Protective Effects and Molecular Mechanism of Fermented noni (<i>Morinda citrifolia</i>) Fruit Juice on Hyperuricemia Cell Model

LIU Yue; BI Yingxin; YIN Yuhe; CHEN Changwu; MENG Xianglong; WANG Mengyuan; WANG Mingchuan; CHEN Xinying; LI Zhandong; LIU Xianjun; LI Hao

doi:10.13386/j.issn1002-0306.2022080056

Volume 44 Issue 14

Jul. 2023

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Science and Technology of Food Industry > 2023 > 44(14): 370-376. > DOI: 10.13386/j.issn1002-0306.2022080056

LIU Yue, BI Yingxin, YIN Yuhe, et al. Protective Effects and Molecular Mechanism of Fermented noni (Morinda citrifolia) Fruit Juice on Hyperuricemia Cell Model[J]. Science and Technology of Food Industry, 2023, 44(14): 370−376. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022080056.

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Protective Effects and Molecular Mechanism of Fermented noni (Morinda citrifolia) Fruit Juice on Hyperuricemia Cell Model

1.
School of Chemistry and Life Science, Changchun University of Technology, Changchun 130012, China
2.
College of Biological and Food Engineering, Jilin Engineering Normal University, Changchun 130052, China
3.
Department of Burns Surgery, The First Hospital of Jilin University, Changchun 130021, China
4.
Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun 130033, China

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Received Date: August 07, 2022
Available Online: May 19, 2023

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Abstract

Abstract

Objective: To explore the protective effect and molecular mechanisms of noni (Morinda citrifolia) fruit juice on human renal cortical epithelial cells (HK-2) with hyperuricemi. Methods: Morinda citrifolia pulp was prepared and fermented by pectinase and Lactobacillus plantarum to obtain fermented noni juice. Hyperuricemia model of HK-2 cells was established based on by adenosine combined with xanthine oxidase (XO). The cytotoxicity of fermented noni juice on HK-2 cells was detected by CCK-8 experiment. The uric acid content in the supernatant of HK-2 cell culture solution after the treatment of fermented noni juice was detected and the expression levels of hyperuricemia marker proteins urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were detected by Western blotting to verify the regulatory effect of fermented noni juice on HK-2 cells with hyperuricemia. By detecting the expression levels of interleukin-1β (IL-1β) and Tumor necrosis factor-α (TNF-α) in HK-2 cells, the effect of fermented noni juice on inflammatory reaction in HK-2 cells with hyperuricemia was determined. By detecting the expression level of phosphorylated nuclear transcription factor kappa B (NF-κB) p-p65/p65 in HK-2 cells, the regulatory effect of fermented noni juice on NF-κB signaling pathway was verified. Results: When the treatment concentration was lower than 60 μL/mL, the fermented noni juice did not show cytotoxicity. With the treatment of fermented noni juice, the uric acid content which was dose-dependent in the supernatant of cell culture solution was decreased significantly. The expressions of URAT1 and GLUT9 in the experimental group treated with fermented noni juice were significantly lower than those in model group. The fermented noni juice could significantly inhibit the expression levels of IL-1β and TNF-α in hyperuricemia model of HK-2 cell and significantly inhibited the expression of p-p65 in disease model. Conclusion: Fermented noni juice could reduce the content of uric acid in HK-2 cells with hyperuricemia, and then inhibit inflammatory reaction by regulating NF-κB signaling pathway, thus playing a protective role.
- fermented Morinda citrifolia juice,
- hyperuricemia,
- HK-2 cell,
- NF-κB signaling pathway

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References

[1]	RIZZO M, OBRADOVIC M, LABUDOVIC-BOROVIC M, et al. Uric acid metabolism in pre-hypertension and the metabolic syndrome[J]. Curr Vasc Pharmacol,2014,12(4):572−585. doi: 10.2174/1570161111999131205160756
[2]	ZHANG Y, TAN X, LIN Z, et al. Fucoidan from Laminaria japonica inhibits expression of GLUT9 and URAT1 via PI3K/Akt, JNK and NF-κB pathways in uric acid-exposed HK-2 cells[J]. Mar Drugs,2021,19(5):238. doi: 10.3390/md19050238
[3]	WU J, QIU L, CHENG X Q, et al. Hyperuricemia and clustering of cardiovascular risk factors in the Chinese adult population[J]. Sci Rep,2017,7(1):5456. doi: 10.1038/s41598-017-05751-w
[4]	CHEN M, YE C, ZHU J, et al. Bergenin as a novel urate-lowering therapeutic strategy for hyperuricemia[J]. Front Cell Dev Biol,2020,8:703. doi: 10.3389/fcell.2020.00703
[5]	CHOI H K, MOUNT D B, REGINATO A M, et al. American college of physicians; American physiological society. Pathogenesis of gout[J]. Ann Intern Med,2005,143(7):499−516. doi: 10.7326/0003-4819-143-7-200510040-00009
[6]	LIPKOWITZ M S. Regulation of uric acid excretion by the kidney[J]. Curr Rheumatol Rep,2012,14(2):179−188. doi: 10.1007/s11926-012-0240-z
[7]	GUSTAFSSON D, UNWIN R. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality[J]. BMC Nephrol,2013,14:164. doi: 10.1186/1471-2369-14-164
[8]	刘会芳, 夏雨, 徐倩, 等. 高尿酸通过 TLR4/NF-κB 信号通路诱导肾小管上皮细胞上皮-间充质转化的作用研究[J]. 第三军医大学学报,2017,39(19):1919−1925. [LIU H F, XIA Y, XU Q, et al. A study on the role of high uric acid in inducing epithelial mesenchymal transition of renal tubular epithelial cells through the TLR4/NF-κB signaling pathway[J]. Journal of the Third Military Medical University,2017,39(19):1919−1925. LIU H F, XIA Y, XU Q, et al. A study on the role of high uric acid in inducing epithelial mesenchymal transition of renal tubular epithelial cells through the TLR4/NF-κB signaling pathway [J]. Journal of the Third Military Medical University, 2017, 39 (19): 1919-1925.
[9]	CHUNG K W, JEONG H O, LEE B, et al. Involvement of Nf-κbiz and related cytokines in age-associated renal fibrosis[J]. Oncotarget,2017,8(5):7315−7327. doi: 10.18632/oncotarget.14614
[10]	ZHANG M, GUO Y, FU H, et al. Chop deficiency prevents uuo-induced renal fibrosis by attenuating fibrotic signals originated from Hmgb1/tlr4/nfκb/il-1β Signaling[J]. Cell Death Dis,2015,6(8):e1847. doi: 10.1038/cddis.2015.206
[11]	MORTON J F. The ocean-going noni, or Indian Mulberry (Morinda citrifolia, Rubiaceae) and some of its "colorful" relatives[J]. Economic Botany,1992,46:241−256. doi: 10.1007/BF02866623
[12]	BUTAUD, FRANCOIS J, RAHARIVELOMANANA, et al. Herbal medicine in the Marquesas Islands[J]. J Ethnopharmacol,2015,161:200−213. doi: 10.1016/j.jep.2014.09.045
[13]	WANG M Y, WEST B J, JENSEN C J, et al. Morinda citrifolia (Noni): A literature review and recent advances in Noni research[J]. Acta Pharmacol Sin,2002,23(12):1127−1141.
[14]	HOU C, LIU D, WANG M, et al. Novel xanthine oxidase-based cell model using HK-2 cell for screening antihyperuricemic functional compounds[J]. Free Radic Biol Med,2019,136:135−145. doi: 10.1016/j.freeradbiomed.2019.04.007
[15]	WESTENDORF J, METTLICH C. The benefits of noni juice: An epidemiological evaluation in Europe[J]. J Med Food Plants,2009,1:64−79.
[16]	WEST B J, DENG S, ISAMI F, et al. The potential health benefits of Noni juice: A review of human intervention studies[J]. Foods,2018,7(4):58. doi: 10.3390/foods7040058
[17]	PALU A, DENG S, WEST B, et al. Xanthine oxidase inhibiting effects of noni (Morinda citrifolia) fruit juice[J]. Phytother Res, 2009: 1790-1791.
[18]	LI X, LIU Y, SHAN Y, et al. MicroRNAs involved in the therapeutic functions of Noni (Morinda citrifolia L.) fruit juice in the treatment of acute gouty arthritis in mice induced with monosodium urate[J]. Foods,2021,10(7):1638. doi: 10.3390/foods10071638
[19]	LEE D, YU J S, HUANG P, et al. Identification of anti-inflammatory compounds from Hawaiian Noni (Morinda citrifolia L.) fruit juice[J]. Molecules,2020,25(21):4968. doi: 10.3390/molecules25214968
[20]	COUTINHO DE SOUSA B, REIS MACHADO J, DA SILVA M V, et al. Morinda citrifolia (Noni) fruit juice reduces inflammatory cytokines expression and contributes to the maintenance of intestinal mucosal integrity in DSS experimental colitis[J]. Mediators Inflamm,2017,2017:6567432.
[21]	BRAGA T T, FORESTO-NETO O, CAMARA NOS. The role of uric acid in inflammasome-mediated kidney injury[J]. Curr Opin Nephrol Hypertens,2020,29(4):423−431. doi: 10.1097/MNH.0000000000000619
[22]	BRAGA T T, FORNI M F, CORREA-COSTA M, et al. Soluble uric acid activates the NLRP3 inflammasome[J]. Sci Rep,2017,7:39884. doi: 10.1038/srep39884
[23]	KIM S M, LEE S H, KIM Y G, et al. Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy[J]. Am J Physiol Renal Physiol,2015,308(9):F993−F1003. doi: 10.1152/ajprenal.00637.2014
[24]	YANG Q, FU C, ZHANG X, et al. Adiponectin protects against uric acid-induced renal tubular epithelial inflammatory responses via the AdipoR1/AMPK signaling pathway[J]. Int J Mol Med,2019,43(3):1542−1552.
[25]	YU S, REN Q, WU W. Effects of losartan on expression of monocyte chemoattractant protein-1 (MCP-1) in hyperuricemic nephropathy rats[J]. J Recept Signal Transduct Res,2015,35(5):458−461. doi: 10.3109/10799893.2015.1006332
[26]	WEI C, XI-MEI D, YING L, et al. Uric acid induces endothelial dysfunction by activating the HMGB1/RAGE signaling pathway[J]. Biomed Res Int,2017,2017:4391920.
[27]	ZHANG Q, LENARDO M J, BALTIMORE D. 30 Years of NF-κB: A blossoming of relevance to human pathobiology[J]. Cell,2017,168(1):37−57.
[28]	BA LDWIN, ALBERT S. The Nf-kappa B and I Kappa B proteins: New discoveries and insights[J]. Annu Rev Immunol,1996,14(1):649−683. doi: 10.1146/annurev.immunol.14.1.649
[29]	邹筱芳, 巫冠中. 尿酸肾损伤的分子机制研究进展[J]. 安徽医药,2015,19(1):5−9. [ZOU X F, WU G Z. Progress in molecular mechanisms of uric acid induced kidney injury[J]. Anhui Medical Journal,2015,19(1):5−9. doi: 10.3969/j.issn.1009-6469.2015.01.002 ZOU X F, WU G Z. Progress in molecular mechanisms of uric acid induced kidney injury [J]. Anhui Medical Journal, 2015, 19 (1): 5-9 doi: 10.3969/j.issn.1009-6469.2015.01.002
[30]	GARCIA-VALLADARES I, KHAN T, ESPINOZA L R. Efficacy and safety of febuxostat in patients with hyperuricemia and gout[J]. Ther Adv Musculoskelet Dis,2011,3(5):245−253. doi: 10.1177/1759720X11416405
[31]	ZHOU Y, FANG L, JIANG L, et al. Uric acid induces renal inflammation via activating tubular NF-κB signaling pathway[J]. PLoS One,2012,7(6):e39738. doi: 10.1371/journal.pone.0039738
[32]	LIU H, XIONG J, HE T, et al. High uric acid-induced epithelial-mesenchymal transition of renal tubular epithelial cells via the TLR4/NF-κB signaling pathway[J]. Am J Nephrol,2017,46(4):333−342. doi: 10.1159/000481668
[33]	WANG M X, ZHAO X J, CHEN T Y, et al. Nuciferine alleviates renal injury by inhibiting inflammatory responses in fructose-fed rats[J]. J Agric Food Chem,2016,64(42):7899−7910. doi: 10.1021/acs.jafc.6b03031
[34]	CHANG Y Y, LIN Y L, YANG D J, et al. Hepatoprotection of noni juice against chronic alcohol consumption: Lipid homeostasis, antioxidation, alcohol clearance, and anti-inflammation[J]. J Agric Food Chem,2013,61(46):11016−11024. doi: 10.1021/jf4038419

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