Biological properties and clinical applications of berberine

doi:10.1007/s11684-019-0724-6

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 Fan^1,²(

)

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.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-019-0724-6
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I5/564

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]
		Antiproliferation, induces G₁ arrest and apoptosis		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

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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