Angelicone Ameliorates Ulcerative Colitis in Mice via Modulating Gut Microbiota

Abstract

Ulcerative colitis (UC) is a persistent, periodically reoccurring inflammatory condition that impacts the gastrointestinal tract. Angelicone, a principal compound extracted from Angelica sinensis, may offer a potential alternative therapeutic approach for UC through the downregulation of inflammatory mediators. Nonetheless, the pharmacological impacts and molecular pathways of angelicone in UC management, particularly in relation to gut microbiota, remain unexplored. The current study scrutinized the modifications in gut microbiota in mice afflicted with UC, induced by 3% dextran sodium sulfate (DSS), utilizing 16S rRNA sequencing. The study demonstrated that angelicone substantially enhanced clinical indices, mitigated colonic damage, decreased cytokine levels, and reestablished the integrity of the intestinal epithelial barrier in UC mice. Furthermore, we discerned distinct bacterial genera that were responsive to angelicone treatment. Importantly, angelicone augmented the abundance of gut microbiota and partially reinstated the disrupted intestinal microbial composition, inclusive of the phyla Proteobacteria, Firmicutes, and Bacteroidetes. To summarize, our research offers novel perspectives into the intervention mechanisms of angelicone in the treatment of UC.

Keywords

angelicone - gut microbiota - ulcerative colitis - dextran sodium sulfate - 16S rRNA - Angelica sinensis - Apiaceae

Publication History

Received: 14 August 2024

Accepted after revision: 24 March 2025

Accepted Manuscript online:
24 March 2025

Article published online:
17 April 2025

• References

• 1 Du LL, Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterol Clin N 2020; 49: 643-654
• 2 Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet 2017; 389: 1756-1770
• 3 Liu Y, Li BG, Su YH, Zhao RX, Song P, Li H, Cui XH, Gao HM, Zhai RX, Fu XJ, Ren X. Potential activity of Traditional Chinese Medicine against ulcerative colitis: A review. J Ethnopharmacol 2022; 289: 115084
• 4 Nascimento RPD, Machado APDF, Galvez J, Cazarin CBB, Maróstica Junior MR. Ulcerative colitis: Gut microbiota, immunopathogenesis and application of natural products in animal models. Life Sci 2020; 258: 118129
• 5 Schirmer M, Stražar M, Avila-Pacheco J, Rojas-Tapias DF, Brown EM, Temple E, Deik A, Bullock K, Jeanfavre S, Pierce K, Jin S, Invernizzi R, Pust MM, Costliow Z, Mack DR, Griffiths AM, Walters T, Boyle BM, Kugathasan S, Vlamakis H, Hyams J, Denson L, Clish CB, Xavier RJ. Linking microbial genes to plasma and stool metabolites uncovers host-microbial interactions underlying ulcerative colitis disease course. Cell Host Microbe 2024; 32: 209-226.e7
• 6 Gomes CF, Chapman TP, Satsangi J. De-escalation of medical therapy in inflammatory bowel disease. Curr Opin Pharmacol 2020; 55: 73-81
• 7 Troncone E, Monteleone G. The safety of non-biological treatments in ulcerative colitis. Expert Opin Drug Saf 2017; 16: 779-789
• 8 Wang Y, Hao Y, Yuan L, Tian H, Sun X, Zhang Y. Ferroptosis: A new mechanism of traditional Chinese medicine for treating ulcerative colitis. Front Pharmacol 2024; 15: 1379058
• 9 Wang M, Fu R, Xu D, Chen Y, Yue S, Zhang S, Tang Y. Traditional Chinese Medicine: A promising strategy to regulate the imbalance of bacterial flora, impaired intestinal barrier and immune function attributed to ulcerative colitis through intestinal microecology. J Ethnopharmacol 2024; 318: 116879
• 10 Zhou YL, Wu J, Wang HL, Feng WW, Peng F, Zhang RQ, Yan HL, Liu J, Tan YZ, Peng C. Fuzi lizhong pills alter microbial community compositions and metabolite profiles in ulcerative colitis rat with spleen-kidney yang deficiency syndrome. J Ethnopharmacol 2024; 335: 118645
• 11 Wang L, Zhang H, Tang F, Yan H, Feng W, Liu J, Wang Y, Tan Y, Chen H. Therapeutic effects of Valeriana jatamansi on ulcerative colitis: Insights into mechanisms of action through metabolomics and microbiome analysis. J Proteome Res 2023; 22: 2669-2682
• 12 Zou YF, Li CY, Fu YP, JiZe XP, Zhao YZ, Peng X, Wang JY, Yin ZQ, Li YP, Song X, Li LX, Zhao XH, Feng B, Huang C, Ye G, Tang HQ, Chen J, Li R, Chen XF, Tian ML. Angelica sinensis aboveground part polysaccharide and its metabolite 5-MT ameliorate colitis via modulating gut microbiota and TLR4/MyD88/NF-κB pathway. Int J Biol Macromol 2023; 242: 124689
• 13 Liu C, He YX, Zhang JN, Yang F, Wang SY, Hu JL, Yu Y. Angelica oil restores the intestinal barrier function by suppressing S100A8/A9 in mice with ulcerative colitis. Phytomedicine 2023; 108: 154490
• 14 Jang JC, Lee KM, Ko SG. Angelica acutiloba kitagawa extract attenuates DSS-induced murine colitis. Mediat Inflamm 2016; 2016: 9275083
• 15 Cheng F, Zhang Y, Li Q, Zeng F, Wang K. Inhibition of dextran sodium sulfate-induced experimental colitis in mice by Angelica sinensis polysaccharide. J Med Food 2020; 23: 584-592
• 16 Xu Y, Zhu BW, Sun R, Li X, Wu D, Hu JN. Colon-targeting Angelica sinensis polysaccharide nanoparticles with dual responsiveness for alleviation of ulcerative colitis. Acs Appl Mater Inter 2023; 15: 26298-26315
• 17 Chang J, Leong RW, Wasinger VC, Ip M, Yang M, Phan TG. Impaired intestinal permeability contributes to ongoing bowel symptoms in patients with inflammatory bowel disease and mucosal healing. Gastroenterology 2017; 153: 723
• 18 Kobayashi K, Matsunaga K, Tsugami Y, Wakasa H, Nishimura T. IL-1β is a key inflammatory cytokine that weakens lactation-specific tight junctions of mammary epithelial cells. Exp Cell Res 2021; 409: 112938
• 19 Liu C, Wu Y, Wang Y, Yang F, Ren L, Wu H, Yu Y. Integrating 16 S rRNA gene sequencing and metabolomics analysis to reveal the mechanism of oil in alleviating ulcerative colitis in mice. J Pharm Biomed Anal 2024; 249: 116367
• 20 Zhu W, Jin Z, Yu J, Liang J, Yang Q, Li F, Shi X, Zhu X, Zhang X. Baicalin ameliorates experimental inflammatory bowel disease through polarization of macrophages to an M2 phenotype. Int Immunopharmacol 2016; 35: 119-126
• 21 Hee LS. Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intest Res 2015; 13: 11
• 22 Lechuga S, Ivanov AI. Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms. Bba-Mol Cell Res 2017; 1864: 1183-1194
• 23 Lee HR, Jeong YJ, Park SA, Kim HJ, Heo TH. Geraniin alleviates inflammation in Caco-2 cells and dextran sulfate sodium-induced colitis mice by targeting IL-1β . J Agric Food Chem 2024; 72: 7882-7893
• 24 Wu P, Jiang WD, Jiang J, Zhao J, Liu Y, Zhang YA, Zhou XQ, Feng L. Dietary choline deficiency and excess induced intestinal inflammation and alteration of intestinal tight junction protein transcription potentially by modulating NF-kappa B, STAT and p 38 MAPK signaling molecules in juvenile Jian carp. Fish Shellfish Immunol 2016; 58: 462-473
• 25 He XX, Li YH, Yan PG, Meng XC, Chen CY, Li KM, Li JN. Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis. World journal of gastroenterology 2021; 27: 4722-4737
• 26 Ju T, Song Z, Qin D, Cheng J, Li T, Hu G, Fu S. Neohesperidin attenuates dss-induced ulcerative colitis by inhibiting inflammation, reducing intestinal barrier damage, and modulating intestinal flora composition. J Agric Food Chem 2024; 72: 20419-20431
• 27 Imhann F, Vich Vila A, Bonder MJ, Fu J, Gevers D, Visschedijk MC, Spekhorst LM, Alberts R, Franke L, van Dullemen HM, Ter Steege RWF, Huttenhower C, Dijkstra G, Xavier RJ, Festen EAM, Wijmenga C, Zhernakova A, Weersma RK. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut 2018; 67: 108-119
• 28 Mukhopadhya I, Hansen R, El-Omar EM, Hold GL. IBD-what role do proteobacteria play?. Nat Rev Gastroenterol Hepatol 2012; 9: 219-230
• 29 Berkes J, Viswanathan VK, Savkovic SD, Hecht G. Intestinal epithelial responses to enteric pathogens: Effects on the tight junction barrier, ion transport, and inflammation. Gut 2003; 52: 439-451
• 30 Peng L, Gao X, Nie L, Xie J, Dai T, Shi C, Tao L, Wang Y, Tian Y, Sheng J. Astragalin attenuates dextran sulfate sodium (DSS)-induced acute experimental colitis by alleviating gut microbiota dysbiosis and inhibiting NF-κB activation in mice. Front Immunol 2020; 11: 2058
• 31 Cai Y, Li S, Zhang X, Cao X, Liu D, Zhu Y, Ye S, Xu Z, Liao Q, Hong Y, Xie Z. Integrated microbiome-metabolomics analysis reveals the potential therapeutic mechanism of Zuo-Jin-Wan in ulcerative colitis. Phytomedicine 2022; 98: 153914
• 32 Delday M, Mulder I, Logan ET, Grant G. Bacteroides thetaiotaomicron ameliorates colon inflammation in preclinical models of crohnʼs disease. Inflamm Bowel Dis 2019; 25: 85-96
• 33 Zhou Y, Zhi F. Lower level of bacteroides in the gut microbiota is associated with inflammatory bowel disease: A meta-analysis. Biomed Res Int 2016; 2016: 5828959
• 34 Bang B, Lichtenberger LM. Methods of inducing inflammatory bowel disease in mice. Curr Protoc Pharmacol 2009; 5: 5.58
• 35 Duan S, Wang H, Gao Y, Wang X, Lyu L, Wang Y. Oral intake of titanium dioxide nanoparticles affect the course and prognosis of ulcerative colitis in mice: Involvement of the ROS-TXNIP-NLRP3 inflammasome pathway. PART Fibre Toxicol 2023; 20: 24
• 36 Viennois E, Chen F, Laroui H, Baker MT, Merlin D. Dextran sodium sulfate inhibits the activities of both polymerase and reverse transcriptase: lithium chloride purification, a rapid and efficient technique to purify RNA. BMC Res Notes 2013; 6: 360
• 37 Sun XW, Li HR, Jin XL, Tang X, Wang DW, Zhang X, Zhang JG. Structural and functional differences in small intestinal and fecal microbiota: 16S rRNA gene investigation in rats. Microorganisms 2024; 12: 1764