药学学报, 2018, 53(2): 163-168
引用本文:
林媛, 司书毅, 蒋建东. 小檗碱的抗菌作用[J]. 药学学报, 2018, 53(2): 163-168.
LIN Yuan, SI Shu-yi, JIANG Jian-dong. Antibacterial activity of berberine[J]. Acta Pharmaceutica Sinica, 2018, 53(2): 163-168.

小檗碱的抗菌作用
林媛1, 司书毅2, 蒋建东1,2
1. 中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050;
2. 中国医学科学院、北京协和医学院医药生物技术研究所, 北京 100050
摘要:
小檗碱是我国原创的抗菌药,因具有多种生物学活性近年来广受关注,它首先被用于治疗肠道的细菌性感染。小檗碱对多种微生物有不同程度的抑制作用,但一般效果较弱,最低抑菌浓度大多在64 µg·mL-1以上;而效果比较好的是痢疾杆菌,是其选择性之一。同时,因为口服小檗碱吸收差,绝大多数小檗碱集留在肠道中,是其选择性之二,构成其治疗肠道病原菌感染的基础。本文对小檗碱的抗菌作用药效、作用机制及临床应用研究进展进行综述,以期为小檗碱类药物的进一步研发提供参考。
关键词:    小檗碱      抗菌      机制      临床应用     
Antibacterial activity of berberine
LIN Yuan1, SI Shu-yi2, JIANG Jian-dong1,2
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Meteria Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Berberine is an original antibacterial drug in China, and is widely used for its diverse biological functions. It is first used in clinic to treat intestinal bacterial infections. Berberine has different inhibitory effects on various microorganisms, but the effect is very weak with the minimum inhibitory concentration over 64 �g·mL-1 in most of the study bacteria. The effect is better for Bacillus dysteriae, which is one aspect of its selectivity. At the same time, because of the poor absorption of berberine in oral administration, it is retained in the intestine to reach a high concentration, which provides a basis for tissue selectivity in the treatment of intestinal bacterial infections. In this paper, we reviewed the antibacterial action, mechanism, clinical application of berberine, in order to provide a clue for the future direction of berberine research.
Key words:    berberine    antibacterial    mechanism    clinical application   
收稿日期: 2017-08-21
DOI: 10.16438/j.0513-4870.2017-0816
基金项目: 重大协同创新项目-重大前沿研究(2016-I2M-1-011);国家"重大新药创制"科技重大专项资助项目(2015ZX09102007-016-002);国家自然科学基金资助项目(81773784).
通讯作者: 蒋建东,Tel:86-10-63017906,E-mail:jiang.jdong@163.com
Email: jiang.jdong@163.com
相关功能
PDF(1796KB) Free
打印本文
0
作者相关文章
林媛  在本刊中的所有文章
司书毅  在本刊中的所有文章
蒋建东  在本刊中的所有文章

参考文献:
[1] Li GR. Illustrated Handbook for 800 Kinds of Chinese Medicinal Herbs (800种中草药彩色图鉴)[M]. Fujian:Fujian Science and Technology Press, 2017.
[2] Imenshahidi M, Hosseinzadeh H. Berberis vulgaris and berberine:an update review[J]. Phytother Res, 2016, 30:1745-1764.
[3] Ortiz LM, Lombardi P, Tillhon M, et al. Berberine, an epiphany against cancer[J]. Molecules, 2014, 19:12349-12367.
[4] Huang ZJ, Zeng Y, Lan P, et al. Advances in structural modifications and biological activities of berberine:an active compound in traditional Chinese medicine[J]. Mini Rev Med Chem, 2011, 11:1122-1129.
[5] Li B, Zhu WL, Chen KX. Advances in the study of berberine and its derivatives[J]. Acta Pharm Sin (药学学报), 2008, 43:773-787.
[6] Amin AH, Subbaiah TV, Abbasi KM. Berberine sulfate:antimicrobial activity, bioassay, and mode of action[J]. Can J Microbiol, 1969, 15:1067-1076.
[7] Freile ML, Giannini F, Pucci G, et al. Antimicrobial activity of aqueous extracts and of berberine isolated from Berberis heterophylla[J]. Fitoterapia, 2003, 74:702-705.
[8] Yu HH, Kim KJ, Cha JD, et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus[J]. J Med Food, 2005, 8:454-461.
[9] Chu M, Zhang MB, Liu YC, et al. Role of berberine in the treatment of methicillin-resistant Staphylococcus aureus infections[J]. Sci Rep, 2016, 6:24748.
[10] Kang S, Li Z, Yin Z, et al. The antibacterial mechanism of berberine against Actinobacillus pleuropneumoniae[J]. Nat Prod Res, 2015, 29:2203-2206.
[11] Peng L, Kang S, Yin Z, et al. Antibacterial activity and mechanism of berberine against Streptococcus agalactiae[J]. Int J Clin Exp Pathol, 2015, 8:5217-5223.
[12] Liang RM, Yong XL, Duan YQ, et al. Potent in vitro synergism of fusidic acid (FA) and berberine chloride (BBR) against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA)[J]. World J Microbiol Biotechnol, 2014, 30:2861-2869.
[13] Yang Y, Ye XL, Li XG, et al. Synthesis and antimicrobial activity of 8-alkylberberine derivatives with a long aliphatic chain[J]. Planta Med, 2007, 73:602-604.
[14] Joshi PV, Shirkhedkar AA, Prakash K, et al. Antidiarrheal activity, chemical and toxicity profile of Berberis aristata[J]. Pharm Biol, 2011, 49:94-100.
[15] Fu H, Liu LG, Peng JP, et al. Transcriptional profile of the Shigella flexneri response to an alkaloid:berberine[J]. FEMS Microbiol Lett, 2010, 303:169-175.
[16] Li C, Xie J, Chen X, et al. Comparison of Helicobacter pylori urease inhibition by rhizoma coptidis, cortex phellodendri and berberine:mechanisms of interaction with the sulfhydryl group[J]. Planta Med, 2016, 82:305-311.
[17] Liu YX, Xiao CL, Wang YX, et al. Synthesis, structureactivity relationship and in vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives[J]. Eur J Med Chem, 2012, 52:151-158.
[18] Rabbani GH, Butler T, Knight J, et al. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae[J]. J Infect Dis, 1987, 155:979-984.
[19] Iwazaki RS, Endo EH, Ueda-Nakamura T, et al. In vitro antifungal activity of the berberine and its synergism with fluconazole[J]. Antonie Van Leeuwenhoek, 2010, 97:201-205.
[20] Cong L, Liao Y, Yang S, et al. In vitro activity of berberine alone and in combination with antifungal drugs against planktonic forms and biofilms of Trichosporon Asahii[J]. Mycopathologia, 2017. DOI:10.1007/s11046-017-0119-7.
[21] Guan KZ, Zhang WJ, Peng XQ. Effect of antibacterial activities of berberine by introduction of lipophilic aryl in its 9-position[J]. Pharmacy Today (今日药学), 2011, 21:411-413.
[22] Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine[J]. Phytother Res, 2008, 22:999-1012.
[23] Yang Y, Lei ZY, Wu FP, et al. The advance on antimicrobial effect of berberine[J]. Prog Modern Biomed (现代生物医学进展), 2010, 10:1783-1785.
[24] Stermitz FR, Lorenz P, Tawara JN, et al. Synergy in a medicinal plant:antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor[J]. Proc Natl Acad Sci U S A, 2000, 97:1433-1437.
[25] Bae J, Lee D, Kim YK, et al. Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1[J]. Mol Cells, 2013, 35:151-157.
[26] Krishnan P, Bastow KF. The 9-position in berberine analogs is an important determinant of DNA topoisomerase Ⅱ inhibition[J]. Anticancer Drug Des, 2000, 15:255-264.
[27] Li TK, Bathory E, LaVoie EJ, et al. Human topoisomerase I poisoning by protoberberines:potential roles for both drugDNA and drug-enzyme interactions[J]. Biochemistry, 2000, 39:7107-7116.
[28] Kettmann V, Kost'alova D, Holtje HD. Human topoisomerase I poisoning:docking protoberberines into a structure-based binding site model[J]. J Comput Aided Mol Des, 2004, 18:785-796.
[29] Das S, Kumar GS, Ray A, et al. Spectroscopic and thermodynamic studies on the binding of sanguinarine and berberine to triple and double helical DNA and RNA structures[J]. J Biomol Struct Dyn, 2003, 20:703-714.
[30] Wu LT, Tsou MF, Ho CC, et al. Berberine inhibits arylamine N-acetyltransferase activity and gene expression in Salmonella typhi[J]. Curr Microbiol, 2005, 51:255-261.
[31] Wang D, Yu L, Xiang H, et al. Global transcriptional profiles of Staphylococcus aureus treated with berberine chloride[J]. FEMS Microbiol Lett, 2008, 279:217-225.
[32] Domadia PN, Bhunia A, Sivaraman J, et al. Berberine targets assembly of Escherichia coli cell division protein FtsZ[J]. Biochemistry, 2008, 47:3225-3234.
[33] Sun N, Chan FY, Lu YJ, et al. Rational design of berberinebased FtsZ inhibitors with broad-spectrum antibacterial activity[J]. PLoS One, 2014, 9:e97514.
[34] Boberek JM, Stach J, Good L. Genetic evidence for inhibition of bacterial division protein FtsZ by berberine[J]. PLoS One, 2010, 5:e13745.
[35] Oh KB, Oh MN, Kim JG, et al. Inhibition of sortasemediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors[J]. Appl Microbiol Biotechnol, 2006, 70:102-106.
[36] Sun D, Abraham SN, Beachey EH. Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli[J]. Antimicrob Agents Chemother, 1988, 32:1274-1277.
[37] Sack RB, Froehlich JL. Berberine inhibits intestinal secretory response of Vibrio cholerae and Escherichia coli enterotoxins[J]. Infect Immun, 1982, 35:471-475.
[38] Chu M, Ding R, Chu ZY, et al. Role of berberine in antibacterial as a high-affinity LPS antagonist binding to TLR4/MD-2 receptor[J]. BMC Complement Altern Med, 2014, 14:89.
[39] Feng R, Shou JW, Zhao ZX, et al. Transforming berberine into its intestine-absorbable form by the gut microbiota[J]. Sci Rep, 2015, 5:12155.
[40] Wang Y, Shou JW, Li XY, et al. Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism[J]. Metabolism, 2017, 70:72-84.
[41] Wu LG, Chen M. Clinical theraputic effect on hyperlipidemia and weight reduction by berberine and oryzanol[J]. J Clin Cardiol (China) (临床心血管病杂志), 2007, 23:576-578.
[42] Zhang X, Zhao Y, Zhang M, et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats[J]. PLoS One, 2012, 7:e42529.
[43] Lv Z, Peng G, Liu W, et al. Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment[J]. Antimicrob Agents Chemother, 2015, 59:3726-3735.
[44] Li CG, Yan L, Jing YY, et al. Berberine augments ATPinduced inflammasome activation in macrophages by enhancing AMPK signaling[J]. Oncotarget, 2017, 8:95-109.
[45] Zhou H, Feng L, Xu F, et al. Berberine inhibits palmitateinduced NLRP3 inflammasome activation by triggering autophagy in macrophages:a new mechanism linking berberine to insulin resistance improvement[J]. Biomed Pharmacother, 2017, 89:864-874.
[46] Wang H, Li K, Ma L, et al. Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy[J]. Virol J, 2017, 14:2.
[47] Cheng LL, Wang M, Wu MH, et al. Interaction mechanism between berberine and the enzyme lysozyme[J]. Spectrochim Acta A Mol Biomol Spectrosc, 2012, 97:209-214.
[48] Liu RH, Xiao Y, Chen HY, et al. Berberine hydrochloride enema application of bacterial enteritis in children[J]. Med J West China (西部医学), 2014, 36:1635-1636.
[49] Khin Maung U, Myo K, Nyunt Nyunt W, et al. Clinical trial of berberine in acute watery diarrhoea[J]. Br Med J (Clin Res Ed), 1985, 291:1601-1605.
[50] Chen G, Xu Y, Jing J, et al. The anti-sepsis activity of the components of Huanglian Jiedu Decoction with high lipid A-binding affinity[J]. Int Immunopharmacol, 2017, 46:87-96.
[51] Tao MC, Xia XJ, Cao Y. In vitro anti-fungal effect of coptidis decoction for detoxification or combined with western medicine[J]. Chin Arch Tradit Chin Med (中华中医药学刊), 2009, 27:585-587.
[52] Lin YH, Lin JH, Chou SC, et al. Berberine-loaded targeted nanoparticles as specific Helicobacter pylori eradication therapy:in vitro and in vivo study[J]. Nanomedicine (Lond), 2015, 10:57-71.
相关文献:
1.王庆华, 杜婷婷, 张智慧, 季鸣, 胡海宇, 陈晓光.绿原酸的药理作用及机制研究进展[J]. 药学学报, 2020,55(10): 2273-2280
2.王瑜, 王前梅, 冯伟, 袁慊, 姚璞, 孙凤军, 夏培元.莫西沙星纳米药物对耐药铜绿假单胞菌的抑菌活性及其机制[J]. 药学学报, 2020,55(10): 2460-2465
3.鲁海嘉, 张东峰, 黄海洪.抗革兰氏阴性菌药物的研究进展[J]. 药学学报, 2019,54(9): 1554-1563
4.范田运, 杨元帅, 胡辛欣, 汪燕翔, 游雪甫, 宋丹青.全新骨架环化小檗碱衍生物抗MRSA活性研究[J]. 药学学报, 2019,54(9): 1627-1635
5.彭希希, 王赛赛, 付琛, 胡昌华, 廖国建.新型环脂肽抗生素达托霉素研究进展[J]. 药学学报, 2018,53(6): 839-844
6.范田运, 胡欣欣, 汪燕翔, 唐胜, 游雪甫, 宋丹青.新型环化小檗碱衍生物的设计合成及抗MRSA活性研究[J]. 药学学报, 2018,53(6): 887-894
7.许文彦 赵思蒙 曾广智 贺文军 徐会敏 谭宁华.一些重要天然活性环肽化学和生物活性研究进展[J]. 药学学报, 2012,47(3): 271-279
8.马玉龙;郭彤.载铜蒙脱石及其杀灭大肠杆菌机制的研究[J]. 药学学报, 2007,42(3): 318-322