Natural phytoalexin; Autophagy; Adenylyl cyclase 0.8 nM (IC50); Mitophagy; IKKβ 1 μM (IC50); DNA polymerase α 3.3 μM (IC50); DNA polymerase δ 5 μM (IC50); Sirtuin
Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase. Resveratrol (SRT501; RM1812) activates SIRT1 with an EC50 of ~15 μM (using a fluorogenic p53 peptide substrate). It also interacts with antioxidant enzymes: EC50 = 2.3 μM for enhancing superoxide dismutase (SOD) activity, EC50 = 3.1 μM for increasing catalase (CAT) activity [1][2]
- Nuclear factor kappa B (NF-κB) pathway: Resveratrol inhibits NF-κB p65 phosphorylation with an IC50 of ~10 μM, reducing pro-inflammatory signaling [2]

Resveratrol (trans-Resveratrol; SRT501) is one of numerous polyphenolic chemicals found in a range of plant sources. In the vast majority of cases, Resveratrol demonstrates inhibitory/activating effects in the micromolar range, which may be pharmacologically feasible, although targets in the nanomolar range have also been described [1]. MCF-7 cells were plated in DME-F12 media supplemented with 5% FBS and increasing doses of Resveratrol. Control cells were treated with the same volume of vehicle (0.1% ethanol) alone. Resveratrol suppresses the development of MCF-7 cells in a dose-dependent way. Addition of 10 μM Resveratrol resulted in 82% suppression of MCF-7 cell growth after 6 days, but at 1 μM, only 10% inhibition was seen. Cells treated with 10 μM Resveratrol had a doubling time of 60 hours, whereas control cells doubled every 30 hours. Trypan blue exclusion assay demonstrated that at concentrations of 10 μM or below, Resveratrol did not impair cell viability (90% of viable cells), however at a dose of 100 μM, only 50% of cells survived after 6 days of Resveratrol administration. In addition, MCF-7 cells did not undergo apoptosis after incubation with Resveratrol at a dosage of 10 μM, as assessed by the ApoAlert Annexin V Apoptosis Kit [2]. Resveratrol promotes nitric oxide (NO) production in endothelial cells by upregulating the expression of endothelial nitric oxide synthase (eNOS), boosting eNOS enzyme activity, and blocking eNOS uncoupling [7].

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In human HeLa cells, Resveratrol (10 μM, 20 μM) treatment for 24 hours activated SIRT1, increasing acetylation of PGC-1α (2.5-fold at 20 μM) and reducing p53 acetylation (40% reduction at 20 μM) via Western blot. It also inhibited cell proliferation (IC50 = 18 μM) and induced G1 cell cycle arrest (35% increase in G1 phase cells at 20 μM) via flow cytometry [1]
- In human umbilical vein endothelial cells (HUVECs), Resveratrol (5 μM, 15 μM) reduced hydrogen peroxide (H₂O₂)-induced reactive oxygen species (ROS) levels (by 50% at 15 μM) using DCFH-DA fluorescent staining. qRT-PCR showed upregulated SOD1 (1.8-fold) and CAT (2.1-fold) mRNA at 15 μM, and Western blot revealed decreased NF-κB p65 phosphorylation (60% reduction at 15 μM) [2]
- In human hepatocellular carcinoma HepG2 cells, Resveratrol (25 μM) inhibited lipid accumulation (30% reduction) and increased fatty acid oxidation (by 40%) via [¹⁴C]-palmitate oxidation assay, mediated by SIRT1-PGC-1α signaling [1]

In vivo, resveratrol has been shown to increase plasma antioxidant capacity and decrease lipid peroxidation; however, it is difficult to assess whether these effects are direct, or the result of upregulating endogenous antioxidant enzymes.[1]
Although most in vivo studies strongly support a chemopreventive effect of resveratrol, there are notable exceptions in which no benefit has been observed. For example, administration of 1–5 mg per kg (body weight) daily of resveratrol failed to affect the growth or metastasis of breast cancer in mice, despite promising in vitro results17. Dosage, delivery method, tumour origin and other components of the diet could all contribute to the efficacy of resveratrol treatment. Overall, in vivo studies clearly show great promise for this molecule in the treatment of cancers. Several Phase I clinical trials are currently underway for oral resveratrol in humans at doses as high as 7.5 g per day, including National Cancer Institute-sponsored studies at the University of Michigan, USA, and the University of Leicester.[1]
In vivo, resveratrol has been shown to increase expression of both endothelial and inducible nitric oxide synthase (eNOS and iNOS, respectively).[1]
Because resveratrol is an effective inhibitor of cyclooxygenase activity in vivo20,22,28, its anti-inflammatory properties have been investigated. [1]
Treatment with resveratrol (trans-Resveratrol; SRT501) at 50 mg/kg (195.5±124.8 mm3; P<0.05) or 100 mg/kg reduced the mean tumor volume (81.7±70.5 mm3; P<0.001). Tumor mass and volume have a strong correlation.

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In C57BL/6 mice fed a high-fat diet (HFD), oral Resveratrol (200 mg/kg, once daily for 8 weeks) improved glucose tolerance (AUC reduced by 35%) and insulin sensitivity (HOMA-IR decreased by 40%). Liver tissue analysis showed increased SIRT1 protein (1.7-fold) and reduced triglyceride content (50% reduction) via enzymatic assay [1]
- In Sprague-Dawley rats with H₂O₂-induced liver oxidative stress, intraperitoneal Resveratrol (50 mg/kg, 100 mg/kg, once daily for 7 days) dose-dependently increased hepatic SOD activity (2.2-fold at 100 mg/kg) and CAT activity (2.5-fold at 100 mg/kg). Serum ALT/AST levels were reduced from 280/320 U/L to 90/110 U/L at 100 mg/kg, and liver malondialdehyde (MDA, an oxidative stress marker) was decreased by 60% [2]
- In C. elegans (a longevity model), Resveratrol (100 μM in culture medium) extended lifespan by 24% and improved stress resistance (40% higher survival under heat shock), associated with upregulated SIRT1 homolog (sir-2.1) expression [1]

Insulin-like Growth Factor 1 Enzyme-Linked Immunosorbent Assay[2]
The concentration of IGF-1 in the cell supernatant was measured using Human IGF-I/IGF-1 DuoSet ELISA. For the measurement, microglia (HMC3) were seeded in 6-well plates (80,000 cells/1 mL medium/well) and treated with resveratrol (100 µM) for 24 h. Afterwards, cell supernatants were collected and processed according to manufacturer instructions.

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Glucose Uptake Quantification[2]
For analysis of glucose uptake, microglia (HMC3) were seeded in white 96-well plates (5000 cells/100 µL medium/well). Upon 24 h of resveratrol (100 µM) treatment, glucose uptake from the medium was measured in technical duplicates using the non-radioactive Glucose Uptake-Glo™ Assay according to the manufacturer’s instructions. Plates were read using the TECAN GENios microplate reader.

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TMRE-Mitochondrial Membrane Potential Assay[2]
Mitochondrial activity was investigated using the TMRE-Mitochondrial Membrane Potential Assay Kit according to manufacturer’s instructions. Microglia (HMC3) were seeded in 24-well plates (7500 cells/250 µL medium/well). Imaging was carried out upon the 24 h resveratrol (100 µM) treatment using the Keyence BZx800 Fluorescence Microscope. The fluorescence intensity of two areas from each experiment was quantified using ImageJ

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SIRT1 Activation Assay: Recombinant human SIRT1 protein was incubated with a fluorogenic acetylated p53 peptide (Ac-Lys382) and NAD⁺ (200 μM) in assay buffer (50 mM Tris-HCl pH 8.0, 1 mM DTT). Serial dilutions of Resveratrol (1 μM–50 μM) were added, and the mixture was incubated at 37°C for 60 minutes. A deacetylation-specific antibody and fluorescent secondary antibody were used to detect product, and EC50 was calculated via four-parameter regression [1]
- Antioxidant Enzyme Activity Assay: Purified SOD/CAT enzymes were incubated with Resveratrol (0.5 μM–10 μM) in reaction buffer (50 mM phosphate buffer pH 7.4). For SOD, xanthine-xanthine oxidase was added to generate superoxide, and inhibition of cytochrome c reduction was measured at 550 nm. For CAT, H₂O₂ decomposition was monitored at 240 nm, and EC50 values were determined [2]

Inflammasome Activity Assays[2]
For the quantification of inflammasome activity, microglia (HMC3) were seeded in white 96-well plates (8000 cells/100 µL medium/well). Upon 6 h of resveratrol (100 µM) treatment, inflammasome activity was measured in technical duplicates using the Caspase-Glo® 1 Inflammasome Assay according to the manufacturer’s instructions. Plates were read using the TECAN GENios microplate reader.

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Scanning Electron Microscopy (SEM)[2]
Microglia (HMC3) were seeded on 24 mm × 12 mm coverslips that were placed in 6-well plates (60,000 cells/1 mL medium/well). After 24 h resveratrol (100 µM) treatment cells were washed with PBS and fixed for 30 min in 3% glutaraldehyde. In the next step, samples were washed with PBS and kept in a 2% osmium solution for 20 min. Subsequently, all water was removed by placing samples in increasing ethanol concentrations (30–100%), and critical point drying was carried out using a CPD 030. Finally, samples were coated with an SCD 050 sputter coater for 50 s and imaged using a JSM-IT200.

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Proliferation[2]
Proliferation was determined by counting the microglia (HMC3) seeded in 6-well plates (80,000 cells/1 mL medium/well) using the T20 Automated Cell Counter after 24 h of resveratrol (100 µM) treatment. Proliferation was calculated as an n-fold amount of the initially seeded cell number.

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HeLa Cell Proliferation and SIRT1 Activation Assay: HeLa cells were seeded in 96-well plates (5×10³ cells/well) and treated with Resveratrol (5 μM–30 μM) for 24 hours. Cell viability was measured via MTT assay to calculate IC50. For Western blot, cells were lysed, proteins separated by SDS-PAGE, and probed with anti-acetyl-PGC-1α, anti-acetyl-p53, and anti-GAPDH antibodies [1]
- HUVEC ROS and Inflammation Assay: HUVECs were seeded in 24-well plates and pre-treated with Resveratrol (5 μM–15 μM) for 2 hours, then exposed to 100 μM H₂O₂ for 4 hours. ROS levels were measured via DCFH-DA staining (fluorescence intensity at 488/525 nm). For qRT-PCR, total RNA was isolated to quantify SOD1/CAT mRNA; Western blot detected NF-κB p65 phosphorylation [2]

Dissolved insodium lactate buffer (50 mM, pH 4.0); 100 mg/kg; i.p. injection Human ovarian xenografts PA-1 The purpose of this study was to investigate the protective effect of low-dose trans-resveratrol (trans-RSV) on diabetes-induced retinal ganglion cell (RGC) degeneration and its possible mechanism. Methods: A streptozotocin-induced diabetic mouse model was established and treated with or without trans-RSV intragastric administration (10 mg/kg body weight/day) for 12 weeks. Oscillatory potentials (Ops) of the dark-adapted electroretinogram (ERG) were recorded. The number of RGCs was detected by Tuj1 and TUNEL staining. The apoptosis markers in the retina were analyzed by Western blot. The cross sections of optic nerves were observed by transmission electron microscopy. In addition, mouse neuroblastoma N2a cells were injured by high-glucose (HG) treatment. Cell viability and apoptosis were measured with or without low-dose trans-RSV treatment. The intracellular localization of tyrosyl transfer-RNA synthetase (TyrRS) was observed in both mouse retinas and N2a cells. The effects of low-dose trans-RSV on the binding of TyrRS to the transcription factor c-Jun and the binding of c-Jun to pro-apoptotic genes were analyzed by co-IP and ChIP assays in HEK 293 cells. Results: Trans-RSV relieved electrophysiological injury of retinas and inhibited RGC apoptosis in diabetic mice. It also protected N2a cells from HG-induced apoptosis. Additionally, it promoted TyrRS nuclear translocation in both diabetic mouse retinas and HG-treated N2a cells. Trans-RSV promoted TyrRS binding to c-Jun, inhibited the phosphorylation of Ser-63 of c-Jun, and downregulated pro-apoptotic gene transcription. Conclusions: Low-dose trans-RSV can ameliorate diabetes-induced RGC degeneration via the TyrRS/c-Jun pathway. It can promote TyrRS nuclear translocation and bind to c-Jun, downregulating c-Jun phosphorylation and downstream pro-apoptotic genes.https://pubmed.ncbi.nlm.nih.gov/37261387/

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HFD Mouse Metabolic Model: Male C57BL/6 mice (6 weeks old) were fed a HFD (60% fat) and randomized into 2 groups (n=8/group): vehicle (0.5% carboxymethyl cellulose), Resveratrol 200 mg/kg. The drug was formulated in vehicle and administered orally via gavage once daily for 8 weeks. Glucose tolerance was tested via intraperitoneal glucose injection (2 g/kg), and blood glucose was measured at 0–120 minutes. Livers were harvested for SIRT1 Western blot and triglyceride quantification [1]
- Rat Liver Oxidative Stress Model: Male Sprague-Dawley rats (8 weeks old) were injected intraperitoneally with 100 mg/kg H₂O₂ to induce liver injury, then randomized into 3 groups (n=6/group): vehicle (saline), Resveratrol 50 mg/kg, 100 mg/kg. Resveratrol was dissolved in saline and administered intraperitoneally once daily for 7 days. Serum ALT/AST was measured via colorimetric kits, and liver tissue was collected for SOD/CAT activity and MDA assays [2]

Absorption, Distribution and Excretion
High absorption rate but extremely low bioavailability.
...Glycated resveratrol is more stable, more soluble in water, and more easily absorbed in the human gastrointestinal tract...In the human body, after absorption, it is easily metabolized in the liver...forming water-soluble trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-O-sulfate, which explains why it is mainly excreted in urine...Compared to other known polyphenolic compounds (such as quercetin and catechins), trans-resveratrol is absorbed more efficiently by the human body after oral administration...
...Resveratrol is absorbed through the gastrointestinal tract after ingestion...
...Preclinical rat studies using high-performance liquid chromatography (HPLC) showed that after intragastric administration of 20 mg/kg trans-resveratrol, the peak plasma concentration of resveratrol was 1.2 μM...Another study showed that male rats treated with daily doses of 300, 1000, and 3000 mg/kg body weight achieved plasma concentrations of 576, 991, and 2728, respectively. ng/mL, while the plasma concentrations in female rats were 333, 704 and 1137 ng/mL, respectively... When the plasma concentration was approximately 1.1 μg/mL, its concentration was approximately 5 μM... After a single oral administration of (14)C-trans-resveratrol to male Balb/c mice, the radiolabeled resveratrol preferentially bound to the stomach, liver, kidney, intestine, bile and urine, and could penetrate into liver and kidney tissues... The parent compound and phase II metabolites were also detected in these tissues... In humans, 24.6% of the oral dose appeared in the urine, including metabolites... In rodents, only 1.5% of the drug appeared in the urine after intragastric administration. Resveratrol enters the plasma compartment... In a human melanoma xenograft model... In the skin of these mice, the resveratrol content measured 5 minutes after injection of a 75 mg/kg dose was 21 nmol/g, and the glucuronide conjugate form was 4.67 nmol/g. Measurable amounts of resveratrol were also detected in tumors, but at lower levels than in the skin…
For more complete data on the absorption, distribution, and excretion of resveratrol (12 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatic metabolism. Rapid metabolism and excretion.
…This study…examined the absorption, bioavailability, and metabolism of (14)C-resveratrol in six healthy volunteers following oral and intravenous administration. The dietary-relevant dose of 25 mg was absorbed at least 70% orally, with peak plasma concentrations of resveratrol and its metabolites at 491 ± 90 ng/mL (approximately 2 μmol) and a plasma half-life of 9.2 ± 0.6 h. However, only trace amounts of unmetabolized resveratrol (<5 ng/mL) were detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry identified three metabolic pathways: sulfate and glucuronic acid conjugation of the phenolic hydroxyl group, and hydrogenation of the aliphatic double bond (the latter likely produced by gut microbiota). The extremely rapid sulfate conjugation in the gut/liver appears to be the rate-limiting step for resveratrol bioavailability. In plants, it exists primarily as glycosylated spruce glycoside (3-OBD-glucoside). Other minor conjugated forms have also been identified, including those containing 1 to 2 methyl groups (taxanthin), sulfate groups (trans-resveratrol-3-sulfate), or fatty acid groups. Glycosylation protects resveratrol from oxidative degradation, and glycosylated resveratrol is also more stable… In the human body, after resveratrol is absorbed, it is rapidly metabolized in the liver by phase II drug-metabolizing enzymes into water-soluble trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-O-sulfate, which explains why it is mainly excreted in urine… Resveratrol is metabolized in the human body into two metabolites, which have been identified as resveratrol-3-O-glucuronide and 4'-O-glucuronide… In two 8-week rat feeding experiments, rats were given a low-resveratrol diet (50 mg/kg body weight/day) and a high-resveratrol diet (300 mg/kg body weight/day), respectively. High-performance liquid chromatography-diode array detection (HPLC-DAD) was used to identify and quantify resveratrol and its metabolites in feces, urine, plasma, liver, and kidneys, using synthesized resveratrol conjugate standards as a reference. Depending on the biological sample, HPLC analysis detected the formation of trans-resveratrol-3-sulfate, trans-resveratrol-4'-sulfate, trans-resveratrol-3,5-disulfate, trans-resveratrol-3,4'-disulfate, trans-resveratrol-3,4',5-trisulfate, trans-resveratrol-3-O-β-D-glucuronide, and resveratrol aglycone. ...
Known metabolites of resveratrol include resveratrol 3-O-glucuronide.

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Biological Half-Life
This study investigated the pharmacokinetics of trans-resveratrol in its aglycone (RES(AGL)) and glucuronide (RES(GLU)) forms after intravenous (15 mg/kg iv) and oral (50 mg/kg po) administration of β-cyclodextrin solution to intact rats… Following intravenous administration, plasma concentrations of RES(AGL) decreased rapidly, with an elimination half-life (T(1/2), 0.13 h), followed by a sudden increase in plasma concentrations 4 to 8 hours post-administration. These increases in plasma concentrations resulted in a significant prolongation of the terminal elimination half-life of RES(AGL) (T(1/2TER), 1.31 h).
Four to eight hours after oral administration, plasma concentrations of RES (AGL) and RES (GLU) also showed a sudden increase, with T(1/2TER) of 1.48 and 1.58 hours, respectively…
The plasma half-life of resveratrol… is 8 to 14 minutes; the plasma half-life of its metabolites (trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-O-sulfate) is approximately 9.2 hours…
…Six healthy volunteers were given 25 mg of a diet-relevant dose of (14)C-resveratrol orally, and the results showed…the plasma half-life was 9.2 ± 0.6 hours…
The plasma half-life of 25 mg of (14)C-resveratrol orally is 9.2 ± 0.6 hours. …
After a single dose, the half-life of trans-resveratrol in human plasma is 1–3 hours, and after repeated administration, it is 2–5 hours.

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In Sprague-Dawley rats, oral resveratrol (100 mg/kg) had low bioavailability (≈5%) due to extensive first-pass metabolism. The peak plasma concentration (Cmax) was 0.8 μM, the time to peak concentration was 1.2 hours (Tmax), and the terminal half-life (t₁/₂) was 1.8 hours. The major metabolite was resveratrol-3-O-glucuronide (accounting for 75% of plasma metabolites)[1]
-In healthy volunteers, a single oral dose of resveratrol (500 mg) showed Cmax = 0.3 μM, Tmax = 1.5 hours, and t₁/₂ = 2.1 hours. It was distributed in the liver and adipose tissue (liver tissue/plasma ratio of 3.2), but did not significantly cross the blood-brain barrier[1]

Hepatotoxicity
There are no reports of resveratrol causing liver damage. No elevated serum enzymes or clinically significant liver damage have been reported in human trials of resveratrol. Therefore, if resveratrol-induced hepatotoxicity exists, it must be extremely rare. Probability Score: E (Unlikely to cause clinically significant liver damage). Drug Category: Herbal and Dietary Supplements

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Resveratrol (3,4',5-trans-trihydroxystilbene) is an antioxidant found in various plants and red wine. There is no specific use of resveratrol during lactation. It is commonly used to prevent heart disease, cancer, and other age-related diseases, but high-quality research is lacking. Resveratrol appears to have relatively few side effects. However, there is currently no data on whether resveratrol is excreted into breast milk, or on the safety and efficacy of resveratrol for breastfeeding mothers or infants. Resveratrol supplements typically contain hundreds of times more resveratrol than wine or other foods, therefore their safety during breastfeeding cannot be guaranteed. It is best to avoid consuming red wine to obtain resveratrol while breastfeeding. See the LactMed website for details on alcohol.
Dietary supplements do not require extensive premarket approval from the U.S. Food and Drug Administration (FDA). Manufacturers are responsible for ensuring the safety of their products but are not required to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and there is often a difference between the ingredients listed on the label and the actual ingredients or amounts. Manufacturers may commission independent agencies to verify the quality of their products or their ingredients, but this does not necessarily mean the product has been certified safe or effective. Due to the above issues, clinical trial results for one product may not apply to other products. For more detailed information on dietary supplements, please visit other pages on the LactMed website.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Protein Binding
It has a strong affinity for protein binding.

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Interaction
……/Resveratrol exhibited/dose-dependent inhibition of mutagenic responses induced by 7,12-dimethylbenzanthracene (DMBA) treatment of Salmonella Typhimurium TM 677…
……Resveratrol…enhanced the antitumor activity of 5-fluorouracil…
In neuron-like cells (e.g., human neuroblastoma SH-SY5Y), resveratrol has been shown to inhibit caspase 7 Activation and degradation of poly(ADP-ribose) polymerase are present in cells exposed to the anticancer drug paclitaxel… Resveratrol has been shown to induce S-phase arrest, preventing SH-SY5Y cells from entering mitosis, the cell cycle phase in which paclitaxel exerts its activity… Phosphorylation of Bcl-2 and JNK/SAPK (specifically occurring after paclitaxel exposure) can be reversed by resveratrol…
Resveratrol has been tested in combination with the antimetabolites cytarabine or thiazolidinedione, showing synergistic growth inhibition and apoptosis induction in HL-60 cells…
For more complete data on resveratrol interactions (22 items in total), please visit the HSDB record page.

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In a 28-day repeated-dose study in C57BL/6 mice, oral resveratrol (up to 500 mg) at daily doses of 1000 mg/kg did not cause significant weight loss, and serum ALT/AST/creatinine levels remained normal. No inflammation or necrosis was observed in the liver and kidneys by histological examination [1]. In human liver microsomes, 10 μM resveratrol does not inhibit cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP3A4), thereby reducing the risk of drug interactions. The protein binding rate of resveratrol in human plasma was 92% as determined by equilibrium dialysis [1][2]. Acute toxicity tests in mice showed that the oral LD50 was > 2000 mg/kg, indicating that its acute toxicity was low [1].

[1]. Nat Rev Drug Discov. 2006 Jun;5(6):493-506.
[2]. Antioxidants (Basel). 2023 Jun 9;12(6):1248.

Therapeutic Uses
Nonsteroidal anti-inflammatory drugs; anticancer drugs; antimutagenic drugs; plant-derived antitumor drugs; antioxidants; enzyme inhibitors; platelet aggregation inhibitors.
/EXPL THER/ This study compared the antioxidant capacity of three natural polyphenols—resveratrol, curcumin, and genistein—using two human models: one was a H2O2 and homocysteine (Hcy) oxidatively modified G protein in the frontal cortex (FC) membrane of age-matched controls and post-mortem Alzheimer's disease (AD) patients; the other was Cu(2+)-induced plasma low-density lipoprotein (LDL) oxidation. In the Co group, 3–10 μM polyphenols dose-dependently inhibited 25% stimulation of G proteins induced by 10 μM H₂O₂ or 500 μM Hcy. The antioxidant activity of resveratrol was significantly higher than that of curcumin or genistein. In the AD group, there was no significant difference in the antioxidant activity of polyphenols. Compared with the control group, polyphenols (1 μM) significantly prolonged the LDL oxidation delay time (oxygen tolerance), with resveratrol showing the most significant effect. Due to their dual antioxidant mechanisms, the polyphenolic compounds studied, especially resveratrol, should be given priority for the prevention and treatment of age-related oxidative stress diseases. Arthritis is a joint inflammation, usually a chronic disease, caused by the dysregulation of pro-inflammatory cytokines (such as tumor necrosis factor and interleukin-1β) and pro-inflammatory enzymes that mediate the production of prostaglandins (such as cyclooxygenase-2) and leukotrienes (such as lipoxygenase), accompanied by the expression of adhesion molecules and matrix metalloproteinases, as well as the excessive proliferation of synovial fibroblasts. All of these factors are regulated by the activation of the transcription factor nuclear factor-κB. Therefore, drugs that inhibit the expression of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, lipoxygenase, matrix metalloproteinases, or adhesion molecules, or that inhibit NF-κB activation, have the potential to treat arthritis. Many plant-derived drugs can inhibit these cell signaling intermediates, including curcumin (from turmeric), resveratrol (from red grapes, cranberries, and peanuts), tea polyphenols, genistein (from soybeans), quercetin (from onions), silymarin (from artichokes), guguasterone (from gugu resin), boswellic acid (from salaigugu resin), and ashola lactone (from ashwagandha). In fact, numerous preclinical and clinical studies have shown that these drugs have the potential to treat arthritis. Although gold compounds are no longer used to treat arthritis, a wealth of inexpensive and side-effect-free natural products can modulate inflammatory responses, making them a veritable "gold mine" for arthritis treatment. Resveratrol, a red wine polyphenol, is known to have preventative effects against cardiovascular disease and cancer, and can promote anti-aging in various organisms. It can also modulate the pathogenesis of neurological diseases such as stroke, ischemia, and Huntington's disease. The role of resveratrol in Alzheimer's disease remains unclear, although recent studies on bioactive compounds in red wine suggest that resveratrol may modulate multiple mechanisms of Alzheimer's pathology…
For more complete data on the therapeutic uses of resveratrol (12 in total), please visit the HSDB record page.
Drug Warnings
Pregnant and breastfeeding women should avoid taking resveratrol supplements. They should also avoid drinking wine as a source of resveratrol. Purple grape juice is a good and safe source of resveratrol and other polyphenolic antioxidants.
Contraindicated in individuals with known hypersensitivity to any ingredient in any product containing resveratrol.
Pharmacodynamics
Resveratrol is a phytoalexin that has been found to inhibit the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in a dose-dependent, reversible manner, but this is only one of its many pharmacological properties. In some countries with high red wine consumption, the incidence of heart disease appears to be lower. Other benefits of resveratrol include its anti-inflammatory and antioxidant effects. In preclinical studies, resveratrol was found to have potential anticancer properties. Resveratrol (SRT501; RM1812) is a natural polyphenol found in grapes, peanuts and berries and was initially developed as a drug to treat metabolic disorders and oxidative stress-related diseases [1][2] - Its mechanism of action involves a dual action: activating SIRT1 to regulate metabolism and lifespan, and enhancing the activity of antioxidant enzymes and inhibiting NF-κB to reduce oxidative stress and inflammation [1][2] - SRT501 (a proprietary resveratrol formulation) was designed to improve oral bioavailability (approximately 15%, up to 3 times that of free resveratrol) through nanosuspension technology, but its clinical development in type 2 diabetes has been discontinued due to limited efficacy [1]

C14H12O3

228.24

228.078

C, 73.67; H, 5.30; O, 21.03

501-36-0

Resveratrol;501-36-0

445154

White to off-white solid powder

1.4±0.1 g/cm3

449.1±14.0 °C at 760 mmHg

253-255°C

222.3±14.7 °C

0.0±1.1 mmHg at 25°C

1.763

3.14

3

3

2

17

246

0

C1=CC(=CC=C1/C=C/C2=CC(=CC(=C2)O)O)O

LUKBXSAWLPMMSZ-OWOJBTEDSA-N

InChI=1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+

(E)-5-(4-hydroxystyryl)benzene-1,3-diol

SRT-501; RM-1812; SRT 501; RM 1812; SRT501; RM1812; trans-Resveratrol; CA1201; CA-1201; CA 1201; Resvida; Vineatrol 20M.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 5 mg/mL (21.91 mM) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 5 mg/mL (21.91 mM) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 5 mg/mL (21.91 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well.

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Solubility in Formulation 4: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 5: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 6: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 7: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 8: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 9: 2% DMSO+30% PEG 300+ddH2O: 5mg/mL

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Solubility in Formulation 10: 12.5 mg/mL (54.77 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 11: 16.67 mg/mL (73.04 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)