<em>Polygonum tinctorium</em> leaf extract ameliorates high-fat diet-induced intestinal epithelial damage in mice

Kawaguchi,Shogo; Sakuraba,Hirotake; Kikuchi,Hidezumi; Matsuki,Kota; Hayashi,Yudai; Ding,Jiangli; Tanaka,Yusuke; Seya,Kazuhiko; Matsumiya,Tomoh; Hiraga,Hiroto; Fukuda,Shinsaku; Sasaki,Kenroh; Imaizumi,Tadaatsu

doi:10.3892/etm.2023.11811

Polygonum tinctorium leaf extract ameliorates high-fat diet-induced intestinal epithelial damage in mice

Authors:
- Shogo Kawaguchi
- Hirotake Sakuraba
- Hidezumi Kikuchi
- Kota Matsuki
- Yudai Hayashi
- Jiangli Ding
- Yusuke Tanaka
- Kazuhiko Seya
- Tomoh Matsumiya
- Hiroto Hiraga
- Shinsaku Fukuda
- Kenroh Sasaki
- Tadaatsu Imaizumi
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Affiliations: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan, Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan, Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan, Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Science, Hirosaki, Aomori 036-8564, Japan, Division of Pharmacognosy, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan
Published online on: January 26, 2023 https://doi.org/10.3892/etm.2023.11811
Article Number: 112
Copyright: © Kawaguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dietary fat strongly influences the intestinal mucosal barrier, which protects against invading pathogenic bacteria. A high-fat diet (HFD) compromises the integrity of epithelial tight junctions (TJs) and reduces mucin production, leading to intestinal barrier disruption and metabolic endotoxemia. It has been shown that the active constituents of indigo plants can protect against intestinal inflammation; however, their protective role in HFD-induced intestinal epithelial damage remains unknown. The present study aimed to investigate the effects of Polygonum tinctorium leaf extract (indigo Ex) on HFD-induced intestinal damage in mice. Male C57BL6/J mice were fed a HFD and injected intraperitoneally with either indigo Ex or phosphate-buffered saline (PBS) for 4 weeks. The expression levels of TJ proteins, zonula occludens-1 and Claudin-1, were analyzed by immunofluorescence staining and western blotting. The colon mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-12p40, IL-10 and IL-22 were measured by reverse transcription-quantitative PCR. The results revealed that indigo Ex administration attenuated the HFD-induced shortening of the colon. Colon crypt length was shown to be significantly greater in the indigo Ex-treated group mice compared with that in the PBS-treated group mice. Moreover, indigo Ex administration increased the number of goblet cells, and ameliorated the redistribution of TJ proteins. Notably, indigo Ex significantly increased the colon mRNA expression levels of IL-10. Indigo Ex displayed little effect on the gut microbial composition of HFD-fed mice. Taken together, these results suggested that indigo Ex may protect against HFD-induced epithelial damage. The leaves of indigo plants contain promising natural therapeutic compounds that could be used to treat obesity-associated intestinal damage and metabolic inflammation.

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1	Garcia-Hernandez V, Quiros M and Nusrat A: Intestinal epithelial claudins: Expression and regulation in homeostasis and inflammation. Ann NY Acad Sci. 1397:66–79. 2017.PubMed/NCBI View Article : Google Scholar
2	Chekakkot C, Ghim J and Ryu SH: Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med. 50:1–9. 2018.PubMed/NCBI View Article : Google Scholar
3	Suzuki T: Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci. 70:631–659. 2013.PubMed/NCBI View Article : Google Scholar
4	Massier L, Blüher M, Kovacs P and Chakaroun RM: Impaired intestinal barrier and tissue bacteria: Pathomechanisms for metabolic diseases. Front Endocrinol (Lausanne). 12(616506)2021.PubMed/NCBI View Article : Google Scholar
5	Forgie AJ, Fouhse JM and Willing BP: Diet-microbe-host interactions that affect gut mucosal integrity and infection resistance. Front Immunol. 10(1802)2019.PubMed/NCBI View Article : Google Scholar
6	Rohr MW, Narasimhulu CA, Rudeski-Rohr TA and Parthasarathy S: Negative effects of a high-fat diet on intestinal permeability: A review. Adv Nutr. 11:77–91. 2020.PubMed/NCBI View Article : Google Scholar
7	Martinez KB, Leone V and Chang EB: Western diets, gut dysbiosis, and metabolic diseases: Are they linked? Gut Microbes. 8:130–142. 2017.PubMed/NCBI View Article : Google Scholar
8	Carmody RN, Gerber GK, Luevano JM Jr, Gatti DM, Somes L, Svenson KL and Turnbaugh PJ: Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe. 17:72–84. 2015.PubMed/NCBI View Article : Google Scholar
9	Mouries J, Brescia P, Silvestri A, Spadoni I, Sorribas M, Wiest R, Mileti E, Galbiati M, Invernizzi P, Adorini L, et al: Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol. 71:1216–1228. 2019.PubMed/NCBI View Article : Google Scholar
10	Tanaka S, Nemoto Y, Takei Y, Morikawa R, Oshima S, Nagaishi T, Okamoto R, Tsuchiya K, Nakamura T, Stutte S and Watanabe M: High-fat diet-derived free fatty acids impair the intestinal immune system and increase sensitivity to intestinal epithelial damage. Biochem Biophys Res Commun. 522:971–977. 2020.PubMed/NCBI View Article : Google Scholar
11	Cani PD, Bibiloni R, Knauf C, Waget A, Neurinck AM, Delzenne NM and Burcelin R: Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 57:1470–1480. 2008.PubMed/NCBI View Article : Google Scholar
12	Kataoka M, Hirata K, Kunikata T, Ushio S, Iwaki K, Ohashi K, Ikeda M and Kurimoto M: Antibacterial action of tryptanthrin and kaempferol, isolated from the indigo plant (Polygonum tinctorium Lour.), against Helicobacter pylori-infected Mongolian gerbils. J Gastroenterol. 36:5–9. 2001.PubMed/NCBI View Article : Google Scholar
13	Hoessel R, Leclerc S, Endicott JA, Nobel ME, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, et al: Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat Cell Biol. 1:60–67. 1999.PubMed/NCBI View Article : Google Scholar
14	Asari T, Kikuchi H, Kawaguchi S, Sakuraba H, Yoshida S, Akemoto Y, Maeda T, Shinji O, Murai Y, Higuchi N, et al: Polygonum tinctorium leaves suppress sodium dextran sulfate-induced colitis through interleukin-10-related pathway. Biochem Biophys Rep. 30(101272)2020.PubMed/NCBI View Article : Google Scholar
15	Hagiyama M, Takeuchi F, Sugano A, Yoneshige A, Inoue T, Wada A, Kajiyama H, Takaoka Y, Sasaki K and Ito A: Indigo plant leaf extract inhibits the binding of SARS-CoV-2 spike protein to angiotensin-converting enzyme 2. Exp Ther Med. 23(274)2022.PubMed/NCBI View Article : Google Scholar
16	Schneider CA, Rasband WS and Eliceiri KW: NIH image to ImageJ: 25 Years of image analysis. Nat Methods. 9:671–675. 2012.PubMed/NCBI View Article : Google Scholar
17	Gulhane M, Murray L, Lourie R, Tong H, Sheng YH, Wang R, Kang A, Schreiber V, Wong KY, Magor G, et al: High fat diets induce colonic epithelial cell stress and inflammation that is reversed by IL-22. Sci Rep. 6(28990)2016.PubMed/NCBI View Article : Google Scholar
18	Heazlewood CK, Cook MC, Eri R, Price GR, Tauro SB, Taupin D, Thornton DJ, Png CW, Crockford TL, Cornall RJ, et al: Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 5(e54)2008.PubMed/NCBI View Article : Google Scholar
19	Birchenough GM, Johansson ME, Gustafsson JK, Bergström JH and Hannson GC: New developments in goblet cell mucus secretion and function. Mucosal Immunol. 8:712–719. 2015.PubMed/NCBI View Article : Google Scholar
20	Dai YJ, Liu WB, Abasubong KP, Zhang DD, Li XF, Xiao K, Wang X and Jiang GZ: The mechanism of lipopolysaccharide escaping the intestinal barrier in Megalobrama amblycephala fed a high-fat diet. Front sNutr. 9(853409)2022.PubMed/NCBI View Article : Google Scholar
21	Ghezzal S, Postal BG, Quevrain E, Brot L, Seksik P, Leturque A, Thenet S and Carrière V: Palmitic acid damages gut epithelium integrity and initiates inflammatory cytokine production. Biochim Biophys Acta Mol Cell Biol Lipids. 1865(158530)2020.PubMed/NCBI View Article : Google Scholar
22	Nascimento JC, Matheus VA, Oliveira RB, Tada SFS and Collares-Buzato CB: High-fat diet induces disruption of the tight junction-mediated paracellular barrier in the proximal small intestine before the onset of type 2 diabetes and endotoxemia. Dig Did Sci. 66:3359–3374. 2021.PubMed/NCBI View Article : Google Scholar
23	Capaldo CT and Nusrat A: Cytokine regulation of tight junctions. Biochim Biophys Acta. 1788:864–871. 2009.PubMed/NCBI View Article : Google Scholar
24	Escoula Q, Bellenger S, Narce M and Bellenger J: Docosahexaenoic and eicosapentaenoic acids prevent altered-Muc2 secretion induced by palmitic acid by alleviating endoplasmic reticulum stress in LS174T goblet cells. Nutrients. 11(2179)2019.PubMed/NCBI View Article : Google Scholar
25	Reiche J and Huber O: Post-translational modifications of tight junction transmembrane proteins and their direct effect on barrier function. Biochim Biophys Acta Biomembr. 1862(183330)2020.PubMed/NCBI View Article : Google Scholar
26	Butt AM, Khan IB, Hussain M, Idress M, Lu J and Tong Y: Role of post translational modifications and novel crosstalk between phosphorylation and O-beta-GlcNAc modifications in human claudin-1, -3 and -4. Mol Biol Rep. 39:1359–1369. 2012.PubMed/NCBI View Article : Google Scholar
27	Lin YH, Luck H, Khan S, Schneeberger PHH, Tsai S, Clemente-Casares X, Lei H, Leu YL, Chan YT, Chen HY, et al: Aryl hydrocarbon receptor agonist indigo protects against obesity-related insulin resistance through modulation of intestinal and metabolic tissue immunity. Int J Obes (Lond). 43:2407–2421. 2019.PubMed/NCBI View Article : Google Scholar
28	Kimura H, Tokuyama-Nakai S, Hirabayashi Y, Ishihara T, Jisaka M and Yokota K: Anti-inflammatory and bioavailability studies on dietary 3,5,4'-trihydroxy-6,7-methylenedioxyflavone-O-glycosides and their aglycone from indigo leaves in a murine model of inflammatory bowel disease. J Pharm Biomed Anal. 193(113716)2021.PubMed/NCBI View Article : Google Scholar
29	Hasnain SZ, Tauro S, Das I, Tong H, Chen AC, Jeffery PL, McDonald V, Florin TH and McGuckin MA: IL-10 promotes production of intestinal mucus by suppressing protein misfolding and endoplasmic reticulum stress in goblet cells. Gastroenterol. 144:357–368.e9. 2013.PubMed/NCBI View Article : Google Scholar
30	Hildebrandt MA, Hoffman C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F and Wu GD: High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterol. 137:1716–1724.e1-e2. 2009.PubMed/NCBI View Article : Google Scholar
31	Murphy EA, Velazquez KT and Herbert KM: Influence of high-fat diet on gut microbiota: A driving force for chronic disease risk. Curr Opin Clin Nutr Metab Care. 18:515–520. 2015.PubMed/NCBI View Article : Google Scholar