Protective effect of procyanidin B2-3′-O-gallate on ulcerative colitis in mice

Abstract

Ulcerative colitis (UC) is a globally prevalent disease with a continuously increasing incidence rate. Galloylated procyanidins (GPCs) are promising polyphenols for UC treatment. In this study, the protective effects of B2-3′-O-gallate (B2- 3′-G), a typical GPC derived from grape seeds, were explored for the first time using a dextran sulfate sodium (DSS)-induced colitis mouse model. Treatment with B2-3′-G obviously mitigated body weight loss and reduced the Disease Activity Index (DAI). DSS-triggered splenomegaly and colonic shortening were also relieved after B2-3′-G administration. Hematoxylin and eosin (H&E) staining results indicated that B2-3′-G preserved the integrity of colonic mucosa, restored crypt morphology and inhibited inflammatory cell infiltration. Alcian Blue/Periodic Acid-Schiff (AB-PAS) staining further showed that B2-3′-G treatment increased the number of goblet cells, enhanced mucus secretion, and improved the continuity and thickness of the intestinal mucus layer. Collectively, these results confirm that B2-3′-G alleviates DSS-induced colitis by reducing intestinal inflammation and restoring colonic barrier function.

Keywords

Galloylated procyanidins / B2-3′-O-gallate / Ulcerative colitis

References

[1] Williams T, Ashleigh G, Larbi B, et al. Determinants of IBD Heritability: Genes, Bugs, and More. Inflamm Bowel Dis, 2018, 24 (6): 1133-48.

[2] Michael HW, Oleg S, Hyun SK, et al. US Inflammatory Bowel Disease Prevalence: Surveillance Data from the U.S. National Health and Nutrition Examination Survey. Prev Med Rep, 2023, 33 (Suppl C): 102173.

[3] Zhang C, Zhang JT, Zhang YL, et al. Identifying neutrophil-associated subtypes in ulcerative colitis and confirming neutrophils promote colitis-associated colorectal cancer. Front Immunol, 2023, 14: 1095098.

[4] Laurie BG, Konstantinos P, Adam SC, et al. Review article: emerging drug therapies in inflammatory bowel disease. Aliment Pharmacol Ther, 2022, 55 (7): 789-804.

[5] Spranger I, Sun BS, Mateus AM, et al. Chemical characterization and antioxidant activities of oligomeric and polymeric procyanidin fractions from grape seeds. Food Chem, 2008, 108: 519-32.

[6] Sachin V, Subhash L, Vishwaraman M, et al. Anti- inflammatory and anti-arthritic activity of type-A procyanidine polyphenols from bark of Cinnamomum zeylanicum in rats. Food Sci Hum Wellness, 2013, 2 (2): 59-67.

[7] Mu JJ, Xu JW, Wang LL, et al. Anti-inflammatory effects of purple sweet potato anthocyanin extract in DSS- induced colitis: modulation of commensal bacteria and attenuated bacterial intestinal infection. Food Funct, 2021, 12 (22): 11503-14.

[8] Ai LY, Ren YM, Zhu MM, et al. Synbindin restrains proinflammatory macrophage activation against microbiota and mucosal inflammation during colitis. Gut, 2021, 70 (12): 2261-72.

[9] Wang R, Dang M, Zhu W, et al. Galloyl group in b-type proanthocyanidin dimers was responsible for its differential inhibitory activity on 3T3-L1 preadipocytes due to the strong lipid raft-perturbing potency. J Agric Food Chem, 2021, 69 (17), 5216-25.

[10] Luo L, Bai R, Zhao Y, et al. Protective effect of grape seed procyanidins against H₂O₂-induced oxidative stress in PC- 12 neuroblastoma cells: structure-activity relationships. Food Sci, 2018, 83 (10), 2622-8.

[11] Zhang ST, Li LX, Cui Y, et al. Preparative high-speed counter-current chromatography separation of grape seed proanthocyanidins according to degree of polymerization. Food Chem, 2017, 219: 399-407.

[12] Yu YX, Zuo CY, Li MR, et al. Novel l-Cysteine Incomplete Degradation Method for Preparation of Procyanidin B2-3′-O-Gallate and Exploration of its in Vitro Anti-inflammatory Activity and in Vivo Tissue Distribution. J Agric Food Chem, 2024, 72 (8): 4023-34.

[13] Zhang ST, Wang F, Yu YX, et al. Procyanidin B2-3′-O- Gallate Derived from Grape Seed Polymeric Procyanidins via the Galloyl-Attached Nucleophilic Degradation as a Potential Hepatoprotective Agent. J Agric Food Chem, 2024, 72 (34): 18918-29.

[14] Yu YX, Sun MY, Han PY, et al. Large-Scale Semisynthesis of Bioactive Procyanidin B2 3,3′-di-O-gallate: Structural Characterization, Simulated In Vitro Digestion, and Protective Effects against Colitis. J Agric Food Chem, 2026, 74 (6): 5304-17.

[15] Yong F, Oluf P. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol, 2021, 19 (1): 55-71.

[16] Pan YS, Bharati K. Ulcerative colitis, frailty, and beyond. Expert Rev Gastroenterol Hepatol, 2026, 20 (4): 303-11.

[17] Samara MD, Karen Z. Ulcerative Colitis. Surg Clin North Am, 2026, 106 (1): 121-32.

[18] Roda G, Ng SC, Kotze PG, et al. Publisher Correction: Crohn’s disease. Nat Rev Dis Primers, 2020, 6 (1): 26.

[19] Guo XX, Xu Y, Geng RX, et al. Curcumin Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice Through Regulating Gut Microbiota. Mol Nutr Food Res, 2022, 66 (8): e2100943.

[20] Sheng KL, Zhang GH, Sun M, et al. Grape seed proanthocyanidin extract ameliorates dextran sulfate sodium-induced colitis through intestinal barrier improvement, oxidative stress reduction, and inflammatory cytokines and gut microbiota modulation. Food Funct, 2020, 11 (9): 7817-29.