Table 2.
Effects of resveratrol in diabetic cardiovascular complications.
| Study Type | Model | Dose/Dosing Method/Period | Outcome | Proposed Mechanism | Ref. |
|---|---|---|---|---|---|
| In vivo | SD rats (STZ DM model) | RES 2.5 mg/kg, oral 15 days | ↑Phosphorylation of eNOS ↓Blood glucose |
RES improves diabetic myocardial GLUT4 translocation and glucose uptake through the AMPK pathway and by regulating the status of Cav-1 and Cav-3. | [100] |
| In vivo | Wistar rats (STZ DM model) | RES 5 mg/kg, intraperitoneal inject 42 days | ↑Contractile responses to noradrenaline ↑Relaxation response to Ach ↓Blood glucose |
[101] | |
| In vivo | C57BL/6 mice (HFD) and db/db mice (T2DM model) | RES 5, 30, 50 mg/kg, oral for 4 weeks | ↓Plasma insulin levels ↓Hyperglycemia↓Fasting BP ↓Angiogenesis ↑Endothelial protection |
RES protects diabetic wound healing through its SIRT1-dependent endothelial cell protection and pro-angiogenesis, involving inhibition of FOXO1 and de-inhibition of c-Myc expression. | [102] |
| In vivo | C57BL/6 mice (HFD) and db/db mice (T2DM model) | RES (0.3% mixed in chow) for 8 weeks | ↓Blood glucose, FFA ↓ICAM-1, VCAM-1, MCP-1 ↓NF-κB activity |
RES ameliorates diabetic vascular inflammation and macrophage infiltration by inhibiting the NF-κB pathway. | [103] |
| In vivo | SD rats (STZ model/HFD) | RES 10 mg/kg, gavage for 8 months | ↓Insulin sensitivity ↓TG, TC, LDLc ↓ROS |
UCP2 mediates RES to improve cardiac function, inhibit myocardial cell apoptosis, and participate in the improvement of mitochondrial function. | [104] |
| In vivo | CD1 mice (STZ T1DM model) | RES 100 mg/kg, oral for 3 months | ↑SERCA2 promoter activity ↑SIRT1 |
RES enhances SERCA2a expression and improves cardiac function through activation of SIRT1. | [105] |
| In vivo | SD rats (STZ-NA model) | RES 5 mg/kg, oral for 4 months | ↓Antioxidant enzymes activities ↓Oxidative markers |
RES treatment may delay or attenuate the progression of diabetes-related cardiac complications by reducing oxidative stress. | [106] |
| In vivo | SD rats (HFD T2DM model) | RES 50 mg/kg, gavage for 16 weeks | ↓Cardiac dysfunction and hypertrophy ↓SOD activity ↓ATP content |
RES activates SIRT1 and increases PGC-1α deacetylation, thereby regulating mitochondrial function and alleviating cardiac injury in diabetic rats. | [107] |
| In vivo | mice (STZ T1DM model) | RES 25 mg/kg, intraperitoneal inject for 5 days | ↓Apoptosis ↑Mitochondrial biogenesis |
Activation of SIRT1 by RES ameliorates myocardial injury in DCM through PGC-1α -mediated mitochondrial regulation. | [108] |
| In vivo | SD rats (STZ T1DM model) | RES 80 mg/kg, intraperitoneal inject for 12 weeks | ↑Glucose and lipid metabolism ↑Cardiac function ↓TNF-α, IL-6, IL-1β |
Res alleviates cardiac dysfunction caused by diabetes through down-regulation of the AT1R-ERK/P38 MAPK signaling pathway. | [109] |
| In vivo | ZDF rats | RES 200 mg/kg, oral for 6 weeks | ↑The apparent Km to palmitoyl-CoA ↓Mitochondrial reactive oxygen ↓Lipid accumulation |
Resveratrol reduces liver fibrosis, p-COA respiratory sensitivity, active lipid accumulation, and mitochondrial reactive oxygen emission rates. | [110] |
| In vivo | Wistar albino rats (DHEA-induced PCOS model) | RES 20 mg/kg, oral for 28 days | ↓Serum testosterone levels ↓Number of TUNEL (+) granulosa cells ↓Number of Graafian follicles ↓Body weights |
Resveratrol activates SIRT1 and AMPK to induce antioxidant and anti-inflammatory systems of PCOS. | [111] |
| In vivo | ICR mice (HFD model) | RES 50 mg/kg, gavage for 7 days | ↓Collagen deposition ↓HIF-1α accumulation ↓Fibrosis and inflammation |
Resveratrol reduces HIF-1α accumulation by promoting proteasome degradation of HIF-1α by regulating AMPK/SIRT1. | [112] |
| In vivo | SD rats (STZ model) | RES 0.1, 1, 5, 10, 50 μg/kg, intravitreal inject or tail vein injects for 12 weeks | ↑Insulin level ↓AGEs, LDL, Ox-LDL, caspase 3 activity ↓Damage of DR |
Resveratrol reduces the inflammatory state and damage of DR through PON1. | [113] |
| In vivo | SD rats (STZ T1DM model) | RES 25 mg/kg, oral for 8 weeks | ↓Cardiac cell size ↓Oxidative stress ↓Fibrosis |
Resveratrol activates SIRT3, maintains mitochondrial function, and regulates the acetylation of TFAM. | [114] |
Ach: Acetylcholine; AGEs: Advanced glycation end products; AMPK: Adenosine 5-monophosphate (AMP)-activated protein kinase; AT1R: AGTR1, Angiotensin II receptor type 1; ATP: Adenosine triphosphate; BP: Blood pressure; Cav-1: Caveolin 1; Cav-3: Caveolin 3; DHEA: Dehydroepiandrosterone; DM: Diabetes mellitus; DR: Diabetic retinopathy; eNOS: Endothelial nitric oxide synthase; FFA: Free fatty acid; FOXO1: Forkhead transcription factor 1; GLUT4: Glucose transporter 4; HIF-1α: Hypoxia inducible factor 1 subunit alpha; ICAM-1: Intercellular adhesion molecule 1; IL-1β: Interleukin 1 Beta; IL-6: Interleukin 6; LDL: Low density lipoprotein; LDLc: Low-density lipoprotein cholesterol; MAPK: Mitogen-activated protein kinase; MCP-1: CCL2, C-C motif chemokine ligand 2; NF-κB: Nuclear factor kappa B subunit 1; Ox-LDL: Oxidized low-density lipoprotein; p-COA: palmitoyl-CoA; PCOS: Polycystic ovary syndrome; PGC-1α: Peroxisome proliferator-activated receptor-gamma coactivator 1alpha; PON1: Paraoxonase 1; RES: Resveratrol; ROS: Reactive oxygen species; SERCA2: ATP2A2, ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2; SIRT1: Sirtuin 1; SIRT3: Sirtuin 3; SOD: Superoxide dismutase; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; TC: Total cholesterol; TFAM: Recombinant transcription factor A, Mitochondrial; TG: Triglycerides; TNF-α: Tumor necrosis factor; UCP2: Uncoupling protein 2; VCAM-1: Vascular cell adhesion molecule 1. ↑: Increase; ↓: Decrease.