Dendrobium officinalis Six Nostrum Promotes Intestinal Urate Underexcretion
via Regulations of Urate Transporter Proteins in Hyperuricemic
Rats

Hongzhang      Ge; Zetian      Jiang; Bo      Li; Peiyao      Xu; Hansong      Wu; Xinglishang      He; Wanfeng      Xu; Zhi      Huang; Taoxiu      Xiong; Ping      Wang; Guiyuan      Lv; Suhong      Chen

doi:10.2174/1386207325666220830141531

Abstract

Background: Dendrobium officinalis Six nostrum (DOS) can be prepared by adding Dendrobium officinalis into Simiao Wan in accordance with the Traditional Chinese Medicine (TCM) theory and other previous findings. Our previous study has shown that DOS treatment can lead to a marked decrease in Serum UA (SUA) levels. The purpose of this study was to explore the effects of DOS on intestinal UA excretion in hyperuricemia and its underlying mechanisms.

Methods: DOS was administered intragastrically to hyperuricemic rats induced by oral administration of HX and PO for 7 weeks. The SUA level, fecal UA and XOD activity were detected. The expressions of UA transporters (ABCG2, GLUT9, and PDZK1), CNT2, and tight junction proteins (ZO- 1 and claudin-1) in the intestine were assayed by IHC staining. The serum LPS and DAO levels were detected by ELISA kits. The intestinal histological changes were assessed using H&E staining.

Results: DOS treatment decreased the SUA level while markedly increasing the fecal UA level by 28.85%~35.72%. Moreover, DOS effectively up-regulated the expression of ABCG2 and PDZK1 and down-regulated the expression of GLUT9 in the intestine. DOS markedly decreased the serum LPS level by 21.4%~32.1% and DAO activity by 12.3%~19.7%, which in turn ameliorated the intestinal pathology. As a result, it could protect intestinal barrier function, as indicated by the increase of villus height (V), the reduction of the crypt depth (C), and the elevation of the V/C ratio. It also increased the expression of ZO-1 and claudin-1. In addition, DOS significantly down-regulated the expression of CNT2, which reduced purine nucleoside transportation from the intestine into the blood, and inhibited XOD activity, leading to a decrease in UA production.

Conclusion: DOS exerted anti-hyperuricemic effects via regulation of intestinal urate transporters and could protect intestinal barrier function by restoring the expressions of ZO-1 and claudin-1.

Keywords: Dendrobium officinalis six nostrum, hyperuricemia, uric acid, intestinal excretion, intestinal barrier, xanthine oxidase.

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[1]
Gliozzi, M.; Malara, N.; Muscoli, S.; Mollace, V. The treatment of hyperuricemia. Int. J. Cardiol.,  2016, 213, 23-27.
 [http://dx.doi.org/10.1016/j.ijcard.2015.08.087] [PMID: 26320372]

[2]
Li, Y.; Shen, Z.; Zhu, B.; Zhang, H.; Zhang, X.; Ding, X. Demographic, regional and temporal trends of hyperuricemia epidemics in mainland China from 2000 to 2019: A systematic review and meta-analysis. Glob. Health Action,  2021, 14(1), 1874652.
 [http://dx.doi.org/10.1080/16549716.2021.1874652] [PMID: 33475474]

[3]
Ding, X.Q.; Pan, Y.; Wang, X.; Ma, Y.X.; Kong, L.D. Wuling San ameliorates urate under-excretion and renal dysfunction in hyperuricemic mice. Chin. J. Nat. Med.,  2013, 11(3), 214-221.
 [http://dx.doi.org/10.1016/S1875-5364(13)60019-9] [PMID: 23725832]

[4]
Kodithuwakku, N.D.; Feng, Y.; Zhang, Y.; Pan, M.; Fang, W.; Li, Y. The molecular insight into the antihyperuricemic and renoprotective effect of Shuang Qi gout capsule in mice. J. Ethnopharmacol.,  2015, 163, 278-289.
 [http://dx.doi.org/10.1016/j.jep.2015.01.013] [PMID: 25614106]

[5]
Wang, R.; Ma, C.H.; Zhou, F.; Kong, L.D. Siwu decoction attenuates oxonate-induced hyperuricemia and kidney inflammation in mice. Chin. J. Nat. Med.,  2016, 14(7), 499-507.
 [http://dx.doi.org/10.1016/S1875-5364(16)30059-0] [PMID: 27507200]

[6]
Wang, Y.; Lin, Z.; Zhang, B.; Nie, A.; Bian, M. Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia. Nutr. Metab. (Lond.),  2017, 14(1), 38.
 [http://dx.doi.org/10.1186/s12986-017-0190-6] [PMID: 28630638]

[7]
Liu, Z.; Su, X.; Xiao, M.; Zhou, P.; Guo, J.; Huang, Y.; Zhan, Y. Association between eating away from home and hyperuricemia: A population-based nationwide cross-sectional study in China. Bio-Med Res. Int.,  2019, 2019, 1-7.
 [http://dx.doi.org/10.1155/2019/2792681] [PMID: 31687384]

[8]
Liu, R.; Han, C.; Wu, D.; Xia, X.; Gu, J.; Guan, H.; Shan, Z.; Teng, W. Prevalence of hyperuricemia and gout in Mainland China from 2000 to 2014: A systematic review and meta-analysis. BioMed Res. Int.,  2015, 2015, 1-12.
 [http://dx.doi.org/10.1155/2015/762820] [PMID: 26640795]

[9]
Dalbeth, N.; Gosling, A.L.; Gaffo, A.; Abhishek, A. Gout. Lancet,  2021, 397(10287), 1843-1855.
 [http://dx.doi.org/10.1016/S0140-6736(21)00569-9] [PMID: 33798500]

[10]
Mehmood, A.; Zhao, L.; Ishaq, M.; Xin, W.; Zhao, L.; Wang, C.; Hossen, I.; Zhang, H.; Lian, Y.; Xu, M. Anti-hyperuricemic potential of stevia (Stevia rebaudiana Bertoni) residue extract in hyperuricemic mice. Food Funct.,  2020, 11(7), 6387-6406.
 [http://dx.doi.org/10.1039/C9FO02246E] [PMID: 32613954]

[11]
Hosomi, A.; Nakanishi, T.; Fujita, T.; Tamai, I. Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2. PLoS One,  2012, 7(2), e30456.
 [http://dx.doi.org/10.1371/journal.pone.0030456] [PMID: 22348008]

[12]
Ichida, K.; Matsuo, H.; Takada, T.; Nakayama, A.; Murakami, K.; Shimizu, T.; Yamanashi, Y.; Kasuga, H.; Nakashima, H.; Nakamura, T.; Takada, Y.; Kawamura, Y.; Inoue, H.; Okada, C.; Utsumi, Y.; Ikebuchi, Y.; Ito, K.; Nakamura, M.; Shinohara, Y.; Hosoyamada, M.; Sakurai, Y.; Shinomiya, N.; Hosoya, T.; Suzuki, H. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat. Commun.,  2012, 3(1), 764.
 [http://dx.doi.org/10.1038/ncomms1756] [PMID: 22473008]

[13]
Yun, Y.; Yin, H.; Gao, Z.; Li, Y.; Gao, T.; Duan, J.; Yang, R.; Dong, X.; Zhang, L.; Duan, W. Intestinal tract is an important organ for lowering serum uric acid in rats. PLoS One,  2017, 12(12), e0190194.
 [http://dx.doi.org/10.1371/journal.pone.0190194] [PMID: 29267361]

[14]
Mandal, A.K.; Mount, D.B. The molecular physiology of uric acid homeostasis. Annu. Rev. Physiol.,  2015, 77(1), 323-345.
 [http://dx.doi.org/10.1146/annurev-physiol-021113-170343] [PMID: 25422986]

[15]
Nigam, S.K.; Bhatnagar, V. The systems biology of uric acid transporters. Curr. Opin. Nephrol. Hypertens.,  2018, 27(4), 305-313.
 [http://dx.doi.org/10.1097/MNH.0000000000000427] [PMID: 29847376]

[16]
Cleophas, M.; Joosten, L.; Stamp, L.; Dalbeth, N.; Woodward, O.; Merriman, T. ABCG2 polymorphisms in gout: Insights into disease susceptibility and treatment approaches. Pharm. Genomics Pers. Med.,  2017, 10, 129-142.
 [http://dx.doi.org/10.2147/PGPM.S105854] [PMID: 28461764]

[17]
Okafor, O.N.; Farrington, K.; Gorog, D.A. Allopurinol as a therapeutic option in cardiovascular disease. Pharmacol. Ther.,  2017, 172, 139-150.
 [http://dx.doi.org/10.1016/j.pharmthera.2016.12.004] [PMID: 27916655]

[18]
Benn, C.L.; Dua, P.; Gurrell, R.; Loudon, P.; Pike, A.; Storer, R.I.; Vangjeli, C. Physiology of hyperuricemia and urate-lowering treatments. Front. Med. (Lausanne),  2018, 5, 160.
 [http://dx.doi.org/10.3389/fmed.2018.00160] [PMID: 29904633]

[19]
Guo, Y.; Li, H.; Liu, Z.; Li, C.; Chen, Y.; Jiang, C.; Yu, Y.; Tian, Z. Impaired intestinal barrier function in a mouse model of hyperuricemia. Mol. Med. Rep.,  2019, 20(4), 3292-3300.
 [http://dx.doi.org/10.3892/mmr.2019.10586] [PMID: 31432190]

[20]
Lv, Q.; Xu, D.; Zhang, X.; Yang, X.; Zhao, P.; Cui, X.; Liu, X.; Yang, W.; Yang, G.; Xing, S. Association of hyperuricemia with immune disorders and intestinal barrier dysfunction. Front. Physiol.,  2020, 11, 524236.
 [http://dx.doi.org/10.3389/fphys.2020.524236] [PMID: 33329010]

[21]
Vancamelbeke, M.; Vermeire, S. The intestinal barrier: A fundamental role in health and disease. Expert Rev. Gastroenterol. Hepatol.,  2017, 11(9), 821-834.
 [http://dx.doi.org/10.1080/17474124.2017.1343143] [PMID: 28650209]

[22]
Shi, L.; Xu, L.; Yang, Y.; Song, H.; Pan, H.; Yin, L. Suppressive effect of modified Simiaowan on experimental gouty arthritis: An in vivo and in vitro study. J. Ethnopharmacol.,  2013, 150(3), 1038-1044.
 [http://dx.doi.org/10.1016/j.jep.2013.10.023] [PMID: 24184191]

[23]
Chen, X.; Ge, H.Z.; Lei, S.S.; Jiang, Z.T.; Su, J.; He, X.; Zheng, X.; Wang, H.Y.; Yu, Q.X.; Li, B.; Lv, G.Y.; Chen, S.H. Dendrobium officinalis six nostrum ameliorates urate under-excretion and protects renal dysfunction in lipid emulsion-induced hyperuricemic rats. Biomed. Pharmacother.,  2020, 132, 110765.
 [http://dx.doi.org/10.1016/j.biopha.2020.110765] [PMID: 33120237]

[24]
Guo, L.F.; Chen, X.; Lei, S.S.; Li, B.; Zhang, N.Y.; Ge, H.Z.; Yang, K.; Lv, G.Y.; Chen, S.H. Effects and mechanisms of Dendrobium officinalis six nostrum for treatment of hyperuricemia with hyperlipidemia. Evid. Based Complement. Alternat. Med.,  2020, 2020, 1-12.
 [http://dx.doi.org/10.1155/2020/2914019] [PMID: 32308702]

[25]
Ma, Z.; Long, L.; Liu, J.; Cao, Y. Montmorillonite adsorbs uric acid and increases the excretion of uric acid from the intestinal tract in mice. J. Pharm. Pharmacol.,  2010, 61(11), 1499-1504.
 [http://dx.doi.org/10.1211/jpp.61.11.0009] [PMID: 19903375]

[26]
Morimoto, C.; Tamura, Y.; Asakawa, S.; Kuribayashi-Okuma, E.; Nemoto, Y.; Li, J.; Murase, T.; Nakamura, T.; Hosoyamada, M.; Uchida, S.; Shibata, S. ABCG2 expression and uric acid metabolism of the intestine in hyperuricemia model rat. Nucleosides Nucleotides Nucleic Acids,  2020, 39(5), 744-759.
 [http://dx.doi.org/10.1080/15257770.2019.1694684] [PMID: 31983315]

[27]
Gray, J.H.; Owen, R.P.; Giacomini, K.M. The concentrative nucleoside transporter family, SLC28. Pflugers Arch.,  2004, 447(5), 728-734.
 [http://dx.doi.org/10.1007/s00424-003-1107-y] [PMID: 12856181]

[28]
Yong, T.; Chen, S.; Xie, Y.; Chen, D.; Su, J.; Shuai, O.; Jiao, C.; Zuo, D. Hypouricemic effects of Ganoderma applanatum in hyperuricemia mice through OAT1 and GLUT9. Front. Pharmacol.,  2018, 8, 996.
 [http://dx.doi.org/10.3389/fphar.2017.00996] [PMID: 29379442]

[29]
Yong, T.; Zhang, M.; Chen, D.; Shuai, O.; Chen, S.; Su, J.; Jiao, C.; Feng, D.; Xie, Y. Actions of water extract from Cordyceps militaris in hyperuricemic mice induced by potassium oxonate combined with hypoxanthine. J. Ethnopharmacol.,  2016, 194, 403-411.
 [http://dx.doi.org/10.1016/j.jep.2016.10.001] [PMID: 27717908]

[30]
Zhu, L.; Dong, Y.; Na, S.; Han, R.; Wei, C.; Chen, G. Saponins extracted from Dioscorea collettii rhizomes regulate the expression of urate transporters in chronic hyperuricemia rats. Biomed. Pharmacother.,  2017, 93, 88-94.
 [http://dx.doi.org/10.1016/j.biopha.2017.06.022] [PMID: 28624426]

[31]
Chen, M.; Lu, X.; Lu, C.; Shen, N.; Jiang, Y.; Chen, M.; Wu, H. 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.,  2018, 20(1), 20.
 [http://dx.doi.org/10.1186/s13075-018-1512-4] [PMID: 29415757]

[32]
Shimizu, T.; Sugiura, T.; Wakayama, T.; Kijima, A.; Nakamichi, N.; Iseki, S.; Silver, D.L.; Kato, Y. PDZK1 regulates breast cancer resistance protein in small intestine. Drug Metab. Dispos.,  2011, 39(11), 2148-2154.
 [http://dx.doi.org/10.1124/dmd.111.040295] [PMID: 21816982]

[33]
DeBosch, B.J.; Kluth, O.; Fujiwara, H.; Schürmann, A.; Moley, K. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9. Nat. Commun.,  2014, 5(1), 4642.
 [http://dx.doi.org/10.1038/ncomms5642] [PMID: 25100214]

[34]
Mehmood, A.; Zhao, L.; Wang, C.; Hossen, I.; Raka, R.N.; Zhang, H. Stevia residue extract increases intestinal uric acid excretion via interactions with intestinal urate transporters in hyperuricemic mice. Food Funct.,  2019, 10(12), 7900-7912.
 [http://dx.doi.org/10.1039/C9FO02032B] [PMID: 31789332]

[35]
Woodward, O.M. ABCG2: The molecular mechanisms of urate secretion and gout. Am. J. Physiol. Renal Physiol.,  2015, 309(6), F485-F488.
 [http://dx.doi.org/10.1152/ajprenal.00242.2015] [PMID: 26136557]

[36]
Guo, Y.; Yu, Y.; Li, H.; Ding, X.; Li, X.; Jing, X.; Chen, J.; Liu, G.; Lin, Y.; Jiang, C.; Liu, Z.; He, Y.; Li, C.; Tian, Z. Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice. Eur. J. Nutr.,  2021, 60(4), 2217-2230.
 [http://dx.doi.org/10.1007/s00394-020-02414-x] [PMID: 33104864]

[37]
Wang, H.; Mei, L.; Deng, Y.; Liu, Y.; Wei, X.; Liu, M.; Zhou, J.; Ma, H.; Zheng, P.; Yuan, J.; Li, M. Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis. Nutrition,  2019, 62, 63-73.
 [http://dx.doi.org/10.1016/j.nut.2018.11.018] [PMID: 30852460]

[38]
Otani, S.; Coopersmith, C.M. Gut integrity in critical illness. J. Intensive Care,  2019, 7(1), 17.
 [http://dx.doi.org/10.1186/s40560-019-0372-6] [PMID: 30923621]

[39]
Seo, K.; Seo, J.; Yeun, J.; Choi, H.; Kim, Y.I.; Chang, S.Y. The role of mucosal barriers in human gut health. Arch. Pharm. Res.,  2021, 44(4), 325-341.
 [http://dx.doi.org/10.1007/s12272-021-01327-5] [PMID: 33890250]

[40]
Liu, X.; Sun, R.; Li, Z.; Xiao, R.; Lv, P.; Sun, X.; Olson, M.A.; Gong, Y. Luteolin alleviates non-alcoholic fatty liver disease in rats via restoration of intestinal mucosal barrier damage and microbiota imbalance involving in gut-liver axis. Arch. Biochem. Biophys.,  2021, 711, 109019.
 [http://dx.doi.org/10.1016/j.abb.2021.109019] [PMID: 34478730]

[41]
Cui, Y.; Okyere, S.K.; Gao, P.; Wen, J.; Cao, S.; Wang, Y.; Deng, J.; Hu, Y. Ageratina adenophora disrupts the intestinal structure and immune barrier integrity in rats. Toxins (Basel),  2021, 13(9), 651.
 [http://dx.doi.org/10.3390/toxins13090651] [PMID: 34564656]

[42]
Rhee, S.H. Lipopolysaccharide: Basic biochemistry, intracellular signaling, and physiological impacts in the gut. Intest. Res.,  2014, 12(2), 90-95.
 [http://dx.doi.org/10.5217/ir.2014.12.2.90] [PMID: 25349574]

[43]
Wang, Y.; Zhi-jian, L.; Bian, M.; Zhang, B. School of Chinese Materia Medica, Beijing University of Chinese Medicine. Effects on intervention of intestinal barrier with Uyghur medicine Cichorium intybus Linn in hyperuricemia. Chin. J. Tradit. Chin. Med. Pharm.,  2018, 33, 1718-1723.

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DOI https://dx.doi.org/10.2174/1386207325666220830141531	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

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Dendrobium officinalis Six Nostrum Promotes Intestinal Urate Underexcretion via Regulations of Urate Transporter Proteins in Hyperuricemic Rats

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