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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. Srinivasan and Pari 2010, 2012, 2013 [30, 31, 33]
↓ 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 Prasath and Subramanian 2011, 2013 [39, 45]
↓ 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/6 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 Rodríguez-Rodríguez 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). 3 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]