戴承恩;李海龙;何小平;郑芬芬;竺画柳;刘良丰;杜伟;
DAI Cheng-en;LI Hai-long;HE Xiao-ping;ZHENG Fen-fen;ZHU Hua-liu;LIU Liang-feng;DU Wei;Zhejiang Yalin Biological Technology Co.,Ltd.;Research Institute of Subtropical Forestry,Chinese Academy of Forestry;

• 1:浙江亚林生物科技股份有限公司
• 2:中国林业科学研究院亚热带林业研究所

摘要(Abstract)：

中药有效成分得以发挥其药理活性在很大程度上取决于人体内肠道益生菌的微生态环境。益生菌通过影响中药有效成分的代谢、转化、吸收等作用而改变中草药的功效或增添新的内容。益生菌和中药的结合是功能性食品及中药研发的创新点,也是中药现代化研究的新思路。该文简要地综述了国内外肠道益生菌代谢中药主要有效成分的研究进展,中药有效成分对肠道益生菌的调节作用,益生菌在中药中的应用现状,研究和开发益生菌中药产品存在的主要问题和前景分析,旨在为中药发酵工程提供理论指导和实际应用价值。
The pharmacological activity of active ingredients from Chinese medicine depends greatly on the microecological environment of probiotics in the human body.After effective ingredients from traditional Chinese medicines are metabolized or biotransformed by probiotics,their metabolites can increase pharmacological activity,and can be absorbed more easily to improve the bioavailability.Therefore,the combination of Chinese medicines with probiotics is the innovation point in R&D of functional food and Chinese medicines,and also a new thinking for the modernization of Chinese medicine.This review summarizes and analyses the research progress on metabolism effects of gut microbiota on Chinese medicines components,the regulating effect of effective ingredients from Chinese medicine on intestinal probiotics,the application status of probiotics in traditional Chinese medicines,and the main problems and prospects in the research and development of Chinese medicines products with probiotic,aiming to provide theoretical guidance and practical value for the fermentation engineering of Chinese herbal medicine.

关键词(KeyWords)： 中药;有效成分;药理活性;益生菌;功能性食品;代谢
traditional Chinese medicine;effective ingredients;pharmacological activity;probiotics;functional foods;metabolism

Abstract:

Keywords:

基金项目(Foundation): 杭州市富阳区科技计划项目(2016NK002)

作者(Author): 戴承恩;李海龙;何小平;郑芬芬;竺画柳;刘良丰;杜伟;
DAI Cheng-en;LI Hai-long;HE Xiao-ping;ZHENG Fen-fen;ZHU Hua-liu;LIU Liang-feng;DU Wei;Zhejiang Yalin Biological Technology Co.,Ltd.;Research Institute of Subtropical Forestry,Chinese Academy of Forestry;

Email:

DOI: 10.19540/j.cnki.cjcmm.20170919.012

参考文献(References)：

• [1]Sanders M E,Guarner F,Guerrant R,et al.An update on the use and investigation of probiotics in health and disease[J].Gut,2013,62(5):787.
• [2]Sánchez B,Delgado S,Blanco-Míguez A,et al.Probiotics,gut microbiota and their influence on host health and disease[J].Mol Nutr Food Res,2017,61(1):1.
• [3]Borchers A T,Selmi C,Meyers F J,et al.Probiotics and immunity[J].J Gastroenterol,2009,44(1):26.
• [4]Islam S U.Clinical uses of probiotics[J].Medicine,2016,95(5):e2658.
• [5]Sartor R B.Microbial influences in inflammatory bowel diseases[J].Gastroenterology,2008,134(2):577.
• [6]Alok A,Singh I D,Singh S,et al.Probiotics:a new era of biotherapy[J].Adv Biomed Res,2017,6:31.
• [7]Serra A,MaciàA,Romero M P,et al.Metabolic pathways of the colonic metabolism of flavonoids(flavonols,flavones and flavanones)and phenolic acids[J].Food Chem,2012,130(2):383.
• [8]Trinh H T,Joh E H,Kwak H Y,et al.Anti-pruritic effect of baicalin and its metabolites,baicalein and oroxylin A,in mice[J].Acta Pharmacol Sin,2010,31(6):718.
• [9]Myung-Ah J,Se-Eun J,Hong S W,et al.The role of intestinal microflora in anti-inflammatory effect of baicalin in mice[J].Biomol Ther,2012,20(1):36.
• [10]Elghali S,Mustafa S,Amid M,et al.Bioconversion of daidzein to equol by Bifidobacterium breve,15700 and Bifidobacterium longum,BB536[J].J Funct Foods,2012,4(4):736.
• [11]Setchell K D,Brown N M,Lydekingolsen E.The clinical importance of the metabolite equola clue to the effectiveness of soy and its isoflavones[J].J Nutr,2002,132(12):3577.
• [12]Mu1oz Y,Garrido A,Valladares L.Equol is more active than soy isoflavone itself to compete for binding to thromboxane A 2,receptor in human platelets[J].Thromb Res,2009,123(5):740.
• [13]Braune A,Blaut M.Deglycosylation of puerarin and other aromatic C-glucosides by a newly isolated human intestinal bacterium[J].Environ Microbiol,2011,13(2):482.
• [14]黄慧学,谭珍媛,邓家刚,等.人肠道菌群对芒果苷体外代谢转化的研究[J].中国中药杂志,2011,36(4):443.
• [15]Sanugul K,Akao T,Li Y,et al.Isolation of a human intestinal bacterium that transforms mangiferin to norathyriol and inducibility of the enzyme that cleaves a C-glucosyl bond[J].Biol Pharm Bull,2005,28(9):1672.
• [16]Yang C Y,Tsai S Y,Chao P D L,et al.Determination of hesperetin and its conjugate metabolites in serum and urine[J].J Food Drug Anal,2002,10(3):143.
• [17]Lee N K,Choi S H,Park S H,et al.Antiallergic activity of hesperidin is activated by intestinal microflora.[J].Pharmacology,2004,71(4):174.
• [18]Yang H L,Chen S C,Kumar K J S,et al.Antioxidant and antiinflammatory potential of hesperetin metabolites obtained from hesperetin-administered rat serum:an in vivo approach[J].J Agr Food Chem,2012,60(1):522.
• [19]杨秀伟,张建业,徐嵬,等.山柰苷的人肠内细菌生物转化研究[J].药学学报,2005,40(8):717.
• [20]Vissiennon C,Nieber K,Kelber O,et al.Route of administration determines the anxiolytic activity of the flavonols kaempferol,quercetin and myricetin-are they prodrugs?[J].J Nutr Biochem,2012,23(7):733.
• [21]Li L,Luo G A,Liang Q L,et al.Rapid qualitative and quantitative analyses of Asian ginseng in adulterated American ginseng preparations by UPLC/Q-TOF-MS[J].J Pharm Biomed Anal,2010,52(1):66.
• [22]Jayeul L,Euiju L,Donghyun K,et al.Studies on absorption,distribution and metabolism of ginseng in humans after oral administration[J].J Ethnopharmacol,2008,122(1):143.
• [23]Bae E A,Han M J,Choo M K,et al.Metabolism of 20(S)-and20(R)-ginsenoside Rg3by human intestinal bacteria and its relation to in vitro biological activities[J].Biol Pharm Bull,2002,25(1):58.
• [24]Bae E A,Han M J,Kim E J,et al.Transformation of ginseng saponins to ginsenoside Rh2by acids and human intestinal bacteria and biological activities of their transformants[J].Arch Pharm Res,2004,27(1):61.
• [25]Jung I H,Lee J H,Hyun Y J,et al.Metabolism of ginsenoside Rb1by human intestinal microflora and cloning of its metabolizingβ-D-glucosidase from Bifidobacterium longum H-1[J].Biol Pharm Bull,2012,35(4):573.
• [26]Akao T.Differences in the metabolism of glycyrrhizin,glycyrrhetic acidand glycyrrhetic acid monoglucuronide by human intestinal flora[J].Biol Pharm Bull,2000,23(12):1418.
• [27]Rui H,Xu Y,Peng J,et al.The effects of 18β-glycyrrhetinic acid and glycyrrhizin on intestinal absorption of paeoniflorin using the everted rat gut sac model[J].J Nat Med,2017,71(1):198.
• [28]Kobayashi T,Komata M,Takemura N,et al.Simultaneous highperformance liquid chromatographic determination of sennoside A metabolites in rat and mouse feces[J].J Tradit Med,2009,26:80.
• [29]Matsumoto M,Ishige A,Yazawa Y,et al.Promotion of intestinal peristalsis by Bifidobacterium spp.capable of hydrolysing sennosides in mice[J].PLo S ONE,2012,7(2):e31700.
• [30]Takayama K,Morita T,Tabuch N.The effect of anthraquinones in daiokanzoto on increasing the synthesis of sennoside A-metabolic enzyme derived from bifidobacteria[J].J Tradit Med,2014,30:215.
• [31]Akao T,Che Q M,Kobashi K,et al.A purgative action of barbaloin is induced by Eubacterium sp.strain BAR,a human intestinal anaerobe,capable of transforming barbaloin to aloe-emodin anthrone[J].Biol Pharm Bull,1996,19(1):136.
• [32]Inao M,Mochida S,Matsui A,et al.Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis[J].J Hepatol,2004,41(4):584.
• [33]Jin M J,Kim I S,Kim D H,et al.Effects of intestinal microbiota on the bioavailability of geniposide in rats[J].J Agr Food Chem,2014,62(40):9632.
• [34]Khanal T,Kim H G,Choi J H,et al.Biotransformation of geniposide by human intestinal microflora on cytotoxicity against Hep G2 cells[J].Toxicol Lett,2012,209(3):246.
• [35]Kang M J,Khanal T,Kim H G,et al.Role of metabolism by human intestinal microflora in geniposide-induced toxicity in Hep G2cells[J].Arch Pharm Res,2012,35(4):733.
• [36]Liu Z Q,Jiang Z H,Liu L,et al.Mechanisms responsible for poor oral bioavailability of paeoniflorin:role of intestinal disposition and interactions with sinomenine[J].Pharm Res,2006,23(12):2768.
• [37]Abdel-Hafez A A,Meselhy M R,Nakamura N,et al.New paeonilactone-A adducts formed by anaerobic incubation of paeoniflorin with lactobacillus brevis in the presence of arylthiols[J].Chem Pharm Bull,2001,49(7):918.
• [38]Hsiu S L,Lin Y T,Wen K C,et al.A deglucosylated metabolite of paeoniflorin of the root of Paeonia lactiflora and its pharmacokinetics in rats[J].Planta Med,2003,69(12):1113.
• [39]He J X,Akao T,Tani T.Influence of co-administered antibiotics on the pharmacokinetic fate in rats of paeoniflorin and its active metabolite paeonimetabolin-I from Shaoyao-Gancao-tang[J].J Pharm Pharmacol,2003,55(3):313.
• [40]He J X,Goto E,Akao T,et al.Interaction between ShaoyaoGancao-Tang and a laxative with respect to alteration of paeoniflorin metabolism by intestinal bacteria in rats[J].Phytomedicine,2007,14(7):452.
• [41]Liang J,Xu F,Zhang Y Z,et al.The profiling and identification of the absorbed constituents and metabolites of Paeoniae Radix Rubra decoction in rat plasma and urine by the HPLC-DAD-ESIIT-TOF-MSn,technique:a novel strategy for the systematic screening and identification of absorbed[J].J Pharm Biomed Anal,2013,83(5):108.
• [42]杨肖锋,宋纯清.龙胆苦苷的肠内菌群代谢研究[J].中国中药杂志,2000,25(11):673.
• [43]Han H,Xiong A Z,He C Y,et al.Combination of UHPLC/QTOF-MS,NMR spectroscopy,and ECD calculation for screening and identification of reactive metabolites of gentiopicroside in humans[J].Anal Bioanal Chem,2014,406(6):1781.
• [44]Wang Z,Tang S,Jin Y,et al.Two main metabolites of gentiopicroside detected in rat plasma by LC-TOF-MS following 2,4-dinitrophenylhydrazine derivatization[J].J Pharm Biomed Anal,2015,107(3):1.
• [45]Borcsa B,Widowitz U,Csupor D,et al.Semisynthesis and pharmacological investigation of lipo-alkaloids prepared from aconitine[J].Fitoterapia,2011,82(3):365.
• [46]Xin Y,Pi Z F,Song F R,et al.Study on the metabolic characteristics of aconite alkaloids in the extract of Radix Aconiti under intestinal bacteria of rat by UPLC/MSntechnique[J].Chin J Chem,2012,30(3):656.
• [47]王明雷,周秋丽,王本祥.氧化苦参碱肠内菌代谢及吸收入血活性成分的研究[J].中国中药杂志,2001,26(4):272.
• [48]Wu X L,Hang T J,Shen J P,et al.Determination and pharmacokinetic study of oxymatrine and its metabolite matrine in human plasma by liquid chromatography tandem mass spectrometry[J].J Pharm Biomed Anal,2006,41(3):918.
• [49]陈万一,周远大,康纪平,等.青藤碱在Beagle犬体内的药动学和绝对生物利用度研究[J].中国中药杂志,2009,34(4):468.
• [50]Yao Y M,Tan Z R,Hu Z Y,et al.Determination of sinomenine in human plasma by HPLC/ESI/ion trap mass spectrum[J].Clin Chim Acta,2005,356(1/2):212.
• [51]Cheng W M,Qiu F,Yao X S.Three major urinary metabolites of sinomenine in rats[J].J Asian Nat Prod Res,2007,9(1):13.
• [52]Tomas-Barberan F,García-Villalba R,Quartieri A,et al.In vitro transformation of chlorogenic acid by human gut microbiota[J].Mol Nutr Food Res,2014,58(5):1122.
• [53]Couteau D,Mccartney A L,Gibson G R,et al.Isolation and characterization of human colonic bacteria able to hydrolyse chlorogenic acid[J].J Appl Microbiol,2001,90(6):873.
• [54]Gonthier M P,Verny M A,Besson C,et al.Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats[J].J Nutr,2003,133(6):1853.
• [55]Rio D D,Stalmach A,Calani L,et al.Bioavailability of coffee chlorogenic acids and green tea flavan-3-ols[J].Nutrients,2010,2(8):820.
• [56]Ludwig I A,Pazd P M,Concepción C,et al.Catabolism of coffee chlorogenic acids by human colonic microbiota[J].Biofactors,2013,39(6):623.
• [57]Nowak R,Nowacka-Jechalke N,Juda M,et al.The preliminary study of prebiotic potential of Polish wild mushroom polysaccharides:the stimulation effect on Lactobacillus strains growth[J].Eur J Nutr,2017.
• [58]石林林,王源,冯怡.麦冬多糖MDG-1对膳食诱导肥胖模型小鼠肠道益生菌群多样性影响的研究[J].中国中药杂志,2015,40(4):716.
• [59]Shi L L,Li Y,Wang Y,et al.MDG-1,an ophiopogon,polysaccharide,regulate gut microbiota in high-fat diet-induced obese C57BL/6 mice[J].Int J Biol Macromol,2015,81:576.
• [60]Guo M Z,Ding S,Zhao C H,et al.Red Ginseng and Semen Coicis can improve the structure of gut microbiota and relieve the symptoms of ulcerative colitis[J].J Ethnopharmacol,2015,162(10):7.
• [61]Viveros A,Chamorro S,Pizarro M,et al.Effects of dietary polyphenol-rich grape products on intestinal microflora and gut morphology in broiler chicks[J].Poult Sci,2011,90(3):566.
• [62]张蔚,江曙,钱大玮,等.芒柄花苷与人体肠道细菌的相互作用研究[J].药学学报,2014,49(8):1162.
• [63]Xie W,Gu D,Li J,et al.Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in highfat diet-fed C57BL/6J mice[J].PLo S ONE,2011,6(9):e24520.
• [64]Chang C J,Lin C S,Lu C C,et al.Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota[J].Nat Commun,2015,6:7489.
• [65]Wang J H,Bose S,Kim G C,et al.Flos Lonicera Ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota[J].PLo S ONE,2014,9(1):e86117.
• [66]彭颖,金晶,杨静玉,等.3种健脾补气方药对脾气虚证大鼠肠道菌群的影响[J].中国中药杂志,2008,33(21):2530.
• [67]Kim H S,Kim J Y,Park M S,et al.Cloning and expression of beta-glucuronidase from lactobacillus brevis in E.coli and application in the bioconversion of baicalin and wogonoside[J].J Microb Biot,2009,19(12):1650.
• [68]Ku S,Zheng H,Park M S,et al.Optimization ofβ-glucuronidase activity from lactobacillus delbrueckii,Rh2and and its use for biotransformation of baicalin and wogonoside[J].J Korean Soc Appl Bi,2011,54(2):275.
• [69]Malashree L,Mudgil P,Dagar S S,et al.β-Glucosidase activity of Lactobacilli for biotransformation of soy isoflavones[J].Food Biotechnol,2012,26(2):154.
• [70]Kim B G,Shin K S,Yoon T J,et al.Fermentation of Korean Red Ginseng by Lactobacillus plantarum,M-2 and its immunological activities[J].Appl Biochem Biotechnol,2011,165(5/6):1107.
• [71]Cho K,Woo H J,Park K H,et al.Effects of pre-fermentation enzyme treatments of leaves,stems,and roots of ginseng on Lactobacillus,fermentation characteristics and ginsenoside metabolite formation[J].Korean J Chem Eng,2011,28(1):209.
• [72]Quan L H,Kim Y J,Li G H,et al.Microbial transformation of ginsenoside Rb1to compound K by Lactobacillus paralimentarius[J].World J Microb Biot,2013,29(6):1001.
• [73]Zhong F L,Dong W W,Wu S,et al.Biotransformation of gypenosideⅩⅦto compound K by a recombinantβ-glucosidase[J].Biotechnol Lett,2016,38(7):1187.
• [74]Lv B,Yang X G,Feng X D,et al.Enhanced production of glycyrrhetic acid 3-O-mono-β-D-glucuronide by fed-batch fermentation using p H and dissolved oxygen as feedback parameters[J].Chinese J Chem Eng,2016,24(4):506.
• [75]Bel-Rhlid R,Thapa D,Kraehenbuehl K,et al.Biotransformation of caffeoyl quinic acids from green coffee extracts by Lactobacillus johnsonii,NCC 533[J].Amb Express,2013,3(1):28.
• [76]Kim J A,Park M S,Kang S A,et al.Production ofγ-aminobutyric acid during fermentation of Gastrodia elata BL.by co-culture of Lactobacillus brevis GABA 100 with Bifidobacterium bifidum BGN4[J].Food Sci Biotechnol,2014,23(2):459.
• [77]Zhang R,Zhang B L,Xie T,et al.Biotransformation of rutin to isoquercitrin using recombinantα-L-rhamnosidase from Bifidobacterium breve[J].Biotechnol Lett,2015,37(6):1257.
• [78]Bhat R,Chandrashekara K A,Krishnan P,et al.Lactobacillus plantarum,mediated fermentation of Psidium guajava L.fruit extract[J].J Biosci Bioeng,2015,119(4):430.
• [79]Yang S Y,Li H L.Optimization of pine pollen fermentation conditions using Lactobacillus paracasei[J].Food Sci Biotechnol,2015,24(1):155.