Suppression of human monocyte tissue factor induction by red wine phenolics and synthetic derivatives of resveratrol

forrás: http://www.ncbi.nlm.nih.gov/pubmed/16507316


2014-10-28 13:42:48


Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction.


Resveratrol induces gastric cancer cell apoptosis via reactive oxygen species, but independent of sirtuin1

forrás: http://www.ncbi.nlm.nih.gov/pubmed/22211760


2014-10-28 13:38:15


The currently available chemotherapeutic regimens against gastric cancer are not very effective, leading to high recurrence and poor survival. Resveratrol is a naturally occurring polyphenol with potent apoptosis-inducing activity. However, the mechanism underlying its actions remains unknown. In the present study, human gastric adenocarcinoma SGC7901 cells were treated with resveratrol (0, 25, 50, 100 and 200 μmol/L) for 48 h, and cellular apoptosis DNA damage were determined. In certain experiments, cells were incubated with superoxide dismutase (100 U/mL), catalase (300 U/mL) or sirtinol (10 μmol/L) to determine the role of reactive oxygen species (ROS) and sirtuin1 in resveratrol-induced cellular apoptosis. Treatment with resveratrol (50-200 μmol/L) for 48 h significantly induced apoptosis and DNA damage in human gastric cancer SGC7901 cells. This was due to the increased generation of ROS following resveratrol treatment because incubation of cells with superoxide dismutase (100 U/mL) or catalase (300 U/mL) attenuated resveratrol-induced cellular apoptosis. Interestingly, treatment with resveratrol (25-200 μmol/L) did not affect the level and activity of sirtuin1, whereas the sirtuin1 inhibitor sirtinol (10 μmol/L) significantly reduced sirtuin1 activity. Furthermore, treatment with sirtinol (10 μmol/L) did not have any effect on apoptosis induced by resveratrol. These data provide evidence that resveratrol induces apoptosis via ROS, but independent of sirtuin1, in the human gastric cancer cell line SGC7901.


A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice

forrás: http://www.ncbi.nlm.nih.gov/pubmed/18523577


2014-10-28 13:29:37


Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg(-1) day(-1)), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.


Inducţia factorului de supresie a monocitelor umane de către fenolii din vinul roşu şi derivaţii sintetici ai resveratrolului

forrás: http://www.ncbi.nlm.nih.gov/pubmed/16507316


2014-10-28 13:42:48


Prevenirea afecţiunilor cardio-vasculare prin suplimenţi nutriţionali creşte în popularitate pretutindeni în lume. Studii epidemiologice multiple au găsit că utilizarea moderată de alcool, în mod particular de vin roşu, scade rata de mortalitate cauzată de afecţiunile coronariene ale inimii (CHD). Inflamaţia cronică şi ateroscleroza asociată cu CHD culminează cu o expresie intravasculară aberantă a factorului de ţesut (TF), care declanşează coagularea sângelui, ceea ce conduce la tromboză, o cauză majoră a atacului de cord. Am arătat mai devreme că doi fenoli din vinul roşu, resveratrolul şi quercetina, au supresat  inducţia TF la celulele endoteliale. În studiul prezent noi am investigat eficacitatea a şapte derivaţi ai resveratrolului, care s-au arătat a fi eficienţi în reglarea creşterii celulelor canceroase in vitro, la concentraţii mult mai joase decât compusul de origine, resveratrolul, şi am urmărit cu ajutorul acestor derivaţi inhibarea inducţiei TF în celulele mononucleare periferice ale sângelui (PBMC). Am testat de asemenea posibilul efect sinergic al resveratrolului şi quercetinei cu alţi polifenoli majori din vinul roşu, în supresarea expresiei TF indusă de lipopolizaharide,  în PBMC-ul uman. Am găsit că anumiţi derivaţi ai resveratrolului erau de 2 pana la 10 ori mai eficienţi decât resveratrolul în inhibarea inducerii TF. Studiul nostru nu a găsit nici o dovadă pentru sinergie la polifenolii din vinul roşu. Aceste date sugerează că alteraţiile structurale ale resveratrolului pot fi eficiente în a produce agenţi antitrombotici puternici care vor avea potenţial terapeutic în îmbunătăţirea sănătăţii cardiovasculare şi prevenirea CHD. Printre fenolii majori ai vinului roşu, quercetina apare ca fiind supresorul predominant al inducţiei TF.


Resveratrolul induce apoptoza celulelor canceroase gastrice via speciile de oxigen reactive, dar independent de sirtuina1.

forrás: http://www.ncbi.nlm.nih.gov/pubmed/22211760


2014-10-28 13:38:16


Tratamentele chemoterapice disponibile în mod curent împotriva cancerului gastric nu sunt foarte eficiente, ducând la recidive şi slabă supravieţuire. Resveratrolul este un polifenol apărut pe cale naturală cu puternică acţiune de inducere a apoptozei. Cu toate acestea mecanismele care stau la baza acţiunilor sale rămân necunoscute. În studiul prezent celule ale adenocarcinomului uman gastric SGC7901au fost tratate cu resveratrol (0,25, 50, 100 şi 200 µmol/L) pentru 48 de ore, şi a fost determinată distrugerea ADN-ului prin apoptoză celulară. În anumite experimente unele celule au fost incubate cu superoxid dismutază (100 U/ml), catalază (300 U/ml) sau sirtinol (10 µmol/L) pentru a determina rolul speciilor de oxigen reactive (ROS) şi a sirtuinei1 în apoptoza celulară indusă de resveratrol. Tratamentul cu resveratrol (50-200 µmol/L) timp de 48 de ore a indus semnificativ apoptoza şi distrugerea ADN-ului la celulele de cancer uman gastric SGC7901. Aceasta a fost datorită generaţiilor mărite de ROS care au urmat tratamentului cu resveratrol, deoarece incubaţia celulelor cu superoxid distutază (100 U/ml) sau catalază (300 U/ml) a atenuat apoptoza celulară indusă de resveratrol. În mod interesant, tratamentul cu resveratrol (25-200 µmol/L) nu a afectat nivelul şi activitatea sirtuinei1, în timp ce inhibitorul de sirtuină1, sirtinol (10 µmol/L), a redus semnificativ activitatea sirtuinei1. Mai mult, tratamentul cu sirtinol (10 µmol/L) nu a avut nici un efect asupra apoptozei indusă de resveratrol. Aceste date furnizează probe că resveratrolul induce apoptoza via ROS, dar independent de sirtuina1, la linia celulară a cancerului gastric uman SGC7901.


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