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Frontiers of Medicine

Front. Med.    2020, Vol. 14 Issue (5) : 564-582     https://doi.org/10.1007/s11684-019-0724-6
REVIEW
Biological properties and clinical applications of berberine
Danyang Song1, Jianyu Hao1(), Daiming Fan1,2()
1. Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
2. State key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, China
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Abstract

Berberine, an isoquinoline alkaloid isolated from the Chinese herb Coptis chinensis and other Berberis plants, has a wide range of pharmacological properties. Berberine can be used to treat many diseases, such as cancer and digestive, metabolic, cardiovascular, and neurological diseases. Berberine has protective capacities in digestive diseases. It can inhibit toxins and bacteria, including Helicobacter pylori, protect the intestinal epithelial barrier from injury, and ameliorate liver injury. Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis. Recent evidence has confirmed that berberine improves the efficacy and safety of chemoradiotherapies. In addition, berberine regulates glycometabolism and lipid metabolism, improves energy expenditure, reduces body weight, and alleviates nonalcoholic fatty liver disease. Berberine also improves cardiovascular hemodynamics, suppresses ischemic arrhythmias, attenuates the development of atherosclerosis, and reduces hypertension. Berberine shows potent neuroprotective effects, including antioxidative, antiapoptotic, and anti-ischemic. Furthermore, berberine exerts protective effects against other diseases. The mechanisms of its functions have been extensively explored, but much remains to be clarified. This article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive, metabolic, cardiovascular, and neurological diseases.

Keywords berberine      Coptis chinensis      pharmacological properties      mechanism      clinical applications     
Corresponding Author(s): Jianyu Hao,Daiming Fan   
Just Accepted Date: 17 January 2020   Online First Date: 27 April 2020    Issue Date: 12 October 2020
 Cite this article:   
Danyang Song,Jianyu Hao,Daiming Fan. Biological properties and clinical applications of berberine[J]. Front. Med., 2020, 14(5): 564-582.
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http://journal.hep.com.cn/fmd/EN/10.1007/s11684-019-0724-6
http://journal.hep.com.cn/fmd/EN/Y2020/V14/I5/564
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Fig.1  Chemical structure of berberine.
Fig.2  Major diseases affected by berberine.
Fig.3  Effects of berberine on intestinal injury.
Fig.4  Effects of berberine on liver injury.
Fig.5  Effects of berberine on Helicobacter pylori.
Fig.6  Effects of berberine on cancer proliferation, invasion, and metastasis.
Origin Cell line Effect of berberine Mechanism Experiment model Year Authors
Human leukemia HL-60 Antiproliferation, induces apoptosis and cell cycle arrest Complexes with DNA In vitro 1995 Kuo et al. [42]
Human leukemia HL-60 Antiproliferation, induces apoptosis Downregulates nucleophosmin/B23 and telomerase activity In vitro 1999 Wu et al. [50]
Human leukemia U937 Antiproliferation Inhibits telomerase activity In vitro 1999 Wu et al. [50]
Oral cancer OC2, KB Antiproliferation Reduces AP-1 expression, inhibits COX-2 protein In vitro and In vitro 2004 Kuo et al. [61]
Human breast cancer MCF-7 Antiproliferation, induces apoptosis and G0/G1 arrest Upregulates interferon-β and TNF-α In vitro 2005 Kang et al. [46]
Human hepatoma HepG2 Antiproliferation, induces apoptosis Activates caspases 8, caspases 3 and PARP In vitro 2006 Hwang [54]
Human epidermoid carcinoma A431 Antiproliferation, induces G1 arrest and apoptosis Upregulates Cip/p21 and Kip/p27 protein, disrupts mitochondrial membrane potential, activates caspase 3 and PARP In vitro 2006 Mantena et al. [44]
Human oral squamous carcinoma cancer HSC-3 Antiproliferation, induces cell cycle arrest and apoptosis Induces ROS and Ca 21 production, suppresses the levels of mitochondrial membrane potential (MMP) In vitro 2007 Lin et al. [45]
Human colonic carcinoma SW620 Antiproliferation, induces apoptosis Generates reactive oxygen species
and activates JNK/p38 MAPK and FasL
In vitro 2007 Hsu et al. [59]
Non-small cell lung cancer A549 Induce autophagy, enhances radio-sensitivity Induces autophagy In vitro and In vitro 2008 Peng et al. [49]
Human leukemia Jurkat Antiproliferation, induces apoptosis Modifies cysteine 179 of IkBa kinase, suppresses nuclear factor-kB–regulated antiapoptotic gene products In vitro 2008 Pandey et al. [63]
Acute lymphoblastic leukemia EU-1,Sup-B13 Antiproliferation, induces apoptosis Downregulates DAXX expression and promotes MDM2 degradation In vitro 2010 Zhang et al. [57]
Prostate cancer LNCaP Antiproliferation Suppresses androgen receptor In vitro and In vitro 2011 Li et al. [67]
Human breast cancer MCF7,T47D Antiproliferation Suppresses TPA-induced VEGF and fibronectin In vitro 2013 Kim et al. [69]
Esophageal squamous cell carcinoma ECA109,TE13 Induces autophagy, enhances radio-sensitivity Decreases hypoxic activity In vitro and In vitro (ECA109) 2013 Yang et al. [77]
Human neuroblastoma SK-N-SH,NB-1691 Antiproliferation, induces apoptosis Inhibits the transcription of DAXX In vitro 2013 Li et al. [58]
Human lung adenocarcinoma A549 Induces apoptosis and G0/G1 arrest Induces FOXO3a and p53, activates p38a MAPK In vitro 2014 Zheng et al. [47]
Human ovarian A2780 Sensitizes the effect of cisplatin Downregulates miR-93 and inhibits the PTEN/Akt pathway In vitro 2015 Chen et al. [79]
Human glioblastoma U87, U251 Antiproliferation, induce senescence Downregulates EGFR and inhibits the EGFR–MEK–ERK signaling pathway In vitro and In vitro (U87) 2015 Liu et al. [48]
Colon cancer KM12C Antiproliferation Binds RXRa to suppress b-catenin signaling In vitro and In vitro 2017 Ruan et al. [66]
Diffuse large B cell lymphoma HEK-293T Antiproliferation, impedes mitophagy-dependent necroptosis, induces mitophagy-dependent necroptosis Accelerates PCYT1A mRNA degradation and inhibits the MYC-driven aberration of choline metabolism In vitro and In vitro 2017 Xiong et al. [60]
Ovarian cancer A2780,HO8910 Antiproliferation, increases sensitivity to PARP inhibition, homologous recombination repair Induces oxidative DNA damage and impairs homologous recombination repair In vitro and In vitro (A2780) 2017 Hou et al. [55]
Breast cancer cell MCF-7 Reverses resistance to doxorubincin Inhibits AMPK-HIF-1a In vitro and In vitro 2017 Pan et al. [78]
Colon intestinal IMCE Antitumorigenesis Block IL-6 and TNF-a, inhibits EGFR-ERK signaling In vitro and In vitro 2017 Li et al. [64]
Ovarian cancer SKOV3 Antiproliferation Suppresses the arachidonic acid metabolic pathway and phosphorylation of FAK In vitro 2017 Zhao et al. [82]
Gefitinib-resistant non-small cell lung cancer H1975 Antiproliferation, suppression of lipogenesis Induces reactive oxygen species generation and activates the AMPK pathway In vitro 2018 Fan et al. [81]
Tab.1  Antiproliferation effect of berberine
Origin Cell line Effect of berberine Mechanism Experiment model Year Authors
Lewis lung carcinoma Lewis lung carcinoma Antiproliferation, antimetastasis Represses AP-1 transcriptional activity and u-PA expression In vitro and in vivo 2001 Mitani et al. [80]
Human gastric adenocarcinoma RF-1, RF-48 Antimetastasis Decreases the expression of COX-2, MMP-2, and MMP-9 In vitro 2006 Yu et al. [71]
Human gastric cancer SNU-5 Antimetastasis Downregulates the expression of matrix metalloproteinases-1, -2, and -7 In vitro 2006 Lin et al. [73]
Nasopharyngeal carcinoma 5-8F Anti-invasion Downregulates NM23-H1 expression In vitro and in vivo 2008 Liu et al. [75]
Human tongue squamous cancer SCC-4 Antimetastasis, anti-invasion Inhibits FAK, IKK, NF-kB, u-PA and MMP-2 and MMP-9 In vitro 2009 Ho et al. [62]
Nasopharyngeal carcinoma 5-8F Antimetastasis Inhibits Ezrin phosphorylation In vitro and in vivo 2009 Tang et al. [76]
Human melanoma A375 Antimetastasis Reduces ERK activity and COX-2, induces AMPK activation In vitro 2012 Kim et al. [72]
Non-small cell lung cancer A549 Antiproliferation, antimetastasis Inhibits TGF-b1-induced epithelial-to-mesenchymal transition In vitro and in vivo 2014 Qi et al. [70]
Triple-negative breast cancer MDA-MB231 Anti-invasion Downregulates TGF-b1 In vitro and in vivo 2018 Kim et al. [74]
Tab.2  Anti-invasive and antimetastatic effects of berberine
Fig.7  Effects of berberine on glycometabolism.
Fig.8  Effects of berberine on lipid metabolism, obesity, and nonalcoholic fatty liver disease.
Fig.9  Effects of berberine on cardiovascular diseases.
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