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No Beneficial Effects of Resveratrol on the Metabolic Syndrome: A Randomized Placebo-Controlled Clinical Trial.

CONTEXT: Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications. OBJECTIVE: To investigate effects of long-term RSV treatment on inflammation and MetS. SETTING AND DESIGN: A randomized, placebo-controlled, double-blind, parallel group clinical trial conducted at Aarhus University Hospital. PARTICIPANTS: Middle-aged community-dwelling men (N = 74) with MetS, 66 of whom completed all visits (mean ± standard error of

TSC2 N-terminal lysine acetylation status affects to its stability modulating mTORC1 signaling and autophagy.

There is a growing evidence of the role of protein acetylation in different processes controlling metabolism. Sirtuins (histone deacetylases nicotinamide adenine dinucleotide-dependent) activate autophagy playing a protective role in cell homeostasis. This study analyzes tuberous sclerosis complex (TSC2) lysine acetylation, in the regulation of mTORC1 signaling activation, autophagy and cell proliferation. Nicotinamide 5mM (a concentration commonly used to inhibit SIRT1), increased TSC2 acetylation in its N-terminal domain, and concomitantly with an augment in its ubiquitination protein status

Resveratrol Protects against Titanium Particle-Induced Aseptic Loosening Through Reduction of Oxidative Stress and Inactivation of NF-κB.

Aseptic implant loosening is closely associated with chronic inflammation induced by implant wear debris, and reactive oxygen species (ROS) play an important role in this process. Resveratrol, a plant compound, has been reported to act as an antioxidant in many inflammatory conditions; however, its protective effect and mechanism against wear particle-induced oxidative stress remain unknown. In this study, we evaluated resveratrol's protective effects against wear particle-induced oxidative stress in RAW 264.7 macrophages. At non-toxic concentrations, resveratrol showed dose-dependent inhibiti

A combination of pterostilbene with autophagy inhibitors exerts efficient apoptotic characteristics in both chemosensitive and chemoresistant lung cancer cells.

The emergence of multidrug resistance (MDR), meaning that cancer cells develop simultaneous resistance to different drugs, has limited the clinical efficacy and application of chemotherapy. Pterostilbene, a naturally occurring phytoalexin exerts a variety of pharmacologic activities, including cancer prevention, cytotoxicity, and antioxidant activity. In this study, results proved the capability of pterostilbene to effectively inhibit the cell viability of docetaxel-induced MDR human lung cancer cell lines through cell cycle arrest and apoptosis. Meanwhile, the observation of LC3-II production

Resveratrol inhibits IgE-mediated basophilic mast cell degranulation and passive cutaneous anaphylaxis in mice.

Resveratrol is a phytoalexin abundantly found in red grape skin and is effective in antitumor and antiinflammation associated with immune responses. This study investigated whether resveratrol suppressed immunoglobulin (Ig)E-mediated allergic responses and passive cutaneous anaphylaxis (PCA) in rat RBL-2H3 mast cells and in BALB/c mice. The release of β-hexosaminidase and histamine was enhanced in mast cells sensitized with anti-dinitrophenyl (DNP)-IgE and subsequently stimulated by DNP-human serum albumin (HSA), indicative of mast cell degranulation. When mast cells were pretreated with nonto

Activation of peroxisome proliferator-activated receptor-γ coactivator 1α ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury.

Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), affects podocyte damage. Aldosterone-induced injury decreased PGC-1α expression, and induced mitochondrial and podocyte damage in dose- and time-dependent manners. The suppression of endogenous PGC-1α by RNAi caused podocyt

Resveratrol from Dietary Supplement to a Drug Candidate: An Assessment of Potential.

Resveratrol (RVT) is a well known phyto-chemical and is widely used in dietary supplements and botanical products. It shows a wide range of pharmacological/beneficial effects. Therefore, it can be a potential candidate to be developed as phyto-pharmaceutical. Multiple diseases are reported to be treated by the therapeutic effect of RVT since it has antioxidant, anti-cancer activity and anti-inflammatory activities. It also has a major role in diabetes, arthritis, cardiac disorder and platelet aggregation etc. The major requirements are establishments regarding safety, efficacy profile and phys

Resveratrol and Its Role in the Management of B-Cell Malignancies-A Recent Update.

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical studies have indicated its potential for management of B cell malignancies. However, these claims must be substantiated by a greater number of clinical trials in diverse populations, in order to establish its safety and efficacy profile. In addition to this, the

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… In a study conducted by Kobylka et al., modifications at positions 3,4,5 as well as 3′,4′ and 5′ were assessed, indicating improved pharmacological actions of the visualized stilbene derivatives [ 66 ]. … Aza- and Azo-Stilbenes: Bio-Isosteric Analogs of Resveratrol. Molecules. 2020;25:605. doi: 10.3390/molecules25030605. 68. Nam K.Y., Damodar K., Lee Y., Park L.S., Gim J.G., Park J.P., Jeon S.H., Lee J.T. …

Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits.

Polydatin is a natural potent stilbenoid polyphenol and a resveratrol derivative with improved bioavailability. Polydatin possesses potential biological activities predominantly through the modulation of pivotal signaling pathways involved in inflammation, oxidative stress, and apoptosis. Various imperative biological activities have been suggested for polydatin towards promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, anti-microbial, as well as health-promoting roles on the renal system, the respiratory s

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… Determination of stilbenes (trans-astringin, cis-and trans-piceid, and cis-and trans-resveratrol) in Portuguese wines J. Agric. Food Chem. 1999 47 2666 2670 10.1021/jf9900884 10552542 18. Wang D.-G. Liu W.-Y. Chen G.-T. … Effect of powdery mildew on the stilbene content J. Agric. Food Chem. 2001 49 210 215 10.1021/jf000745o 11170579 20. Fakhri S. Gravandi M.M. Abdian S.A.-O. Akkol E.A.-O. Farzaei M.A.-O. Sobarzo-Sánchez E.A.-O. …

Resveratrol Inhibits Growth of Experimental Abdominal Aortic Aneurysm Associated With Upregulation of Angiotensin-Converting Enzyme 2.

OBJECTIVE: Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. APPROACH AND RESULTS: Ace2 deletion in apolipoprotein-deficient mice (ApoE-/-Ace2-/y ) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers. In humans, serum ACE2 activity was negatively associated w

Effects of combining rapamycin and resveratrol on apoptosis and growth of TSC2-deficient xenograft tumors.

Lymphangioleiomyomatosis (LAM) is a rare neoplastic metastatic disease affecting women of childbearing age. LAM is caused by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) as a consequence of tuberous sclerosis complex (TSC) 1/2 inactivation. Clinically, LAM results in cystic lung destruction. mTORC1 inhibition using rapamycin analogs (rapalogs) is partially effective in reducing disease progression and improving lung function. However, cessation of treatment results in continued progression of the disease. In the present study, we investigated the effectiveness of t

Type I interferons directly down-regulate BCL-6 in primary and transformed germinal center B cells: differential regulation in B cell lines derived from endemic or sporadic Burkitt's lymphoma.

Type I interferons (IFN) exert multiple effects on both the innate and adaptive immune system in addition to their antiviral and antiproliferative activities. Little is known, however about the direct effects of type I IFNs on germinal center (GC) B cells, the central components of adaptive B cell responses. We used Burkitt's lymphoma (BL) lines, as a model system of normal human GC B cells, to examine the effect of type I IFNs on the expression of BCL-6, the major regulator of the GC reaction. We show that type I IFNs, but not IFNγ, IL-2 and TNFα rapidly down-regulate BCL-6 protein and mRNA e

Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation.

Autophagy that is induced by starvation or cellular stress can enable cancer cell survival by sustaining energy homeostasis and eliminating damaged organelles and proteins. In response to stress, cancer cells have been reported to accumulate the protein p62/SQSTM1 (p62), but its role in the regulation of autophagy is controversial. Here, we report that the plant phytoalexin resveratrol (RSV) triggers autophagy in imatinib-sensitive and imatinib-resistant chronic myelogenous leukemia (CML) cells via JNK-dependent accumulation of p62. JNK inhibition or p62 knockdown prevented RSV-mediated autoph

Dietary Polyphenols and Their Biological Significance

Dietary polyphenols represent a wide variety of compounds that occur in fruits, vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis, anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. Most of these biological actions have bee

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… Stilbenes Stibenes are structurally characterized by the presence of a 1,2-diphenylethylene nucleus with hydroxyls substitued on the aromatic rings, and exist in the form of monomers or oligomers. The best known compound is trans-resveratrol, possessing a trihydroxystilbene skelelton. … Iinuma M Antibacterial activity of stilbene oligomers against vancomycin-resistant Enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) and their synergism with antibiotics Biocontrol Sci 2007 12 7 14 17408003 10.4265/bio.12.7 175 Furneri P.M. Piperno A. Sajia A. Bisignano G. …

Интерферонские регулятивные факторы как потенциальная терапевтическая цель для нейроинфламмации: фокус на болезни Альцгеймера.

Регулирующие факторы интерферона (ИРФ) являются важнейшими модуляторами иммунной и подстрекательской реакции, однако их роль в болезни Альцгеймера (AD) и других нейродегенеративных расстройствах остается неполной. В то время как IRF признаются за их регулирующие функции в нейроинфламмации, микроглиальной активации и выживании нейронов, их двойная роль как факторов патологического воспаления и посредников нейрозащитных путей подчеркивает сложный нормативный парадокс в нейродегенеративных расстройствах. Цель этого обзора заключается в обобщении текущих данных о нейрофламмации в области АД и связ

Polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9).

BACKGROUND: Abnormalities in lipid and glucose metabolism are constantly observed in type 2 diabetes. However, these abnormalities can be ameliorated by polydatin. Considering the important role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic diseases, we explore the possible mechanism of polydatin on lipid and glucose metabolism through its effects on PCSK9. METHODS: An insulin-resistant HepG2 cell model induced by palmitic acid (PA) and a db/db mice model were used to clarify the role of polydatin on lipid and glucose metabolism. RESULTS: In insulin-resistant HepG2 ce

The expression of sphingosine-1 phosphate receptor-1 in chronic lymphocytic leukemia cells is impaired by tumor microenvironmental signals and enhanced by piceatannol and R406.

Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of clonal B lymphocytes. Proliferation occurs in lymphoid tissues upon interaction of leukemic cells with a supportive microenvironment. Therefore, the mobilization of tissue-resident CLL cells into the circulation is a useful therapeutic strategy to minimize the reservoir of tumor cells within survival niches. Because the exit of normal lymphocytes from lymphoid tissues depends on the presence of sphingosine-1 phosphate (S1P) and the regulated expression of S1P receptor-1 (S1PR1), we investigated whether the e

Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling.

Two different mechanisms are considered to be the primary cause of aging. Cumulative DNA damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Constitutive stimulation of mitogen- and nutrient-sensing mTOR/S6 signaling is the second mechanism (TOR concept). The flow- and laser scanning- cytometric methods were developed to measure the level of the constitutive DNA damage/ROS- as well as of mTOR/S6- signaling in individual cells. Specifically, persistent activation of ATM and expression of γH2AX in untreated cells

Нацеливание на природные полифенолы антиоксидантов в целях защиты от нейроинфламмации и нейродегенеративных заболеваний: всеобъемлющий обзор.

Полифенолы, природные фитонутриенты, встречающиеся в растительных продуктах питания, привлекли значительное внимание к их потенциальному терапевтическому воздействию в неврологических заболеваниях и нейроинфламмации. Эти соединения обладают различными возможностями нейрозащиты, включая антиоксидантные, антивоспалительные и антиамильоидные свойства, которые способствуют смягчению развития таких нейродегенеративных заболеваний, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), деменция, множественный склероз (MS), Строк и болезнь Хантингтона (HD). Полифенолы были тщательно изучены на предме

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… Polyphenols are categorized as flavonoids, phenolic acids, lignans, and stilbenes, each defined by unique structural characteristics ( Sejbuk et al., 2024 ). … Lignans, found in seeds and whole grains, and stilbenes such as resveratrol, located in grapes and berries, illustrate the structural diversity of polyphenols ( Majedi and Ahamad, 2024 ). This extensive variety of structural kinds highlights their intricate biological functions. …

A Review of Resveratrol as a Potent Chemoprotective and Synergistic Agent in Cancer Chemotherapy.

Background: Cancer has become a major disease endangering human health around the world. Conventional chemotherapy suffers from many side effects including pain, cardiotoxicity, hepatotoxicity, and renal toxicity. This review aims to describe a natural product of resveratrol as a chemoprotective and synergistic agent in the modulation of cancer chemotherapy. Methods: The publications were identified by comprehensive searching of SciFinder, PubMed, Web of Science, and our own reference library. Search terms included combinations of "resveratrol," "cancer," "natural products," "chemotherapy," an