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Promising Anti-atherosclerotic Effect of Berberine: Evidence from In Vitro, In Vivo, and Clinical Studies

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Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 178))

Abstract

Elevated levels of plasma cholesterol, impaired vascular wall, and presence of inflammatory macrophages are important atherogenic risk factors contributing to atherosclerotic plaque formation and progression. The interventions modulating these risk factors have been found to protect against atherosclerosis development and to decrease atherosclerosis-related cardiovascular disorders. Nutritional approaches involving supplements followed by improving dietary habits and lifestyle have become growingly attractive and acceptable methods used to control atherosclerosis risk factors, mainly high levels of plasma cholesterol. There are a large number of studies that show berberine, a plant bioactive compound, could ameliorate atherosclerosis-related risk factors. In the present literature review, we put together this studies and provide integrated evidence that exhibits berberine has the potential atheroprotective effect through reducing increased levels of plasma cholesterol, particularly low-density lipoprotein (LDL) cholesterol (LDL-C) via LDL receptor (LDLR)-dependent and LDL receptor-independent mechanisms, inhibiting migration and inflammatory activity of macrophages, improving the functionality of endothelial cells via anti-oxidant activities, and suppressing proliferation of vascular smooth muscle cells. In conclusion, berberine can exert inhibitory effects on the atherosclerotic plaque development mainly through LDL-lowering activity and suppressing atherogenic functions of mentioned cells. As the second achievement of this review, among the signaling pathways through which berberine regulates intracellular processes, AMP-activated protein kinase (AMPK) has a central and critical role, showing that enhancing activity of AMPK pathway can be considered as a promising therapeutic approach for atherosclerosis treatment.

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Abbreviations

3′-UTR:

3′-untranslated region

ABCA1:

ATP-binding membrane cassette transport protein A1

AMP:

Adenosine monophosphate

AMPK:

AMP-activated protein kinase

EMMPRIN:

Exhibited a decreased expression of MMPs and extracellular MMP inducer

eNOS:

endothelial nitric oxide synthase

ERK:

Extracellular receptor-activated kinase

HMG-CoA:

3-hydroxy-3-methyl-glutaryl-coenzyme A

HNF1α:

hepatocytes nuclear factor 1α

HUVECs:

Human umbilical vein endothelial cells

IL-6:

Interleukin 6

JNK:

c-Jun N-terminal kinase

LDL:

Low-density lipoprotein

LDL-C:

LDL cholesterol

LDLR:

LDL receptor

LOX 1:

Low-density lipoprotein receptor 1

LXRα:

Liver X receptor α

lysoPC:

Lysophosphatidylcholine

MAP:

Mitogen-activated protein

MCP-1:

Monocyte chemoattractant protein-1

MIP-1α:

Macrophage inflammatory Protein 1 alpha

MMPs:

Matrix metalloproteinases

NADPH:

Nicotinamide adenine dinucleotide phosphate

NAFLD:

Non-alcohol fatty liver disease

NOD:

Nonobese diabetic

PCSK9:

Proprotein convertase subtilisin kexin 9

PCSK9:

Proprotein convertase subtilisin/kexin type 9

ROS:

Reactive oxygen species

SR-BI:

Scavenger receptor class B type I

SREBP2:

sterol regulatory element-binding protein 2

TG:

Triglyceride

VCAM-1:

Vascular cell adhesion molecule-1

VSMCs:

Vascular smooth muscle cells

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Acknowledgments

The authors appreciate the cooperation of Departments of Medical Immunology and Medical Biotechnology of Mashhad University of Medical Sciences.

Conflicts of Interest

The authors declare that there are no conflicts of interest and financial support for the present review article.

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Authors and Affiliations

  1. Department of Cardiology, Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Alireza Fatahian

  2. Department of Medical Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Saeed Mohammadian Haftcheshmeh

  3. Department of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, Iran

    Sara Azhdari

  4. Department of Horticulture, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran

    Helaleh Kaboli Farshchi

  5. Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran

    Banafsheh Nikfar

  6. Halal research center of IRI, FDA, Tehran, Iran

    Amir Abbas Momtazi-Borojeni

  7. Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Abbas Momtazi-Borojeni

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  1. Alireza Fatahian
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  2. Saeed Mohammadian Haftcheshmeh
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  3. Sara Azhdari
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  4. Helaleh Kaboli Farshchi
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  5. Banafsheh Nikfar
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  6. Amir Abbas Momtazi-Borojeni
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Correspondence to Banafsheh Nikfar or Amir Abbas Momtazi-Borojeni .

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  1. Department of Biology, University of Copenhagen, Copenhagen, Denmark

    Stine Helene Falsig Pedersen

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Fatahian, A., Haftcheshmeh, S.M., Azhdari, S., Farshchi, H.K., Nikfar, B., Momtazi-Borojeni, A.A. (2020). Promising Anti-atherosclerotic Effect of Berberine: Evidence from In Vitro, In Vivo, and Clinical Studies. In: Pedersen, S.H.F. (eds) Reviews of Physiology, Biochemistry and Pharmacology . Reviews of Physiology, Biochemistry and Pharmacology, vol 178. Springer, Cham. https://doi.org/10.1007/112_2020_42

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