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

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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Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles

Particle and Fibre Toxicology ◽

10.1186/s12989-019-0332-2 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 15

Author(s):

Zhangjian Chen ◽

Di Zhou ◽

Shuo Han ◽

Shupei Zhou ◽

Guang Jia

Keyword(s):

Titanium Dioxide ◽

Gut Microbiota ◽

Titanium Dioxide Nanoparticles ◽

Oral Exposure ◽

Sequencing Analysis ◽

Dependent Manner ◽

Indirect Pathway ◽

Rdna Sequencing ◽

Underlying Mechanisms

Abstract Background Due to its excellent physicochemical properties and wide applications in consumer goods, titanium dioxide nanoparticles (TiO2 NPs) have been increasingly exposed to the environment and the public. However, the health effects of oral exposure of TiO2 NPs are still controversial. This study aimed to illustrate the hepatotoxicity induced by TiO2 NPs and the underlying mechanisms. Rats were administered with TiO2 NPs (29 nm) orally at exposure doses of 0, 2, 10, 50 mg/kg daily for 90 days. Changes in the gut microbiota and hepatic metabolomics were analyzed to explore the role of the gut-liver axis in the hepatotoxicity induced by TiO2 NPs. Results TiO2 NPs caused slight hepatotoxicity, including clear mitochondrial swelling, after subchronic oral exposure at 50 mg/kg. Liver metabolomics analysis showed that 29 metabolites and two metabolic pathways changed significantly in exposed rats. Glutamate, glutamine, and glutathione were the key metabolites leading the generation of energy-related metabolic disorders and imbalance of oxidation/antioxidation. 16S rDNA sequencing analysis showed that the diversity of gut microbiota in rats increased in a dose-dependent manner. The abundance of Lactobacillus_reuteri increased and the abundance of Romboutsia decreased significantly in feces of TiO2 NPs-exposed rats, leading to changes of metabolic function of gut microbiota. Lipopolysaccharides (LPS) produced by gut microbiota increased significantly, which may be a key factor in the subsequent liver effects. Conclusions TiO2 NPs could induce slight hepatotoxicity at dose of 50 mg/kg after long-term oral exposure. The indirect pathway of the gut-liver axis, linking liver metabolism and gut microbiota, played an important role in the underlying mechanisms.

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The Emerging Role of Gut Microbiota in Cardiovascular Diseases

Indian Heart Journal ◽

10.1016/j.ihj.2021.04.008 ◽

2021 ◽

Author(s):

Dilip Kumar ◽

Sanjeev S. Mukherjee ◽

Rabin Chakraborty ◽

Rana Rathod Roy ◽

Arindam Pandey ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Gut Microbiota

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MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

Acta Endocrinologica ◽

10.1530/eje-14-0874 ◽

2015 ◽

Vol 172 (4) ◽

pp. R167-R177 ◽

Cited By ~ 77

Author(s):

Kristine H Allin ◽

Trine Nielsen ◽

Oluf Pedersen

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Short Chain Fatty Acids ◽

Intestinal Content ◽

Low Grade ◽

Bacterial Fermentation ◽

Underlying Mechanisms

Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gut microbiota in the pathophysiology and pathogenesis of type 2 diabetes.

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Neuroprotective Effects ofClostridium butyricumagainst Vascular Dementia in Mice via Metabolic Butyrate

BioMed Research International ◽

10.1155/2015/412946 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 51

Author(s):

Jiaming Liu ◽

Jing Sun ◽

Fangyan Wang ◽

Xichong Yu ◽

Zongxin Ling ◽

...

Keyword(s):

Gut Microbiota ◽

Vascular Dementia ◽

Morphological Examination ◽

Neuroprotective Effects ◽

Akt Phosphorylation ◽

Underlying Mechanisms ◽

Related Proteins ◽

Common Carotid Arteries ◽

Hematoxylin Eosin

Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms ofClostridium butyricum. Following rUCCAO,C. butyricumwas intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed thatC. butyricumsignificantly attenuated the cognitive dysfunction and histopathological changes in VaD mice.C. butyricumnot only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover,C. butyricumcould regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest thatC. butyricummight be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.

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The role of influenza vaccination in the prevention of pulmonary and cardiovascular diseases

Russian Military Medical Academy Reports ◽

10.17816/rmmar76445 ◽

2021 ◽

Vol 40 (3) ◽

pp. 63-67

Author(s):

Andrey V. Vasin

Keyword(s):

Cardiovascular Diseases ◽

Influenza Vaccination ◽

Research Data ◽

Influenza Vaccines ◽

World Health ◽

Acute Respiratory Disease ◽

Effective Role ◽

Cardiovascular Pathologies ◽

Health Organization

Influenza is an acute respiratory disease that causes annual epidemics and periodic pandemics with high mortality. It is characterized by the development of severe complications, the main of which are pulmonary and cardiovascular ones. The only effective method of preventing influenza, and therefore the influenza-associated complications, is vaccination, which is carried out annually on the basis of World Health Organization influenza vaccines composition recommendations. This article provides the review of the research data confirming the effective role of influenza vaccination in the prevention of pulmonary and cardiovascular pathologies (bibliography: 12 refs).

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Implication of Gut Microbiota in Cardiovascular Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5394096 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Wenyi Zhou ◽

Yiyu Cheng ◽

Ping Zhu ◽

M. I. Nasser ◽

Xueyan Zhang ◽

...

Keyword(s):

Cell Death ◽

Cardiovascular Diseases ◽

Programmed Cell Death ◽

Gut Microbiota ◽

Intestinal Flora ◽

Short Chain Fatty Acids ◽

Secondary Bile Acid ◽

Cardiac Disorders ◽

The Relationship

Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.

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Pivotal Role Of The Interaction Between Herbal Medicines And Gut Microbiota On Disease Treatment

Current Drug Targets ◽

10.2174/1389450121666200324151530 ◽

2020 ◽

Vol 21 ◽

Cited By ~ 1

Author(s):

Tingting Zhao ◽

Zhe Wang ◽

Zhilong Liu ◽

Youhua Xu

Keyword(s):

Cardiovascular Diseases ◽

Gut Microbiota ◽

Neurodegenerative Diseases ◽

Disease Progression ◽

Herbal Medicines ◽

Underlying Mechanism ◽

Disease Treatment ◽

Endocrine Diseases ◽

Health And Disease

: With the recognition of the important role of gut microbiota in both health and disease progression, attempts to modulate its composition as well as its co-metabolism with the organism have attracted special attention. Abundant studies have demonstrated that dysfunction or imbalance of gut microbiota is closely with disease including endocrine diseases, neurodegenerative diseases, tumors, cardiovascular diseases, et al. Herbal medicines have been applied for preventing and treating disease worldwide for hundreds of years. Although the underlying mechanism seems to be complex, one of the important one is through modulating gut microbiota. In this review, co-metabolism between herbal medicines and microbiota, as well as the potential pathways are summarized from most recent published papers.

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Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications

Current Neuropharmacology ◽

10.2174/1570159x19666210629145351 ◽

2021 ◽

Vol 19 ◽

Author(s):

Xu Wang ◽

Zhen Liang ◽

Shengnan Wang ◽

Di Ma ◽

Mingqin Zhu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Gut Microbiota ◽

Demyelinating Disease ◽

Inflammatory Diseases ◽

Intestinal Barrier ◽

Autoimmune Response ◽

Therapeutic Implications ◽

The Central Nervous System ◽

Underlying Mechanisms

: The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on the gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota has also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.

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