Table 2.
The effects of tea on diabetes mellitus and its complications by in vitro and in vivo studies.
| Tea Types | Constituents | Diseases Types | Study Types | Models | Dose | Effects | Mechanisms | Ref. |
|---|---|---|---|---|---|---|---|---|
| Green tea | EGCG | Diabetic cardiovascular disease | In vivo | Alloxan-induced diabetic rabbits | 50 mg/kg/day | Improved late endothelial progenitor cells(L-EPCs); Promoted reendothelialization. |
Activated Akt/eNOS pathway | [136] |
| EGCG | Diabetic cardiomyopathy | In vivo | Wistar rats | 50 mg/kg/day | Enhanced cardiac function; Increased ADSC repair capability; |
↑ Insulin-like growth factor 1 ↑ H9c2 cell cycle |
[137] | |
| EGCG | diabetic neuropathy | In vivo | Male Wistar rats | 0.1% (w/v) | Improved cerebral function. | ↓ Neuronal degeneration ↓ Apoptotic cell death |
[138] | |
| Polyphenols | Diabetic Retinopathy | In vivo | Wistar-Kyoto rats | 5.7 g/kg/day | Protected the retina against glutamate toxicity. | ↓ ROS | [122] | |
| Polyphenols | Diabetic cardiovascular disease | In vivo | Male Wistar rats | 0.8, 1.6, and 3.2 g/L | Reduced fat deposit; Ameliorated hypoadiponectinemia in HF-fed rats; Relieved high glucose-induced adiponectin decrease. |
↓ Extracellular signal regulated kinase 1/2 phosphorylation ↑ PPARγ ↓ Adiponectin decrease |
[139] | |
| Polyphenols | Diabetic cardiovascular disease | In vitro | Cardiac muscle of rats | 200 mg/kg | Ameliorated the effects of high-fructose diet on insulin signaling, lipid metabolism and inflammation. | ↑ PI3k, Akt1 ↑ Glut1, Glut4, glycogen synthase 1 ↑ Anti-inflammatory protein ↓ GSK-3β, TNF, IL-1B and IL-6 |
[53] | |
| Diabetic cardiovascular disease | In vivo | STZ-induced rats | 300 mg/kg/day | Protected rat heart. | ↓ [Ca2+] and [Na+] ↑ Activities of Ca2+-ATPase and Na+/K+-ATPase |
[94] | ||
| Diabetic cardiovascular disease | In vivo | STZ-induced rats | 300 mg/kg/day | Reduced the risk of diabetic cardiovascular disease. | ↓ Cholesterol, triglyceride ↓ Free fatty acid and LDL-C ↑ HDL-C |
[140] | ||
| Diabetic cardiomyopathy | In vivo | Diabetic rats | 300 mg/kg/day | Treated diabetic cardiomyopathy. | ↓ AGEs ↓ Ollagen cross-linking |
[100] | ||
| diabetic retinopathy | In vivo | Rats | 200 mg/kg/day | Prevented and treated diabetic retinopathy. | ↓ SOD and catalase enzyme | [123] | ||
| Diabetic hepatopathy | In vivo | Male Wistar rats | 1.5% (w/v) | Prevented diabetic tissue injury. | ↑ GSH-Px, SOD, catalase | [126] | ||
| Diabetic hepatopathy | In vivo | Male Wistar rats | 1.5% (w/v) | Pretected tissue. | ↑ GSH-Px, SOD, catalase ↓ MDA, alkaline phosphatase |
[141] | ||
| Diabetic nephropathy and hepatopathy | In vivo | Male Sprague-Dawley rats | 0.1% (w/v) | Protected renal and hepatic tissues from injury. | ↑ Total antioxidant levels ↓ Malonyldialdehyde (MDA) ↓ Angiotensin II AT1 receptor |
[130] | ||
| Diabetes mellitus-induced periodontitis | In vivo | STZ-induced rats | N/A | Treated diabetes mellitus-induced periodontitis. | ↓ TNF-α and RANKL ↑ RUNX-2, OPG ↑ Interleukin-10 (IL-10) |
[131] | ||
| diabetic spinal cord | In vivo | STZ-induced rats | N/A | Improved diabetic spinal cord. | ↑ GFAP | [142] | ||
| Black tea | T1DM | In vivo | Female CD-1 mice | 0.01% (w/v) | Promoted insulin secretion and regenerated damaged pancreas and protected pancreatic β- cells. | ↓ Nitrosative stressRUNX-2, OPG↓ ROS | [20] | |
| Diabetes mellitus | In vivo | STZ-induced rats | 0.5 mL/day | Regenerated damaged pancreas and protected pancreatic β-cells. | ↓ Nitrosative stress | [143] | ||
| T2DM | In vivo | STZ-induced rats | 0.01 mL/g/day | Ameliorated diabetes mellitus associated oxidative stress. | ↑ GSH | [144] | ||
| Diabetic complication | In vivo | Diabetic animals | 50 mg/mL | Attenuated oxidative stress mediated tissue damage. | ↓ DNA fragmentation ↓ Activation of caspase-3 ↑ Oxidative stress related parameters |
[108] | ||
| Diabetic tissue injury | In vivo | Adult male Wistar albino rat | 50 and 100 mg/kg/day | Protected the liver | ↑ Cellular antioxidant capacity ↓ Membrane lipid peroxidation ↓ Oxidative stress |
[17] | ||
| EGC, GC, GCG | bone metabolism | In vitro | Cultured rat osteoblast-like osteosarcoma cell line UMR-106 | N/A | Improved bone metabolism | ↑ Osteoblast activity ↓ Osteoclast differentiation |
[132] | |
| White tea | T2DM | In vivo | Male Sprague-Dawley rats | 0.5% (w/v) | Lowered blood sugar levels. | ↑ Insulin sensitivity ↑ The synthesis of liver glycogen |
[62] | |
| Diabetic cardiovascular diseases | In vivo | Male Wistar rats | 0.01 mg/mL | Prevented cardiovascular diseases. | ↑ Insulin sensitivity ↑ Cardiac acetate and alanine contents and protein oxidation |
[88] | ||
| Diabetes mellitus | In vitro | human hepatocellular carcinoma (HepG2) cell | 25 mg/mL | Improved glucose and lipid metabolism. | ↓ Glucose uptake and transport | [145] | ||
| Diabetic reproductive dysfunction | In vivo | STZ-induced prediabetic rat model | 10 mg/mL | Improved epididymal sperm motility and restored sperm viability. | ↓ GLUT3 protein ↑ Lactate dehydrogenase ↑ Lactate content. |
[146] | ||
| Dark tea | EGCG, ECG | Diabetes mellitus | In vitro | N/A | 50 mg/mL | Treated diabetes mellitus. | ↓ α-glucosidase | [65] |
| TP,TPS | Diabetes mellitus | In vivo | Diabetic rats | 50 mg/kg | Reduced postprandial blood sugar. | ↓ α-glucosidase | [147] | |
| Polysaccharides | T2DM | In vivo | Male ICR mice | 40 mg/kg | Lowered the blood glucose levels and reversed oxidative stress. | ↑ SOD activity ↑ Malondialdehyde contents ↑ GSH-Px |
[148] | |
| T2DM | In vivo | Male ICR mice | 1 and 5 mg/kg | Improved insulin resistance. | ↓ α-glucosidase Maintain α-amylase |
[66] | ||
| T2DM | In vitro In vivo |
HepG2 cells db/db mice |
100, 200, and 400 mg/kg/day | Improved insulin resistance and maintained glucose homeostasis. | ↑ Glucose uptake ↓ Intestinal sucrase, maltase, and porcine pancreatic amylase activity |
[5] | ||
| T2DM | In vivo | Male Sprague−Dawley rats | 400 mg/kg/day | Alleviated insulin resistance and chronic kidney disease. | ↓ SIRP-α ↑ PI3K/Akt ↑ Nrf2 expression in kidney ↓ GSK-3β phosphorylation Activated Akt/GLUT4, FoxO1 and mTOR/S6k1 pathways |
[69] | ||
| diabetic nephropathy | In vivo | db/db mice and db/m mice | 1 g/kg/day | Attenuated the increases in urinary albumin, serum creatinine, and mesangial matrix. | ↓ AGEs ↓ Receptor for AGE expression in glomeruli ↓ Carbonyl compounds |
[73] | ||
| Onloog tea | Polysaccharide | diabetic tissue and kidney | In vivo | STZ-induced diabetic diabetic mice | 50, 100, and 200 mg/kg | Prevented diabetic tissue and kidney diseases. | ↑ SOD and GSH-PX activity ↓ MDA |
[87] |
| Polysaccharide | Diabetic immune disease | In vivo | STZ-induced diabetic mice | 100, 300, and 600 mg/kg in mice 50, 100, and 200 mg/kg in rats |
Improved immunomodulatory function. | ↑ The activity of NK cellsIntensify DTH ↑ Phagocytotic function of peritoneal macrophage |
[149] | |
| Yellow tea | EGCGGCG | Diabetes mellitus | In vitro | N/A | 1% (w/v) | CGC reduced postprandial blood sugar more effectively. | ↓ α-glucosidase | [71] |
| Diabetic complications | In vivo | db/db mice | N/A | Lowered the serum total and low-density lipoprotein cholesterol and triglyceride levels. Increased glucose tolerance. |
↓ The lipid synthesis ↓ SRET fator1, SREP 1 ↓ Acetyl-CoA carboxylase α, ↓ Fatty acid synthase |
[15] | ||
| Tea | EGCG | T1DM | In vitro | RINm5F cells | 20-40 uM | Protected pro-inflammatory cytokine and induced injuries in insulin-producing cells. | ↓ iNOS and NO | [47] |
| T1DM | in vivo | C57BL/KsJ mice | 100 mg/kg/day | Protected pancreatic islets. | ↓ iNOS | [150] | ||
| EGCG | T2DM | In vivo | Diabetic patients | 300, 600, and 900 mg/day | Decreased pathogenesis of proinflammation and improved diabetes mellitus. | ↓ Free radicals ↓ S100A12-RAGE axis by stimulating sRAGE |
[57] | |
| Catechins | T2DM | In vivo In vitro |
Male obese KK-ay and C57BL/6J mice; 3T3-L1 adipocytes |
20 mg/kg/day | Decreased glucose levels and increased glucose tolerance in animals. | ↓ ROS ↓ JNK phosphorylation ↑ GLUT-4 translocation |
[48] | |
| EGCG | T2DM | In vitro | Human HepG2 cells | N/A | Attenuated insulin signaling blockade. | ↓ Phosphorylation of IRS-1 ↑ 5′AMPK |
[52] | |
| EGCG | T2DM | In vivo | Sprague-Dawley rats | 1-100 uM | Improved endothelial dysfunction and insulin resistance and protected against myocardial I/R injury. | ↑ NO via PI3k pathway ↑ Plasma adiponectin |
[95] | |
| diabetic nephropathy | In vivo | Diabetic SHR rats | 5.7 g/kg/day | Reduced podocyte apoptosis, foot process effacement and albuminuria. | ↓ GSK3-p53 ↑ LRP6 |
[78] | ||
| diabetic nephropathy | In vivo | STZ-induced diabetic rats | 5% (w/v) | Improved diabetic nephropathy. | ↓ MMP-9, TIMP-1 ↑ MMP-2 ,TIMP-2 |
[83] | ||
| diabetic nephropathy | In vivo | Male Sprague-Dawley rats | 0.25% and 0.5% (w/w) | Reduced renal oxidative damage and inflammatory reactions. | ↑ Activity of 5′-lipoxygenase ↓ Ieukotriene B-4 |
[81] | ||
| Catechins | diabetic nephropathy | In vivo | Sprague-Dawley rats | 0.25% and 0.5% (w/w) | Improved kidney function. | ↓ Thromboxane A(2) synthesis ↑ Prostacyclin synthesis |
[151,152] |
Abbreviations: iNOS, inducible nitric oxide synthase; RANKL, receptor activator of nuclear factor kappa-B ligand; OPG, osteoprotegerin; RUNX-2, runt-related transcription factor 2; GFAP, glial fibriliary acidic protein; SRET, sterol regulatory element-binding transcription factor 1; SREP, synthase and sterol response element-binding protein; TIMP, tissue inhibitor of metalloproteinases; STZ, streptozotocin; SHR, spontaneous hypertension rat, ICR, Institute of Cancer Research; Akt, protein kinase B; eNOS, endothelial nitric oxide synthase; PPARγ, peroxisome proliferator-activated receptorγ; PI3K, phosphatidylinositol 3-hydroxykinase; GLUT, glucose transporter type; GSK-3β, glycogen synthase kinase-3β; TNF, tumor necrosis factor; AGEs, advanced glycation end products; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; SIRP, signal regulatory protein; Nrf2, nuclear factor-erythrocyte-associated factor 2; mTOR, the target of rapamycin; S6k1, ribosomal protein S6 kinase 1; JNK, jun NH2-terminal kinase; w/v, weight/volume; w/w, weight/weight.