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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Inhibitory effects of emodin, baicalin, schizandrin and berberine on hefA gene: Treatment of Helicobacter pylori-induced multidrug resistance
Yan-Qiang Huang, Gan-Rong Huang, Ming-Hui Wu, Hua-Ying Tang, Zan-Song Huang, Xi-Han Zhou, Wen-Qiang Yu, Jian-Wei Su, Xiao-Qiang Mo, Bing-Pu Chen, Li-Juan Zhao, Xiao-Feng Huang, Hong-Yu Wei, Lian-Deng Wei
Yan-Qiang Huang, Gan-Rong Huang, Hua-Ying Tang, Xiao-Qiang Mo, Bing-Pu Chen, Li-Juan Zhao, Xiao-Feng Huang, Hong-Yu Wei, Lian-Deng Wei, Department of Medical Microbiology and Immunology, Youjiang Medical College for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Ming-Hui Wu, Zan-Song Huang, Xi-Han Zhou, Wen-Qiang Yu, Jian-Wei Su, Institute of Digestive Disease, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Author contributions: Huang GR, Wu MH, Tang HY, Huang XF, Wei LD and Wei HY performed the majority of experiments; Zhou XH, Yu WQ, and Su JW provided vital reagents and analytical tools and were also involved in editing the manuscript; Chen BP, Mo XQ, Zhao LJ and Huang ZS co-ordinated and provided the collection of all the human material in addition to providing financial support for this work; Huang YQ designed the study and wrote the manuscript; Huang YQ and Huang GR contributed equally to this work.
Supported by Grants from Guangxi Key Discipline Fund (Pathogenic Microbiology), No. [2013]16; Key Laboratory Fund of Colleges and Universities in Guangxi, No. Gui Jiao Ke Yan [2014]6; National Natural Science Foundation of China, No. 31460023; and Natural Science Foundation of Guangxi, No. 2014GXNSFAA118206.
Ethics approval: The study was reviewed and approved by the Youjiang Medical College Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Guangxi Zhuang Autonomous Region Science and Technology Agency (IACUC protocol number: SCXK 2012-0003).
Conflict-of-interest: The authors declare no conflicts of interest to disclose.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yan-Qiang Huang, Associate Professor, Department of Medical Microbiology and Immunology, Youjiang Medical College for Nationalities, No. 98 Countryside Road, Baise 533000, Guangxi Zhuang Autonomous Region, China. hyq77615@163.com
Telephone: +86-776-2853272 Fax: +86-776-2853272
Received: November 2, 2014
Peer-review started: November 2, 2014
First decision: December 2, 2014
Revised: December 22, 2014
Accepted: February 5, 2015
Article in press: February 5, 2015
Published online: April 14, 2015
AIM: To investigate the inhibitory effects of emodin, baicalin, etc. on the hefA gene of multidrug resistance (MDR) in Helicobacter pylori (H. pylori).
METHODS: The double dilution method was used to screen MDR H. pylori strains and determine the minimum inhibitory concentrations (MICs) of emodin, baicalin, schizandrin, berberine, clarithromycin, metronidazole, tetracycline, amoxicillin and levofloxacin against H. pylori strains. After the screened MDR stains were treated with emodin, baicalin, schizandrin or berberine at a 1/2 MIC concentration for 48 h, changes in MICs of amoxicillin, tetracycline, levofloxacin, metronidazole and clarithromycin were determined. MDR strains with reduced MICs of amoxicillin were selected to detect the hefA mRNA expression by real-time quantitative PCR.
RESULTS: A total of four MDR H. pylori strains were screened. Treatment with emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some strains, decreased by 1 to 2 times, but did not significantly change the MICs of clarithromycin, levofloxacin, and metronidazole against MDR strains. In the majority of strains with reduced MICs of amoxicillin, hefA mRNA expression was decreased; one-way ANOVA (SPSS 12.0) used for comparative analysis, P < 0.05.
CONCLUSION: Emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some H. pylori strains, possibly by mechanisms associated with decreasing hefA mRNA expression.
Core tip: Clinical signs of Helicobacter pylori (H. pylori)-induced drug resistance have become more and more prevalent, thus resulting in reduced cure rates. In this study, we used herbal extracts, such as berberine, to inhibit multidrug resistance in H. pylori. The results indicated that the minimum inhibitory concentration of amoxicillin and tetracycline was lowered after the intervention; the regulatory mechanism was related to down-regulation of efflux pump hefA mRNA expression. This suggests a novel strategy for prophylaxis and treatment of H. pylori-induced resistance.
