A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea‐Predominant Irritable Bowel Syndrome
Abstract
We aimed to evaluate clinical symptoms in diarrhea predominant irritable bowel syndrome (IBS‐D) receiving berberine hydrochloride in a randomized double‐blind placebo‐controlled clinical trial. Overall, 196 patients with IBS‐D were recruited for this study; consequently, 132 patients randomized to receive daily 400 mg of berberine hydrochloride, delivered twice daily or placebo for 8 weeks followed by a 4‐week washout period. After a 2‐week run‐in period, diarrhea, abdominal pain, urgent need for defecation frequency and any adverse events were recorded daily. Prior to administration of the medication and after completing the treatment, assessment of IBS symptom scores, depression and anxiety scale scores and the IBS scale for quality of life (QOL) was carried out. The effects of berberine hydrochloride on IBS‐D, defined by a reduction of diarrhea frequency (P = 0.032), abdominal pain frequency (P < 0.01) and urgent need for defecation frequency (P < 0.01), were significantly more pronounced in the berberine group than the placebo group in the 8 weeks of treatment. A trend of improvement (P < 0.05) was observed with berberine hydrochloride for IBS symptom score, depression score and anxiety score and the IBSQOL, compared with placebo. At last, berberine hydrochloride was well tolerated. So we concluded that berberine hydrochloride is well tolerated and reduces IBS‐D symptoms, which effectively improved patients QOL. Copyright © 2015 John Wiley & Sons, Ltd.
Citing Literature
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- Yucong Shi, Huachong Xu, Yike Xiao, Pei Liu, Peng Pang, Sizhi Wu, Li Deng, Xiaoyin Chen, Gegen Qinlian Decoction Downregulates the TLR7 Signalling Pathway to Control Influenza A Virus Infection, Biomedicine & Pharmacotherapy, 10.1016/j.biopha.2019.109471, 121, (109471), (2020).
- Jill K. Deutsch, Joshua Levitt, David J. Hass, Complementary and Alternative Medicine for Functional Gastrointestinal Disorders, The American Journal of Gastroenterology, 10.14309/ajg.0000000000000539, 115, 3, (350-364), (2020).
- Francesco Di Pierro, Alexander Bertuccioli, Rosanna Giuberti, Mariella Saponara, Leandro Ivaldi, Role of a berberine-based nutritional supplement in reducing diarrhea in subjects with functional gastrointestinal disorders, Minerva Gastroenterologica e Dietologica, 10.23736/S1121-421X.19.02649-7, 66, 1, (2020).
- Chao Deng, Yanni Lou, Yu Gao, Bo Deng, Fei Su, Liqun Jia, Efficacy and safety of Shengjiang Xiexin decoction in prophylaxis of chemotherapy-related diarrhea in small cell lung cancer patients: study protocol for a multicenter randomized controlled trial, Trials, 10.1186/s13063-020-04275-5, 21, 1, (2020).
- Lin Xiao, Abishek Jung Poudel, Lixia Huang, Yang Wang, Ahmed M.E. Abdalla, Guang Yang, Nanocellulose hyperfine network achieves sustained release of berberine hydrochloride solubilized with β-cyclodextrin for potential anti-infection oral administration, International Journal of Biological Macromolecules, 10.1016/j.ijbiomac.2020.03.030, 153, (633-640), (2020).
- Li LI, Hui-Min ZHU, Qi YAN, Song-Ya LI, Fei LI, The antibacterial activity of Berberis heteropoda Schrenk and its effect on irritable bowel syndrome in rats, Chinese Journal of Natural Medicines, 10.1016/S1875-5364(20)30042-X, 18, 5, (356-368), (2020).
- Solomon Habtemariam, Berberine pharmacology and the gut microbiota: A hidden therapeutic link, Pharmacological Research, 10.1016/j.phrs.2020.104722, 155, (104722), (2020).
- Jia Jin, Ming Xu, Yixuan Liu, Zhixiao Ji, Kaili Dai, Lun Zhang, Lei Wang, Fei Ye, Gang Chen, Zhengbing Lv, Alginate-based composite microspheres coated by berberine simultaneously improve hemostatic and antibacterial efficacy, Colloids and Surfaces B: Biointerfaces, 10.1016/j.colsurfb.2020.111168, (111168), (2020).
- Bo Wang, An-Jun Deng, Zhi-Hong Li, Nan Wang, Hai-Lin Qin, Syntheses and Structure–Activity Relationships in Growth Inhibition Activity against Human Cancer Cell Lines of 12 Substituted Berberine Derivatives, Molecules, 10.3390/molecules25081871, 25, 8, (1871), (2020).
- Aini Pervaiz, Haroon Khan, Surriya Amin, Therapeutic Potential of Alkaloids as Anti-Bacterial Agents: Drugs of Future, Current Bioactive Compounds, 10.2174/1573407213666170221153319, 15, 1, (31-40), (2019).
- Dahua Fan, Liping Liu, Zhengzhi Wu, Meiqun Cao, Combating Neurodegenerative Diseases with the Plant Alkaloid Berberine: Molecular Mechanisms and Therapeutic Potential, Current Neuropharmacology, 10.2174/1570159X16666180419141613, 17, 6, (563-579), (2019).
- Marina Raju, Yogesh A. Kulkarni, Sarika Wairkar, Therapeutic potential and recent delivery systems of berberine: A wonder molecule, Journal of Functional Foods, 10.1016/j.jff.2019.103517, 61, (103517), (2019).
- Mohsen Imenshahidi, Hossein Hosseinzadeh, Berberine and barberry (): A clinical review, Phytotherapy Research, 10.1002/ptr.6252, 33, 3, (504-523), (2019).
- Xie Zhang, Xiao-Dong Liu, Yan-Fang Xian, Feng Zhang, Peng-Yun Huang, Ying Tang, Qiu-Ju Yuan, Zhi-Xiu Lin, Berberine enhances survival and axonal regeneration of motoneurons following spinal root avulsion and re-implantation in rats, Free Radical Biology and Medicine, 10.1016/j.freeradbiomed.2019.08.029, (2019).
- Ladislav Kokoska, Pavel Kloucek, Olga Leuner, Pavel Novy, Plant-Derived Products as Antibacterial and Antifungal Agents in Human Health Care, Current Medicinal Chemistry, 10.2174/0929867325666180831144344, 26, 29, (5501-5541), (2019).
- Dai-Qiang Liu, Shu-Ping Chen, Jia Sun, Xiao-Mei Wang, Nan Chen, Ya-Qun Zhou, Yu-Ke Tian, Da-Wei Ye, Berberine protects against ischemia-reperfusion injury: a review of evidence from animal models and clinical studies, Pharmacological Research, 10.1016/j.phrs.2019.104385, (104385), (2019).
- Ye Wang, Li Zhang, Zhixia Du, Jin Pei, Linfang Huang, Chemical Diversity and Prediction of Potential Cultivation Areas of Cistanche Herbs, Scientific Reports, 10.1038/s41598-019-56379-x, 9, 1, (2019).
- Hong-Yu Xu, Chang-Shun Liu, Chuan-Li Huang, Li Chen, Yu-Rong Zheng, Si-Hang Huang, Xiao-Ying Long, Nanoemulsion Improves Hypoglycemic Efficacy of Berberine by Overcoming its Gastrointestinal Challenge, Colloids and Surfaces B: Biointerfaces, 10.1016/j.colsurfb.2019.06.006, (2019).
- Matthew Woo, Seth Shaffer, Antidiarrheal Drugs, Reference Module in Biomedical Sciences, 10.1016/B978-0-12-801238-3.65619-2, (2019).
- Yihan Wu, Di Wang, Xiaoqin Yang, Chaomei Fu, Liang Zou, Jinming Zhang, Traditional Chinese medicine Gegen Qinlian decoction ameliorates irinotecan chemotherapy-induced gut toxicity in mice, Biomedicine & Pharmacotherapy, 10.1016/j.biopha.2018.11.095, 109, (2252-2261), (2019).
- Sheyda Ranjbar, Seyed Afshin Seyednejad, Shekoufeh Nikfar, Roja Rahimi, Mohammad Abdollahi, How can we develop better antispasmodics for irritable bowel syndrome?, Expert Opinion on Drug Discovery, 10.1080/17460441.2019.1593369, (1-14), (2019).
- Bahare Salehi, Zeliha Selamoglu, Bilge Sener, Mehtap Kilic, Arun Kumar Jugran, Nunziatina de Tommasi, Chiara Sinisgalli, Luigi Milella, Jovana Rajkovic, Maria Flaviana B. Morais-Braga, Camila F. Bezerra, Janaína E. Rocha, Henrique D.M. Coutinho, Adedayo Oluwaseun Ademiluyi, Zabta Khan Shinwari, Sohail Ahmad Jan, Ebru Erol, Zulfiqar Ali, Elise Adrian Ostrander, Javad Sharifi-Rad, María de la Luz Cádiz-Gurrea, Yasaman Taheri, Miquel Martorell, Antonio Segura-Carretero, William C. Cho, Berberis Plants—Drifting from Farm to Food Applications, Phytotherapy, and Phytopharmacology, Foods, 10.3390/foods8100522, 8, 10, (522), (2019).
- Yuan Tian, Jingwei Cai, Wei Gui, Robert G. Nichols, Imhoi Koo, Jingtao Zhang, Mallappa Anitha, Andrew D. Patterson, Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation, Drug Metabolism and Disposition, 10.1124/dmd.118.083691, 47, 2, (86-93), (2018).
- Ye Wang, Zhi-Tian Zuo, Tao Shen, Heng-Yu Huang, Yuan-Zhong Wang, Authentication of Dendrobium Species Using Near-Infrared and Ultraviolet–Visible Spectroscopy with Chemometrics and Data Fusion , Analytical Letters, 10.1080/00032719.2018.1451874, 51, 17, (2790-2819), (2018).
- Mengyao Bai, Yun Liu, Feiye Zhou, Yuqing Zhang, Qin Zhu, Linlin Zhang, Qi Zhang, Shushu Wang, Kecheng Zhu, Xiao Wang, Libin Zhou, Berberine inhibits glucose oxidation and insulin secretion in rat islets, Endocrine Journal, 10.1507/endocrj.EJ17-0543, 65, 4, (469-477), (2018).
- Ly Thi Huong Nguyen, Sang-Hyun Ahn, Uy Thai Nguyen, In-Jun Yang, Dang-Gui-Liu-Huang Tang a traditional herbal formula, ameliorates imiquimod-induced psoriasis-like skin inflammation in mice by inhibiting IL-22 production, Phytomedicine, 10.1016/j.phymed.2018.04.051, (2018).
- Zhang Yanjie, Lou Benyong, Huang Yali, Huang Xiaodong, Wu Huazhong, Crystal structure of 9,10-dimethoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ium 5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-olate trihydrate, C35H33NO12, Zeitschrift für Kristallographie - New Crystal Structures, 10.1515/ncrs-2018-0061, 233, 5, (865-867), (2018).
- Mei Zhang, Benyong Lou, Xiaodong Huang, Yali Huang, Crystal structure of 9,10-dimethoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ium chloride — 4-hydroxy-3-methoxybenzoic acid — water (2/1/5), C48H54N2Cl2O17, Zeitschrift für Kristallographie - New Crystal Structures, 10.1515/ncrs-2017-0293, 233, 2, (291-293), (2018).
- Shaomin Yang, Zhijian Yu, Wuping Sun, Changyu Jiang, Xiyuan Ba, Qian Zhou, Donglin Xiong, Lizu Xiao, Qiwen Deng, Yue Hao, The antiviral alkaloid berberine ameliorates neuropathic pain in rats with peripheral nerve injury, Acta Neurologica Belgica, 10.1007/s13760-018-1006-9, (2018).
- Hu-Shan Cui, Yu-Min Li, Wei Fang, Jiu-Ke Li, Yuan-Min Dai, Lian-Shun Zheng, Effect of berberine on lipopolysaccharide-induced monocyte chemotactic protein-1 and interleukin-8 expression in a human retinal pigment epithelial cell line, International Ophthalmology, 10.1007/s10792-017-0697-x, 38, 5, (2053-2060), (2017).
- MY Zhang, YY Yu, SF Wang, Q Zhang, HW Wu, JY Wei, W Yang, SY Li, HJ Yang, Cardiotoxicity evaluation of nine alkaloids from Rhizoma Coptis , Human & Experimental Toxicology, 10.1177/0960327117695633, 37, 2, (185-195), (2017).
- Mohammad Adil, Mohd Nizam Mansoori, Divya Singh, Amit Dattatraya Kandhare, Manju Sharma, Pioglitazone-induced bone loss in diabetic rats and its amelioration by berberine: A portrait of molecular crosstalk, Biomedicine & Pharmacotherapy, 10.1016/j.biopha.2017.08.001, 94, (1010-1019), (2017).
- Ana Cristina Alves de Almeida, Felipe Meira de-Faria, Ricardo José Dunder, Luis Paulo Bognoni Manzo, Alba Regina Monteiro Souza-Brito, Anderson Luiz-Ferreira, Recent Trends in Pharmacological Activity of Alkaloids in Animal Colitis: Potential Use for Inflammatory Bowel Disease, Evidence-Based Complementary and Alternative Medicine, 10.1155/2017/8528210, 2017, (1-24), (2017).
- Ting Liu, Yue Cui, Xiumin Tian, Songhe Li, Fei Han, Bin Ji, Yunli Zhao, Zhiguo Yu, Detection of chemical constituents in Gegenqinlian decoction by ultra-high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry, Anal. Methods, 10.1039/C7AY02082A, 9, 40, (5890-5902), (2017).
- Chao Deng, Bo Deng, Liqun Jia, Huangying Tan, Pan Zhang, Sida Liu, Yanan Zhang, Aiping Song, Lin Pan, Preventive Effects of a Chinese Herbal Formula, Shengjiang Xiexin Decoction, on Irinotecan-Induced Delayed-Onset Diarrhea in Rats, Evidence-Based Complementary and Alternative Medicine, 10.1155/2017/7350251, 2017, (1-10), (2017).
- Lawrence R. Schiller, Antidiarrheal Drug Therapy, Current Gastroenterology Reports, 10.1007/s11894-017-0557-x, 19, 5, (2017).
- Oratai Neamsuvan, Thamakorn Ruangrit, A survey of herbal weeds that are used to treat gastrointestinal disorders from southern Thailand: Krabi and Songkhla provinces, Journal of Ethnopharmacology, 10.1016/j.jep.2017.06.039, 209, (318-327), (2017).
- Oratai Neamsuvan, Thamakorn Ruangrit, A survey of herbal weeds that are used to treat gastrointestinal disorders from southern Thailand: Krabi and Songkhla provinces, Journal of Ethnopharmacology, 10.1016/j.jep.2016.11.033, 196, (84-93), (2017).
- Yong-Jiang Li, Xiong-Bin Hu, Xiu-Ling Lu, De-Hua Liao, Tian-Tian Tang, Jun-Yong Wu, Da-Xiong Xiang, Nanoemulsion-based delivery system for enhanced oral bioavailability and Caco-2 cell monolayers permeability of berberine hydrochloride, Drug Delivery, 10.1080/10717544.2017.1410257, 24, 1, (1868-1873), (2017).
- Maryam Mosaffa-Jahromi, Ali-Mohammad Tamaddon, Suleiman Afsharypuor, Alireza Salehi, Seyed Hassan Seradj, Mehdi Pasalar, Peyman Jafari, Kamran Bagheri Lankarani, Effectiveness of Anise Oil for Treatment of Mild to Moderate Depression in Patients With Irritable Bowel Syndrome, Journal of Evidence-Based Complementary & Alternative Medicine, 10.1177/2156587216628374, 22, 1, (41-46), (2016).
- H. Dorota Halicka, Jorge Garcia, Jiangwei Li, Hong Zhao, Zbigniew Darzynkiewicz, Synergy of 2-deoxy-d-glucose combined with berberine in inducing the lysosome/autophagy and transglutaminase activation-facilitated apoptosis, Apoptosis, 10.1007/s10495-016-1315-5, 22, 2, (229-238), (2016).
- Chang-Shun Liu, Yu-Rong Zheng, Ying-Feng Zhang, Xiao-Ying Long, Research progress on berberine with a special focus on its oral bioavailability, Fitoterapia, 10.1016/j.fitote.2016.02.001, 109, (274-282), (2016).
- Solomon Habtemariam, Berberine and inflammatory bowel disease: A concise review, Pharmacological Research, 10.1016/j.phrs.2016.09.041, 113, (592-599), (2016).
- Eric Yarnell, Herbs for Emerging Viral Infectious Diseases, Alternative and Complementary Therapies, 10.1089/act.2016.29062.eya, 22, 4, (164-174), (2016).
- Yan-hong Li, Man Zhang, Hai-bo Fu, Hai-tao Xiao, Zhao-xiang Bian, Pre-clinical toxicity of a combination of berberine and 5-aminosalicylic acid in mice, Food and Chemical Toxicology, 10.1016/j.fct.2016.08.031, 97, (150-158), (2016).
- Rosaliana Libro, Sabrina Giacoppo, Thangavelu Soundara Rajan, Placido Bramanti, Emanuela Mazzon, Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview, Molecules, 10.3390/molecules21040518, 21, 4, (518), (2016).




