr: Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J. 473:4527–4550. 2016. View Article : Google Scholar : PubMed/NCBI
95	Wójcik P, Gęgotek A, Žarković N and Skrzydlewska E: Oxidative stress and lipid mediators modulate immune cell functions in autoimmune diseases. Int J Mol Sci. 22:7232021. View Article : Google Scholar : PubMed/NCBI
96	Cheng JJ, Ma XD, Ai GX, Yu QX, Chen XY, Yan F, Li YC, Xie JH, Su ZR and Xie QF: Palmatine protects against MSU-induced gouty arthritis via regulating the NF-κB/NLRP3 and Nrf2 pathways. Drug Des Devel Ther. 16:2119–2132. 2022. View Article : Google Scholar : PubMed/NCBI
97	Zeng D, Yin C, Wei H, Li Y, Yang Y, Nie H, Pan Y, Xu R, Tai Y, Du J, et al: Activation of Nrf2 antioxidant signaling alleviates gout arthritis pain and inflammation. Biomed Pharmacother. 170:1159572024. View Article : Google Scholar : PubMed/NCBI
98	Zamudio-Cuevas Y, Hernández-Díaz C, Pineda C, Reginato AM, Cerna-Cortés JF, Ventura-Ríos L and López-Reyes A: Molecular basis of oxidative stress in gouty arthropathy. Clin Rheumatol. 34:1667–1672. 2015. View Article : Google Scholar : PubMed/NCBI
99	Wu H, Wang Y, Ren Z, Li Y, Huang J, Lin Z and Zhang B: Overnutrition-induced gout: An immune response to NLRP3 inflammasome dysregulation by XOD activity increased in quail. Front Immunol. 13:10748672022. View Article : Google Scholar : PubMed/NCBI
100	Maiuolo J, Oppedisano F, Gratteri S, Muscoli C and Mollace V: Regulation of uric acid metabolism and excretion. Int J Cardiol. 213:8–14. 2016. View Article : Google Scholar : PubMed/NCBI
101	Kiltz U, Alten R, Fleck M, Krüger K, Manger B, Müller-Ladner U, Nüsslein H, Reuss-Borst M, Schwarting A, Schulze-Koops H, et al: Evidence-based recommendations for diagnostics and treatment of gouty arthritis in the specialist sector : S2e guidelines of the German society of rheumatology in cooperation with the AWMF. Z Rheumatol. 76:118–124. 2017.(In German). View Article : Google Scholar : PubMed/NCBI
102	Zhao S: Clinical efficacy of traditional Chinese medicine soup in the treatment of gout with damp-heat stasis and the pharmacological effects of total flavonoids of the monarch extract Poria cocos (Poria cocos). Capital Food Med. 26:187–188. 2019.
103	Engel B, Just J, Bleckwenn M and Weckbecker K: Treatment options for gout. Dtsch Arztebl Int. 114:215–222. 2017.PubMed/NCBI
104	Levy RM, Pillai L and Burnett PB: Nutritional benefits of flavocoxid in patients with osteoarthritis: Efficacy and safety. Nutr Diet Suppl. 2:27–38. 2010. View Article : Google Scholar : PubMed/NCBI