A New Therapeutic Candidate for Cardiovascular Diseases: Berberine

Cai, Yun; Xin, Qiqi; Lu, Jinjin; Ming, Yu; Lin, Qian; Cong, Weihong; Chen, Ke-ji

doi:10.3389/fphar.2021.631100

Cited by 47 publications

(37 citation statements)

References 111 publications

(139 reference statements)

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“…BBR has a wide range of pharmacological and therapeutic effects, and BBR has been widely used for its antimicrobial and antiprotozoal activities ( 2 ). Recently, as research continues, BBR has also been found to play a role in mood disorders ( 3 ), high blood pressure ( 4 ), hypercholesterolemia ( 5 ), hyperlipidemia ( 5 ), diabetes ( 6 ), heart failure ( 7 ), colorectal cancer ( 8 ), and other diseases. Because of its many effects, BBR is as commonly used as are aspirin and metformin.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m6A Methylation

Zhao

Zeng

Guo³

et al. 2021

Front. Oncol.

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BackgroundCancer stem cells (CSCs) are able to survive after cancer therapies, resulting in tumor progression and recurrence, as is seen in colorectal cancer. Therapies targeting CSCs are regarded as novel and promising strategies for efficiently eradicating tumors. Berberine, an isoquinoline alkaloid extracted from the Chinese herbal medicine Coptis chinensis, was found to have antitumor activities against colorectal cancer, without knowing whether it exerts inhibitory effects on colorectal CSCs and the potential mechanisms.MethodsIn this study, we examined the inhibitory roles of Berberine on CSCs derived from HCT116 and HT29 by culturing in serum-free medium. We also examined the effects of Berberine on m6A methylation via regulating fat mass and obesity-associated protein (FTO), by downregulating β-catenin.ResultsWe examined the effects of Berberine on the tumorigenicity, growth, and stemness of colorectal cancer stem-like cells. The regulatory effect of Berberine on N6-methyladenosine (m6A), an abundant mRNA modification, was also examined. Berberine treatment decreased cell proliferation by decreasing cyclin D1 and increasing p27 and p21 and subsequently induced cell cycle arrest at the G1/G0 phase. Berberine treatment also decreased colony formation and induced apoptosis. Berberine treatment transcriptionally increased FTO and thus decreased m6A methylation, which was reversed by both FTO knockdown and the addition of the FTO inhibitor FB23-2. Berberine induced FTO-related decreases in stemness in HCT116 and HT29 CSCs. Berberine treatment also increased chemosensitivity in CSCs and promoted chemotherapy agent-induced apoptosis. Moreover, we also found that Berberine treatment increased FTO by decreasing β-catenin, which is a negative regulator of FTO.ConclusionsOur observation that Berberine effectively decreased m6A methylation by decreasing β-catenin and subsequently increased FTO suggests a role of Berberine in modulating stemness and malignant behaviors in colorectal CSCs.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m6A Methylation

Zhao

Zeng

Guo³

et al. 2021

Front. Oncol.

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“…It has been reported that probiotics can influence the lipid metabolism and effectively alleviate atherosclerosis by means of regulating gut microbiota to reduce TMAO ( Liang et al, 2020 ). As a promising therapeutic candidate for CVD, performing in a somewhat similar way like probiotics but not like antibiotics, berberine has exhibited its pharmacological effects on modulating dysmetabolism and atherosclerosis experimentally and clinically though its poor bioavailability is also perceived ( Liu et al, 2016 ; Cao and Su, 2019 ; Cai et al, 2021 ). The possible explanation is that berberine displays its antiatherogenic properties via the active interaction with gut microbiota.…”

Section: The Interaction Between Berberine and Intestinal Microbiotamentioning

confidence: 99%

“…Berberine has been recognized as a pivotal therapeutic candidate for CVD because of its pleiotropic effects on modulating oxidative stress and inflammation related atherosclerosis ( Cai et al, 2021 ). It has been proved that berberine interrupts atherosclerosis via manipulating gut microbiota compositions and functional metabolites ( Wang et al, 2017 ; Agus et al, 2021 ), and meanwhile gut microbiota transforms berberine into intestinal absorbable form ( Feng et al, 2015 ; Feng et al, 2018b ).…”

Section: Insights Of Berberine Into the Gut-heart Axismentioning

confidence: 99%

“…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. In recent years, emerging evidence has demonstrated that natural product berberine, an alkaloid from Chinese herb Coptis chinensis ( Figure 1 ), exhibits a broad spectrum of biological activities in the prevention and treatment of cardiovascular diseases (CVD) ( Cai et al, 2021 ). Nevertheless, the regulatory mechanisms of berberine involving CVD, especially how berberine influences CVD risk factor atherosclerosis, remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2021

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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.

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“…In recent years, the role of BBR in the prevention and treatment of ASCVD is drawing increasing attention ( Cai et al, 2021 ). In the present study, we found that BBR treatment lowered the blood pressure and ameliorated the vascular dysfunction and pathological remodeling in the Ang II-induced mice.…”

Section: Discussionmentioning

confidence: 99%

Berberine Improves Vascular Dysfunction by Inhibiting Trimethylamine-N-oxide via Regulating the Gut Microbiota in Angiotensin II-Induced Hypertensive Mice

Wang

Zhou

et al. 2022

Front. Microbiol.

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Berberine (BBR) has been demonstrated to exert cardiovascular protective effects by regulating gut microbiota. However, few studies examine the effect of BBR on the gut microbiota in hypertension. This study aims to investigate the role of BBR in regulating microbial alterations and vascular function in hypertension. C57BL/6 J mice were infused with Ang II (0.8 mg/kg/day) via osmotic minipumps and treated with BBR (150 mg/kg/day) or choline (1%) for 4 weeks. Blood pressure was detected by tail-cuff measurement once a week. Abdominal aorta pulse wave velocity (PWV) and endothelium dependent vasodilatation were measured to evaluate vascular function. Vascular remodeling was assessed by histological staining of aortic tissue. The fecal microbiota was profiled using 16S ribosomal DNA (rDNA) sequencing. Plasma trimethylamine (TMA)/trimethylamine-N-oxide (TMAO) and hepatic FMO3 expression were measured. We found that BBR treatment significantly alleviated the elevated blood pressure, vascular dysfunction, and pathological remodeling in Ang II-induced hypertensive mice, while choline treatment aggravated hypertension-related vascular dysfunction. 16S rDNA gene sequencing results showed that BBR treatment altered gut microbiota composition (reduced the Firmicutes/Bacteroidetes (F/B) ratio and increased the abundances of Lactobacillus). Moreover, BBR inhibited FMO3 expression and plasma TMA/TMAO production in hypertensive mice. TMAO treatment increased the apoptosis and oxidative stress of human aortic endothelial cells (HAECs) and aggravated Ang II-induced HAECs dysfunction in vitro. These results indicate that the protective effect of BBR in hypertension might be attributed (at least partially) to the inhibition of TMAO production via regulating the gut microbiota.

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A New Therapeutic Candidate for Cardiovascular Diseases: Berberine

Cited by 47 publications

References 111 publications

RETRACTED: Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m6A Methylation

RETRACTED: Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m6A Methylation

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

Berberine Improves Vascular Dysfunction by Inhibiting Trimethylamine-N-oxide via Regulating the Gut Microbiota in Angiotensin II-Induced Hypertensive Mice

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