Research

Jump to: Review

19 pages, 3549 KiB

Open AccessArticle

Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice

by Alejandro Sánchez-Melgar, Pedro J. Izquierdo-Ramírez, Christian Griñán-Ferré, Mercè Pallàs, Mairena Martín and José Luis Albasanz

Int. J. Mol. Sci. 2022, 23(14), 7580; https://doi.org/10.3390/ijms23147580 - 08 Jul 2022

Cited by 6 | Viewed by 2045

Abstract

Cholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism [...] Read more.

Cholesterol metabolism seems dysregulated and linked to amyloid-β (Aβ) formation in neurodegeneration, but the underlying mechanisms are poorly known. Resveratrol (RSV) is a polyphenol with antioxidant activity and neuroprotective properties. Here, we analyzed the effect of age and RSV supplementation on cholesterol metabolism in the brain and blood serum, and its potential link to Aβ processing, in SAMP8 mice—an animal model of aging and Alzheimer’s disease. In the brain, our results revealed an age-related increase in ApoE and unesterified cholesterol in the plasma membrane whereas LDL receptor, HMG-CoA reductase, HMG-CoA-C1 synthase, and ABCA1 transporter remained unaltered. Furthermore, BACE-1 and APP gene expression was decreased. This dysregulation could be involved in the amyloidogenic processing pathway of APP towards Aβ formation. In turn, RSV exhibited an age-dependent effect. While levels of unesterified cholesterol in the plasma membrane were not affected by RSV, several participants in cholesterol uptake, release, and de novo synthesis differed, depending on age. Thus, RSV supplementation exhibited a different neuroprotective effect acting on Aβ processing or cholesterol metabolism in the brain at earlier or later ages, respectively. In blood serum, HDL lipoprotein and free cholesterol were increased by age, whereas VLDL and LDL lipoproteins remained unaltered. Again, the protective effect of RSV by decreasing the LDL or increasing the HDL levels also seems to depend on the intervention’s moment. In conclusion, age is a prominent factor for cholesterol metabolism dysregulation in the brain of SAMP8 mice and influences the protective effects of RSV through cholesterol metabolism and Aβ processing. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Graphical abstract

13 pages, 3239 KiB

Open AccessArticle

Resveratrol Attenuates the Proliferation of Prostatic Stromal Cells in Benign Prostatic Hyperplasia by Regulating Cell Cycle Progression, Apoptosis, Signaling Pathways, BPH Markers, and NF-κB Activity

by Jowon Jang, Junhui Song, Jiyun Lee, Sung-Kwon Moon and Bokyung Moon

Int. J. Mol. Sci. 2021, 22(11), 5969; https://doi.org/10.3390/ijms22115969 - 31 May 2021

Cited by 4 | Viewed by 3195

Abstract

Resveratrol can inhibit cell proliferation and metastasis and induce apoptosis. However, the mechanisms of action through which resveratrol inhibits the abnormal proliferation of prostate stromal cells, causing prostatic hyperplasia, have not been fully elucidated. Here, we evaluated the inhibitory effects of resveratrol on [...] Read more.

Resveratrol can inhibit cell proliferation and metastasis and induce apoptosis. However, the mechanisms of action through which resveratrol inhibits the abnormal proliferation of prostate stromal cells, causing prostatic hyperplasia, have not been fully elucidated. Here, we evaluated the inhibitory effects of resveratrol on cell proliferation associated with prostatic hyperplasia using WPMY-1 cells. Our results showed that resveratrol inhibited the proliferation of WPMY-1 cells via the induction of G₀/G₁-phase cell cycle arrest, which was caused by downregulated expression of cyclins and cyclin-dependent kinases regulated by increased p21WAF1 and p27KIP1 expression level. In addition, resveratrol treatment suppressed the phosphorylation of phosphatidylinositol 3-kinase/AKT and extracellular signal-regulated kinase 1/2. The expression levels of molecular markers affecting prostate development were also reduced by treatment with resveratrol. Finally, resveratrol attenuated the binding activity of the transcription factor nuclear factor-κB in WPMY-1 cells, and accelerated apoptotic cell death via intrinsic cascade pathway. These results indicate that resveratrol may be useful for the prevention or treatment of prostatic hyperplasia. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Graphical abstract

23 pages, 9931 KiB

Open AccessArticle

Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota

by Jin-Xian Liao, Yu-Wei Chen, Ming-Kuei Shih, You-Lin Tain, Yao-Tsung Yeh, Min-Hsi Chiu, Sam K. C. Chang and Chih-Yao Hou

Int. J. Mol. Sci. 2021, 22(10), 5273; https://doi.org/10.3390/ijms22105273 - 17 May 2021

Cited by 22 | Viewed by 3573

Abstract

Resveratrol can affect the physiology or biochemistry of offspring in the maternal–fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring [...] Read more.

Resveratrol can affect the physiology or biochemistry of offspring in the maternal–fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4–8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut–liver axis in the offspring. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Figure 1

16 pages, 12857 KiB

Open AccessArticle

Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties

by Jelica Grujić-Milanović, Vesna Jaćević, Zoran Miloradović, Djurdjica Jovović, Ivica Milosavljević, Sladjan D. Milanović and Nevena Mihailović-Stanojević

Int. J. Mol. Sci. 2021, 22(9), 5006; https://doi.org/10.3390/ijms22095006 - 08 May 2021

Cited by 18 | Viewed by 2667

Abstract

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed [...] Read more.

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Figure 1

Review

Jump to: Research

22 pages, 889 KiB

Open AccessReview

The Effect of Resveratrol on the Cardiovascular System from Molecular Mechanisms to Clinical Results

by Roland Gal, Laszlo Deres, Kalman Toth, Robert Halmosi and Tamas Habon

Int. J. Mol. Sci. 2021, 22(18), 10152; https://doi.org/10.3390/ijms221810152 - 21 Sep 2021

Cited by 38 | Viewed by 6396

Abstract

Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects of natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies of RES have focused on its favorable effects on pathological conditions related to cardiovascular diseases [...] Read more.

Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects of natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies of RES have focused on its favorable effects on pathological conditions related to cardiovascular diseases and their risk factors. The aim of this review was to summarize the wide beneficial effects of resveratrol on the cardiovascular system, including signal transduction pathways of cell longevity, energy metabolism of cardiomyocytes or cardiac remodeling, and its anti-inflammatory and antioxidant properties. In addition, this paper discusses the significant preclinical and human clinical trials of recent years with resveratrol on cardiovascular system. Finally, we present a short overview of antiviral and anti-inflammatory properties and possible future perspectives on RES against COVID-19 in cardiovascular diseases. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Figure 1

18 pages, 711 KiB

Open AccessReview

The Clinical Significance of Drug–Food Interactions of Direct Oral Anticoagulants

by Grzegorz Grześk, Daniel Rogowicz, Łukasz Wołowiec, Agnieszka Ratajczak, Wojciech Gilewski, Małgorzata Chudzińska, Anna Sinkiewicz and Joanna Banach

Int. J. Mol. Sci. 2021, 22(16), 8531; https://doi.org/10.3390/ijms22168531 - 08 Aug 2021

Cited by 23 | Viewed by 7111

Abstract

Cardiovascular diseases are the most common cause of death in the world. For almost 60 years, vitamin K antagonists (VKAs) were the mainstay of anticoagulation therapy, but in recent years direct oral anticoagulants (DOACs) have become the anticoagulant treatment of choice. DOACs were [...] Read more.

Cardiovascular diseases are the most common cause of death in the world. For almost 60 years, vitamin K antagonists (VKAs) were the mainstay of anticoagulation therapy, but in recent years direct oral anticoagulants (DOACs) have become the anticoagulant treatment of choice. DOACs were initially considered drugs with no significant food interactions; however, clinical observations from daily practice have proved otherwise as interactions with food ingredients have been reported. Food, dietary supplements or herbs may contain substances that, when administered concomitantly with DOACs, can potentially affect the plasma concentration of the drugs. The aim of this paper was to evaluate the clinical significance of drug–food interactions of DOACs, such as dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban. Patients treated with anticoagulants should avoid products containing St. John’s wort and take special care with other food ingredients. As the interest in dietary supplements is on the rise, healthcare providers can contribute to the development of well-designed clinical trials on interactions between DOACs and food, and distribute sufficient knowledge about the proper use of these supplements among patients. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Figure 1

12 pages, 1129 KiB

Open AccessReview

Effects of Maternal Resveratrol Intake on the Metabolic Health of the Offspring

by Purificación Ros, Jesús Argente and Julie A. Chowen

Int. J. Mol. Sci. 2021, 22(9), 4792; https://doi.org/10.3390/ijms22094792 - 30 Apr 2021

Cited by 5 | Viewed by 2833

Abstract

Maternal nutritional imbalances, in addition to maternal overweight and obesity, can result in long-term effects on the metabolic health of the offspring, increasing the risk of common non-communicable disorders such as obesity, diabetes and cardiovascular disease. This increased disease risk may also be [...] Read more.

Maternal nutritional imbalances, in addition to maternal overweight and obesity, can result in long-term effects on the metabolic health of the offspring, increasing the risk of common non-communicable disorders such as obesity, diabetes and cardiovascular disease. This increased disease risk may also be transmitted across generations. Unfortunately, lifestyle interventions have shown reduced compliancy and limited efficacy. Resveratrol is a natural polyphenolic compound reported to have pleiotropic beneficial actions including a possible protective effect against the metabolic programming induced by poor dietary habits during development. However, studies to date are inconclusive regarding the potential metabolic benefits of maternal resveratrol supplementation during pregnancy and lactation on the offspring. Moreover, the responses to metabolic challenges are suggested to be different in males and females, suggesting that the effectiveness of treatment strategies may also differ, but many studies have been performed only in males. Here we review the current evidence, both in humans and animal models, regarding the possible beneficial effects of maternal resveratrol intake on the metabolic health of the offspring and highlight the different effects of resveratrol depending on the maternal diet, as well as the differential responses of males and females. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Figure 1

19 pages, 1205 KiB

Open AccessReview

Resveratrol, Metabolic Dysregulation, and Alzheimer’s Disease: Considerations for Neurogenerative Disease

by Alex J. T. Yang, Ahmed Bagit and Rebecca E. K. MacPherson

Int. J. Mol. Sci. 2021, 22(9), 4628; https://doi.org/10.3390/ijms22094628 - 28 Apr 2021

Cited by 36 | Viewed by 5962

Abstract

Alzheimer’s disease (AD) has traditionally been discussed as a disease where serious cognitive decline is a result of Aβ-plaque accumulation, tau tangle formation, and neurodegeneration. Recently, it has been shown that metabolic dysregulation observed with insulin resistance and type-2 diabetes actively [...] Read more.

Alzheimer’s disease (AD) has traditionally been discussed as a disease where serious cognitive decline is a result of Aβ-plaque accumulation, tau tangle formation, and neurodegeneration. Recently, it has been shown that metabolic dysregulation observed with insulin resistance and type-2 diabetes actively contributes to the progression of AD. One of the pathologies linking metabolic disease to AD is the release of inflammatory cytokines that contribute to the development of brain neuroinflammation and mitochondrial dysfunction, ultimately resulting in amyloid-beta peptide production and accumulation. Improving these metabolic impairments has been shown to be effective at reducing AD progression and improving cognitive function. The polyphenol resveratrol (RSV) improves peripheral metabolic disorders and may provide similar benefits centrally in the brain. RSV reduces inflammatory cytokine release, improves mitochondrial energetic function, and improves Aβ-peptide clearance by activating SIRT1 and AMPK. RSV has also been linked to improved cognitive function; however, the mechanisms of action are less defined. However, there is evidence to suggest that chronic RSV-driven AMPK activation may be detrimental to synaptic function and growth, which would directly impact cognition. This review will discuss the benefits and adverse effects of RSV on the brain, highlighting the major signaling pathways and some of the gaps surrounding the use of RSV as a treatment for AD. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Figure 1

18 pages, 721 KiB

Open AccessReview

Preventive Aspects of Early Resveratrol Supplementation in Cardiovascular and Kidney Disease of Developmental Origins

by Chien-Ning Hsu, Chih-Yao Hou and You-Lin Tain

Int. J. Mol. Sci. 2021, 22(8), 4210; https://doi.org/10.3390/ijms22084210 - 19 Apr 2021

Cited by 20 | Viewed by 3073

Abstract

The increase in the incidence of cardiovascular diseases (CVDs) and kidney disease has stimulated research for strategies that could prevent, rather than just treat, both interconnected disorders. Resveratrol, a polyphenolic compound with pleiotropic biofunctions, has shown health benefits. Emerging epidemiological data supports that [...] Read more.

The increase in the incidence of cardiovascular diseases (CVDs) and kidney disease has stimulated research for strategies that could prevent, rather than just treat, both interconnected disorders. Resveratrol, a polyphenolic compound with pleiotropic biofunctions, has shown health benefits. Emerging epidemiological data supports that early life environmental insults are regarded as increased risks of developing CVDs and kidney disease in adulthood. Conversely, both disorders could be reversed or postponed by shifting interventions from adulthood to earlier stage by so-called reprogramming. The purpose of this review is first to highlight current epidemiological studies linking cardiovascular and renal programming to resulting CVD and kidney disease of developmental origins. This will be followed by a summary of how resveratrol could exert a positive influence on CVDs and kidney disease. This review also presents an overview of the evidence documenting resveratrol as a reprogramming agent to protect against CVD and kidney disease of developmental origins from animal studies and to outline the advances in understanding the underlying molecular mechanisms. Overall, this review reveals the need for future research to further clarify the reprogramming effects of resveratrol before clinical translation. Full article

(This article belongs to the Special Issue Health Benefits of Resveratrol 3.0)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Health Benefits of Resveratrol 3.0

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issues

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI