Table 2.
Protective effects of flavonoids against diabetic complications—animal study evidence.
| Flavonoid name | Administration, Dosage form | Experimental design | Treatment | Duration | Upregulation | Downregulation | References |
|---|---|---|---|---|---|---|---|
| Quercetin | Oral, reconstituted solution | STZ-induced diabetic rats | 50 mg/kg/day | 6 weeks | 1. Reduction of serum TNF-α and CRP levels 2. Reduction in the activation of the transcription factor NF-κB 3. Lowering SBP 4. Amelioration of the exaggerated contractile responses of aorta to PE and KCl 5. Prevention of leukocyte infiltration in the adventitia, inhibition of endothelial cells pyknosis and reduction in collagen deposition within aorta sections | (59) | |
| Kaempferol | Oral, reconstituted solution | STZ-induced type 2 diabetic rats fed HFD | 50, 150 mg/kg/day | 10 weeks | Enhanced the insulin-induced glucose-lowering effect | 1. Reduction in TC, TG, LDL-C, and NEFA levels 2. Decreased serum TNF-α and IL-6 levels | (60) |
| Genistein | Oral, reconstituted solution | STZ-induced diabetic rats | 300 mg/kg/day | 24 weeks | Augmentation of total antioxidant reserve of the hearts. | 1. Reduction in TNF-α, CRP, and TGF-β-1 2. Amelioration of the ultrastructural degenerative changes in the cardiac tissues | (61) |
| Luteolin | Oral, reconstituted solution | STZ-induced diabetic mice | 20 mg/kg/day | 15 weeks | Prevention of cardiac fibrosis, hypertrophy, and dysfunction in diabetic mice | (62) | |
| ECGC | Oral, reconstituted solution | STZ-nicotinamide-induced diabetic rats | 2 mg/kg/day on alternate days | 1 month | 1. Increased levels of SOD and CAT activities and GSH content in cardiac tissue 2. Significant improvement in most of the cardiac muscle fibres | 1. Suppressed oxidative stress by reducing the levels of superoxide, 4-hydroxynonenal and protein carbonyl 2. Decreased level of DNA damage in the myocardium 3. Ameliorated the diabetes-induced damage in heart tissues 4. Reduction in the cardiac fibrosis in cardiac tissues 5. Decreased levels of IL-1β, IL-6 and TNF-α and adhesion molecules ICAM-1 and VCAM-1 6. Reduction in the number of apoptotic and necrotic cells | (63) |
| Anthocyanins | Oral, reconstituted solution | STZ-induced diabetic mice | 250 mg/kg/day | 4 weeks | Reduction in cardiac hypertrophy and fibrosis | (64) | |
| Hesperetin | Oral, reconstituted solution | STZ-induced diabetic rats | 100 mg/kg/day | 24 weeks | Restored retinal GSH levels close to normal levels | 1. Reduction of TNF-α and IL-1β in retinae 2. Inhibition of the expression of caspase-3, GFAP and AQP4 in retinae 3. Prevention of photoreceptor degeneration | (65) |
| Eriodictyol | Oral, reconstituted solution | STZ-induced diabetic rats | 10 mg/kg/day | 10 days | 1. Reduction of retinal TNF-α, ICAM-1, VEGF and eNOS 2. Suppressed diabetes-related lipid peroxidation and the blood-retinal-barrier breakdown | (25) | |
| Naringenin | Oral, reconstituted solution | Diabetic mice | 1 and 2% of the diet | 10 weeks | 1. Reduction of IL-1β, IL-6, MCP-1, and TGF-β-1 2. Lowered protein kinase C activity and suppressed NF-κB p65 activity, mRNA expression, and protein production in kidney | (66) | |
| Chrysin | Oral, reconstituted solution | HFD/STZ-induced type 2 diabetic rats | 40 mg/kg/day | 16 weeks | Improved renal pathology | 1. Reduction of renal TNF-α expression and NF-κB activation 2. Suppressed TGF-β-1, fibronectin and collagen-IV protein expressions in renal tissues. 3. Reduction of serum IL-1β and IL-6 | (67) |
STZ, streptozotocin; TNF-α, tumor necrosis factor alpha; hs-CRP, high-sensitivity-CRP; NF-κB, Nuclear Factor kappa-light-chain-enhancer of activated B cells; SBP, systolic blood pressure; Phenylephrine, PE; HFD, high-fat-diet; TC, total cholesterol; TG, triglycerides; LDL-C, low-density-lipoprotein-C; NEFA, Non-Esterified Fatty Acids; IL-6, interleukin-6; TGF-β-1, ECGC, Epigallocatechin Gallate; transforming growth factor-β-1; SOD, superoxide dismutase; CAT, catalase; GSH, glutathione; IL-1β, interleukin-1β; ICAM-1, Intercellular Adhesion Molecule-1; VCAM-1, vascular cellular adhesion molecule-1; GFAP, glial fibrillary acidic protein; AQP4, aquaporin-4; VEGF, vascular endothelial growth factor; eNOS, endothelial nitric oxide synthase; MCP-1, monocyte chemoattractant protein-1.