resveratrol (DB02709) / Alzheimer's Disease Cooperative Study - LARVOL DELTA

Resveratrol's Multifaceted Potential in Alzheimer's Disease: Insights from Preclinical and Clinical Evidence. (PubMed, Mol Neurobiol) - "RSV holds promise as a potential therapeutic agent. Still, challenges such as poor bioavailability and rapid metabolism require optimized delivery systems and further research to establish clinical efficacy and optimal dosing."

Journal • Preclinical • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • CSF Aβ40 • MMP9

Evidence of Clinical Efficacy and Pharmacological Mechanisms of Resveratrol in the Treatment of Alzheimer's Disease. (PubMed, Curr Alzheimer Res) - "While having a high safety profile, resveratrol has efficacy in AD patients to a certain extent, and more data are required to validate the efficacy of resveratrol for the treatment of AD in the future. Suppression of the PI3K signaling pathways could hold significant importance in the treatment of AD patients using resveratrol."

Clinical • Alzheimer's Disease • CNS Disorders • Aβ42 • CSF Aβ40 • CSF Aβ42 • EGFR • HRAS • Plasma Aβ40

A phase II study of muscadine grape skin extract in men with biochemically recurrent prostate cancer. (ASCO-GU 2017) - P1/2; "...MPX demonstrated antitumor effects in PCa through antioxidant activity of its principal polyphenol components, ellagic acid, quercetin, and resveratrol... These data suggest that both 500 and 4000 mg of MPX are safe. The lengthening PSADT in patients treated with MPX is not significantly greater than that provided by placebo. A subgroup analysis of patients more likely to benefit (those with the AA genotype of MnSOD) is ongoing."

Clinical • P2 data • Prostate Cancer

Bioinformatics analysis identified immune infiltration, risk and drug prediction models of copper-induced death genes involved in salivary glands damage of primary Sjögren's syndrome. (PubMed, Medicine (Baltimore)) - "Drug model suggested that "Bathocuproine disulfonate CTD 00001350," "Vitinoin CTD 00007069," and "Resveratrol CTD 00002483" were the drugs most strongly associated with copper-induced death genes. In summary, copper-induced death genes are associated with SGs injury in pSS, which is worthy of clinicians' attention."

Journal • Immunology • Sjogren's Syndrome • ATP7A • ATP7B • SLC31A1

Effects of Resveratrol Supplementation on the Cognitive Function of Patients with Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials. (PubMed, Drugs Aging) - "Supplementation with resveratrol seems to influence the progressive cognitive and functional decline in AD patients, when compared with a placebo group."

Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

[VIRTUAL] RECRUITMENT AND RETENTION IN TWO DECADES OF NIH-FUNDED ALZHEIMER’S DISEASE CLINICAL TRIALS (CTAD 2020) - "Actual recruitment rates for the eight trials were: vitamin E/donepezil=0.50 participants per site per month; simvastatin=0.25 participants per site per month; high dose B vitamin supplements=0.43 participants per site per month; huperzine A=0.23 participants per site per month; valproate=0.21 participants per site per month; DHA=1.36 participants per site per month; IVIg=0.58 participants per site per month, and resveratrol=0.57 participants per site per month... Recruitment is consistently challenging in AD trials. These results may suggest that those designing clinical trials anticipated fewer participants enrolled per site over time. Actual recruitment rates ranged from 0.21 to 1.36 subjects/site/month and appeared to depend more on trial specific factors (disease severity, intervention under study) than effects of time."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Experimental models for aging and their potential for novel drug discovery. (PubMed, Curr Neuropharmacol) - "Besides, classical antiaging drugs such as resveratrol, rapamycin and metformin, denominated DR mimetics, are reviewed. Notwithstanding, non-human primates are still necessary prior to clinical trials, since they allow an easier extrapolation to humans due to their anatomical and physiological similarities. In this review, the different models and approaches for antiaging studies were evaluated."

Journal • Biosimilar

On the pharmacology of oxidative burst of human neutrophils. (PubMed) - Physiol Res - "Different mechanisms are concerned in controlling the assembly of NADPH oxidase and the regulatory role of calcium ions is suggested. Compounds decreasing the amount of extracellular ROS generation, yet affecting but minimally intracellular ROS generation, are promising for further investigation in vivo."

Journal • Biosimilar

γ-Secretase Dependent Nuclear Targeting of Dystroglycan. (PubMed) - "...Using resveratrol treatment of LNCaP cells cultured at low cell density in order to up-regulate notch and activate proteolysis, we identified significant increases in the levels of a 26 kDa β-dystroglycan fragment...Using resveratrol treatment of LNCaP cells cultured at low cell density in order to up-regulate notch and activate proteolysis, we identified significant increases in the levels of a 26kDa β-dystroglycan fragment. These data therefore support a cell density-dependent γ-secretase and furin mediated proteolysis of β-dystroglycan, which could be notch stimulated, leading to nuclear targeting and subsequent degradation."

Journal • Biosimilar • Prostate Cancer

Engineering of a microbial coculture of Escherichia coli strains for the biosynthesis of resveratrol. (PubMed) - Microb Cell Fact - "To our knowledge, this is the first time that a coculture of bacterial strains is used for the biosynthesis of resveratrol from glycerol, having the potential for a greater improvement in the product yield and avoiding the use of precursors such as p-coumaric acid, yeast extract or an expensive inhibitor such as cerulenin."

Journal • Biosimilar

Total Synthesis of Viniferifuran, Resveratrol-Piceatannol Hybrid, Anigopreissin A and Analogues - Investigation of Demethylation Strategies. (PubMed, Adv Synth Catal) - "We found that boron trichloride/tetra-n-butylammonium iodide (BCl3/TBAI) is typically more effective than boron tribromide (BBr3). Based on these findings we carried out the first syntheses of dehydro-δ-viniferin, resveratrol-piceatannol hybrid and anigopreissin A. In addition, we have developed a short and efficient route to viniferifuran that was obtained in 13% yield over six steps."

Journal • Biosimilar

Short Term Efficacy and Safety of Perispinal Administration of Etanercept in Mild to Moderate Alzheimer's Disease (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: Life Extension Foundation Inc.; Trial primary completion date: Jun 2015 ➔ Dec 2015

Trial primary completion date • Alzheimer's Disease • Biosimilar • Immunology • Inflammation • Reperfusion Injury

Facile synthesis of resveratrol analogues and inducing osteogenesis in mesenchymal stem cells (ACS-Sp 2017) - "In order to address both concerns, we have devised a way to exclude copper from the system, thus allowing the synthesis to be done under aerobic conditions with no special apparatus. Our progress toward a broadly applicable method will be discussed in the context of novel resveratrol analogue synthesis."

Preclinical • Biosimilar

Involvement of miR-539-5p in the inhibition of de novo lipogenesis induced by resveratrol in white adipose tissue. (PubMed) - Food Funct - "In addition, significant reductions in SREBP1 protein expression and fasn gene expression were found in resveratrol-treated rats. In conclusion, the up-regulation of miR-539-5p is involved in the inhibition of de novo lipogenesis induced by resveratrol in WAT."

Journal • Biosimilar • Obesity

Protective role of benzoselenophene derivatives of resveratrol on the induced oxidative stress in intestinal myofibroblasts and osteocytes. (PubMed, Chem Biol Interact) - "Some of the synthesized RE analogs have shown anti-bacterial role in IBD and anti-resorptive activity in bone pathologies related to inflammatory and osteoporotic processes. Thus, we suggest benzoselenophene derivatives as good candidates for alternative therapy and/or therapeutic support in these pathologies."

Journal • Biosimilar • Immunology • Inflammation • Inflammatory Bowel Disease

Resveratrol and Myopathy. - Nutrients - "Here, we review the potential for resveratrol to ameliorate or correct mitochondrial metabolic deficiencies responsible for myopathies, due to inherited fatty acid β-oxidation or to respiratory chain defects, for which no treatment exists to date. We also review recent data supporting therapeutic effects of resveratrol in the Duchenne Muscular Dystrophy, a fatal genetic disease affecting the production of muscle dystrophin, associated to a variety of mitochondrial dysfunctions, which likely contribute to disease pathogenesis."

Journal • Review • Biosimilar • Gene Therapies

Lysophosphatidic Acid Promotes Epithelial to Mesenchymal Transition in Ovarian Cancer Cells by Repressing SIRT1. (PubMed) - Cell Physiol Biochem - "We have identified a mechanism that relates SIRT1 down-regulation to LPA-induced EMT in OC cells and may open new arenas on developing novel anti-cancer therapeutics."

Journal • Biosimilar • Oncology • Ovarian Cancer

Natural Compounds as Therapeutic Agents in the Treatment Cystic Fibrosis. (PubMed) - J Genet Syndr Gene Ther - "Of note, several of these compounds are naturally occurring, and are present in spices from the grocery store and over the counter preparations in health food stores. In this short review, we look at three such compounds, genistein, curcumin, and resveratrol, and evaluate the scientific support for their use as therapeutic agents in the treatment of patients with CF."

Journal • Biosimilar • Fibrosis • Immunology

Resveratrol and Coumarin: Novel Agricultural Antibacterial Agent against Ralstonia solanacearum In Vitro and In Vivo. (PubMed) - Molecules - "A further pot experiment demonstrated that coumarin and resveratrol significantly inhibited early adhesion and colonization of R. solanacearum in tobacco plants and the corresponding control efficacies were 68% and 85% after incubation for 13 days, respectively. The findings of this study suggest that both resveratrol and coumarin have potential as non-toxic antimicrobial strategies for controlling tobacco bacterial wilt disease."

Journal • Biosimilar

Regulation of eIF2α expression and renal interstitial fibrosis by resveratrol in rat renal tissue after unilateral ureteral obstruction. (PubMed) - Ren Fail - "Results After comparison of the treatment groups with model group, we observed that the degree of renal tubular damage, relative area of renal interstitial collagen and eIF2α, ATF4 protein expression were also significantly reduced (p<0.05, p  <0.01) in the high-dose resveratrol group. Conclusion Resveratrol can reduce the level of eIF2α protein expression, which further reduces the ATF4 levels."

Journal • Biosimilar • Fibrosis • Immunology • Renal Disease • Systemic Sclerosis

Are miRNA-103, miRNA-107 and miRNA-122 Involved in the Prevention of Liver Steatosis Induced by Resveratrol? (PubMed) - "This study provides new evidences which show that srebf1 is a target gene for miRNA-103-3p and miRNA-107-3p, fasn a target gene for miRNA-122-5p and cpt1a a target gene for miRNA-107-3p. Moreover, the reduction in liver steatosis induced by resveratrol in rats fed an obesegenic diet is mediated, at least in part, by the increase in CPT1a protein expression and activity, via a decrease in miRNA-107-3p expression."

Journal • Biosimilar • Metabolic Disorders • Obesity

Chemical Characterization, Free Radical Scavenging, and Cellular Antioxidant and Anti-Inflammatory Properties of a Stilbenoid-Rich Root Extract of Vitis vinifera. (PubMed) - Oxid Med Cell Longev - "Furthermore, the root extract could induce the antiatherogenic hepatic enzyme paraoxonase 1 and downregulate proinflammatory gene expression (interleukin 1β, inducible nitric oxide synthase) in macrophages. Collectively our data suggest that the root extract of Vitis vinifera exhibits free radical scavenging as well as cellular antioxidant and anti-inflammatory properties."

Journal • Biosimilar • Immunology • Inflammation

Synthesis and tyrosinase inhibition activity of trans-stilbene derivatives. (PubMed) - Bioorg Chem - "Compound 21 ((E)-2,3-bis(4-Hydroxyphenyl)acryonitrile) was found to be the most active with an IC50 value of 5.06μM which is less than half of the value 10.78μM observed for resveratrol (common standard used in murine tyrosinase activity studies) under similar conditions. The results obtained from the present study reveal structural/functional group sensitivity for the tyrosinase inhibitory activity of stilbenoid moieties and are expected to be very helpful for the design and synthesis of novel, selective and effective tyrosinase inhibitors."

Journal • Biosimilar

Combination chemoprevention with grape antioxidants. (PubMed) - Mol Nutr Food Res - "Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape-ingredients alone or together with other agents could impart 'additive synergism' against cancer."

Journal • Biosimilar • Oncology

Tetrahydroxystilbene Glucoside Inhibits Excessive Autophagy and Improves Microvascular Endothelial Dysfunction in Prehypertensive Spontaneously Hypertensive Rats. (PubMed) - Am J Chin Med - "Pretreatment of young SHRs with the mTOR inhibitor rapamycin blocked the antiautophagic and vasodilative effects of TSG. Furthermore, we sought to determine if and how tetrahydroxystilbene glucoside (TSG), a resveratrol analogue and active ingredient of Polygonum multiflorum Thunb used for its cardiovascular protective properties in traditional Chinese medicine, influences vascular endothelial function. In summary, mesenteric endothelial dysfunction in prehypertensive SHRs was at least partly attributable to excessive autophagy in vascular tissues. TSG partly restored microvascular endothelial dysfunction through activating the Akt/mTOR pathway, which consequently suppressed autophagy, indicating that TSG could be potentially applied to protect vascular function against subclinical changes in prehypertension."

Journal • Biosimilar • Cardiovascular