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肠道菌群对黄酮类化合物的代谢作用及生物学活性影响研究进展

  • 金杜欣 ,
  • 曹维 ,
  • 赵秀丽 ,
  • 刘瑞 ,
  • 吴满刚 ,
  • 葛庆丰 ,
  • 于海
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  • 1(扬州大学 广陵学院,江苏 扬州,225000)
    2(扬州大学 食品科学与工程学院,江苏 扬州,225127)
    3(扬州大学 公共卫生学院,江苏 扬州,225127)
第一作者:博士,讲师(通信作者,E-mail:jinduxin@yzu.edu.cn)

收稿日期: 2023-05-16

  修回日期: 2023-06-21

  网络出版日期: 2024-05-09

基金资助

江苏省高等学校基础科学(自然科学)研究面上项目(21KJB350021);扬州大学科技创新培育基金项目(135030532)

Research progress on the metabolic action and biological effects of flavonoids mediated by intestinal flora

  • JIN Duxin ,
  • CAO Wei ,
  • ZHAO Xiuli ,
  • LIU Rui ,
  • WU Mangang ,
  • GE Qingfeng ,
  • YU Hai
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  • 1(Guangling College of Yangzhou University, Yangzhou 225000, China)
    2(School of Food Science and Engineering, Yangzhou University, Yangzhou 225127, China)
    3(School of Public Health, Yangzhou University, Yangzhou 225127, China)

Received date: 2023-05-16

  Revised date: 2023-06-21

  Online published: 2024-05-09

摘要

黄酮类化合物是广泛存在于日常饮食中、由植物合成的次生代谢产物,具有多重生物学活性,如抗氧化、抗炎、抗癌、抗心血管疾病等。然而,黄酮类化合物的结构特点导致其在体内的生物利用度极低。近年来,研究发现黄酮类化合物能够在肠道菌群的作用下发生代谢转化,一定程度上提高了生物利用度,且其代谢产物具有与母药相似或更高的生物学活性。因此,解析黄酮类化合物在肠道菌群作用下的代谢规律及其代谢产物的生物学活性可为阐释其体内药效机理提供重要的理论参考依据。文章综述了黄酮类化合物在肠道微生物作用下的代谢反应,对黄酮类化合物经体内肠道菌群作用后代谢产物的生物学活性及机制进行相应的讨论,为明确黄酮类化合物在体内发挥生物学活性的有效形式提供理论支撑。

本文引用格式

金杜欣 , 曹维 , 赵秀丽 , 刘瑞 , 吴满刚 , 葛庆丰 , 于海 . 肠道菌群对黄酮类化合物的代谢作用及生物学活性影响研究进展[J]. 食品与发酵工业, 2024 , 50(7) : 324 -330 . DOI: 10.13995/j.cnki.11-1802/ts.036157

Abstract

Flavonoids are secondary metabolites that are widely found in daily diet and synthesized by plants.They possess multiple biological activities, such as antioxidant, anti-inflammatory, anticancer, and anti-cardiovascular diseases.However, the in vivo bioavailability of flavonoids is very low due to their structural characteristics.Recently, studies have found that flavonoids can undergo metabolic transformation under the action of gut microbiota, and their bioavailability can be improved to a certain extent.Moreover, the gut bacterial transformation products of flavonoids exhibit similar or higher biological activities than their mother drugs.Hence, it can provide important theoretical basis to interpret the in vivo pharmaceutical effect and mechanisms of flavonoids via analyzing the metabolic rules of flavonoids under the action of intestinal flora and studying the biological activities of their metabolites.In this review, the metabolic reactions of flavonoids under the action of gut bacteria are summarized, and biological activities and mechanisms of flavonoids metabolites after fermented by intestinal flora are discussed, which could provide theoretical support for clarifying the effective forms of flavonoids exerting biological activities in in vivo.

参考文献

[1] BATTINO M, GIAMPIERI F, CIANCIOSI D, et al.The roles of strawberry and honey phytochemicals on human health:A possible clue on the molecular mechanisms involved in the prevention of oxidative stress and inflammation[J].Phytomedicine, 2021, 86:153170.
[2] YEH T S, YUAN C Z, ASCHERIO A, et al.Long-term dietary flavonoid intake and subjective cognitive decline in US men and women[J].Neurology, 2021, 97(10):e1041-e1056.
[3] 龚涛. 宣木瓜类黄酮提取纯化及鸭肉抗氧化保鲜应用实验研究[D].合肥:合肥工业大学, 2017.
GONG T.Study on extraction and purification of flavonoids from Chaenomeles speciosa, application of antioxidation and preservation of duck[D].Hefei:Hefei University of Technology, 2017.
[4] 范芳玉, 杨璇, 刘宇, 等.刺梨果渣天然防腐剂的制备及其在红酸汤中的应用[J].食品安全质量检测学报, 2022, 13(22):7399-7406.
FAN F Y, YANG X, LIU Y, et al.Preparation of natural preservative of the Rosa roxburghii Tratt pomace and its application in red sour soup[J].Journal of Food Safety & Quality, 2022, 13(22):7399-7406.
[5] 王磊, 王辉, 康福忠, 等.山楂的生物活性成分及其在畜禽业中的研究进展[J].饲料研究, 2022, 45(21):146-149.
WANG L, WANG H, KANG F Z, et al.Research progress on bioactive constituents of hawthorn and their application in livestock and poultry industry[J].Feed Research, 2022, 45(21):146-149.
[6] WAN M L Y, CO V A, EL-NEZAMI H.Dietary polyphenol impact on gut health and microbiota[J].Critical Reviews in Food Science and Nutrition, 2021, 61(4):690-711.
[7] MUROTA K, NAKAMURA Y, UEHARA M.Flavonoid metabolism:The interaction of metabolites and gut microbiota[J].Bioscience, Biotechnology, and Biochemistry, 2018, 82(4):600-610.
[8] LOGAN I E, SHULZHENKO N, SHARPTON T J, et al.Xanthohumol requires the intestinal microbiota to improve glucose metabolism in diet-induced obese mice[J].Molecular Nutrition & Food Research, 2021, 65(21):e2100389.
[9] ÁLVAREZ-CILLEROS D, MARTÍN M Á, RAMOS S.Protective effects of (-)-epicatechin and the colonic metabolite 3,4-dihydroxyphenylacetic acid against glucotoxicity-induced insulin signalling blockade and altered glucose uptake and production in renal tubular NRK-52E cells[J].Food and Chemical Toxicology, 2018, 120:119-128.
[10] PEIROTÉN Á, ÁLVAREZ I, LANDETE J M.Production of flavonoid and lignan aglycones from flaxseed and soy extracts by Bifidobacterium strains[J].International Journal of Food Science & Technology, 2020, 55(5):2 22-2131.
[11] 周琪, 窦同意, 丁乐乐, 等.β-葡萄糖醛酸苷酶的重组表达及对黄芩苷的生物转化[J].大连医科大学学报, 2017, 39(2):110-115.
ZHOU Q, DOU T Y, DING L L, et al.Bioconversion of baicalin to baicalein with recombinant β-glucuronidase in Escherichia coli[J].Journal of Dalian Medical University, 2017, 39(2):110-115.
[12] WEI B, WANG Y K, QIU W H, et al.Discovery and mechanism of intestinal bacteria in enzymatic cleavage of C-C glycosidic bonds[J].Applied Microbiology and Biotechnology, 2020, 104(5):1883-1890.
[13] NAKAMURA K, ZHU S, KOMATSU K, et al.Deglycosylation of the isoflavone C-glucoside puerarin by a combination of two recombinant bacterial enzymes and 3-oxo-glucose[J].Applied and Environmental Microbiology, 2020, 86(14):e00607-e00620.
[14] WANG S, LIU S Q, WANG J, et al.A newly isolated human intestinal strain deglycosylating flavonoid C-glycosides[J].Archives of Microbiology, 2022, 204(6):310.
[15] ZANDI K, MUSALL K, OO A, et al.Baicalein and baicalin inhibit SARS-CoV-2 RNA-dependent-RNA polymerase[J].Microorganisms, 2021, 9(5):893.
[16] ISIKA D K, SADIK O A.Selective structural derivatization of flavonoid acetamides significantly impacts their bioavailability and antioxidant properties[J].Molecules, 2022, 27(23):8133.
[17] 伍明江, 吴晓磊, 张德芹, 等.UPLC-Q-TOF/MS鉴定芦丁在大鼠体内的代谢产物[J].中国实验方剂学杂志, 2017, 23(17):91-97.
WU M J, WU X L, ZHANG D Q, et al.Identification of metabolites of rutin in rats by UPLC-Q-TOF/MS[J].Chinese Journal of Experimental Traditional Medical Formulae, 2017, 23(17):91-97.
[18] PARAISO I L, PLAGMANN L S, YANG L P, et al.Reductive metabolism of xanthohumol and 8-prenylnaringenin by the intestinal bacterium Eubacterium ramulus[J].Molecular Nutrition & Food Research, 2019, 63(2):e1800923.
[19] BURAPAN S, KIM M, HAN J.Demethylation of polymethoxyflavones by human gut bacterium, Blautia sp.MRG-PMF1[J].Journal of Agricultural and Food Chemistry, 2017, 65(8):1620-1629.
[20] WEN L R, JIANG Y M, YANG J L, et al.Structure, bioactivity, and synthesis of methylated flavonoids[J].Annals of the New York Academy of Sciences, 2017, 1398(1):120-129.
[21] CUI M Y, LU A R, LI J X, et al.Two types of O-methyltransferase are involved in biosynthesis of anticancer methoxylated 4′-deoxyflavones in Scutellaria baicalensis Georgi[J].Plant Biotechnology Journal, 2022, 20(1):129-142.
[22] 田苗苗, 郭佳婧, 刘娟, 等.大肠杆菌表达类黄酮O-甲基转移酶合成槲皮素甲基化衍生物[J].食品与生物技术学报, 2022, 41(7):111-119.
TIAN M M, GUO J J, LIU J, et al.Synthesis of quercetin methylated derivatives by expression of FOMT in Escherichia coli[J].Journal of Food Science and Biotechnology, 2022, 41(7):111-119.
[23] YANG G H, HONG S, YANG P J, et al.Discovery of an ene-reductase for initiating flavone and flavonol catabolism in gut bacteria[J].Nature Communications, 2021, 12(1):790.
[24] 武锦春. 正常人肠道菌群对酸枣仁总黄酮的体外代谢研究[D].太原:山西大学, 2021.
WU J C.Study on the in vitro metabolism of total flavonoids in Ziziphi Spinosae Semen by normal human intestinal flora[D].Taiyuan:Shanxi University, 2021.
[25] FENG X C, LI Y, BROBBEY OPPONG M, et al.Insights into the intestinal bacterial metabolism of flavonoids and the bioactivities of their microbe-derived ring cleavage metabolites[J].Drug Metabolism Reviews, 2018, 50(3):343-356.
[26] TAMURA M, TSUSHIDA T, SHINOHARA K.Isolation of an isoflavone-metabolizing, Clostridium-like bacterium, strain TM-40, from human faeces[J].Anaerobe, 2007, 13(1):32-35.
[27] 梁文欧, 赵力超, 方祥, 等.大豆异黄酮与肠道微生物相互作用研究进展[J].食品科学, 2019, 40(9):283-289.
LIANG W O, ZHAO L C, FANG X, et al.Progress in the research of the interactions of soy isoflavones with gut microbiota[J].Food Science, 2019, 40(9):283-289.
[28] YAMASHITA S, LIN I, OKA C, et al.Soy isoflavone metabolite equol inhibits cancer cell proliferation in a PAP associated domain containing 5-dependent and an estrogen receptor-independent manner[J].The Journal of Nutritional Biochemistry, 2022, 100:108910.
[29] KALUZHSKIY L, ERSHOV P, YABLOKOV E, et al.Human lanosterol 14-α demethylase (CYP51A1) is a putative target for natural flavonoid luteolin 7,3′-disulfate[J].Molecules, 2021, 26(8):2237.
[30] KUTSCHERA M, ENGST W, BLAUT M, et al.Isolation of catechin-converting human intestinal bacteria[J].Journal of Applied Microbiology, 2011, 111(1):165-175.
[31] VOLLMER M, ESDERS S, FARQUHARSON F M, et al.Mutual interaction of phenolic compounds and microbiota:Metabolism of complex phenolic apigenin-C- and kaempferol-O-derivatives by human fecal samples[J].Journal of Agricultural and Food Chemistry, 2018, 66(2):485-497.
[32] RODRIGUEZ-CASTAÑO G P, DORRIS M R, LIU X B, et al.Bacteroides thetaiotaomicron starch utilization promotes quercetin degradation and butyrate production by Eubacterium ramulus[J].Frontiers in Microbiology, 2019, 10:1145.
[33] RIVA A, KOLIMÁR D, SPITTLER A, et al.Conversion of rutin, a prevalent dietary flavonol, by the human gut microbiota[J].Frontiers in Microbiology, 2020, 11:585428.
[34] KERANMU A, PAN L B, FU J, et al.Biotransformation of liquiritigenin into characteristic metabolites by the gut microbiota[J].Molecules, 2022, 27(10):3057.
[35] CHEN T B, WU H, HE Y, et al.Simultaneously quantitative analysis of naringin and its major human gut microbial metabolites naringenin and 3-(4′-hydroxyphenyl) propanoic acid via stable isotope deuterium-labeling coupled with RRLC-MS/MS method[J].Molecules, 2019, 24(23):4287.
[36] LUCA S V, MACOVEI I, BUJOR A, et al.Bioactivity of dietary polyphenols:The role of metabolites[J].Critical Reviews in Food Science and Nutrition, 2020, 60(4):626-659.
[37] QIU T Y, GONG T, ZHANG S, et al.A carbon-carbon hydrolase from human gut probiotics Flavonifractor plautii catalyzes phloretin conversion[J].Food Bioscience, 2022, 50:102178.
[38] CHEN Y, CHEN H, ZHANG W J, et al.Bioaccessibility and biotransformation of anthocyanin monomers following in vitro simulated gastric-intestinal digestion and in vivo metabolism in rats[J].Food & Function, 2019, 10(9):6052-6061.
[39] BRITO SAMPAIO K, LUIZ DE BRITO ALVES J, MANGUEIRA DO NASCIMENTO Y, et al.Nutraceutical formulations combining Limosilactobacillus fermentum, quercetin, and or resveratrol with beneficial impacts on the abundance of intestinal bacterial populations, metabolite production, and antioxidant capacity during colonic fermentation[J].Food Research International, 2022, 161:111800.
[40] ZENG X, ZHENG Y Y, HE Y, et al.Microbial metabolism of naringin and the impact on antioxidant capacity[J].Nutrients, 2022, 14(18):3765.
[41] TANG Y, NAKASHIMA S, SAIKI S, et al.3,4-Dihydroxyphenylacetic acid is a predominant biologically-active catabolite of quercetin glycosides[J].Food Research International, 2016, 89:716-723.
[42] ÁLVAREZ-CILLEROS D, MARTÍN M Á, GOYA L, et al.(-)-Epicatechin and the colonic metabolite 3, 4-dihydroxyphenylacetic acid protect renal proximal tubular cell against high glucose-induced oxidative stress by modulating NOX-4/SIRT-1 signaling[J].Journal of Functional Foods, 2018, 46:19-28.
[43] HAN L, YANG Q, LI J, et al.Protocatechuic acid-ameliorated endothelial oxidative stress through regulating acetylation level via CD36/AMPK pathway[J].Journal of Agricultural and Food Chemistry, 2019, 67(25):7060-7072.
[44] 李佳. 原儿茶酸改善高脂诱导肝脏炎症及作用机制研究[D].杨凌:西北农林科技大学,2021.
LI J.Effect of protocatechuic acid on liver inflammation induced by high fat and its mechanism[D].Yangling:Northwest A & F University, 2021.
[45] LOFFT Z, TAIBI A, MASSARA P, et al.Cranberry proanthocyanidin and its microbial metabolite 3, 4-dihydroxyphenylacetic acid, but not 3-(4-hydroxyphenyl)-propionic acid, partially reverse pro-inflammatory microRNA responses in human intestinal epithelial cells[J].Molecular Nutrition & Food Research, 2022, 66(8):e2100853.
[46] MARQUES C, FERNANDES I, MEIRELES M, et al.Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins[J].Scientific Reports, 2018, 8(1):11341.
[47] BITNER B F, RAY J D, KENER K B, et al.Common gut microbial metabolites of dietary flavonoids exert potent protective activities in β-cells and skeletal muscle cells[J].The Journal of Nutritional Biochemistry, 2018, 62:95-107.
[48] LIU M, WANG L, HUANG B J, et al.3, 4-Dihydroxyphenylacetic acid ameliorates gut barrier dysfunction via regulation of MAPK-MLCK pathway in type 2 diabetes mice[J].Life Sciences, 2022, 305:120742.
[49] OSBORN L J, SCHULTZ K, MASSEY W, et al.A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis[J].Proceedings of the National Academy of Sciences of the United States of America, 2022, 119(48):e2202934119.
[50] TEIXEIRA L L, COSTA G R, DÖRR F A, et al.Potential antiproliferative activity of polyphenol metabolites against human breast cancer cells and their urine excretion pattern in healthy subjects following acute intake of a polyphenol-rich juice of grumixama (Eugenia brasiliensis Lam.)[J].Food & Function, 2017, 8(6):2266-2274.
[51] CATALÁN M, FERREIRA J, CARRASCO-POZO C.The microbiota-derived metabolite of quercetin, 3, 4-dihydroxyphenylacetic acid prevents malignant transformation and mitochondrial dysfunction induced by hemin in colon cancer and normal colon epithelia cell lines[J].Molecules, 2020, 25(18):4138.
[52] SANKARANARAYANAN R, VALIVETI C K, KUMAR D R, et al.The flavonoid metabolite 2, 4, 6-trihydroxybenzoic acid is a CDK inhibitor and an anti-proliferative agent:A potential role in cancer prevention[J].Cancers, 2019, 11(3):427.
[53] STANISŁAWSKA I J, GRANICA S, PIWOWARSKI J P, et al.The activity of urolithin A and M4 valerolactone, colonic microbiota metabolites of polyphenols, in a prostate cancer in vitro model[J].Planta Medica, 2019, 85(2):118-125.
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