A PRELIMINARY STUDY ON THE EFFECT OF CYANIDIN-3,5-O-DIGLUCOSIDE ON 5-FLUOROURACIL INDUCED INTESTINAL MUCOSITIS IN MICE

FAN Jun-feng, LIU Jun-yang, QIN Xiao-hui, WANG Ke-ying, HUANG Chun-xiang, LIU Zhi-qiang, SONG Jia-le

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (2) : 146-154.

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (2) : 146-154.
ORIGINAL ARTICLES

A PRELIMINARY STUDY ON THE EFFECT OF CYANIDIN-3,5-O-DIGLUCOSIDE ON 5-FLUOROURACIL INDUCED INTESTINAL MUCOSITIS IN MICE

  • FAN Jun-feng1, LIU Jun-yang2, QIN Xiao-hui3, WANG Ke-ying2, HUANG Chun-xiang2, LIU Zhi-qiang3, SONG Jia-le2,3
Author information +
History +

Abstract

Objective To explore the effect of cyanidin-3,5-O-diglucoside (C35G) on 5-fluorouracil (5-FU)-induced intestinal mucositis in mice. Methods BALB/c male mice were randomly divided into normal group, model group, low-dose and high-dose C35G groups. Except for the normal group, mice in other groups were treated with 5-FU to induce a mouse model of intestinal mucositis for 4 days. Mice in the C35G low-dose and high-dose groups were intragastrically administrated with C35G (50 and 150 mg/kg) for 7 consecutive days. Finally, all mice were euthanized, and blood and colon tissues were collected. The levels of TNF-α, IL-1β and IL-10 in the serum were detected by enzyme-linked immunosorbent assay (ELISA). HE, PAS, and alcian blue staining kits were used to stain the colon tissue sections, and the pathological changes of colon tissues, the content of goblet cells and the secretion of mucin 2 were observed. Western blot was used to detect the expression levels of Wnt and c-Myc in colon tissus. Real-time quantitative PCR was used to detect the expression levels of tight junction proteingenes. Results Compared with the 5-FU group, the preventive intervention of C35G could significantly reduce the colonic mucosal damages in mice exposed to 5-FU. In addition, C35G intervention could also significantly reduce the levels of TNF-α and IL-1β in the serum (P<0.05), increase the level of IL-10 (P<0.01), and significantly increase the expression levels of Wnt and c-Myc in colon tissues. At the same time, the mRNA expression levels of tight junction proteins (Zo1, claudin1, claudin7, occludin) were significantly increased. Conclusion C35G is effective in ameliorating 5-FU-induced intestinal mucositis in mice.

Key words

cyanidin-3 / 5-o-diglucoside / 5-fluorouracil / intestinal mucosal damage / inflammation

Cite this article

Download Citations
FAN Jun-feng, LIU Jun-yang, QIN Xiao-hui, WANG Ke-ying, HUANG Chun-xiang, LIU Zhi-qiang, SONG Jia-le. A PRELIMINARY STUDY ON THE EFFECT OF CYANIDIN-3,5-O-DIGLUCOSIDE ON 5-FLUOROURACIL INDUCED INTESTINAL MUCOSITIS IN MICE[J]. Acta Nutrimenta Sinica. 2024, 46(2): 146-154

References

[1] Wu J, Gan Y, Li M, et al. Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota[J]. Biomed Pharmacother, 2020, 124:109883.
[2] Gui MX, Huang B, Peng J, et al. Babao Dan alleviates 5-fluorouracil-induced intestinal damage via Wnt/β-catenin pathway[J]. Chin J Integr Med, 2022, 28:1000–1006.
[3] Qu L, Tan W, Yang J, et al. Combination compositions composed of l-glutamine and Si-Jun-Zi-Tang might be a preferable choice for 5-fluorouracil-induced intesti-nal mucositis: an exploration in a mouse model[J]. Front Pharmacol, 2020, 11:918.
[4] 郭锦瑞, 詹臻, 康安, 等. 化疗致肠黏膜炎的病理机制及药物干预策略研究进展[J]. 中国临床药理学与治疗学,2014,19:573–578.
[5] 陈晓慧, 鱼芳, 陈志盛, 等. 化疗引起的消化道黏膜炎与肠道菌群相关性的研究进展[J]. 中国微生态学杂志,2016,28:991–993.
[6] 田丽, 陈长英, 刘倩倩, 等. 化疗药物致消化道黏膜炎的治疗及护理进展[J]. 中华护理杂志,2013,48:658–661.
[7] Dahlgren D, Sjöblom M, Hellström PM, et al. Chemo-therapeutics-induced intestinal mucositis: pathophy-siology and potential treatment strategies[J]. Front Pharmacol, 2021, 12:681417.
[8] 吴嘉振. 广藿香醇治疗5-氟尿嘧啶所致肠黏膜炎的作用机制研究[D].广州:广州中医药大学, 2019.
[9] Chen H, Zhang F, Li R, et al. Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota[J]. Biomed Pharmacother, 2020, 124:109829.
[10] Wang C, Yang S, Gao L, et al. Carboxymethyl pachyman (CMP) reduces intestinal mucositis and regulates the intestinal microflora in 5-fluorouracil-treated CT26 tumour-bearing mice[J]. Food Funct, 2018, 9:2695–2704.
[11] Carvalho PLA, Andrade MER, Trindade LM, et al. Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeo-stasis after mucositis induced by 5-fluorouracil[J]. Biomed Pharmacother, 2021, 133:111012.
[12] de Ávila PHM, de Ávila RI, Dos Santos Filho EX, et al. Mucoadhesive formulation of Bidens pilosa L. (Aste-raceae) reduces intestinal injury from 5-fluorouracil-induced mucositis in mice[J]. Toxicol Rep, 2015, 2:563–573.
[13] Azevedo OG, Oliveira RA, Oliveira BC, et al. Apolipoprotein E COG 133 mimetic peptide improves 5-fluorouracil-induced intestinal mucositis[J]. BMC Gastroenterol, 2012, 12:35.
[14] 朱相展. β-胡萝卜素协同五氟尿嘧啶对食管鳞癌的抗肿瘤作用及机制研究[D]. 郑州:郑州大学, 2016.
[15] Ferrari D, Cimino F, Fratantonio D, et al. Cyanidin-3-O-glucoside modulates the in vitro inflammatory crosstalk between intestinal epithelial and endothelial cells[J]. Mediators Inflamm, 2017, 2017:3454023.
[16] 刘迪, 张浩, 张寒雪, 等. 花青素和矢车菊素的生物活性及抗氧化功能研究进展[J]. 吉林医药学院学报, 2021, 42:58–60.
[17] Gan Y, Fu Y, Yang L, et al. Cyanidin-3-O-glucoside and cyanidin protect against intestinal barrier damage and 2,4,6-trinitrobenzenesulfonic acid-induced colitis[J]. J Med Food, 2020, 23:90–99.
[18] Baster Z, Li L, Kukkurainen S, et al. Cyanidin-3-glucoside binds to talin and modulates colon cancer cell adhesions and 3D growth[J]. FASEB J, 2020, 34:2227–2237.
[19] 屠迪, 易金娥, 邬静, 等. 矢车菊素在体外缓解脂肪变性的L02肝细胞的氧化损伤[J]. 中国兽医杂志, 2013, 49:48–50.
[20] Molonia MS, Occhiuto C, Muscarà C, et al. Cyanidin-3-O-glucoside restores insulin signaling and reduces inflammation in hypertrophic adipocytes[J]. Arch Biochem Biophys, 2020, 691:108488.
[21] 谭婉贤, 熊晏, 赖莉敏, 等. 5-氟尿嘧啶诱导小鼠化疗性肠黏膜炎模型的建立[J]. 中国实验动物学报, 2018, 26:372-377.
[22] 梁婵华, 黄妍, 莫敏敏, 等. 元宝枫籽油改善脂多糖诱导的小鼠肠道炎症[J]. 现代食品科技, 2021, 37:37–45,6.
[23] Sonis ST.The pathobiology of mucositis[J]. Nat Rev Cancer, 2004, 4:277–284.
[24] Bowen JM, Gibson RJ, Coller JK, et al. Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines[J]. Support Care Cancer, 2019, 27:4011–4022.
[25] Jain U, Midgen CA, Woodruff TM, et al. Properdin deficiency protects from 5-fluorouracil-induced small intestinal mucositis in a complement activation-independent, interleukin-10-dependent mechanism[J]. Clin Exp Immunol, 2017, 188:36–44.
[26] 姚庆华, 汪潞, 谷建钟. 中医药治疗放化疗所致肠黏膜损伤的研究进展[C]//中国医师协会中西医结合医师大会第三次会议论文集, 2012:133.
[27] Liu JH, Hsieh CH, Liu CY, et al. Anti-inflammatory effects of Radix aucklandiae herbal preparation ameliorate intestinal mucositis induced by 5-fluoro-uracil in mice[J]. J Ethnopharmacol, 2021, 271:113912.
[28] 黄兴成, 庄滢滢, 郑晗盈, 等. 菊粉对化疗小鼠肠黏膜免疫系统损伤的保护作用[J]. 营养学报, 2020, 42:260–265.
[29] 陈南耀, 余丹, 陈晓东. TLR4对H2O2诱导的PC12细胞凋亡及β-catenin、c-myc蛋白表达的影响[J]. 郑州大学学报(医学版), 2019, 54:555–559.
[30] 李蕊, 张桂红, 王涛. 黄芪多糖通过调控Wnt信号通路对关节炎大鼠软骨细胞凋亡及CHRNA7/MMP水平的影响[J]. 辽宁中医杂志, 2023, 50:188–192,224.
[31] He S, Tang S.Wnt/β-catenin signaling in the develop-ment of liver cancers[J]. Biomed Pharmacother, 2020, 132:110851.
[32] 王希, 廖吕钊, 江荣林. 肠上皮细胞紧密连接蛋白的结构功能及其调节[J]. 浙江医学, 2018, 40:895–898.
[33] Fideles L, Miranda J, Da C, et al. Molecules role of rutin in 5-fluorouracil-induced intestinal mucositis: prevention of histological damage and reduction of inflammation and oxidative stress[J]. Molecules, 2020, 25:2786.
[34] Zhao B, Wu J, Li J, et al. Lycopene alleviates DSS-induced colitis and behavioral disorders via mediating microbes-gut-brain axis balance[J]. J Agric Food Chem, 2020, 68:3963–3975.
[35] Gan YX, Ai GX, Wu JZ, et al. Patchouli oil ameliorates 5-fluorouracil-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport[J]. J Ethnopharmacol, 2020, 250:112519.

Accesses

Citation

Detail

Sections
Recommended

/