Table 1 Important anti-diabetic potential and the underlying mechanism of dietary flavonoids
From: Antidiabetic properties of dietary flavonoids: a cellular mechanism review
Structure of flavonoid (s) | Plants/Dietary source | Specific mechanism of action | Model | References |
|---|---|---|---|---|
Diosmin | Scrophularia nodosa L., and citrus fruits | Stimulating the insulin production from the existing β-cells of pancreas. | STZ-nicotinamide-induced diabetic rats. | |
↓ Lipids profile, improving lipid metabolizing enzymes, antioxidant and ↓ lipid peroxidation. | ||||
↓ Blood glucose, lipid peroxides, NO and ↑ body weight. | STZ-induced diabetic neuropathy rats | Jain 2014 [32] | ||
↓ Glycation. | STZ-diabetic rats | Vertommen 1994 [34] | ||
Fisetin | Strawberries, onion and persimmon | Improved glucose homeostasis. | STZ-diabetic rats | Prasath 2014 [38] |
↑ Glycolysis, ↓ gluconeogenesis. | STZ-diabetic rats | |||
↓ Blood glucose, HbA1c, NF-κB p65, IL-1β and nitric oxide. | ||||
Suppress HATs, particularly p300, leading to deacetylation of the p65 subunit of NF-κB. | THP-1 cell line | Kim 2012 [40] | ||
Reduced cataract formation. | STZ-diabetic cataract in mice | Kan 2015 [41] | ||
↑ HDL, ↓ LDL and VLDL. | STZ-diabetic rats | Prasath and Subramanian 2014 [42] | ||
Stimulate the NF-κB pathway, downregulated of adhesion molecules, inhibition of monocyte-endothelial adhesion. | Human umbilical vein endothelial cells and C57BL/6 mice | Kwak 2014 [43] | ||
Improved glycemic and antioxidant status. | STZ-diabetic rats. | Prasath and Subramanian 2013 [44] | ||
↑ Mitochondrial function. | ||||
|  |  | ↓ Level methylglyoxal-dependent protein glycation. | C57BL/6-Ins2 Akita mice | Maher 2011 [46] |
Morin | Prunus dulcis (Mill.) D.A. Webb., Chlorophora tinctoria (L.) Gaud., Psidium guajava L., fruits and wine | ↑ Insulin sensitivity and ↓ oxidative stress. | HFD-STZ-induced diabetic rats | Sendrayaperumal 2014 [49] |
Inhibition of PTP1B, which behaves as an activator and sensitizer of the insulin receptor stimulating the metabolic pathways. | HepG2 cell line | Paoli 2013 [52] | ||
Preventing the destruction of β-cells of the islets of Langerhans. | STZ induced diabetic rats | Vanitha 2014 [53] | ||
Inhibition in ROS generation, translocation of apoptotic proteins, up-regulation of antioxidantgenes and Bcl-2 gene expression. | Hepatocytes cell line | Kapoor 2012 [54] | ||
Eriodictyol | Eriodictyon californicum (Hook. & Arn.) Torr, Millettia duchesnei De Wild., Eupatorium arnottianum Griseb and lemon | ↑ Glucose uptake and improve insulin resistance | HepG2 cell line | Zhang 2012 [56] |
↓ TNFα, ICAM-1, VEGF, and eNOS. | STZ-induced diabetic rats | Bucolo 2012 [57] | ||
Hesperidin | Orange citrus aurantium | Down-regulates generation of free radical, release of cytokines (TNF- α and IL-1β). | Neuropathy rats | Visnagri 2014 [60] |
Anti-angiogenic, anti-inflammatory effects. | STZ-induced diabetic rats. | Shi 2012 [62] | ||
↓ Blood glucose by altering the activity of glucose-regulating enzymes. | STZ-induced type 1 diabetic rats | Akiyama 2010 [63] | ||
Reduced oxidative stress, apoptosis and improving cardiac function via the PPAR-γ pathway. | STZ-isoproternol induced diabetic rats | Yo 2014 [64] | ||
↓ Inflammatory cytokies | HFD-STZ-induced type 2 diabetic rats. | Mahmoud 2012 [65] | ||
↓ HbA1c, glucose, CES LDL, TC, TG levels, systolic and diastolic blood pressure. | STZ-nicotinamide induced myocardial infarction in diabetes in rats | Kakadiya 2010 [66] | ||
Regulation of glucose and lipid metabolism. | Goto-Kakizaki type 2 diabetes rats | Akiyama 2009 [67] | ||
Regulation of glycolysis, gluconeogenesis, hepatic glycogen stores. | C57BL/KsJ-db/db mice | Jung 2014 [68] | ||
↓ Lipid peroxidation, ↑ GSH, GR and GST | STZ-induced diabetes rats | Ashafaq 2014 [69] | ||
Naringenin | Cochlospermum vitifolium (Willd.) Spreng., grapefruits, oranges and tomatoes | Inhibition of intestinal α-glucosidase activity. | High HFD-STZ induced diabetic rats. | Priscilla 2014 [73] |
Reduced oxidative damage | STZ-induced diabetes rats | Fallahi 2012 [75] | ||
↓ Cholesterol and cholesterol ester synthesis. | High-fat induced diabetic mice | Mulvihill 2009 [80] | ||
Improved overall insulin sensitivity and glucose tolerance. | ||||
Suppressed monocyte chemoattractant protein-1 and inhibition of c-Jun NH2-terminal kinase pathway. | HFD-induced obesity | Yoshida 2014 [82] | ||
↓ Hyperglycemia and ↑ antioxidant enzyme (SOD). | STZ-induced hyperalgesia and allodynia in rats | Hasanein 2014 [83] | ||
Stimulated insulin secretion | INS-1E cells | Bhattacharya 2014 [84] | ||
Decreased fasting glucose and inflammatory cytokines. | HFD-fed mice | Yoshida 2013 [85] | ||
|  |  | ↓ Oxidative stress. | STZ-induced diabetes rats | Rahigude 2012 [86] |
Apigenin | Hypericum perforatum L., Matricaria chamomilla L., parsley, onions, oranges, tea, chamomile and wheat sprouts. | ↓ Glucose and G-6-Pase activity and ↑ antioxidant enzymes. | Alloxan-induced diabetic mice | Panda and Kar 2007 [88] |
↓ Apoptosis, ↑ antioxidant and mitochondrial protection. | HIT-T15 pancreatic β-cells | Suh 2012 [90] | ||
Inhibition TNF-α and IL-1β-induced activation of NF-κB. | Human THP-1 monotypic cells | Zhang 2014 [92] | ||
Inhibition the expression of VCAM1, IKKα and IKKepsilon/IKKi. | Human endothelial cells | Yamagata 2010 [93] | ||
Insulin-secretagogue. | Male Wistar rats | Cazarolli 2009 [94] | ||
Baicalein | Scutellaria baicalensis Georgi and Scutellaria lateriflora L. | Improved glucose tolerance, and islet β-cell survival and mass. | HFD-induced obese mice. | Fu 2014 [97] |
Suppressed the activation of NF-κB, ↓ iNOS, TGF-β1, ALP, SGOT and SGPT. | HFD-STZ-induced type 2 diabetic Wistar rats | Ahad 2014 [99] | ||
Reduced AGEs and TNF-α level, decreased NF-κB activation. | STZ-induced diabetic rats | El-Bassossy 2014 [100] | ||
Improvement of insulin resistance, protective by phosphorylating AMPKα AND INS-1. | HFD-induced mice | Pu 2012 [101] | ||
Restored the impairment of PI3K/Akt pathway and ↓ GSK3β. | STZ-induced diabetic Wistar rats | Qi 2015 [102] | ||
Chrysin | Honey, Passiflora caerulea (L.), Pelargonium peltatum (L.), Tilia tomentosa Moench, Pelargonium quercifolium (L.f.) L’Hér. and Pelargonium crispum (Berg.) L’Her | Inhibition of TNF-α pathway, leads to the decreased secretion of pro-inflammatory cytokines. | HFD-STZ-induced type 2 diabetic Wistar albino rats | Ahad 2014 [107] |
Downregulated the increased expression of TGF-β, fibronectin and collagen-IV proteins. | ||||
↓ Blood glucose, oxidative stress, improved learning and memory function. | STZ-induced diabetic rats | Li 2014 [108] | ||
Luteolin | Celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages and apple skins. | inhibition of the NF-κB pathway. | HFD-induced in obesity mice | Liu 2014 [116] |
Increased HO-1 expression and elevated antioxidants. | STZ-Induced Diabetic Rats. | Wang 2011 [117] | ||
Decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS. | Min6 insulin secreting cell line | Ding 2014 [119] | ||
Reduced CREB-binding protein/p300 gene expression. | Human monocytic (THP-1) cell line | Kim 2014 [120] | ||
Suppression of hepatic lipogenesis and increased in uptake of FFAs. | HFD-induced C57BL/6Â J mice | Kwon 2015 [121] | ||
Up-regulated the myocardial eNOS pathway and downstream effects include the enhancement of MnSOD and inhibition of mPTP. | STZ/L-NAME-induced diabetes rats | Yang 2015 [122] | ||
Reduced mast cell and macrophage infiltrations and inflammatory cytokine levels. | Diet-induced obesity | Xu 2014 [123] | ||
Tangeretin | Citrus fruit rinds, mandarin orange and Poncirus trifoliate (L.) Raf. | Stimulated AMPK activation may be associated with anti-inflammatory. | HFD-induced obese mice | Kim 2012 [124] |
↑ Insulin, glycogen. | STZ-induced diabetic rats | Sundaram 2014 [125] | ||
Wogonin | Scutellaria baicalensis Gerogi | Inhibition of p38 MAPK by its specific inhibitor SB203580 increasing PPARα activity and decreasing OPN expression. | STZ induced type 1 diabetes | Zhang 2015 [130] |
Anti-adipogenic effect by acting as a PPARα agonist, which could prevent weight gain. | C57BLKS/J-Leprdb/Leprdb mice and 3 T3-L1 cells | Bak 2014 [128] | ||
Isorhamnetin | Hippophae rhamnoides L., Oenanthe javanica (Blume) DC, Ginkgo biloba L., and Opuntia ficus-indica (L.) Mill. | Insulin secretion, associated with increased GLUT2 and PPARγ. | HFD-induced C57BL/6 mice | RodrÃguez-RodrÃguez 2015 [133] |
Inhibition adipogenesis through downregulation of PPARγ and C/EBPα. | 3 T3-L1 cells | Lee 2009 [134] | ||
Kaempferol | Tea, cruciferous vegetables, grapefruit, Gingko biloba L., and some edible berrie. | Inhibited cellular apoptosis, and reduced caspase-3 activity in beta-cells. | INS-1E β-cells | Zhang 2011 [139] |
↑ Antioxidant and ↓ decreased of lipid peroxidation markers. | STZ-induced diabetic rats | Al-Numair 2015 [141] | ||
↓ PPAR-γ and SREBP-1c expression. | HFD-obese mice | Zang 2015 [143] | ||
Restore deranged activity of membrane-bound ATPases. | STZ-induced diabetes | Al-Numair 2015 [144] | ||
Enhancing β-cell survival, improved cAMP signaling. | INS-1E cells. | Zhang 2013 [145] | ||
↑ GLUT 4, AMPK | HFD-induced diabetic mice | Alkhalidy 2015 [146] | ||
Rutin | Buckwheat, oranges, grapes, lemons, limes, peaches and berries | Inhibited inflammatory cytokines, improving antioxidant and lipid profiles. | HFD-STZ-induced type 2 diabetic model | Niture 2014 [154] |
↓ Glucose, TBARS, caspase-3 and ↑ insulin, Bcl-2 protein. | STZ-induced diabetic rat retina | Ola 2015 [156] | ||
Protected pancreatic beta-cell by decreasing oxidative stress. | STZ induced diabetic rats | Kamalakkannan and Prince 2006 [157] | ||
↓ MDA levels and ↑ SOD and CAT. | STZ-induced type 1 diabetic rats | Butchi 2011 [158] | ||
Quercetin | Chokeberries, black currants, apples and cherries | Increased the activity of glycogen synthase, the rate-limiting enzyme of glycogen synthesis. | Murine H4IIE and human HepG2 cells. | Eid 2015 [164] |
Inhibition of the two transcriptional factors and the activation of mTORC1/p70S6K. | HK-2 and NRK-52E cells | Lu 2015 [167] | ||
Inhibitory effects on NF-kB and caspase-3 expression. | STZ-induced diabetic rats | Kumar 2014 [168] | ||
Ameliorated hyperglycemia and oxidative stress. | Alloxan induced type 2 diabetic mice. | Alam 2014 [169] | ||
Prevented β-cell death via the mitochondrial pathway and NF-κB signaling. | RINm5F β-cells. | Dai 2013 [170] | ||
Reduced expression of inducible iNOS and inhibited translocation of NF-κB. | ||||
Reduced TBARS levels, TC and elevated activities of SOD, CAT, and GSH-Px and HDL-cholesterol. | Diet-C57BL/KsJ-db/db mice | Jeong 2012 [171] | ||
Improved renal function in rats with diabetic nephropathy by inhibiting the overexpressions of TGF-β1 and CTGF. | STZ-induced diabetic rats | Lai 2012 [172] | ||
↓ Glucose and blood HbA1c. | STZ-induced diabetic rats | Kim 2011 [173] | ||
Genistein | Fava bean, soybeans and kudzu. | ↑ cAMP signalling ↑ PKA activation. | HG-induced diabetic mice | Babu 2012 [176] |
↑ Insulin-positive β-cell. | HFD-induced C57BL/6 mice | Fu 2012 [179] | ||
Activation of ERα seems to stimulate muscular GLUT4 functionality, activation of ERβ. | Zucker diabetic fatty rats | Weigt 2015 [182] | ||
↓ Glucose, HbA1c, C-reactive protein, TNFα and TGFβ1 protein expressions. | STZ-induced diabetes rats | Gupta 2015 [183] | ||
↓ Inflammatory markers and improved oxidative stress. | Alloxan-induced diabetic mice | Kim and Lim 2013 [184] | ||
Improved wound angiogenesis. | STZ-induced type 1 diabetic mice | Tie 2013 [185] | ||
Reduced hyperglycemia via minimization of islet cell loss. | Alloxan-induced Sprague–Dawley rats | Yang 2011 [186] | ||
Reduced glucose tolerance and improved insulin levels. | STZ-induced diabetic mice | Fu 2010 [187] | ||
Inhibition the secretion of ECM components and the expression of TGF-beta. | HG-cultured rat mesangial cells | Yuan 2012 [188] | ||
Suppressed the expression of CCAAT/enhancer binding protein alpha (C/EBPalpha). | 3Â T3-L1 cells | Zhang 2009 [189] | ||
↓ TGF-β2, αB-crystallin, and fibronectin. | Human lens epithelial (HLE-B3) cells | Kim 2008 [190] | ||
↓ G6Pase, PEPCK and ↑ lipogenic enzymes activities. | Non-obese diabetic mice | Choi 2008 [191] | ||
Daidzein | Soy milk, soybeans and nuts | Potent α-glucosidase inhibitor and suppress the postprandial hyperglycemia. | STZ-induced diabetic mice | Park 2013 [194] |
↓ Blood glucose and urinary glucose excretion. | HFD-induced type 2 diabetes | Cheong 2014 [196] | ||
Improved the endothelial dysfunction. | STZ-induced diabetic rats. | Roghani 2013 [197] | ||
↑ IRS-1, GLUT4 and enhanced insulin stimulated glucose uptake. | 3 T3-L1and C3H10T1/2 cells | Cho 2010 [198] |
