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Open Access Article

Journal of Modern Biotechnology Research. 2025; 3: (1) ; 1-13 ; DOI: 10.12208/j.jmbr.20250001.

Potential role of carotenoids in inflammatory bowel disease
类胡萝卜素在炎症性肠病中的潜在作用

作者: 丁国熙1, 范瑞1, 王婷1, 周涵朝1, 刘畅1, 康玉强1, 马铭阳1, 温小鹏2, 王珂1,2 *

1 西安交通大学医学部 陕西西安
2 西安交通大学第一附属医院胸外科 陕西西安

*通讯作者: 王珂,单位: 西安交通大学医学部 陕西西安 西安交通大学第一附属医院胸外科 陕西西安;

发布时间: 2025-06-10 总浏览量: 26

摘要

炎症性肠病(IBD),包括克罗恩病和溃疡性结肠炎,是一种慢性免疫介导的消化道炎症性疾病。研究表明,其发病机制与遗传易感性、黏膜屏障功能障碍、肠道微生物群失调、免疫反应异常、环境因素及生活方式等因素密切相关。尽管对揭示IBD的病因有深入研究,但现有的治疗方法仍然有限,且有时伴随严重的后果。因此,迫切需要探索替代治疗方案。本综述评估了当前的药物治疗,包括氨基水杨酸盐、免疫调节剂、皮质类固醇和抗生素等,分析了它们的局限性,并基于临床前和临床研究提出了使用类胡萝卜素的建议。类胡萝卜素是一种具有显著治疗潜力的天然植物,展现出抗氧化、抗癌和抗炎的特性。这些综合作用有助于其在控制和缓解IBD症状方面的治疗潜力。本研究旨在促进未来的研究努力,加速将基于类胡萝卜素的干预措施转化为临床实践,将其作为一种有价值的辅助疗法或传统治疗的潜在替代方案,提高包括IBD在内的炎症性疾病患者的生活质量。

关键词: 类胡萝卜素;炎症性肠病;炎症;消化道

Abstract

Inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, is a chronic immune-mediated inflammatory disorder of the digestive tract. Research has demonstrated that the pathogenesis of IBD is closely linked to several factors, including genetic predisposition, mucosal barrier dysfunction, dysbiosis of the intestinal microbiota, abnormal immune responses, environmental influences, and lifestyle choices. Despite extensive investigations aimed at elucidating the etiology of IBD, available treatments remain limited and can sometimes lead to serious side effects. Consequently, there is an urgent need to explore alternative therapeutic options. This review evaluates current pharmacological treatments, such as aminosalicylates, immunomodulators, corticosteroids, and antibiotics, analyzes their limitations, and offers recommendations for the use of carotenoids based on preclinical and clinical studies. Carotenoids are natural compounds found in plants that possess significant therapeutic potential, exhibiting antioxidant, anticancer, and anti-inflammatory properties. These combined effects enhance their therapeutic potential in managing and alleviating the symptoms of IBD. The aim of this study is to promote future research efforts to expedite the translation of carotenoid-based interventions into clinical practice, positioning them as valuable adjunctive therapies or potential alternatives to conventional treatments, ultimately improving the quality of life for patients with inflammatory diseases, including IBD.

Key words: Carotenoids; Inflammatory bowel disease; Inflammation; Alimentary canal

参考文献 References

[1] Shao B, Yang W, Cao Q. Landscape and predictions of inflammatory bowel disease in China: China will enter the Compounding Prevalence stage around 2030. *Front Public Health*. 2022. 10:1032679. 

[2] Ocansey, D.K.W., et al., Exosome-mediated effects and applications in inflammatory bowel disease. Biol Rev Camb Philos Soc, 2020. 95(5): p. 1287-1307.

[3] Maoka, T., Carotenoids as natural functional pigments. J Nat Med, 2020. 74(1): p. 1-16.

[4] Wang, L., et al., Biotechnology advances in β-carotene production by microorganisms. Trends in Food Science & Technology, 2021. 111: p. 322-332.

[5] Jing, Y., et al., Advances in the synthesis of three typical tetraterpenoids including β-carotene, lycopene and astaxanthin. Biotechnology Advances, 2022. 61: p. 108033.

[6] Li, S., et al., An improved method for the separation of carotenoids and carotenoid isomers by liquid chromatography-mass spectrometry. J Sep Sci, 2021. 44(2): p. 539-548.

[7] Terao, J., Revisiting carotenoids as dietary antioxidants for human health and disease prevention. Food Funct, 2023. 14(17): p. 7799-7824.

[8] Jing, Y., et al., Recent Advances on Biological Synthesis of Lycopene by Using Industrial Yeast. Industrial & Engineering Chemistry Research, 2021. 60(9): p. 3485-3494.

[9] Liu, C., et al., Carotenoids from fungi and microalgae: A review on their recent production, extraction, and developments. Bioresource Technology, 2021. 337: p. 125398.

[10] Hernández-Almanza, A., et al., Lycopene: Progress in microbial production. Trends in Food Science & Technology, 2016. 56: p. 142-148.

[11] Borel, P., et al., Lycopene bioavailability is associated with a combination of genetic variants. Free Radical Biology and Medicine, 2015. 83: p. 238-244.

[12] Muhammad, A., et al., Production of plant natural products through engineered Yarrowia lipolytica. Biotechnology Advances, 2020. 43: p. 107555.

[13] Mitra, S., et al., Potential health benefits of carotenoid lutein: An updated review. Food Chem Toxicol, 2021. 154: p. 112328.

[14] Kong, K.-W., et al. Revealing the Power of the Natural Red Pigment Lycopene. Molecules, 2010. 15, 959-987 DOI: 10.3390/molecules15020959.

[15] Müller, L., et al., Lycopene and Its Antioxidant Role in the Prevention of Cardiovascular Diseases-A Critical Review. Crit Rev Food Sci Nutr, 2016. 56(11): p. 1868-79.

[16] Di Mascio, P., S. Kaiser, and H. Sies, Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys, 1989. 274(2): p. 532-8.

[17] Laurindo, L.F., et al., Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects. Metabolites, 2023. 13(1).

[18] Huang, M.T., G. Ghai, and C.T. Ho, Inflammatory Process and Molecular Targets for Antiinflammatory Nutraceuticals. Compr Rev Food Sci Food Saf, 2004. 3(4): p. 127-139.

[19] Sies, H. and W. Stahl, Lycopene: antioxidant and biological effects and its bioavailability in the human. Proc Soc Exp Biol Med, 1998. 218(2): p. 121-4.

[20] Eleutherio, E.C.A., et al., SOD1, more than just an antioxidant. Archives of Biochemistry and Biophysics, 2021. 697: p. 108701.

[21] Yang, H., et al., The protective role of procyanidins and lycopene against mercuric chloride renal damage in rats. Biomedical and Environmental Sciences, 2011. 24(5): p. 550-559.

[22] Kuhad, A., R. Sethi, and K. Chopra, Lycopene attenuates diabetes-associated cognitive decline in rats. Life Sciences, 2008. 83(3): p. 128-134.

[23] Liu, X., et al. Effect of lycopene on the vascular endothelial function and expression of inflammatory agents in hyperhomocysteinemic rats. in Asia Pacific Journal of Clinical Nutrition. 2007.

[24] Veeramachaneni, S., et al., High Dose Lycopene Supplementation Increases Hepatic Cytochrome P4502E1 Protein and Inflammation in Alcohol-Fed Rats12. The Journal of Nutrition, 2008. 138(7): p. 1329-1335.

[25] Sahin, K., et al., Nrf2/HO-1 signaling pathway may be the prime target for chemoprevention of cisplatin-induced nephrotoxicity by lycopene. Food and Chemical Toxicology, 2010. 48(10): p. 2670-2674.

[26] Marcotorchino, J., et al., Lycopene attenuates LPS-induced TNF-α secretion in macrophages and inflammatory markers in adipocytes exposed to macrophage-conditioned media. Molecular Nutrition and Food Research, 2012. 56(5): p. 725-732.

[27] Feng, D., W.H. Ling, and R.D. Duan, Lycopene suppresses LPS-induced NO and IL-6 production by inhibiting the activation of ERK, p38MAPK, and NF-κB in macrophages. Inflammation Research, 2010. 59(2): p. 115-121.

[28] Palozza, P., et al., Lycopene prevents 7-ketocholesterol-induced oxidative stress, cell cycle arrest and apoptosis in human macrophages. Journal of Nutritional Biochemistry, 2010. 21(1): p. 34-46.

[29] Buijsse, B., et al., Both alpha- and beta-carotene, but not tocopherols and vitamin C, are inversely related to 15-year cardiovascular mortality in Dutch elderly men. J Nutr, 2008. 138(2): p. 344-50.

[30] Pool-Zobel, B.L., et al., Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis, 1997. 18(9): p. 1847-50.

[31] Visioli, F., et al., Protective activity of tomato products on in vivo markers of lipid oxidation. Eur J Nutr, 2003. 42(4): p. 201-6.

[32] Upritchard, J.E., W.H. Sutherland, and J.I. Mann, Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Diabetes Care, 2000. 23(6): p. 733-8.

[33] Watzl, B., et al., Prolonged tomato juice consumption has no effect on cell-mediated immunity of well-nourished elderly men and women. J Nutr, 2000. 130(7): p. 1719-23.

[34] Trivedi, P.P. and G.B. Jena, Mechanistic insight into beta-carotene-mediated protection against ulcerative colitis-associated local and systemic damage in mice. Eur J Nutr, 2015. 54(4): p. 639-52.

[35] Chen, H., et al., Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium. Gut, 2014. 63(5): p. 711-9.

[36] Li, X.Y., et al., Regulation of gut microbiota by vitamin C, vitamin E and β-carotene. Food Res Int, 2023. 169: p. 112749.

[37] Stevens, Y., et al., Effect of a carotenoid-producing Bacillus strain on intestinal barrier integrity and systemic delivery of carotenoids: A randomised trial in animals and humans. Journal of Functional Foods, 2021. 80: p. 104445.

[38] Wu, T., et al., Capsanthin extract prevents obesity, reduces serum TMAO levels and modulates the gut microbiota composition in high-fat-diet induced obese C57BL/6J mice. Food Research International, 2020. 128: p. 108774.

[39] Trivedi, P.P. and G.B. Jena, Mechanistic insight into beta-carotene-mediated protection against ulcerative colitis-associated local and systemic damage in mice. European Journal of Nutrition, 2015. 54(4): p. 639-652.

[40] Ushakumari, U.N. and R. Ramanujan, Isolation of astaxanthin from marine yeast and study of its pharmacological activity. International Current Pharmaceutical Journal, 2013. 2: p. 67-69.

[41] Naguib, Y.M., Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem, 2000. 48(4): p. 1150-4.

[42] Goto, S., et al., Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta, 2001. 1512(2): p. 251-8.

[43] Pereira, C.P.M., et al., Antioxidant and anti‑inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review). Int J Mol Med, 2021. 47(1): p. 37-48.

[44] Terazawa, S., et al., Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion-independent manner. Exp Dermatol, 2012. 21 Suppl 1: p. 11-7.

[45] Sztretye, M., et al., Astaxanthin: A Potential Mitochondrial-Targeted Antioxidant Treatment in Diseases and with Aging. Oxid Med Cell Longev, 2019. 2019: p. 3849692.

[46] Kim, S.H., J.W. Lim, and H. Kim, Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells. Nutrients, 2018. 10(9).

[47] Han, H., J.W. Lim, and H. Kim, Astaxanthin Inhibits Helicobacter pylori-induced Inflammatory and Oncogenic Responses in Gastric Mucosal Tissues of Mice. J Cancer Prev, 2020. 25(4): p. 244-251.

[48] Sakai, S., et al., Astaxanthin, a xanthophyll carotenoid, prevents development of dextran sulphate sodium-induced murine colitis. J Clin Biochem Nutr, 2019. 64(1): p. 66-72.

[49] Zhang, L., et al., Astaxanthin (ATX) enhances the intestinal mucosal functions in immunodeficient mice. Food Funct, 2020. 11(4): p. 3371-3381.

[50] Nagayama, T., et al., Effects of astaxanthin-enriched yeast on mucosal IgA induction in the jejunum and ileum of weanling mice. Anim Sci J, 2014. 85(4): p. 449-53.

[51] Ahn, Y.J. and H. Kim, Lutein as a Modulator of Oxidative Stress-Mediated Inflammatory Diseases. Antioxidants (Basel), 2021. 10(9).

[52] Nagira, M., et al., Ischemia/reperfusion injury in the monolayers of human intestinal epithelial cell line caco-2 and its recovery by antioxidants. Drug Metab Pharmacokinet, 2006. 21(3): p. 230-7.

[53] Sindhu, E.R., et al., Carotenoid lutein protects rats from paracetamol-, carbon tetrachloride- and ethanol-induced hepatic damage. J Pharm Pharmacol, 2010. 62(8): p. 1054-60.

[54] Vieira, M.M., et al., Carotenoids, retinol, and intestinal barrier function in children from northeastern Brazil. J Pediatr Gastroenterol Nutr, 2008. 47(5): p. 652-9.

[55] March, D.S., et al., Intestinal fatty acid-binding protein and gut permeability responses to exercise. Eur J Appl Physiol, 2017. 117(5): p. 931-941.

[56] Zhang, Y., et al., Lignin reinforced hydrogels with multi-functional sensing and moist-electric generating applications. International Journal of Biological Macromolecules, 2021. 193: p. 941-947.

[57] Prabhu Venkatesh, D., et al., In Vitro Evaluation of Antioxidant and Anti-inflammatory Potentials of Herbal Formulation Containing Marigold Flower (Calendula officinalis L.) Tea. Cureus, 2023. 15(8): p. e43308.

[58] Abidov, M., et al., The effects of Xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat. Diabetes Obes Metab, 2010. 12(1): p. 72-81.

[59] Kim, Y.-I., et al., GaN powders from ammonolysis: Preparation, structure, morphology, and optical properties. Solid State Sciences, 2011. 13(1): p. 216-223.

[60] Kijlstra, A., et al., Lutein: More than just a filter for blue light. Progress in Retinal and Eye Research, 2012. 31(4): p. 303-315.

[61] Shiratori, K., et al., Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Experimental Eye Research, 2005. 81(4): p. 422-428.

[62] Jin, X.H., et al., Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats. Invest Ophthalmol Vis Sci, 2006. 47(6): p. 2562-8.

[63] Sasaki, M., et al., Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes. Diabetologia, 2010. 53(5): p. 971-9.

[64] Milani, A., et al., Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol, 2017. 174(11): p. 1290-1324.

[65] Pérez-Gálvez, A., I. Viera, and M. Roca, Carotenoids and Chlorophylls as Antioxidants. Antioxidants (Basel), 2020. 9(6).

[66] Gammone, M.A., et al., Marine Carotenoids against Oxidative Stress: Effects on Human Health. Marine Drugs, 2015. 13(10): p. 6226-6246.

[67] Siems, W., et al., β-Carotene breakdown products may impair mitochondrial functions — potential side effects of high-dose β-carotene supplementation. The Journal of Nutritional Biochemistry, 2005. 16(7): p. 385-397.

[68] Gammone, M.A., G. Riccioni, and N. Orazio Marine Carotenoids against Oxidative Stress: Effects on Human Health. Marine Drugs, 2015. 13, 6226-6246 

[69] Raposo, M.F., A.M. de Morais, and R.M. de Morais, Carotenoids from Marine Microalgae: A Valuable Natural Source for the Prevention of Chronic Diseases. Mar Drugs, 2015. 13(8): p. 5128-55.

[70] Kim, E.-A., et al. Antioxidant, Antiviral, and Anti-Inflammatory Activities of Lutein-Enriched Extract of Tetraselmis Species. Marine Drugs, 2023. 21.

[71] Murillo, A.G., S. Hu, and M.L. Fernandez, Zeaxanthin: Metabolism, Properties, and Antioxidant Protection of Eyes, Heart, Liver, and Skin. Antioxidants (Basel), 2019. 8(9).

[72] Crupi, P., et al. Overview of the Potential Beneficial Effects of Carotenoids on Consumer Health and Well-Being. Antioxidants, 2023. 12.

[73] Rashid, M., et al., Saffron as a Promising Therapy for Inflammatory Bowel Disease. Nutrients, 2024. 16(14).

[74] Wang, Y., et al., Nuciferine modulates the gut microbiota and prevents obesity in high-fat diet-fed rats. Experimental & Molecular Medicine, 2020. 52(12): p. 1959-1975.

[75] de Medeiros, P., et al., Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children. Nutrients, 2018. 10(9).

[76] Ruan, X., et al., Intramolecular heterostructured carbon nitride with heptazine-triazine for enhanced photocatalytic hydrogen evolution. Chemical Engineering Journal, 2022. 428: p. 132579.

[77] Jin, Y., et al., In vivo retinoid metabolic and visual cycle pathways assessment of carotenoid-rich refined red palm-pressed mesocarp olein. Journal of Functional Foods, 2024. 116: p. 106140.

[78] González-Prendes, R., et al., Modulatory Effect of Protein and Carotene Dietary Levels on Pig gut Microbiota. Sci Rep, 2019. 9(1): p. 14582.

[79] Djuric, Z., et al., Colonic Mucosal Bacteria Are Associated with Inter-Individual Variability in Serum Carotenoid Concentrations. Journal of the Academy of Nutrition and Dietetics, 2018. 118 4: p. 606-616.e3.

[80] Bohn, T., et al., Mechanistic aspects of carotenoid health benefits - where are we now? Nutr Res Rev, 2021. 34(2): p. 276-302.

[81] Pabst, O. and E. Slack, IgA and the intestinal microbiota: the importance of being specific. Mucosal Immunol, 2020. 13(1): p. 12-21.

[82] Mantis, N.J. and S.J. Forbes, Secretory IgA: arresting microbial pathogens at epithelial borders. Immunol Invest, 2010. 39(4-5): p. 383-406.

[83] Huus, K.E., et al., Commensal Bacteria Modulate Immunoglobulin A Binding in Response to Host Nutrition. Cell Host Microbe, 2020. 27(6): p. 909-921.e5.

[84] Stadtmueller, B.M., et al., The structure and dynamics of secretory component and its interactions with polymeric immunoglobulins. Elife, 2016. 5.

[85] Bennedsen, M., et al., Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Immunol Lett, 1999. 70(3): p. 185-9.

[86] Baralic, I., et al., Effect of Astaxanthin Supplementation on Salivary IgA, Oxidative Stress, and Inflammation in Young Soccer Players. Evid Based Complement Alternat Med, 2015. 2015: p. 783761.

[87] Singh, D.P., et al., A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, nonalcoholic fatty liver and gut derangement in mice. Int J Obes (Lond), 2016. 40(3): p. 487-96.

[88] Wang, J., et al., Lycopene attenuates western-diet-induced cognitive deficits via improving glycolipid metabolism dysfunction and inflammatory responses in gut–liver–brain axis. International Journal of Obesity, 2019. 43(9): p. 1735-1746.

[89] Schreiber, O., et al., iNOS-dependent increase in colonic mucus thickness in DSS-colitic rats. PLoS One, 2013. 8(8): p. e71843.

[90] Wang, J.L., et al., Differential analysis of intestinal microbiota and metabolites in mice with dextran sulfate sodium-induced colitis. World J Gastroenterol, 2022. 28(43): p. 6109-6130.

[91] Djuric, Z., et al., Colonic Mucosal Bacteria Are Associated with Inter-Individual Variability in Serum Carotenoid Concentrations. Journal of the Academy of Nutrition and Dietetics, 2018. 118(4): p. 606-616.e3.

[92] Singh, N. and C.N. Bernstein, Environmental risk factors for inflammatory bowel disease. United European Gastroenterol J, 2022. 10(10): p. 1047-1053.

[93] Cai, Z., S. Wang, and J. Li, Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front Med (Lausanne), 2021. 8: p. 765474.

[94] Mehta, R.S., et al., Gut microbial metabolism of 5-ASA diminishes its clinical efficacy in inflammatory bowel disease. Nat Med, 2023. 29(3): p. 700-709.

[95] Simpson, J.B., et al., Diverse but desolate landscape of gut microbial azoreductases: A rationale for idiopathic IBD drug response. Gut Microbes, 2023. 15(1): p. 2203963.

[96] Prantera, C. and S. Marconi, Glucocorticosteroids in the treatment of inflammatory bowel disease and approaches to minimizing systemic activity. Therap Adv Gastroenterol, 2013. 6(2): p. 137-56.

[97] Ali, S., et al., Glucocorticoids-Induced Neuropsychiatric Disorders in Patients With Inflammatory Bowel Disease: A Systematic Review. Cureus, 2022. 14(9): p. e28981.

[98] Papamichael, K., et al., Therapeutic drug monitoring with biologic agents in immune mediated inflammatory diseases. Expert Rev Clin Immunol, 2019. 15(8): p. 837-848.

[99] Wu, N., et al., Cost of biologics per treated patient across immune-mediated inflammatory disease indications in a pharmacy benefit management setting: a retrospective cohort study. Clin Ther, 2014. 36(8): p. 1231-41, 1241.e1-3.

[100] Karthikeyan, A., et al., Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook. Pharmaceutics, 2021. 13(4).

引用本文

丁国熙, 范瑞, 王婷, 周涵朝, 刘畅, 康玉强, 马铭阳, 温小鹏, 王珂, 类胡萝卜素在炎症性肠病中的潜在作用[J]. 现代生物技术研究, 2025; 3: (1) : 1-13.