The Effective Role of Natural Product Berberine in Modulating Oxidative Stress and Inflammation Related Atherosclerosis: Novel Insights Into the Gut-Heart Axis Evidenced by Genetic Sequencing Analysis.

Zhen Feng,Yifan Liu,Richard Y Cao,Ying Zhang,Hongchao Zheng,Siyu Liu,Jian Yang

doi:10.3389/fphar.2021.764994

Abstract

The exacerbation of oxidative and inflammatory reactions has been involved in atherosclerotic cardiovascular diseases leading to morbidity and mortality worldwide. Discovering the underlying mechanisms and finding optimized curative approaches to control the global prevalence of cardiovascular diseases is needed. Growing evidence has demonstrated that gut microbiota is associated with the development of atherosclerosis, while berberine, a natural product exhibits antiatherogenic effects in clinical and pre-clinical studies, which implies a potential link between berberine and gut microbiota. In light of these novel discoveries, evidence of the role of berberine in modulating atherosclerosis with a specific focus on its interaction with gut microbiota is collected. This review synthesizes and summarizes antioxidant and anti-inflammatory effects of berberine on combating atherosclerosis experimentally and clinically, explores the interaction between berberine and intestinal microbiota comprehensively, and provides novel insights of berberine in managing atherosclerotic cardiovascular diseases via targeting the gut-heart axis mechanistically. The phenomenon of how berberine overcomes its weakness of poor bioavailability to conduct its antiatherogenic properties is also discussed and interpreted in this article. An in-depth understanding of this emerging area may contribute to identifying therapeutic potentials of medicinal plant and natural product derived pharmaceuticals for the prevention and treatment of atherosclerotic cardiovascular diseases in the future.

Highlights

Medicinal plant-derived traditional Chinese medicines have recently received a lot more recognition likely as a result of the Nobel Prize winning discovery of natural product artemisinin
Focusing on the role of berberine in modulating oxidative stress and inflammation related atherosclerosis in this review article, we have identified that berberine ameliorates doxorubicin-induced cardiotoxicity through Sirtuin1/p66shc pathways, activates peroxisome proliferator-activated receptor gamma (PPARc) to increase atherosclerotic plaque stability, meliorates obesity via downregulating lncRNA Gomafu and modulating UCP1/AMPK/PGC1α signaling pathways, reduces cardiac fibrosis via inhibiting insulin-like growth factor 1 receptor (IGF-1R)/matrix metalloproteinase (MMP)-2/MMP-9 pathways, protects cardiac injury by downregulating the expression of inflammatory cytokines including IL-6, tumor necrosis factor (TNF)-α, IL-10 and IL17A via p38 mitogen-activated protein kinase (MAPK)-mediated nuclear factor-κB (NF-κB) molecular pathways, decreases atherogenesis via activating AMPK/UCP2 signaling pathways, and inhibits atherosclerosis through regulating phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) molecular pathways
The beneficial impact of berberine on atherosclerotic cardiovascular diseases (CVD) via modulating oxidative stress and inflammation is confirmed, and the interplay between berberine and gut microbiota at least partially unravels the phenomenon of how berberine overcomes its weakness of poor bioavailability after oral administration

Summary

Introduction

Medicinal plant-derived traditional Chinese medicines have recently received a lot more recognition likely as a result of the Nobel Prize winning discovery of natural product artemisinin. Berberine was discovered to reduce oxidative stress and vascular inflammation related atherogenesis via activating AMPK/UCP2 signaling pathways in a mouse model of atherosclerosis and cultured human umbilical vein endothelial cells (Wang et al, 2011).

Results

Conclusion