Table 5.

Evidence of anti-diabetic effects of naringenin: in vivo streptozotocin (STZ)-induced diabetes animal studies.

Streptozotocin (STZ)-Induced Diabetes Animal Models
Animal	Naringenin Concentration/Duration	Blood Measures	Other Measures	Reference
Neonatal Wistar rats and New Zealand White rabbits	0.1–1000 mM, 1–2 min	No effect	↓ Intestinal BBMV glucose uptake ↓ renal BBMV glucose uptake	[65]
Wistar rats	5 and 50 mg/kg b.w., 5 days	↓ Glucose levels ↓ Total Cholesterol ↓ Triglycerides ↑ HDL levels	No effect	[66]
Wistar rats	30 mg/kg b.w., 21 days	↓ Glucose levels ↑ Insulin levels ↑ Vitamin E levels	↑ Kidney and liver hexokinase activity ↓ Liver and kidney G6Pase and F16BPase ↓ Glycoprotein levels	[67]
Male BALB/cA mice	0.5–2% dietary intake, 10 weeks	↓ Glucose levels ↑ Insulin levels	↓ Blood urea nitrogen levels ↓ Kidney NF-κB p65 ↓ Renal TNFα ↓ Renal IL-1β ↓ Renal IL-6 ↓ Renal CCP-1	[68]
Wistar albino rats	25, 50 and 100 mg/kg. b.w/day, 28 days	↓ Glucose levels ↑ Insulin levels ↓ Triglyceride, TAG, LDL and NEFA levels	↑ Liver and kidney PPARγ ↑ HSP-27 and HSP-72 protein ↓ Pancreatic, liver and kidney NF-κB protein ↓ Liver TNFα ↓ Renal IL-6	[69]
Albino Wistar rats	50 mg/kg b.w./day, 21 days	↓ Fasting-glucose levels ↓ HbA1c ↑ Insulin levels	↑ SOD ↑ Catalase ↑ GSH peroxidase ↑ Glutathione-S-transferase activity	[70]
Male albino rats	50 mg/kg b.w., 4 weeks	↓ Glucose levels ↑ Insulin levels ↓ HbA1c levels	↓ Lipid peroxide and NO levels ↑ Vitamin C, vitamin E and GSH levels ↓ TNF-α and IL-6 levels	[71]
Albino Wistar rats	25 mg/kg p.o., 2 h	↓ Glucose in response to maltose and sucrose load	↓ α-glucosidase activity	[72]
Male Wistar rats	20, 50, and 100 mg/kg p.o, 8 weeks	↓ Glucose levels	↓ Hyperalgesia ↑ SOD ↑ Body weight	[73]
Male Wistar rats	50 mg/kg b.w., 30 days	↓ Glucose levels	↓ Oxidative stress ↓ Liver ROS ↓ Liver lipid peroxidation ↓ Bax and Bcl-2 mRNA and protein	[74]
Male Wistar rats	25 and 50 mg/kg b.w./day, 5 weeks	↓ Glucose levels ↑ Insulin levels ↓ TNF-α, IL-1β and IL-6 levels	↑ Sciatic IGF expression ↑ Sciatic NGF expression ↓ TBARS, GSH levels ↑ SOD and catalase activity ↓ Sciatic histology	[75]
Sprague-Dawley rats	50 and 100 mg/kg/day, 6 weeks	↑ Glucose tolerance ↓ Glucose levels ↓ Lipid levels	↓ ICAM-1 ↓ Malonaldehyde levels	[76]
Sprague–Dawley rats	50 mg/kg b.w./day, 6 weeks	↓ Glucose levels	↓ Urinary protein levels ↓ Kidney index ↑ Creatinine clearance ratio ↓ ECM deposition ↑ let-7a signaling ↓ TGF-β1 and TGFBR1 mRNA and protein ↓ Smad2 and smad7 mRNA and protein	[77]
Male Wistar rats	50 and 100 mg/kg b.w., 10 weeks	↓ Glucose levels ↓ Total cholesterol levels	↑ Kidney SOD ↑ Kidney Catalase ↑ Kidney GSH ↓ Renal IL-1	[78]
Male Wistar rats	50 mg/kg b.w./day, 5 weeks	↓ Glucose levels ↑ Insulin levels	↓ Retinal TBAR levels ↓ GSH levels ↑ BDNF and TrkB levels ↑ Synaptophysin levels ↑ Bcl-2 protein ↓ Bax and Caspase-3 protein	[79]
Male albino rats	100 mg/kg b.w./day, 4 weeks	↑ Insulin levels ↑ Lipid profile	↑ GLUT4 mRNA ↓ Liver G6Pase activity	[80]
Male albino rats	100 mg/kg/day, 15 days	↓ Glucose levels ↑ Lipid levels	↑ GLUT4 activity ↑ PPARγ in the pancreas	[81]

Brush border membrane vesicle (BBMV); High-density lipoproteins (HDL); Glucose 6-phosphatase (G6Pase); Fructose 1,6-bisphosphatase (F16BPase); Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); Interleukin 1β (IL-1β); Cytochrome c peroxidase-1 (CCP-1); Triacylglycerol (TAG); Non-esterified fatty acids (NEFA); Superoxide dismutase (SOD); Glutathione (GSH); Nitric oxide (NO); Hemoglobin A1c (HbA1c); Insulin-like growth factor (IGF); Nerve growth factor (NGF); Thiobarbituric acid reactive substances (TBARS); Intercellular adhesion molecule 1 (ICAM-1); Extracellular matrix (ECM); Transforming growth factor beta 1 (TGF-β1); Transforming growth factor beta receptor 1 (TGFBR1); Brain-derived neurotrophic factor (BDNF); Tropomyosin receptor kinase B (TrkB).