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Mechanisms of Action of Phenolic Phytochemicals in Diabetes Management

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Role of Phenolic Phytochemicals in Diabetes Management

Abstract

Phenolic phytochemicals have potential therapeutic efficacy against diabetes mellitus. Since diabetes mellitus is a multifactorial disease, it becomes imperative to find a therapeutic option which could be multifactorial in its mechanism of action. Phenolic phytochemicals have the ability to modulate metabolic and signaling pathways at various levels including gene expressions, epigenetic regulation, protein expressions, enzyme activities, etc. All of these therapeutic mechanisms may be extremely complex and overlapping; hence, in this chapter we intend to delineate molecular pathways of antidiabetic effects of phenolic phytochemicals, and simply understand molecular mechanisms of action underlying therapeutic potential of phenolic phytochemicals against diabetes mellitus.

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References

  • Abdel Aziz MT, Motawi T, Rezq A, Mostafa T, Fouad HH, Ahmed HH et al (2012) Effects of a water-soluble curcumin protein conjugate vs. pure curcumin in a diabetic model of erectile dysfunction. J Sex Med 9(7):1815–1833

    Article  CAS  PubMed  Google Scholar 

  • Al Wafai RJ (2013) Nigella Sativa and thymoquinone suppress cyclooxygenase-2 and oxidative stress in pancreatic tissue of streptozotocin-induced diabetic rats. Pancreas 42:841–849

    Article  PubMed  CAS  Google Scholar 

  • Alhusban A, Alkhazaleh E, El-Elimat T (2017) Silymarin ameliorates diabetes-induced proangiogenic response in brain endothelial cells through a GSK-3 β inhibition-induced reduction of VEGF release. J Diabetes Res 2017:1

    Article  CAS  Google Scholar 

  • Al-Trad B, Al-Batayneh K, El-Metwally S, Alhazimi A, Ginawi I, Alaraj M et al (2016) Nigella sativa oil and thymoquinone ameliorate albuminuria and renal extracellular matrix accumulation in the experimental diabetic rats. Eur Rev Med Pharmacol Sci 20(12):2680–2688

    CAS  PubMed  Google Scholar 

  • Atta MS, Almadaly EA, El-Far AH, Saleh RM, Assar DH, Al Jaouni SK et al (2017) Thymoquinone defeats diabetes-induced testicular damage in rats targeting antioxidant, inflammatory and aromatase expression. Int J Mol Sci 18:919

    Article  PubMed Central  CAS  Google Scholar 

  • Babu PVA, Si H, Liu D (2012) Epigallocatechin gallate reduces vascular inflammation in db/db mice possibly through an NF-B-mediated mechanism. Mol Nutr Food Res 56:1424

    Article  CAS  PubMed  Google Scholar 

  • Badr G, Alwasel S, Ebaid H, Mohany M, Alhazza I (2011) Perinatal supplementation with thymoquinone improves diabetic complications and T cell immune responses in rat offspring. Cell Immunol 267(2):133–140

    Article  CAS  PubMed  Google Scholar 

  • Bagdas D, Etoz BC, Gul Z, Ziyanok S, Inan S, Turacozen O et al (2015) In vivo systemic chlorogenic acid therapy under diabetic conditions: wound healing effects and cytotoxicity/genotoxicity profile. Food Chem Toxicol 81:54–61

    Article  CAS  PubMed  Google Scholar 

  • Baluchnejadmojarad T, Roghani M, Khastehkhodaie Z (2010) Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat. Phytother Res 24:1120–1125

    CAS  PubMed  Google Scholar 

  • Bao L, Li J, Zha D, Zhang L, Gao P, Yao T et al (2018) Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-ĸB pathways. Int Immunopharmacol 54:245–253

    Article  CAS  PubMed  Google Scholar 

  • Barbagallo I, Vanella L, Cambria MT, Tibullo D, Godos J, Guarnaccia L et al (2016) Silibinin regulates lipid metabolism and differentiation in functional human adipocytes. Front Pharmacol 6:309

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J et al (2011) Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr 106:383

    Article  PubMed  CAS  Google Scholar 

  • Cazarolli L, Zanatta L, Alberton E, Reis Bonorino Figueiredo M, Folador P, Damazio R et al (2008) Flavonoids: cellular and molecular mechanism of action in glucose homeostasis. Mini Rev Med Chem 8:1032

    Article  CAS  PubMed  Google Scholar 

  • ÄŒerná M (2008) Genetics of autoimmune diabetes mellitus. Wien Med Wochenschr 158(1–2):2–12

    Article  PubMed  Google Scholar 

  • Chang KC, Li L, Sanborn TM, Shieh B, Lenhart P, Ammar D et al (2016) Characterization of Emodin as a therapeutic agent for diabetic cataract. J Nat Prod 79:1439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen CY, Jang JH, Li MH, Surh YJ (2005) Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells. Biochem Biophys Res Commun 331:993–1000

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Zhang L, Yi J, Yang Z, Zhang Z, Li Z (2012) Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity. J Cell Biochem 113:3547

    Article  CAS  PubMed  Google Scholar 

  • Chen R, Peng X, Du W, Wu Y, Huang B, Xue L et al (2015a) Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin via the PPARγ/Akt/NO signaling pathway. Diabetes Res Clin Pract 08:235–242

    Article  CAS  Google Scholar 

  • Chen T, Zheng LY, Xiao W, Gui D, Wang X, Wang N (2015b) Emodin ameliorates high glucose induced-podocyte epithelial-mesenchymal transition in-vitro and in-vivo. Cell Physiol Biochem 35:1425–1436

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Li B, Chen B, Shao Y, Luo Q, Shi X et al (2016) Thymoquinone alleviates the experimental diabetic peripheral neuropathy by modulation of inflammation. Sci Rep 6:31656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen B, He T, Xing Y, Cao T (2017) Effects of quercetin on the expression of MCP-1, MMP-9 and VEGF in rats with diabetic retinopathy. Exp Ther Med Greece 14(6):6022–6026

    CAS  Google Scholar 

  • Cheng B, Gong H, Li X, Sun Y, Zhang X, Chen H et al (2012) Silibinin inhibits the toxic aggregation of human islet amyloid polypeptide. Biochem Biophys Res Commun 419:495

    Article  CAS  PubMed  Google Scholar 

  • Dao TMA, Waget A, Klopp P, Serino M, Vachoux C, Pechere L et al (2011) Resveratrol increases glucose induced GLP-1 secretion in mice: a mechanism which contributes to the glycemic control. PLoS One 6:e20700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dash RP, Ellendula B, Agarwal M, Nivsarkar M (2015) Increased intestinal P-glycoprotein expression and activity with progression of diabetes and its modulation by epigallocatechin-3-gallate: evidence from pharmacokinetic studies. Eur J Pharmacol 767:67

    Article  CAS  PubMed  Google Scholar 

  • Dhanya R, Arya AD, Nisha P, Jayamurthy P (2017) Quercetin, a lead compound against type 2 diabetes ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line. Front Pharmacol 8:336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding L, Li J, Song B, Xiao X, Zhang B, Qi M et al (2016) Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway. Toxicol Appl Pharmacol 304:99

    Article  CAS  PubMed  Google Scholar 

  • dos Reis LCR, de Oliveira VR, Hagen MEK, Jablonski A, FlÔres SH, de Oliveira Rios A (2015) Carotenoids, flavonoids, chlorophylls, phenolic compounds and antioxidant activity in fresh and cooked broccoli (Brassica oleracea var. avenger) and cauliflower (Brassica oleracea var. Alphina F1). LWT Food Sci Technol 61:177–183

    Article  CAS  Google Scholar 

  • Du C, Shi Y, Ren Y, Wu H, Yao F, Wei J et al (2015) Anthocyanins inhibit high-glucose-induced cholesterol accumulation and inflammation by activating LXRα pathway in HK-2 cells. Drug Des Devel Ther 9:5099–5113

    CAS  PubMed  PubMed Central  Google Scholar 

  • Du L, Hao M, Li C, Wu W, Wang W, Ma Z et al (2017) Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high-glucose-cultured lens, and SRA01/04 cells through transforming growth factor-β2/phosphoinositide 3-kinase/Akt pathway. Mol Cell Endocrinol 452:44

    Article  CAS  PubMed  Google Scholar 

  • Ebrahimpour Koujan S, Gargari BP, Mobasseri M, Valizadeh H, Asghari-Jafarabadi M (2015) Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial. Phytomedicine 22:290

    Article  CAS  PubMed  Google Scholar 

  • El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, El-Sayed M, Takewaki T (2005a) Successful abrogation by thymoquinone against induction of diabetes mellitus with streptozotocin via nitric oxide inhibitory mechanism. Int Immunopharmacol 5:195

    Article  CAS  PubMed  Google Scholar 

  • El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, Nikami H, Takewaki T (2005b) Macrophage-derived cytokine and nitric oxide profiles in type I and type II diabetes mellitus: effect of thymoquinone. Acta Diabetol 42:23

    Article  CAS  PubMed  Google Scholar 

  • Fan L, Zhang H, Li X, Yang G, Ru J, Liu T (2018) Emodin protects hyperglycemia-induced injury in PC-12cells by up-regulation of miR-9. Mol Cell Endocrinol Irel 474:194–200

    Article  CAS  Google Scholar 

  • Fang WJ, Wang CJ, He Y, Zhou YL, Peng XD, Liu SK (2018) Resveratrol alleviates diabetic cardiomyopathy in rats by improving mitochondrial function through PGC-1α deacetylation. Acta Pharmacol Sin 39:59

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, Huang SL, Dou W, Zhang S, Chen JH, Shen Y et al (2010) Emodin, a natural product, selectively inhibits 11β-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice. Br J Pharmacol 161:113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Förstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33(7):829–837

    Article  PubMed  CAS  Google Scholar 

  • Fouad AA, Alwadani F (2015) Ameliorative effects of thymoquinone against eye lens changes in streptozotocin diabetic rats. Environ Toxicol Pharmacol 40:960

    Article  CAS  PubMed  Google Scholar 

  • Gao J, Wang F, Wang W, Su Z, Guo C, Cao S (2014) Emodin suppresses hyperglycemia-induced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP. PLoS One 9(4):e93588

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gao Y, Zhang J, Li G, Xu H, Yi Y, Wu Q et al (2015) Protection of vascular endothelial cells from high glucose-induced cytotoxicity by emodin. Biochem Pharmacol 94:39

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Ramirez M, Turch M, Simo-Servat O, Hernandez C, Simo R (2018) Silymarin prevents diabetes-induced hyperpermeability in human retinal endothelial cells. Endocrinol Diabetes y Nutr 65:200

    Article  Google Scholar 

  • Ghadieh HE, Smiley ZN, Kopfman MW, Najjar MG, Hake MJ, Najjar SM (2015) Chlorogenic acid/chromium supplement rescues diet-induced insulin resistance and obesity in mice. Nutr Metab 12:19

    Article  CAS  Google Scholar 

  • Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 106:1449–1458

    Article  CAS  Google Scholar 

  • Gram DX, Ahrén B, Nagy I, Olsen UB, Brand CL, Sundler F et al (2007) Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes. Eur J Neurosci 25:213

    Article  PubMed  Google Scholar 

  • Gu M, Zhao P, Huang J, Zhao Y, Wang Y, Li Y et al (2016) Silymarin ameliorates metabolic dysfunction associated with diet-induced obesity via activation of Farnesyl X receptor. Front Pharmacol 7:345

    PubMed  PubMed Central  Google Scholar 

  • Guigas B, Naboulsi R, Villanueva GR, Taleux N, Lopez-Novoa JM, Leverve XM et al (2007) The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perifused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase. Cell Physiol Biochem 20:925

    Article  CAS  PubMed  Google Scholar 

  • Guo H, Li D, Ling W, Feng X, Xia M (2011) Anthocyanin inhibits high glucose-induced hepatic mtGPAT1 activation and prevents fatty acid synthesis through PKCζ. J Lipid Res 52:908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo S, Meng XW, Yang XS, Liu XF, Ou-Yang CH, Liu C (2018) Curcumin administration suppresses collagen synthesis in the hearts of rats with experimental diabetes. Acta Pharmacol Sin 39:195–204

    Article  PubMed  Google Scholar 

  • Hao F, Kang J, Cao Y, Fan S, Yang H, An Y et al (2015) Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways. Apoptosis 20:1420–1432

    Article  CAS  PubMed  Google Scholar 

  • Heshmati J, Namazi N (2015) Effects of black seed (Nigella sativa) on metabolic parameters in diabetes mellitus: a systematic review. Complement Ther Med 23:275

    Article  PubMed  Google Scholar 

  • Hidalgo J, Teuber S, Morera FJ, Ojeda C, Flores CA, Hidalgo MA et al (2017) Delphinidin reduces glucose uptake in mice jejunal tissue and human intestinal cells lines through FFA1/GPR40. Int J Mol Sci 18:pii: E750

    Article  CAS  Google Scholar 

  • Hintzpeter J, Stapelfeld C, Loerz C, Martin HJ, Maser E (2014) Green tea and one of its constituents, epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. PLoS One 9:e84468

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ho C, Hsu YC, Lei CC, Mau SC, Shih YH, Lin CL (2016) Curcumin rescues diabetic renal fibrosis by targeting superoxide-mediated Wnt signaling pathways. Am J Med Sci 351:286–295

    Article  PubMed  Google Scholar 

  • Holst JJ (2004) Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. AJP Endocrinol Metab 287:E199

    Article  CAS  Google Scholar 

  • Holst JJ, Vilsbøll T, Deacon CF (2009) The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 297:127–136

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Huang K, Lan T, Xie X, Shen X, Liu P et al (2013) Curcumin ameliorates diabetic nephropathy by inhibiting the activation of the SphK1-S1P signaling pathway. Mol Cell Endocrinol 365:231

    Article  CAS  PubMed  Google Scholar 

  • Hwang SH, Kwon SH, Wang Z, Kim TH, Kang YH, Lee JY et al (2016) Optimization of extraction parameters of PTP1β (protein tyrosine phosphatase 1β), inhibitory polyphenols, and anthocyanins from Zea mays L. using response surface methodology (RSM). BMC Complement Altern Med 16:317

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ibrahim UK, Muhammad II, Salleh RM (2011) The effect of pH on color behavior of Brassica oleracea anthocyanin. J Appl Sci 11(13):2406–2410

    Article  CAS  Google Scholar 

  • IIZUKA Y, OZEKI A, TANI T, TSUDA T (2018) Blackcurrant extract ameliorates hyperglycemia in type 2 diabetic mice in association with increased basal secretion of glucagon-like Peptide-1 and activation of AMP-activated protein kinase. J Nutr Sci Vitaminol (Tokyo) 64:258

    Article  CAS  Google Scholar 

  • Javed S, Kohli K, Ali M (2011) Reassessing bioavailability of silymarin. Altern Med Rev 16:239–249

    PubMed  Google Scholar 

  • Jia T, Rao J, Zou L, Zhao S, Yi Z, Wu B et al (2018) Nanoparticle-encapsulated curcumin inhibits diabetic neuropathic pain involving the P2Y12 receptor in the dorsal root ganglia. Front Neurosci 11:755

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiménez-Flores LM, López-Briones S, Macías-Cervantes MH, Ramírez-Emiliano J, Pérez-Vázquez V (2014) A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Molecules 19:8289–8302

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jin Q-H, Shen H-X, Wang H, Shou Q-Y, Liu Q (2013) Curcumin improves expression of SCF/c-kit through attenuating oxidative stress and NF-κB activation in gastric tissues of diabetic gastroparesis rats. Diabetol Metab Syndr 5(1):12. Available from: https://doi.org/10.1186/1758-5996-5-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin S, Chang C, Zhang L, Liu Y, Huang X, Chen Z (2015) Chlorogenic acid improves late diabetes through adiponectin receptor signaling pathways in db/db mice. PLoS One 10(4):e0120842

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kadam S, Kanitkar M, Dixit K, Deshpande R, Seshadri V, Kale V (2018) Curcumin reverses diabetes-induced endothelial progenitor cell dysfunction by enhancing MnSOD expression and activity in vitro and in vivo. J Tissue Eng Regen Med 12:1594

    Article  CAS  PubMed  Google Scholar 

  • Kang JH, Kim CS, Han IS, Kawada T, Yu R (2007) Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages. FEBS Lett 581:4389

    Article  CAS  PubMed  Google Scholar 

  • Kang JH, Tsuyoshi G, Han IS, Kawada T, Kim YM, Yu R (2010) Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity 18:780

    Article  CAS  PubMed  Google Scholar 

  • Karandrea S, Yin H, Liang X, Slitt AL, Heart EA (2017) Thymoquinone ameliorates diabetic phenotype in Diet-Induced Obesity mice via activation of SIRT-1-dependent pathways. PLoS One 12:e0185374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kato M, Tani T, Terahara N, Tsuda T (2015) The anthocyanin delphinidin 3-rutinoside stimulates glucagon-like peptide-1 secretion in murine GLUTag cell line via the Ca2+/calmodulin-dependent kinase II pathway. PLoS One 10:e0126157

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kato M, Nishikawa S, Ikehata A, Dochi K, Tani T, Takahashi T et al (2017) Curcumin improves glucose tolerance via stimulation of glucagon-like peptide-1 secretion. Mol Nutr Food Res 61(3):1600471

    Article  CAS  Google Scholar 

  • Khan N, Mukhtar H (2007) Tea polyphenols for health promotion. Life Sci 81:519–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan MA, Anwar S, Aljarbou AN, Al-Orainy M, Aldebasi YH, Islam S et al (2014) Protective effect of thymoquinone on glucose or methylglyoxal-induced glycation of superoxide dismutase. Int J Biol Macromol 65:16

    Article  CAS  PubMed  Google Scholar 

  • Khazim K, Gorin Y, Cavaglieri RC, Abboud HE, Fanti P (2013) The antioxidant silybin prevents high glucose-induced oxidative stress and podocyte injury in vitro and in vivo. AJP Ren Physiol 305:F691

    Article  CAS  Google Scholar 

  • Kheiripour N, Karimi J, Khodadadi I, Tavilani H, Goodarzi MT, Hashemnia M (2018) Silymarin prevents lipid accumulation in the liver of rats with type 2 diabetes via sirtuin1 and SREBP-1c. J Basic Clin Physiol Pharmacol 29(3):301–308

    Article  CAS  PubMed  Google Scholar 

  • Kim JA, Formoso G, Li Y, Potenza MA, Marasciulo FL, Montagnani M et al (2007) Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and fyn. J Biol Chem 282:13736–13745

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Jeong IH, Kim CS, Lee YM, Kim JM, Kim JS (2011a) Chlorogenic acid inhibits the formation of advanced glycation end products and associated protein cross-linking. Arch Pharm Res 34:495

    Article  CAS  PubMed  Google Scholar 

  • Kim YS, Kim NH, Lee YM, Kim JS (2011b) Preventive effect of Chlorogenic acid on Lens opacity and cytotoxicity in human Lens epithelial cells. Biol Pharm Bull 34:925

    Article  CAS  PubMed  Google Scholar 

  • Kim JJY, Tan Y, Xiao L, Sun YL, Qu X (2013) Green tea polyphenol epigallocatechin-3-gallate enhance glycogen synthesis and inhibit lipogenesis in hepatocytes. Biomed Res Int 2013:1

    Google Scholar 

  • Kittl M, Beyreis M, Tumurkhuu M, Fürst J, Helm K, Pitschmann A et al (2016) Quercetin stimulates insulin secretion and reduces the viability of rat INS-1 Beta-cells. Cell Physiol Biochem 39:278

    Article  CAS  PubMed  Google Scholar 

  • Lee JH, Song MY, Song EK, Kim EK, Moon WS, Han MK et al (2009) Overexpression of SIRT1 protects pancreatic β-cells against cytokine toxicity by suppressing the nuclear factor-κB signaling pathway. Diabetes 58:344–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Volti G, Salomone S, Sorrenti V, Mangiameli A, Urso V, Siarkos I et al (2011) Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice. Cardiovasc Diabetol 10:62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Wang P, Zhu Y, Chen Z, Shi T, Lei W et al (2015) Curcumin inhibits neuronal loss in the retina and elevates Ca 2+/Calmodulin-dependent protein kinase II activity in diabetic rats. J Ocul Pharmacol Ther 31:555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Ding L, Song B, Xiao X, Qi M, Yang Q et al (2016) Emodin improves lipid and glucose metabolism in high fat diet-induced obese mice through regulating SREBP pathway. Eur J Pharmacol 770:99–109

    Article  CAS  PubMed  Google Scholar 

  • Lin J, Tang Y, Kang Q, Chen A (2012) Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro. Lab Investig 92:827–841

    Article  CAS  PubMed  Google Scholar 

  • Lipchock JM, Hendrickson HP, Douglas BB, Bird KE, Ginther PS, Rivalta I et al (2017) Characterization of protein tyrosine phosphatase 1B inhibition by Chlorogenic acid and cichoric acid. Biochemistry 56:96

    Article  CAS  PubMed  Google Scholar 

  • Liu H-S (2005) Inhibitory effect of green tea (−)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway. AJP Endocrinol Metab 288(5):C1094–C1108

    Google Scholar 

  • Liu H, Liu HY, Jiang YN, Li N (2016) Protective effect of thymoquinone improves cardiovascular function, and attenuates oxidative stress, inflammation and apoptosis by mediating the PI3K/Akt pathway in diabetic rats. Mol Med Rep 13:2836–2842

    Article  CAS  PubMed  Google Scholar 

  • Lu M, Tao L, Mei W, Luo R, Fu X, Wang L, Yang WLC (2014) Effect of curcumin on the expression of p-STAT3 and IκB in db/db mice. Zhong Nan Da Xue Xue Bao Yi Xue Ban 39(6):591–597. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25011972

    CAS  PubMed  Google Scholar 

  • Lu Q, Ji XJ, Zhou YX, Yao XQ, Liu YQ, Zhang F et al (2015) Quercetin inhibits the mTORC1/p70S6K signaling-mediated renal tubular epithelial-mesenchymal transition and renal fibrosis in diabetic nephropathy. Pharmacol Res 99:237

    Article  CAS  PubMed  Google Scholar 

  • Lu M, Ho CT, Huang Q (2017a) Extraction, bioavailability, and bioefficacy of capsaicinoids. J Food Drug Anal 25:27–36

    Article  CAS  PubMed  Google Scholar 

  • Lu M, Yin N, Liu W, Cui X, Chen S, Wang E (2017b) Curcumin ameliorates diabetic nephropathy by suppressing NLRP3 Inflammasome signaling. Biomed Res Int 2017:1–10

    CAS  Google Scholar 

  • Lu CP, Huang CY, Wang SH, Chiu CH, Li LH, Hua KF et al (2018a) Improvement of hyperglycemia in a murine model of insulin resistance and high glucose- and inflammasome-mediated IL-1β expressions in macrophages by silymarin. Chem Biol Interact 290:12

    Article  CAS  PubMed  Google Scholar 

  • Lu Q, Hao M, Wu W, Zhang N, Isaac AT, Yin J et al (2018b) Antidiabetic cataract effects of GbE, rutin and quercetin are mediated by the inhibition of oxidative stress and polyol pathway. Acta Biochim Pol 65:35–41

    Article  CAS  PubMed  Google Scholar 

  • Lucini L, Kane D, Pellizzoni M, Ferrari A, Trevisi E, Ruzickova G et al (2016) Phenolic profile and in vitro antioxidant power of different milk thistle [Silybum marianum (L.) Gaertn.] cultivars. Ind Crop Prod 83:11–16

    Article  CAS  Google Scholar 

  • Luna-Vital DA, De Mejia EG (2018) Anthocyanins from purple corn activate free fatty acid-receptor 1 and glucokinase enhancing in vitro insulin secretion and hepatic glucose uptake. PLoS One 13:e0200449

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lv W, Zhang J, Jiao A, Wang B, Chen B, Lin J (2018) Resveratrol attenuates hIAPP amyloid formation and restores the insulin secretion ability in hIAPP-INS1 cell line via enhancing autophagy. Can J Physiol Pharmacol Canada 97:82–89

    Article  CAS  Google Scholar 

  • Ma J, Li Z, Xing S, Ho WTT, Fu X, Zhao ZJ (2011) Tea contains potent inhibitors of tyrosine phosphatase PTP1B. Biochem Biophys Res Commun 407:98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maksymchuk O, Shysh A, Rosohatska I, Chashchyn M (2017) Quercetin prevents type 1 diabetic liver damage through inhibition of CYP2E1. Pharmacol Rep 69:1386

    Article  CAS  PubMed  Google Scholar 

  • Malekinejad H, Rezabakhsh A, Rahmani F, Hobbenaghi R (2012) Silymarin regulates the cytochrome P450 3A2 and glutathione peroxides in the liver of streptozotocin-induced diabetic rats. Phytomedicine 19:583

    Article  CAS  PubMed  Google Scholar 

  • Matsuda T, Ferreri K, Todorov I, Kuroda Y, Smith CV, Kandeel F et al (2005) Silymarin protects pancreatic β-cells against cytokine-mediated toxicity: implication of c-Jun NH2-terminal kinase and Janus kinase/signal transducer and activator of transcription pathways. Endocrinology 146:175

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto T, Watanabe S, Kawamura R, Taguchi K, Kobayashi T (2014) Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of disease. Life Sci 118:200

    Article  CAS  PubMed  Google Scholar 

  • Maugeri A, Mazzone MG, Giuliano F, Vinciguerra M, Basile G, Barchitta M et al (2018) Curcumin modulates DNA methyltransferase functions in a cellular model of diabetic retinopathy. Oxidative Med Cell Longev 2018:1

    Article  Google Scholar 

  • Mei X, Zhou L, Zhang T, Lu B, Sheng Y, Ji L (2018) Chlorogenic acid attenuates diabetic retinopathy by reducing VEGF expression and inhibiting VEGF-mediated retinal neoangiogenesis. Vasc Pharmacol 101:29

    Article  CAS  Google Scholar 

  • Meng B, lu SL, ting SX, sheng GY, fang FX, Li J et al (2015) Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain. Neurosci Lett 605:59–64

    Article  CAS  PubMed  Google Scholar 

  • Meng R, Mahadevan J, Oseid E, Vallerie S, Robertson RP (2016) Silymarin activates c-AMP phosphodiesterase and stimulates insulin secretion in a glucose-dependent manner in HIT-T15 cells. Antioxidants 5:pii: E47

    Article  CAS  Google Scholar 

  • Miladpour B, Rasti M, Owji AA, Mostafavipour Z, Khoshdel Z, Noorafshan A et al (2017) Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro. J Endocrinol Investig 40:513

    Article  CAS  Google Scholar 

  • Oboh G, Isaac AT, Akinyemi AJ, Ajani RA (2014) Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside induced lipid peroxidation in rats’ pancreas by phenolic extracts of avocado pear leaves and fruit. Int J Biomed Sci 10:208–216

    PubMed  PubMed Central  Google Scholar 

  • Ong KW, Hsu A, Tan BKH (2012) Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes. PLoS One 7:e32718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ono T, Takada S, Kinugawa S, Tsutsui H (2015) Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination. Exp Physiol 100:1052

    Article  CAS  PubMed  Google Scholar 

  • Park S, Kang S, Jeong DY, Jeong SY, Park JJ, Yun HS (2015) Cyanidin and malvidin in aqueous extracts of black carrots fermented with Aspergillus oryzae prevent the impairment of energy, lipid and glucose metabolism in estrogen-deficient rats by AMPK activation. Genes Nutr 10:455

    PubMed  Google Scholar 

  • Peng J, Li Q, Li K, Zhu L, Lin X, Lin X et al (2017) Quercetin improves glucose and lipid metabolism of diabetic rats: involvement of Akt signaling and SIRT1. J Diabetes Res 2017:1

    Article  CAS  Google Scholar 

  • Peristiowati Y, Indasah I, Ratnawati R (2015) The effects of catechin isolated from green tea GMB-4 on NADPH and nitric oxide levels in endothelial cells exposed to high glucose. J Intercult Ethnopharmacol 4:114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Persson IAL (2013) Tea flavanols: An overview. In: Tea in health and disease prevention. Academic, Massachusetts, pp 73–78

    Chapter  Google Scholar 

  • Ponugoti B, Kim DH, Xiao Z, Smith Z, Miao J, Zang M et al (2010) SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem 285:33959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Popescu M, Bogdan C, Pintea A, Rugină D, Ionescu C (2018) Antiangiogenic cytokines as potential new therapeutic targets for resveratrol in diabetic retinopathy. Drug Des Devel Ther Volume 12:1985

    Article  Google Scholar 

  • Poretsky L (2010) Principles of diabetes mellitus. Springer, Boston

    Book  Google Scholar 

  • Pullikotil P, Chen H, Muniyappa R, Greenberg CC, Yang S, Reiter CEN et al (2012) Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial cells via p38 MAPK and Nrf-2 that suppresses proinflammatory actions of TNF-α. J Nutr Biochem 23:1134

    Article  CAS  PubMed  Google Scholar 

  • Qiao Y, Gao K, Wang Y, Wang X, Cui BO (2017) Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 mapk/tgf-β1 pathway. Exp Ther Med 13:3223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rachana, Thakur S, Basu S (2015) Oxidative stress and diabetes. In: Free radicals in human health and disease. Springer, New Delhi

    Google Scholar 

  • Radu BM, Iancu AD, Dumitrescu DI, Flonta ML, Radu M (2013) TRPV1 properties in thoracic dorsal root ganglia neurons are modulated by intraperitoneal capsaicin administration in the late phase of type-1 autoimmune diabetes. Cell Mol Neurobiol 33:187

    Article  CAS  PubMed  Google Scholar 

  • Rahimi R, Karimi J, Khodadadi I, Tayebinia H, Kheiripour N, Hashemnia M et al (2018) Silymarin ameliorates expression of urotensin II (U-II) and its receptor (UTR) and attenuates toxic oxidative stress in the heart of rats with type 2 diabetes. Biomed Pharmacother 101:244

    Article  CAS  PubMed  Google Scholar 

  • Real Hernandez LM, Fan J, Johnson MH, De Mejia EG (2015) Berry phenolic compounds increase expression of hepatocyte nuclear factor-1α (HNF-1α) in Caco-2 and normal colon cells due to high affinities with transcription and dimerization domains of HNF-1α. PLoS One 10:e0138768

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rizvi SI, Pandey KB (2010) Activation of the erythrocyte plasma membrane redox system by resveratrol: a possible mechanism for antioxidant properties. Pharmacol Rep 62:726

    Article  CAS  PubMed  Google Scholar 

  • Rouse M, Younès A, Egan JM (2014) Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity. J Endocrinol 223:107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saez-Lopez C, Brianso-Llort L, Torres-Torrenteras J, Simó R, Hammond GL, Selva DM (2017) Resveratrol increases hepatic SHBG expression through human constitutive Androstane receptor: a new contribution to the French paradox. Sci Rep 7:12284

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sampath C, Rashid MR, Sang S, Ahmedna M (2017) Green tea epigallocatechin 3-gallate alleviates hyperglycemia and reduces advanced glycation end products via nrf2 pathway in mice with high fat diet-induced obesity. Biomed Pharmacother 87:73

    Article  CAS  PubMed  Google Scholar 

  • Sanchez MB, Miranda-Perez E, Verjan JCG, de los Angeles Fortis Barrera M, Perez-Ramos J, Alarcon-Aguilar FJ (2017) Potential of the chlorogenic acid as multitarget agent: insulin-secretagogue and PPAR α/γ dual agonist. Biomed Pharmacother 94:169

    Article  CAS  PubMed  Google Scholar 

  • Sarkar P, Bhowmick A, Kalita MC, Banu S (2018) Effects of resveratrol and mangiferin on PPARγ and FALDH gene expressions in adipose tissue of streptozotocin-nicotinamide-induced diabetes in rats. J Dietary Suppl 9:1–17

    Article  CAS  Google Scholar 

  • Scazzocchio B, Varì R, Filesi C, D’Archivio M, Santangelo C, Giovannini C et al (2011) Cyanidin-3-O-β-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes. Diabetes 60:2234–2244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seale P (2015) Transcriptional regulatory circuits controlling brown fat development and activation. Diabetes 64:2369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaqura M, Khalefa BI, Shakibaei M, Zöllner C, Al-Khrasani M, Fürst S et al (2014) New insights into mechanisms of opioid inhibitory effects on capsaicin-induced TRPV1 activity during painful diabetic neuropathy. Neuropharmacology 85:142

    Article  CAS  PubMed  Google Scholar 

  • Sharma R, Dave V, Sharma S, Jain P, Yadav S (2013) Experimental models on diabetes: a comprehensive review. Int J Adv Pharm Sci 4:1–08

    Google Scholar 

  • Shi X, Pi L, Zhou S, Li X, Min F, Wang S et al (2018) Activation of Sirtuin 1 attenuates high glucose-induced neuronal apoptosis by deacetylating p53. Front Endocrinol (Lausanne) 9:274

    Article  Google Scholar 

  • SHIMADA M, MOCHIZUKI K, SAKURAI N, GODA T (2007) Dietary supplementation with epigallocatechin Gallate elevates levels of circulating adiponectin in non-obese Type-2 diabetic Goto-Kakizaki rats. Biosci Biotechnol Biochem 71:2079

    Article  CAS  PubMed  Google Scholar 

  • Shin JY, Sohn J, Park KH (2013) Chlorogenic acid decreases retinal vascular hyperpermeability in diabetic rat model. J Korean Med Sci 28(4):608–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smoliga JM, Baur JA, Hausenblas HA (2011) Resveratrol and health – a comprehensive review of human clinical trials. Mol Nutr Food Res 55:1129

    Article  CAS  PubMed  Google Scholar 

  • Soetikno V, Watanabe K, Sari FR, Harima M, Thandavarayan RA, Veeraveedu PT et al (2011) Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1activity in streptozotocin-induced type I diabetic rats. Mol Nutr Food Res 55(11):1655–1665

    Article  CAS  PubMed  Google Scholar 

  • Son Y, Lee JH, Chung HT, Pae HO (2013) Therapeutic roles of heme oxygenase-1 in metabolic diseases: curcumin and resveratrol analogues as possible inducers of heme oxygenase-1. Oxidative Med Cell Longev 2013:639541

    Article  CAS  Google Scholar 

  • Song JX, Ren H, Gao YF, Lee CY, Li SF, Zhang F et al (2017) Dietary capsaicin improves glucose homeostasis and alters the gut microbiota in obese diabetic ob/ob Mice. Front Physiol 8:602

    Article  PubMed  PubMed Central  Google Scholar 

  • Soobrattee MA, Neergheen VS, Luximon-Ramma A, Aruoma OI, Bahorun T (2005) Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res Fundam Mol Mech Mutagen 579:200

    Article  CAS  Google Scholar 

  • Soto C, Raya L, Juarez J, Perez J, Gonzalez I (2014a) Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic beta-cells in a pancreatectomy model. Phytomedicine Germany 21(3):233–239

    Article  CAS  Google Scholar 

  • Soto C, Raya L, Pérez J, González I, Pérez S (2014b) Silymarin induces expression of pancreatic Nkx6.1 transcription factor and β-cells Neogenesis in a pancreatectomy model. Molecules 19:4654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srinivasan K (2018) Cumin (Cuminum cyminum) and black cumin (Nigella sativa) seeds: traditional uses, chemical constituents, and nutraceutical effects. Food Qual Saf 2:1

    Article  CAS  Google Scholar 

  • Stalmach A, Crozier A, Clifford MN, Williamson G (2011) Phytochemicals in coffee and the bioavailability of chlorogenic acids. In: Teas, cocoa and coffee: plant secondary metabolites and health. Wiley-Blackwell, Chichester/West Sussex/Hoboken, pp 143–168

    Chapter  Google Scholar 

  • Stolf AM, Campos Cardoso C, de MH, Alves de Souza CE, Lomba LA, Brandt AP et al (2018) Effects of silymarin on angiogenesis and oxidative stress in streptozotocin-induced diabetes in mice. Biomed Pharmacother France 108:232–243

    Article  CAS  Google Scholar 

  • Strunz CMC, Roggerio A, Cruz PL, Pacanaro AP, Salemi VMC, Benvenuti LA et al (2017) Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes. J Nutr Biochem 40:219

    Article  CAS  PubMed  Google Scholar 

  • Stumvoll M, Goldstein BJ, Van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365:1333

    Article  CAS  PubMed  Google Scholar 

  • Suganya N, Dornadula S, Chatterjee S, Mohanram RK (2018a) Quercetin improves endothelial function in diabetic rats through inhibition of endoplasmic reticulum stress-mediated oxidative stress. Eur J Pharmacol 819:80

    Article  CAS  PubMed  Google Scholar 

  • Suganya N, Krishnapriya M, Sireesh D, Rajaguru P, Vairamani M, Suresh T et al (2018b) Establishment of pancreatic microenvironment model of ER stress: quercetin attenuates β-cell apoptosis by invoking nitric oxide-cGMP signaling in endothelial cells. J Nutr Biochem 55:142

    Article  CAS  PubMed  Google Scholar 

  • Sun LN, Chen ZX, Liu XC, Liu HY, Guan GJ, Liu G (2014a) Curcumin ameliorates epithelial-to-mesenchymal transition of podocytes in vivo and in vitro via regulating caveolin-1. Biomed Pharmacother 68:1079

    Article  CAS  PubMed  Google Scholar 

  • Sun LN, Yang ZY, Lv SS, Liu XC, Guan GJ, Liu G (2014b) Curcumin prevents diabetic nephropathy against inflammatory response via reversing caveolin-1 Tyr14phosphorylation influenced TLR4 activation. Int Immunopharmacol 23:236

    Article  CAS  PubMed  Google Scholar 

  • Sun W, Liu X, Zhang H, Song Y, Li T, Liu X et al (2017) Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1. Free Radic Biol Med 108:840

    Article  CAS  PubMed  Google Scholar 

  • Tan C, Meng F, Reece EA, Zhao Z (2018) Modulation of nuclear factor-κB signaling and reduction of neural tube defects by quercetin-3-glucoside in embryos of diabetic mice. Am J Obstet Gynecol 219:197.e1

    Article  CAS  Google Scholar 

  • Thilavech T, Ngamukote S, Belobrajdic D, Abeywardena M, Adisakwattana S (2016) Cyanidin-3-rutinoside attenuates methylglyoxal-induced protein glycation and DNA damage via carbonyl trapping ability and scavenging reactive oxygen species. BMC Complement Altern Med 16:138

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tian C, Zhang R, Ye X, Zhang C, Jin X, Yamori Y et al (2013) Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway. Genes Nutr 8:231–239

    Article  CAS  PubMed  Google Scholar 

  • Timmers S, Konings E, Bilet L, Houtkooper RH, Van De Weijer T, Goossens GH et al (2011) Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 14:612–622

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Huang H, Liu P, Tang F, Qin J, Huang W et al (2006) Inhibition of phosphorylation of p38 MAPK involved in the protection of nephropathy by emodin in diabetic rats. Eur J Pharmacol 553:297

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Liu M, Liu WW, Hao WB, Tashiro SI, Onodera S et al (2012a) In vivo recovery effect of silibinin treatment on streptozotocin-induced diabetic mice is associated with the modulations of sirt-1 expression and autophagy in pancreatic-cell. J Asian Nat Prod Res 14:413

    Article  CAS  PubMed  Google Scholar 

  • Wang YJ, Huang SL, Feng Y, Ning MM, Leng Y (2012b) Emodin, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, regulates adipocyte function in vitro and exerts anti-diabetic effect in ob/ob mice. Acta Pharmacol Sin 33:1195

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang Z, Yang L, Fan H, Wu P, Zhang F, Zhang C et al (2017) Screening of a natural compound library identifies emodin, a natural compound from Rheum palmatum Linn that inhibits DPP4. PeerJ 5:e3283

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Watanabe RM, Black MH, Xiang AH, Allayee H, Lawrence JM, Buchanan TA (2007) Genetics of gestational diabetes mellitus and type 2 diabetes. Diabetes Care 30(Suppl. 2):S134–S140

    Article  CAS  PubMed  Google Scholar 

  • Wei J, Wu H, Zhang H, Li F, Chen S, Hou B et al (2018) Anthocyanins inhibit high glucose-induced renal tubular cell apoptosis caused by oxidative stress in db/db mice. Int J Mol Med Greece 41(3):1608–1618

    CAS  Google Scholar 

  • Weisberg S, Leibel R, Tortoriello D (2016) Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice. Nutr Diabetes 6:e205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wimmer RJ, Russell SJ, Schneider MF (2015) Green tea component EGCG, insulin and IGF-1 promote nuclear efflux of atrophy-associated transcription factor Foxo1 in skeletal muscle fibers. J Nutr Biochem 26:1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wongeakin N, Bhattarakosol P, Patumraj S (2014) Molecular mechanisms of curcumin on diabetes-induced endothelial dysfunctions: Txnip, ICAM-1, and NOX2 expressions. Biomed Res Int 2014:161346

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu C-H, Huang S-M, Yen G-C (2011) Silymarin: a novel antioxidant with Antiglycation and Antiinflammatory properties In Vitro and In Vivo. Antioxid Redox Signal 14:353

    Article  CAS  PubMed  Google Scholar 

  • Wu Z, Chen Q, Ke D, Li G, Deng W (2014) Emodin protects against diabetic cardiomyopathy by regulating the AKT/GSK-3β signaling pathway in the rat model. Molecules 19:14782

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu H, Li GN, Xie J, Li R, Chen QH, Chen JZ et al (2016a) Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-β/periostin pathway in STZ-induced diabetic mice. BMC Cardiovasc Disord 16:5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu H, Sheng ZQ, Xie J, Li R, Chen L, Li GN et al (2016b) Reduced HMGB 1-mediated pathway and oxidative stress in resveratrol-treated diabetic mice: a possible mechanism of Cardioprotection of resveratrol in diabetes mellitus. Oxidative Med Cell Longev 2016:9836860

    Google Scholar 

  • Wu H, Chen Z, Chen J-Z, Xie J, Xu B (2018) Resveratrol improves tube formation in AGE-induced late endothelial progenitor cells by suppressing Syndecan-4 shedding. Oxidative Med Cell Longev 2018:1–9

    CAS  Google Scholar 

  • Xiong S, Salazar G, Patrushev N, Alexander RW (2011) FoxO1 mediates an autofeedback loop regulating SIRT1 expression. J Biol Chem 286:5289

    Article  CAS  PubMed  Google Scholar 

  • Xu X-H, Ding D-F, Yong H-J, Dong C-L, You N, Ye X-L et al (2017) Resveratrol transcriptionally regulates miRNA-18a-5p expression ameliorating diabetic nephropathy via increasing autophagy. Eur Rev Med Pharmacol Sci Italy 21(21):4952–4965

    Google Scholar 

  • Xue J, Ding W, Liu Y (2010) Anti-diabetic effects of emodin involved in the activation of PPARγ on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice. Fitoterapia 81:173

    Article  CAS  PubMed  Google Scholar 

  • Yadollah S, Kazemipour N, Bakhtiyari S, Nazifi S (2017) Palmitate-induced insulin resistance is attenuated by Pioglitazone and EGCG through reducing the gluconeogenic key enzymes expression in HepG2 cells. J Med Life 10:244–249

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang J, Sun Y, Xu F, Liu W, Hayashi T, Onodera S et al (2018) Involvement of estrogen receptors in silibinin protection of pancreatic β-cells from TNFα- or IL-1β-induced cytotoxicity. Biomed Pharmacother 102:344–353

    Article  CAS  PubMed  Google Scholar 

  • Yasui K, Tanabe H, Miyoshi N, Suzuki T, Goto S, Taguchi K et al (2011) Effects of (−)-epigallocatechin-3-O-gallate on expression of gluconeogenesis-related genes in the mouse duodenum. Biomed Res 32:313

    Article  CAS  PubMed  Google Scholar 

  • Ye H-Y, Li Z-Y, Zheng Y, Chen Y, Zhou Z-H, Jin J (2016) The attenuation of chlorogenic acid on oxidative stress for renal injury in streptozotocin-induced diabetic nephropathy rats. Arch Pharm Res Korea (South) 39(7):989–997

    Article  CAS  Google Scholar 

  • Ye M, Qiu H, Cao Y, Zhang M, Mi Y, Yu J et al (2017) Curcumin improves palmitate-induced insulin resistance in human umbilical vein endothelial cells by maintaining proteostasis in endoplasmic reticulum. Front Pharmacol 08:148

    Article  CAS  Google Scholar 

  • Ying X, Chen X, Liu H, Nie P, Shui X, Shen Y et al (2015) Silibinin alleviates high glucose-suppressed osteogenic differentiation of human bone marrow stromal cells via antioxidant effect and PI3K/Akt signaling. Eur J Pharmacol 765:394

    Article  CAS  PubMed  Google Scholar 

  • Youreva V, Kapakos G, Srivastava AK (2013) Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells. Can J Physiol Pharmacol Canada 91(3):241–247

    Article  CAS  Google Scholar 

  • Zha W, Bai Y, Xu L, Liu Y, Yang Z, Gao H et al (2018) Curcumin attenuates testicular injury in rats with Streptozotocin-induced diabetes. Biomed Res Int United States 2018:7468019

    Google Scholar 

  • Zhang D-W, Fu M, Gao S-H, Liu J-L (2013) Curcumin and diabetes: a systematic review. Evid Based Complement Alternat Med 2013:1

    Google Scholar 

  • Zhang HT, Shi K, Baskota A, Zhou FL, Chen YX, Tian HM (2014a) Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats. Eur J Pharmacol 740:233

    Article  CAS  PubMed  Google Scholar 

  • Zhang YJ, Lu XW, Song N, Kou L, Wu MK, Liu F et al (2014b) Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons. Int J Oral Sci 6:233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Liang D, Guo L, Liang W, Jiang Y, Li H et al (2015) Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1. Mol Med Rep 12(1):1347–1355

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Zhang ZK, Liang S (2016) Epigallocatechin-3-gallate protects retinal vascular endothelial cells from high glucose stress in vitro via the MAPK/ERK-VEGF pathway. Genet Mol Res 15(2):gmr.15027874

    Google Scholar 

  • Zhao XY, Qiao GF, Li BX, Chai LM, Li Z, Lu YJ et al (2009) Hypoglycaemic and hypolipidaemic effects of emodin and its effect on L-type calcium channels in dyslipidaemic-diabetic rats. Clin Exp Pharmacol Physiol 36:29

    Article  CAS  PubMed  Google Scholar 

  • Zhao JY, Hu YW, Li SF, Hu YR, Ma X, Wu SG et al (2014) Dihydrocapsaicin down-regulates apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells. Lipids Health Dis 13:50

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhao Y, Song W, Wang Z, Wang Z, Jin X, Xu J et al (2018) Resveratrol attenuates testicular apoptosis in type 1 diabetic mice: role of Akt-mediated Nrf2 activation and p62-dependent Keap1 degradation. Redox Biol 14:609

    Article  CAS  PubMed  Google Scholar 

  • Zhong J, Xu C, Reece EA, Yang P (2016) The green tea polyphenol EGCG alleviates maternal diabetes–induced neural tube defects by inhibiting DNA hypermethylation. Am J Obstet Gynecol 215:368.e1

    Article  CAS  Google Scholar 

  • Zhuang M, Qiu H, Li P, Hu L, Wang Y, Rao L (2018) Islet protection and amelioration of type 2 diabetes mellitus by treatment with quercetin from the flowers of Edgeworthia gardneri. Drug Des Devel Ther 12:955–966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Hoda, M., Hemaiswarya, S., Doble, M. (2019). Mechanisms of Action of Phenolic Phytochemicals in Diabetes Management. In: Role of Phenolic Phytochemicals in Diabetes Management. Springer, Singapore. https://doi.org/10.1007/978-981-13-8997-9_4

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