Abstract
Recently available drugs of synthetic origin in management of obesity and diabetes are costly and not affordable by poor people and have potential adverse side effects, and thereby these cause serious other complications among many obese and diabetic patients. As a result, some of these drugs have been withdrawn from the market. For this reason, most of the leading pharmaceutical industries have paid their attention for discovery of potential natural compounds with low-cost and minimal adverse effects for treatment of obesity and diabetes as an alternative strategy. In the earlier chapter, we have discussed that a large variety of natural resources, namely, dietary fruits, vegetables, grains, plants, seaweeds, edible and medicinal mushrooms, marine fishes and cucumbers, and microorganisms, have potential anti-obesity and antidiabetic effects. Their bioactive phytochemicals having diverse skeletal structures and belonging to different chemical classes, such as flavonoids, simple phenolics, lignans, stilbenoids, curcuminoids, tannins, alkaloids, terpenoids, steroids, saponins, organosulfurs, thiosugars, and polysaccharides. A growing body of evidence demonstrates that these natural products have multiple targets of action for prevention and treatment of obesity and diabetes. Most of these natural components exhibit hypolipidemic, hypoglycemic, antioxidant, and anti-inflammatory activities for improvement of insulin resistance, insulin secretion, and insulin action in insulin-responsive tissues for amelioration of lipid and glucose metabolic disorders in cellular and vivo models of obesity and diabetes. In this chapter, we address the pharmacology of some phytochemicals having potent anti-obesity and antidiabetic activity and their major natural sources and molecular targets.
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References
Abe D, Saito T, Nagata Y (2016) Rosmarinic acid regulates fatty acid and glucose utilization by activating the CaMKK/AMPK pathway in C2C12 myotubes. Food Sci Technol Res 22:779–785
Akiyama S, Katsumata SI, Suzuki K et al (2010) Dietary hesperidin exerts hypoglycaemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. J Clin Biochem Nutr 46:87–92
Alam MA, Kauter K, Brown L (2013) Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats. Nutrients 5:637–650
Alkhalidy H, Moore W, Zhang Y et al (2015) Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic β-cell mass in middle-aged obese diabetic mice. J Diabetes Res 2015:532984
Alkhalidy H, Moore W, Zhang Y et al (2018) Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice. J Nutr Biochem 58:90–101
Allister EM, Mulvihill EE, Barrett PHR et al (2008) Inhibition of apo B secretion from HepG2 cells by insulin is amplified by naringenin, independent of the insulin receptor. J Lipid Res 49:2218–2229
Al-Trad B, Alkhateeb H, Alsmadi W et al (2019) Eugenol ameliorates insulin resistance, oxidative stress and inflammation in high fat-diet/streptozotocin-induced diabetic rats. Life Sci 216:183–188
Ambati RR, Phang SM, Ravi S et al (2014) Astaxanthin: sources, extraction, stability, biological activities and its commercial applications-a review. Mar Drugs 12:128–152
An T, Zhang J, Lv B et al (2019) Salvianolic acid B plays an anti-obesity role in high fat diet-induced obese mice by regulating the expression of mRNA, circRNA and lncRNA. Peer J 7:e6506
Anand David AV, Arulmoli R, Parasuram S (2016) Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev 10:84–89
Assini JM, Mulvihill EE, Burke AC et al (2015) Naringenin prevents obesity, hepatic steatosis, and glucose intolerance in male mice independent of fibroblast growth factor 21. Endocrinology 156:2087–2102
Atanassova M, Bagdassarian V (2009) Rutin content in plant products. J Univ Chem Technol Metallur 44:201–203
Aulifa DL, Adnyana IK, Levita J et al (2019) 4-Hydroxyderricin isolated from the sap of Angelica keiskei Koidzumi: evaluation of its inhibitory activity towards dipeptidyl peptidase-IV. Sci Pharm 87:30
Babukumar S, Vinothkumar V, Sankaranarayanan C et al (2017) Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Pharm Biol 55:1442–1449
Bai N, He K, Roller M et al (2008) Active compounds from Lagerstroemia speciosa, insulin-like glucose uptake-stimulatory/inhibitory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells. J Agric Food Chem 56:11668–11674
Bai J, Wang Y, Zhu X et al (2019) Eriodictyol inhibits high glucose-induced extracellular matrix accumulation, oxidative stress, and inflammation in human glomerular mesangial cells. Phytother Res 33:2775–2782
Baiges I, Palmfeldt J, Blade C et al (2010) Lipogenesis is decreased by grape seed proanthocyanidins according to liver proteomics of rats fed a high fat diet. Mol Cell Proteomics 9:1499–1513
Bak EJ, Kim J, Jang S et al (2013) Gallic acid improves glucose tolerance and triglyceride concentration in diet-induced obesity mice. Scand J Clin Lab Invest 73:607–614
Bao Q, Shen X, Qian L et al (2016) Anti-diabetic activities of catalpol in db/db mice. Korean J Physiol Pharmacol 20:153–160
Basha RH, Sankaranarayanan C (2014) β-Caryophyllene, a natural sesquiterpene, modulates carbohydrate metabolism in streptozotocin-induced diabetic rats. Acta Histochem 116:1469–1479
Basha RH, Sankaranarayanan C (2015) Protective effect of β-caryophyllene, a sesquiterpene lactone on plasma and tissue glycoprotein components in streptozotocin-induced hyperglycaemic rats. J Acute Med 5:9–14
Baskaran P, Krishnan V, Ren J et al (2016) Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV-1 channel-dependent mechanisms. Br J Pharmacol 173:2369–2389
Baur JA, Pearson KJ, Price NL et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342
BelHadj S, Hentati O, Elfeki A et al (2013) Inhibitory activities of Ulva lactuca polysaccharides on digestive enzymes related to diabetes and obesity. Arch Physiol Biochem 119:81–87
Benn T, Kim B, Park YK et al (2014) Polyphenol-rich blackcurrant extract prevents inflammation in diet-induced obese mice. J Nutr Biochem 25:1019–1025
Bettaieb A, Hosein E, Chahed S et al (2015) Decreased adiposity and enhanced glucose tolerance in shikonin treated mice. Obesity (Silver Spring) 23:2269–2277
Bettaieb A, Cremonini E, Kang H et al (2016) Anti-inflammatory actions of (-)-epicatechin in the adipose tissue of obese mice. Int J Biochem Cell Biol 81(Pt B):383–392
Bhagwat S, Haytowitz DB, Holden JM (2011) USDA database for the flavonoid content of selected foods: release 3, US Department of Agriculture, Washington. USA. 2011:1–156
Bhattacharya S, Oksbjerg N, Young JF et al (2014a) Caffeic acid, naringenin and quercetin enhance glucose-stimulated insulin secretion and glucose sensitivity in INS-1E cells. Diabetes Obes Metab 16:602–612
Bhattacharya S, Rasmussen MK, Christensen LP et al (2014b) Naringenin and falcarinol stimulate glucose uptake and TBC1D1 phosphorylation in porcine myotube cultures. J Biochem Pharmacol Res 2:91–98
Bilbao LMM, Andres-Lacueva C, Jauregui O et al (2007) Determination of flavonoids in a citrus fruit extract by LC-DAD and LC-MS. Food Chem 101:1742–1747
Birgani GA, Ahangarpour A, Khorsandi L et al (2018) Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model. Braz J Pharm Sci 54:e17171
Bonnefont-Rousselot D (2016) Resveratrol and cardiovascular diseases. Nutrients 8:250
Bose M, Lambert JD, Ju J et al (2008) The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice. J Nutr 138:1677–1683
Boyle SP, Dobson VL, Duthie SJ et al (2000) Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study. Eur J Clin Nutr 54:774–782
Caimari A, Del Bas JM, Crescenti A et al (2013) Low doses of grape seed procyanidins reduce adiposity and improve the plasma lipid profile in hamsters. Int J Obes 37:576–583
Cao X, Xia Y, Liu D et al (2020) Inhibitory effects of Lentinus edodes mycelia polysaccharide on α-glucosidase, glycation activity and high-glucose-induced cell damage. Carbohydr Polymers 246:116659
Casas-Grajales S, Ramos-Tovar E, Chavez-Estrada E et al (2019) Antioxidant and immunomodulatory activity induced by stevioside in liver damage: in vivo, in vitro and in silico assays. Life Sci 224:187–196
Cassady JM, Zennie TM, Chae YH et al (1988) Use of a mammalian cell culture benzo(a) pyrene metabolism assay for the detection of potential anticarcinogens from natural products: inhibition of metabolism by biochanin A, an isoflavone from Trifolium pratense L. Cancer Res 48:6257–6261
Cazarolli LH, Kappel VD, Pereira DF et al (2012) Antihyperglycemic action of apigenin-6-C-β-fucopyranoside from Averrhoa carambola. Fitoterapia 83:1176–1183
Cedernaes J, Waldeck N, Bass J (2019) Neurogenetic basis for circadian regulation of metabolism by the hypothalamus. Genes Dev 33:1136–1158
Celik S, Erdogan S, Tuzcu M (2009) Caffeic acid phenethyl ester (CAPE) exhibits significant potential as an antidiabetic and liver protective agent in streptozotocin-induced diabetic rats. Pharmacol Res 60:270–276
Chang SL, Chang CLT, Chiang YM et al (2004) Polyacetylenic compounds and butanol fraction from Bidens pilosa can modulate the differentiation of helper T cells and prevent autoimmune diabetes in non-obese diabetic mice. Planta Med 70:1045–1051
Chang CLT, Chang SL, Lee YM et al (2007) Cytopiloyne, a polyacetylenic glucoside, prevents type 1 diabetes in nonobese diabetic mice. J Immunol 178:6984–6993
Chang WC, Wu SC, Xu KD et al (2015) Scopoletin protects against methylglyoxal-induced hyperglycemia and insulin resistance mediated by suppression of advanced glycation endproducts (AGEs) generation and anti-glycation. Molecules 20:2786–2801
Chao J, Huo TI, Cheng HY et al (2014) Gallic acid ameliorated impaired glucose and lipid homeostasis in high fat diet-induced NAFLD mice. PLoS One 9:e96969
Chen TH, Chen SC, Chan P et al (2005) Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana. Planta Med 71:108–113
Chen YC, Zeng XY, He Y et al (2013) Rutaecarpine analogues reduce lipid accumulation in adipocytes via inhibiting adipogenesis/lipogenesis with AMPK activation and UPR suppression. ACS Chem Biol 8:2301–2311
Chen Z, Zheng S, Li L et al (2014) Metabolism of flavonoids in humans: a comprehensive review. Curr Drug Metab 15:48–61
Chen CC, Chuang WT, Lin AH et al (2016a) Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation. Toxicol Appl Pharmacol 307:115–122
Chen L, Zhang Y, Sha O et al (2016b) Hypolipidaemic and hypoglycaemic activities of polysaccharide from Pleurotus eryngii in Kunming mice. Int J Biol Macromol 93(Pt A):1206–1209
Chen S, Wen X, Zhang W et al (2017) Hypolipidemic effect of oleanolic acid is mediated by the miR-98-5p/PGC-1β axis in high-fat diet-induced hyperlipidemic mice. FASEB J 31:1085–1096
Chen C, You LJ, Huang Q et al (2018a) Modulation of gut microbiota by mulberry fruit polysaccharide treatment of obese diabetic db/db mice. Food Funct 9:3732–3742
Chen XF, Wang L, Wu YZ et al (2018b) Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial oxidative capacity and biogenesis in skeletal muscle in diabetic rats. Nutr Diabetes 8:1
Chen G, Ni Y, Nagata N et al (2019) Lycopene alleviates obesity-induced inflammation and insulin resistance by regulating M1/M2 status of macrophages. Mol Nutr Food Res 63:1900602
Cheng Z, Pang T, Gu M et al (2006) Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK. Biochim Biophys Acta 1760:1682–1689
Cheng B, Gao W, Wu X et al (2020) Ginsenoside Rg2 ameliorates high-fat diet-induced metabolic disease through SIRT 1. J Agric Food Chem 68:4215–4226
Cheungsamarn S, Rattanamongkolgul S, Luechapudiporn R et al (2012) Curcumin extract for prevention of type 2 diabetes. Diabetes Care 35:2121–2127
Chiang YM, Chang CLT, Chang SL et al (2007) Cytopiloyne, a novel polyacetylenic glucoside from Bidens pilosa, functions as a T helper cell modulator. J Ethnopharmacol 110:532–538
Cho AS, Jeon SM, Kim MJ et al (2010) Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced obese mice. Food Chem Toxicol 48:937–943
Cho S, Choi Y, Park S et al (2012) Carvacrol prevents diet-induced obesity by modulating gene expressions involved in adipogenesis and inflammation in mice fed with high-fat diet. J Nutr Biochem 23:192–201
Choi MS, Jung UJ, Yeo J et al (2008) Genistein and daidzein prevent diabetes onset by elevating insulin level and altering hepatic gluconeogenic and lipogenic enzyme activities in non-obese diabetic (NOD) mice. Diabetes Metab Res Rev 24:74–81
Choi HD, Kim JH, Chang MJ et al (2011) Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res 25:1813–1818
Choi HN, Kang MJ, Lee SJ et al (2014a) Ameliorative effect of myricetin on insulin resistance in mice fed a high-fat, high-sucrose diet. Nutr Res Pract 8:544–549
Choi KM, Lee YS, Kim W et al (2014b) Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice. J Nutr Biochem 25:201–207
Choi RY, Ham JR, Lee MK (2016) Esculetin prevents non-alcoholic fatty liver in diabetic mice fed high-fat diet. Chem Biol Interact 260:13–21
Choi RY, Ham JR, Lee HI et al (2017) Scopoletin supplementation ameliorates steatosis and inflammation in diabetic mice. Phytother Res 31:1795–1804
Cipriani S, Mencarelli A, Palladino G et al (2010) FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res 51:771–784
Collins QF, Liu HY, Pi J et al (2007) Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5′-AMP-activated protein kinase. J Biol Chem 282:30143–30149
Combs TR, Marliss EB (2014) Adiponectin signaling in liver. Rev Endocr Metab Disord 15:137–147
Cremonini E, Bettaieb A, Haj FG et al (2016) (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch Biochem Biophys 599:13–21
Cui L, Kim MO, Seo JH et al (2012) Abietane diterpenoids of Rosmarinus officinalis and their diacylglycerol acyltransferase inhibitory activity. Food Chem 132:1775–1780
Dabeek WM, Marra MV (2019) Dietary quercetin and kaempferol: bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients 11:2288
Dela Sena C, Narayanasamy S, Riedi KM et al (2013) Substrate specificity of purified recombinant human β-carotene-15,15′-oxygenase (BCO1). J Biol Chem 288:37094–37103
Del Bas JM, Ricketts ML, Vague M et al (2009) Dietary procyanidins enhance transcriptional activity of bile acid-activated FXR in vitro and reduce triglyceridemia in vivo in a FXR-dependent manner. Mol Nutr Food Res 53:805–814
De Melo CL, Queiroz MGR, Fonseca SGC et al (2010) Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet. Chem Biol Interact 185:59–65
De Natale C, Minerva V, Patti L et al (2012) Effects of baked products enriched with n-3 fatty acids, folates, β-glucans, and tocopherol in patients with mild mixed hyperlipidemia. J Am Col Nutr 31:211–319
Dhanya R, Arya AD, Nisha P et al (2017) Quercetin, a lead compound against type 2 diabetes, ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line. Front Pharmacol 8:336
Dinda B, Dinda S, DasSharma S et al (2017) Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur J Med Chem 131:68–80
Dineshkumar B, Mitra A, Mahadevappa M (2010) Antidiabetic and hypolipidemic effects of mahanimbine (carbazole alkaloid) from Murraya koenigii (Rutaceae) leaves. Int J Phytomed 2:22–30
Ding H, Zhang Y, Xu C et al (2014a) Norathyriol reverses obesity- and high-fat-diet-induced insulin resistance in mice through inhibition of PTP1B. Diabetologia 57:2145–2154
Ding L, Li J, Song B et al (2014b) Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway. J Pharmacol Exp Ther 351:474–483
Ding Y, Song Z, Li H et al (2019) Honokiol ameliorates high-fat-diet-induced obesity of different sexes of mice by modulating the composition of the gut microbiota. Front Immunol 10:2800
Diwan V, Poudyal H, Brown L (2013) Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats. Cell Biochem Biophys 67:297–304
Doan KV, Ko CM, Kinyua AW et al (2015) Gallic acid regulates body weight and glucose homeostasis through AMPK activation. Endocrinology 156:157–168
Du J, Xie J, Zhang Z et al (2010) TRPM7-mediated Ca2+ signals confer fibrogenesis in human atrial fibrillation. Circ Res 106:992–1003
Du Y, Chen Y, Fu X et al (2020) Effects of piperine on lipid metabolism in high-fat diet induced obese mice. J Funct Foods 71:104011
Du F, Huang R, Lin D et al (2021) Resveratrol improves liver steatosis and insulin resistance in non-alcoholic fatty liver disease in association with the gut microbiota. Front Pharmacol 12:611323
Eid HM, Martineau LC, Saleem A et al (2010) Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol Nutr Food Res 54:991–1003
Eliza J, Daisy P, Ignacimuthu S et al (2009) Normo-glycemic and hypolipidemic effect of costunolide isolated from Costus speciosus (Koen ex. Retz.)Sm. in streptozotocin-induced diabetic rats. Chem Biol Interact 179:329–334
Enoki T, Ohnogi H, Nagamine K et al (2007) Antidiabetic activities of chalcones isolated from a Japanese herb, Angelica keiskei. J Agric Food Chem 55:6013–6017
Escande C, Nin V, Price NL et al (2013) Flavonoid apigenin is an inhibitor of the NAD+ ase CD38. Diabetes 62:1084–1093
Eu CHA, Lim WYA, Ton SH et al (2010) Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat-diet-induced obese rats. Lipids Health Dis 9:81
Eze ED, Afodun AM, Sulaiman SO et al (2018) Lycopene attenuates diabetes-induced oxidative stress in Wistar rats. J Diabetes Endocrinol 9:11–19
Fang P, Yu M, Zhang L et al (2017) Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway. Mol Cell Endocrinol 448:77–86
Fang P, Yu M, Min W et al (2018) Beneficial effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice. Diabetes Res Clin Pract 139:262–271
Fang P, He B, Yu M et al (2019) Treatment with celastrol protects against obesity through suppression of galanin-induced fat intake and activation of PGC-1α/GLUT4 axis-mediated glucose consumption. Biochim Biophys Acta 1865:1341–1350
Faraut B, Giannesini B, Matarazzo V et al (2009) Capsiate administration results in an uncoupling protein 3 downregulation, an enhanced muscle oxidative capacity and a decreased abdominal fat content in vivo. Int J Obes 33:1348–1355
Feng Y, Huang SL, Dou W 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 161:113–126
Feng X, Weng D, Zhou F et al (2016) Activation of PPARγ by a natural flavonoid modulator, apigenin ameliorates obesity-related inflammation via regulation of macrophage polarization. EBioMedicine 9:61–76
Fenni S, Hammou H, Astier J et al (2017) Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response and associated metabolic disorders. Mol Nutr Food Res 61:1601083
Fontecha-Barriuso M, Martin-Sanchez D, Ruiz-Andres O et al (2018) Targeting epigenetic DNA and histone modifications to treat kidney disease. Nephol Dial Transplant 33:1875–1886
Frombaum M, Therond P, Djelidi R et al (2011) Piceatannol is more effective than resveratrol in endothelial cell dimethylarginine dimethylaminohydrolase expression and activity after high-glucose oxidative stress. Free Radic Res 45:293–302
Fu Y, Luo J, Jia Z et al (2014) Baicalein protects against type 2 diabetes via promoting islet β-cell function in obese diabetic mice. Int J Endocrinol 2014:846742
Fujiwara Y, Tsukahara C, Ikeda N et al (2017) Oleuropein improves insulin resistance in skeletal muscle by promoting the translocation of GLUT4. J Clin Biochem Nutr 61:196–202
Fukumitsu S, Aida K, Ueno N et al (2008) Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice. Br J Nutr 100:669–676
Fukumitsu S, Aida K, Shimizu H et al (2010) Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men. Nutr Res 30:441–446
Gandhi GR, Jothi G, Antony PJ et al (2014) Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway. Eur J Pharmacol 745:201–216
Ganesan K, Xu B (2019) Anti-diabetic effects and mechanisms of dietary polysaccharides. Molecules 24:2556
Gao H, Huang YN, Gao B et al (2008) Chebulagic acid is a potent α-glucosidase inhibitor. Biosci Biotechnol Biochem 72:601–603
Gao C, Chen G, Liu L et al (2013) Impact of high glucose and proteasome inhibitor MG132 on histone H2A and H2B ubiquitination in rat glomerular mesangial cells. J Diabetes Res 2013:589474
Geddo F, Antoniotti S, Querio G et al (2021) Plant-derived trans-β-caryophyllene boosts glucose metabolism and ATP synthesis in skeletal muscle cells through cannabinoid type 2 receptor stimulation. Nutrients 13:916
Geeraert B, Crombe F, Hulsmans M et al (2010) Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice. Int J Obes 34:569–577
Genet C, Strehle A, Schmidt C et al (2010) Structure-activity relationship study of betulinic acid, a novel and selective TGR5 agonist and its synthetic derivatives: potential impact in diabetes. J Med Chem 53:178–190
Goboza M, Aboua YG, Chegou N et al (2019) Vindoline efficiently ameliorated diabetes-induced hepatotoxicity by docking oxidative stress, inflammation and hypertriglyceridemia in type 2 diabetes-induced male Wistar rats. Biomed Pharmacother 112:108638
Gonzalez-Garibay AS, Lopez-Vazquez A, Garcia-Banuelos J et al (2020) Effect of ursolic acid on insulin resistance and hyperinsulinemia in rats with diet-induced obesity: role of adipokines expression. J Med Food 23:297–304
Goto T, Kim Y-II, Funakoshi K et al (2011) Farnesol, an isoprenoid, improves metabolic abnormalities in mice via both PPARα-dependent and -independent pathways. Am J Physiol Endocrinol Metab 301:E1022–E1032
Guevara-Cruz M, Godinez-Salas ET, Sanchez-Tapia M et al (2020) Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects. BMJ Open Diab Res Cure 8:e000948
Guo YR, Choung SY (2017a) Germacrone attenuates hyperlipidemia and improves lipid metabolism in high-fat diet-induced obese C57BL/6J mice. J Med Food 20:46–55
Guo YR, Choung SY (2017b) Germacrone inhibits adipogenesis and stimulates lipolysis via AMP-activated protein kinase signalling pathway in 3T3-L1 preadipocytes. J Pharm Pharmacol 69:202–212
Guo J, Chen J, Ren W et al (2020a) Citrus flavone tangeretin is a potential insulin sensitizer targeting hepatocytes through suppressing MEK-ERK1/2 pathway. Biochem Biophys Res Commun 529:277–282
Guo L, Zhu B, Yuan H et al (2020b) Evaluation of serum neutrophil gelatinase-associated lipocalin in older patients with chronic kidney disease. Aging Med (Milton) 3:32–39
Guo S, Wang L, Chen D et al (2020c) Effects of a natural PTP1B inhibitor from Rhodomela confervoides on the amelioration of fatty acid-induced insulin resistance in hepatocytes and hyperglycemia in STZ-induced diabetic rats. RSC Adv 10:3429–3437
Gwon SY, Choi WH, Lee DH et al (2015) Shikonin protects against obesity through the modulation of adipogenesis, lipogenesis and β-oxidation in vivo. J Funct Foods 16:484–493
Gwon SY, Ahn J, Jung CH et al (2020) Shikonin attenuates hepatic steatosis by enhancing beta oxidation and energy expenditure via AMPK activation. Nutrients 12:1133
Hadrich F, Garcia M, Maalej A et al (2016) Oleuropein activated AMPK and induced insulin sensitivity in C2C12 muscle cells. Life Sci 151:167–173
Hameed A, Hafizur RM, Hussain N et al (2018) Eriodictyol stimulates insulin secretion through cAMP/PKA signalling pathway in mice islets. Eur J Pharmacol 820:245–255
Hamid HA, Yusoff MM, Liu M et al (2015) α-Glucosidase and α-amylase inhibitory constituents of Tinospora crispa: isolation and chemical profile confirmation by ultra-high performance liquid chromatography-quadrupole time-of-flight/mass spectrometry. J Funct Foods 16:74–80
Han CY, Ki SH, Kim YW et al (2011) Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activation. Antioxid Redox Signal 14:187–202
Harborne JB, Mabry TJ (1982) The flavonoids: advances in research, 1st edn. Chapman & Hall, New York
Harini R, Ezhumalai M, Pugalendi KV (2012) Antihyperglycemic effect of biochanin A, a soy isoflavone, on streptozotocin-diabetic rats. Eur J Pharmacol 676:89–94
Hashidume T, Sasaki K, Hirata J et al (2018) Effects of sanyaku and its constituent diosgenin on the fasted and postprandial hypertriacylglycerolemia in high-fat-diet-fed KK-Ay mice. J Agric Food Chem 66:9968–9975
He Y, Li Y, Zhao T et al (2013) Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway. PLoS One 8:e70135
Hintzpeter J, Stapelfeld C, Loerz C et al (2014) Green tea and one of its constituents, epigallocatechin-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. PLoS One 9:e84468
Hollman PCH, Arts ICW (2000) Flavonols, flavones and flavanols-nature, occurrence and dietary burdens. J Sci Food Agric 80:1081–1093
Hong Y, Lin Y, Si Q et al (2019) Ginsenoside Rb2 alleviates obesity by activation of brown fat and induction of browning of white fat. Front Endocrinol (Lausanne) 10:153
Hossain CM, Ghosh MK, Satapathy BS et al (2014) Apigenin causes biochemical modulation, GLUT4 and CD38 alternations to improve diabetes and to protect damages of some vital organs in experimental diabetes. Am J Pharmacol Toxicol 9:39–52
Hossain MK, Dayem AA, Han J et al (2016) Molecular mechanism of the anti-obesity and anti-diabetic properties of flavonoids. Int J Mol Sci 17:569
Hou B, Zhao Y, Qiang G et al (2018) Puerarin mitigates diabetic hepatic steatosis and fibrosis by inhibiting TGF-β signaling pathway activation in type 2 diabetic rats. Oxid Med Cell Longev 2018:4545321
Hou N, Mai Y, Qiu X et al (2019) Carvacrol attenuates diabetic cardiomyopathy by modulating the PI3K/Akt/GLUT4 pathway in diabetic mice. Front Pharmacol 10:998
Hsu YJ, Lee TH, Chang CLT et al (2009) Anti-hyperglycemic effects and mechanism of Bidens pilosa water extract. J Ethnopharmacol 122:379–383
Hu JL, Nie SP, Xie MY (2018) Antidiabetic mechanism of dietary polysaccharides based on their gastrointestinal functions. J Agric Food Chem 66:4781–4786
Huang H, Chen G, Liao D et al (2016a) The effects of resveratrol intervention on risk markers of cardiovascular health in overweight and obese subjects: a pooled analysis of randomized controlled trials. Obes Rev 17:1329–1340
Huang MQ, Zhou CJ, Zhang YP et al (2016b) Salvianolic acid B ameliorates hyperglycemia and dyslipidemia in db/db mice through the AMPK pathway. Cell Physiol Biochem 40:933–943
Huang Q, Want T, Yang L et al (2017a) Ginsenoside Rb2 alleviates hepatic lipid accumulation by restoring autophagy via induction of Sirt1 and activation of AMPK. Int J Mol Sci 18:1063
Huang WC, Liao PC, Huang CH et al (2017b) Osthole attenuates lipid accumulation, regulates the expression of inflammatory mediators, and increases antioxidants in FL83B cells. Biomed Pharmacother 91:78–87
Huang W, Zeng J, Liu Z et al (2019) Acetylshikonin stimulates glucose uptake in L6 myotubes via a PLC-β3/PKCδ-dependent pathway. Biomed Pharmacother 112:108588
Hung MW, Wu CW, Kokubu D et al (2019) ε-Viniferin is more effective than resveratrol in promoting adipocyte differentiation with enhanced adiponectin expression and decreased lipid accumulation. Food Sci Technol Res 25:817–826
Hwang YP, Choi JH, Han EH et al (2011) Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through activating adenosine monophosphate-activated protein kinase in human HepG2 cells and obese mice. Nutr Res 31:896–906
Ikarashi N, Takeda R, Ito K et al (2011a) The inhibition of lipase and glucosidase activities by acacia polyphenol. Evid Based Complement Altern Med 2011:272075
Ikarashi N, Toda T, Okaniwa T et al (2011b) Anti-obesity and anti-diabetic effects of acacia polyphenol in obese diabetic KK-Ay mice fed high-fat diet. Evid Based Complement Altern Med 2011:952031
Imaizumi K, Sato S, Kumazawa M et al (2011) Capsaicinoids-induced changes of plasma glucose, free fatty acid and glycerol concentrations in rats. J Toxicol Sci 36:109–116
Islam A, Islam MS, Rahman MK et al (2020) The pharmacological and biological roles of eriodictyol. Arch Pharm Res 43:582–592
Iwata A, Matsubara S, Miyazaki K (2018) Beneficial effects of a β-cryptoxanthin-containing beverage on body mass index and visceral fat in pre-obese men: double-blind, placebo-controlled parallel trials. J Funct Foods 41:250–257
Jain PG, Nayse PG, Patil DJ et al (2020) The possible antioxidant capabilities of formononetin in guarding against streptozotocin-induced diabetic nephropathy in rats. Future J Pharm Sci 6:53
Jang JH, Park JE, Han JS (2020) Scopoletin increases glucose uptake through activation of PI3K and AMPK signaling pathway and improves insulin sensitivity in 3T3-L1 cells. Nutr Res 74:52–61
Jayachandran M, Chandrasekaran B, Namasivayam N (2015) Effect of geraniol, a plant derived monoterpene on lipids and lipid metabolizing enzymes in experimental hyperlipidemic hamsters. Mol Cell Biochem 398:39–53
Jeon SM, Park YB, Choi MS (2004) Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits. Clin Nutr 23:1025–1034
Jeong SO, Son Y, Lee JH et al (2015) Resveratrol analog piceatannol restores the palmitic acid-induced impairment of insulin signaling and production of endothelial nitric oxide via activation of anti-inflammatory and antioxidative heme oxygenase-1 in human endothelial cells. Mol Med Rep 12:937–944
Jeppesen PB, Gregersen S, Rolfsen SED et al (2003) Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat. Metabolism 52:372–378
Ji X, Li C, Qu Y et al (2016) Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated renal oxidative stress and inflammation via Akt/NF-κB pathway. Mol Cell Endocrinol 437:268–279
Jia X, Yang J, Wang Z et al (2014) Polysaccharides from Laminaria japonica show hypoglycemic and hypolipidemic activities in mice with experimentally induced diabetes. Exp Biol Med 239:1663–1670
Jia L, Li W, Li J et al (2016) Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity. Sci Rep 6:36209
Jiang Q, Wang D, Han Y et al (2015) Modulation of oxidized-LDL-receptor-1 (LOX-1) contributes to the antiatherosclerosis effect of oleanolic acid. Int J Biochem Cell Biol 69:142–152
Jiang T, Shuai X, Li J et al (2020) Protein-bound anthocyanin compounds of purple sweet potato ameliorate hyperglycemia by regulating hepatic glucose metabolism in high-fat-diet/streptozotocin-induced diabetic mice. J Agric Food Chem 68:1596–1608
Jiao Y, Wang X, Jiang X et al (2017) Antidiabetic effects of Morus alba fruit polysaccharides on high-fat diet- and streptozotocin-induced type 2 diabetes in rats. J Ethnopharmacol 199:119–127
Jin L, Xue HY, Jin LJ et al (2008) Antioxidant and pancreas-protective effect of aucubin on rats with streptozotocin-induced diabetes. Eur J Pharmacol 582:162–167
Jing L, Zhang Y, Fan S et al (2013) Preventing and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat-diet-induced obesity. Eur J Pharmacol 715:46–55
Ju L, Wen X, Wang C et al (2017) Salidroside, a natural antioxidant, improves β-cell survival and function via activating AMPK pathway. Front Pharmacol 8:749
Jung UJ, Lee MK, Jeong KS et al (2004) The hypoglycemic effect of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/ksJ-db/db mice. J Nutr 134:2499–2503
Jung UJ, Lee MK, Park YB et al (2006a) Effects of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type 2 diabetic mice. Int J Biochem Cell Biol 38:1134–1145
Jung UJ, Lee MK, Park YB et al (2006b) Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice. J Pharmacol Exp Ther 318:476–483
Jung SA, Choi M, Kim S et al (2012) Cinchonine prevents high-fat-diet-induced obesity through downregulation of adipogenesis and adipose inflammation. PPAR Res 2012:541204
Jung UJ, Cho YY, Choi MS (2016) Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high-fat diet-induced obese mice. Nutrients 8:305
Jung E, Park SB, Jung WK et al (2019) Antiglycation activity of aucubin in vitro and in exogenous methylglyoxal injected rats. Molecules 24:3653
Kadakol A, Malek V, Goru SK et al (2015) Esculetin reverses histone 2A/2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy. J Funct Foods 17:127–136
Kadakol A, Malek V, Goru SK et al (2017) Esculetin ameliorates insulin resistance and type 2 diabetic nephropathy through reversal of histone H3 acetylation and H2A lysine119 monoubiquitination. J Funct Foods 35:256–266
Kamikubo R, Kai K, Tsuji-Naito K et al (2016) β-Caryophyllene attenuates palmitate-induced lipid accumulation through AMPK signaling by activating CB2 receptor in human HepG2 hepatocytes. Mol Nutr Food Res 60:2228–2242
Kanagasabapathy G, Malek SNA, Mahmood AA et al (2013) Beta-glucan-rich extract from Pleurotus sajor-caju (Fr) Singer prevents obesity and oxidative stress in C57BL/6J mice fed on a high-fat diet. Evid Based Complement Alternat Med 2013:185259
Kang JH, Kim CS, Han IS et al (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 adopose tissue macrophages. FEBS Lett 581:4389–4396
Kang JH, Goto T, Han IS et al (2010) Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity 18:780–787
Kang JH, Tsuyoshi G, Ngoc HL et al (2011a) Dietary capsaicin attenuates metabolic dysregulation in genetically obese diabetic mice. J Med Food 14:310–315
Kang SI, Ko HC, Shin HS et al (2011b) Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes. Biochem Biophys Res Commun 409:769–777
Kang SI, Shin HS, Kim HM et al (2012) Petalonia binghamiae extract and its constituent fucoxanthin ameliorate high-fat diet-induced obesity by activating AMP-activated protein kinase. J Agric Food Chem 60:3389–3395
Kang KS, Lee W, Jung Y et al (2014) Protective effect of esculin on streptozotocin-induced diabetic renal damage in mice. J Agric Food Chem 62:2069–2076
Kang C, Wang B, Kaliannan K et al (2017) Gut microbiota mediates the protective effects of dietary capsaicin against chronic low-grade inflammation and associated obesity induced by high-fat diet. mBio 8:e00470-17
Kang JW, Park J, Kim HL et al (2018a) Secoisolariciresinol diglucoside inhibits adipogenesis through the AMPK pathway. Eur J Pharmacol 820:235–244
Kang MJ, Kwon EB, Ryu HW et al (2018b) Polyacetylene from Dendropanax morbifera alleviates diet-induced obesity and hepatic steatosis by activating AMPK signaling pathway. Front Pharmacol 9:537
Kaufman PB, Duke JA, Brielmann H et al (1997) A comparative survey of leguminous plants as sources of the isoflavones, genistein and daidzein: implications for human nutrition and health. J Altern Complement Med 3:7–12
Kawabata K, Yoshioka Y, Terao J (2019) Role of intestinal microbiota in the bioavailability and physiological functions of dietary polyphenols. Molecules 24:370
Khanbabaee K, Ree TV (2001) Tannins: classification and definition. Nat Prod Rep 18:641–649
Kim YJ, Jung UJ (2019) Honokiol improves insulin resistance, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Int J Mol Sci 20:2303
Kim EJ, Jung SN, Son KH et al (2007) Antidiabetes and antiobesity effect of cryptotanshinone via activation of AMP-activated protein kinase. Mol Pharmacol 72:62–72
Kim SJ, Lee SJ, Lee S et al (2009) Rutecarpine ameliorates body weight gain through the inhibition of orexigenic neuropeptides NPY and AgRP in mice. Biochem Biophys Res Commun 389:437–442
Kim KY, Nguyen TH, Kurihara H et al (2010) α-Glucosidase inhibitory activity of bromophenol purified from the red alga Polyopes lancifolia. J Food Sci 75:H145–H150
Kim JH, Kang MJ, Choi HN et al (2011) Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutr Res Pract 5:107–111
Kim HY, Park M, Kim K et al (2012a) Hesperetin stimulates cholecystokinin secretion in enteroendocrine STC-1 cells. Biomed Ther (Seoul) 21:121–125
Kim MS, Hur HJ, Kwon DY et al (2012b) Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice. Mol Cell Endocrinol 358:127–134
Kim MA, Kang K, Lee HJ et al (2014) Apigenin isolated from Daphne genkwa Siebold et Zucc. inhibits 3T3-L1 preadipocyte differentiation through a modulation of mitotic clonal expansion. Life Sci 101:64–72
Kim KS, Yang HJ, Lee IS et al (2015) The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice. Sci Rep 5:18325
Kim MJ, Koo YD, Kim M et al (2016) Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis in C2C12 myotubes. Diabetes Metab J 40:406–413
Kim HL, Jung Y, Park J et al (2017a) Farnesol has an anti-obesity effect in high-fat diet-induced obese mice and induces the development of beige adipocytes in human adipose tissue derived- mesenchymal stem cells. Front Pharmacol 8:654
Kim J, Yun EY, Quan FS et al (2017b) Central administration of 1-deoxynojirimycin attenuates hypothalamic endoplasmic reticulum stress and regulates food intake and body weight in mice with high-fat diet-induced obesity. Evid Based Complement Altern Med 2017:3607089
Kim HM, Kim Y, Lee ES et al (2018a) Caffeic acid ameliorates hepatic steatosis and reduces ER stress in high fat diet-induced obese mice by regulating autophagy. Nutrition 55-56:63–70
Kim JS, Lee H, Jung CH et al (2018b) Chicoric acid mitigates impaired insulin sensitivity by improving mitochondrial function. Biosci Biotechnol Biochem 82:1197–1206
Kim KD, Jung HY, Ryu HG et al (2019) Betulinic acid inhibits high-fat diet-induced obesity and improves energy balance by activating AMPK. Nutr Metab Cardiovasc Dis 29:409–420
Klein G, Kim J, Himmeldirk K et al (2007) Antidiabetes and anti-obesity activity of Lagerstroemia speciosa. eCAM 4:401–407
Kong WJ, Zhang H, Song DQ et al (2009) Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism 58:109–119
Kong X, Wang GD, Ma MZ et al (2015) Sesamin ameliorates advanced glycation endproducts-induced pancreatic β-cell dysfunction and apoptosis. Nutrients 7:4689–4704
Krishnamoorthy RM, Venkatraman AC (2017) Polyphenols activate energy sensing network in insulin resistant models. Chem Biol Interact 275:95–107
Kumar S, Ds G, Shin HS et al (2017) Dioscorea spp. (a wild edible tuber): a study of its ethnopharmacological potential and traditional use by the people of similipal biosphere reserve, India. Front Pharmacol 2017:00052
Kunkel SD, Elmore CJ, Bongers KS et al (2012) Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One 7:e39332
Kuo YH, Lin CH, Shih CC (2016a) Dehydroeburicoic acid from Antrodia camphorata prevents the diabetic and dyslipidemic state via modulation of glucose transporter 4, peroxisome proliferator-activated receptor α expression and AMP-activated protein kinase phosphorylation in high-fat-fed mice. Int J Mol Sci 17:872
Kuo YH, Lin CH, Shih CC et al (2016b) Antcin K, a triterpenoid compound from Antrodia camphorata, displays antidiabetic and antihyperlipidemic effects via glucose transporter 4 and AMP-activated protein kinase phosphorylation in muscles. Evid Based Complement Altern Med 2016:4867092
Kuroda M, Iwabuchi K, Mimaki Y (2012) Chemical constituents of Scutellaria lateriflora and their alpha-glucosidase inhibitory activities. Nat Prod Commun 7:471–474
Kwon EY, Choi MS (2019) Dietary eriodictyol alleviates adiposity, hepatic steatosis, insulin resistance, and inflammation in diet-induced obese mice. Int j Mol Sci 20:1227
Kwon JY, Seo SG, Heo YS et al (2012) Piceatannol, a natural polyphenolic stilbene, inhibits adipogenesis via modulation of mitotic clonal expansion and insulin receptor-dependent insulin signaling in early phase of differentiation. J Biol Chem 287:11566–11578
Lafiandra D, Riccardi G, Shewry PR (2014) Improving cereal grain carbohydrates for diet and health. J Cereal Sci 59:312–326
Lagouge M, Argmann C, Gerhart-Hines Z et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122
Lao CD, Ruffin MT IV, Normolle D et al (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6:10
Lee YS, Kim WS, Kim KH et al (2006) Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 55:2256–2264
Lee WH, Lin RJ, Lin SY et al (2011) Osthole enhances glucose uptake through activation of AMP-activated protein kinase in skeletal muscle cells. J Agric Food Chem 59:12874–12881
Lee B, Kwon M, Choi JS et al (2015) Kaempferol isolated from Nelumbo nucifera inhibits lipid accumulation and increases fatty acid oxidation signaling in adipocytes. J Med Food 18:1363–1370
Lee JB, Yoon SJ, Lee SH et al (2017) Ginsenoside Rg3 ameliorated HFD-induced hepatic steatosis through downregulation of STAT5-PPARγ. J Endocrinol 235:223–235
Lee H, Li H, Kweon M et al (2018a) Isobavachalcone from Angelica keiskei inhibits adipogenesis and prevents lipid accumulation. Int J Mol Sci 19:1693
Lee S, Keirsey KI, Kirkland R et al (2018b) Blueberry supplementation influences the gut microbiota, inflammation, and insulin resistance in high-fat-diet-fed rats. J Nutr 148:209–219
Lee CG, Rhee DK, Kim BO et al (2019) Allicin induces beige-like adipocytes via KLF-15 signal cascade. J Nutr Biochem 64:13–24
Li Y, Kim J, Li J et al (2005) Natural antidiabetic compound 1,2,3,4,6-penta-O-galloyl-D-glucopyranoside binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway. Biochem Biophys Res Commun 336:430–437
Li HL, Huang Y, Zhang CN et al (2006a) Epigallocatechin-3-gallate inhibits cardiac hypertrophy through blocking reactive oxidative species-dependent and -independent signal pathways. Free Radic Biol Med 40:1756–1775
Li W, Cui SW, Kakuda Y (2006b) Extraction, fractionation, structural and physical characterization of wheat β-D-glucans. Carbohydr Polym 63:408–416
Li X, Xiao Y, Gao H et al (2009) Grape seed proanthocyanidins ameliorate diabetic nephropathy via modulation of levels of AGE, RAGE and CTGF. Nephron Exp Nephrol 111:e31
Li Y, Kang Z, Li S et al (2010) Ursolic acid stimulates lipolysis in primary-cultured rat adipocytes. Mol Nutr Food Res 54:1609–1617
Li Y, Tran VH, Koolaji N et al (2013a) (S)-[6]-Gingerol enhances glucose uptake in L6 myotubes by activation of AMPK in response to [Ca2+]i. J Pharm Pharm Sci 16:304–312
Li YG, Ji DF, Zhong S et al (2013b) 1-Deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice. Sci Rep 3:1377
Li M, Han Z, Bei W et al (2015) Oleanolic acid attenuates insulin resistance via NF-κB to regulate the IRS1-GLUT4 pathway in HepG2 cells. Evid Based Complement Altern Med 2015:643102
Li J, Ding L, Song B et al (2016a) Emodin improves lipid and glucose metabolism in high fat diet-induced obese mice through regulating SREBP pathway. Eur J Pharmacol 770:99–109
Li Y, Goto T, Yamakuni K et al (2016b) 4-Hydroxyderricin, as a PPARγ agonist, promotes adipogenesis, adiponectin secretion, and glucose uptake in 3T3-L1 cells. Lipids 51:787–795
Li X, Gao Z, Gao H et al (2017) Nephrin loss is reduced by grape seed proanthocyanidins in the experimental diabetic nephropathy rat model. Mol Med Rep 16:9393–9400
Li J, Liu M, Yu H et al (2018a) Mangiferin improves hepatic lipid metabolism mainly through its metabolite-norathyriol by modulating SIRT1/AMPK/SREBP-1c signaling. Front Pharmacol 9:201
Li JB, Zhang R, Han X et al (2018b) Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders. Braz J Med Biol Res 51:e7139
Li YC, Qiao JY, Wang BY et al (2018c) Paeoniflorin ameliorates fructose-induced insulin resistance and hepatic steatosis by activating LKB1/AMPK and AKT pathways. Nutrients 10:1024
Li AN, Chen JJ, Li QQ et al (2019a) Alpha glucosidase inhibitor 1-deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK. Biochem Biophys Res Commun 509:1001–1007
Li Y, Li Q, Wang C et al (2019b) Trigonelline reduced diabetic nephropathy and insulin resistance in type 2 diabetic rats through peroxisome proliferator-activated receptor-γ. Exp Ther Med 18:1331–1337
Li Y, Mai Y, Qiu X et al (2020) Effect of long-term treatment of carvacrol on glucose metabolism in streptozotocin-induced diabetic mice. BMC Complement Med Ther 20:142
Liao CC, Ou TT, Wu CH et al (2013) Prevention of diet-induced hyperlipidemia and obesity by caffeic acid in C57BL/6 mice through regulation of hepatic lipogenesis gene expression. J Agric Food Chem 61:11082–11088
Liao X, Yang L, Chen M et al (2015) The hypoglycemic effect of a polysaccharide (GLP) from Gracilaria lemaneiformis and its degradation products in diabetic mice. Food Funct 6:2542–2549
Liao HH, Zhu JX, Feng H et al (2017) Myricetin possesses potential effects on diabetic cardiomyopathy through inhibiting IκBα/NF-κB and enhancing Nrf2/HO-1. Oxid Med Cell Longev 2017:8370593
Lim J, Liu Z, Apontes P et al (2014) Dual mode of action of mangiferin in mouse liver under high fat diet. PLoS One 9:e90137
Lin CH, Kuo YH, Shih CC (2017) Eburicoic acid, a triterpene compound from Antrodia camphorata, displays antidiabetic and antihyperlipidemic effects in palmitate treated C2C12 myotubes and in high-fat diet-fed mice. Int J Mol Sci 18:2314
Lin CH, Kuo YH, Shih CC (2018) Antidiabetic and hypolipidemic activities of eburicoic acid, a triterpenoid compound from Antrodia camphorata, by regulation of Akt phosphorylation, gluconeogenesis and PPARα in streptozotocin-induced diabetic mice. RSC Adv 8:20462–20476
Liou CJ, Dai YW, Wang CL et al (2019) Maslinic acid protects against obesity-induced non-alcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway. FASEB J 33:11791–11803
Liu D, Zhen W, Yang Z et al (2006) Genistein acutely stimulates insulin secretion in pancreatic β-cells through a cAMP-dependent protein kinase pathway. Diabetes 55:1043–1050
Liu J, Sun H, Duan W et al (2007) Maslinic acid reduces blood glucose in KK-Ay mice. Biol Pharm Bull 30:2075–2078
Liu Y, Qi H, Wang Y et al (2012) Allicin protects against myocardial apoptosis and fibrosis in streptozotocin-induced diabetic rats. Phytomedicine 19:693–698
Liu J, Chen Z, Zhang Y et al (2013a) Rhein protects pancreatic β-cells from dynamin-related protein 1-mediated mitochondrial fission and cell apoptosis under hyperglycemia. Diabetes 62:3927–3935
Liu Y, Wan L, Xiao Z et al (2013b) Antidiabetic activity of polysaccharides from tuberous root of Liriope spicata var. prolifera in KK-Ay mice. Evid Based Complement Alternat Med 2013:349790
Liu YW, Zhu X, Zhang L et al (2013c) Upregulation of glyoxalase 1 by mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats. Eur J Pharmacol 721:355–364
Liu J, Wang X, Chen YP et al (2014) Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase. Chin J Nat Med 12:259–265
Liu J, Lee J, Hernandez MAS et al (2015a) Treatment of obesity with celastrol. Cell 161:999–1011
Liu M, Xu L, Yin L et al (2015b) Potent effects of dioscin against obesity in mice. Sci Rep 5:7973
Liu Q, Li X, Li C et al (2015c) 1-Deoxynojirimycin alleviates insulin resistance via activation of insulin signaling PI3K/Akt pathway in skeletal muscle of db/db mice. Molecules 20:21700–21714
Liu ZW, Wang JK, Qiu C et al (2015d) Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway. Acta Pharmacol Sin 36:323–333
Liu JY, Zheng CZ, Hao XP et al (2016a) Catalpol ameliorates diabetic atherosclerosis in diabetic rabbits. Am J Transl Res 8:4278–4288
Liu Q, Li X, Li C et al (2016b) 1-Deoxynojirimycin alleviates liver injury and improves hepatic glucose metabolism in db/db mice. Molecules 21:279
Liu H, Zhong H, Yin Y et al (2017a) Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats. Biomed Pharmacother 91:964–969
Liu W, Zhao S, Wang J et al (2017b) Grape seed proanthocyanidin extract ameliorates inflammation and adiposity by modulating gut microbiota in high-fat diet mice. Mol Nutr Food Res 61:1601082
Liu WY, Liou SS, Hong TY et al (2017c) Protective effects of hesperidin (citrus flavanone) on high glucose induced oxidative stress and apoptosis in a cellular model for diabetic retinopathy. Nutrients 9:1312
Liu G, Liang L, Yu G et al (2018a) Pumpkin polysaccharide modifies the gut microbiota during alleviation of type 2 diabetes in rats. Int J Biol Macromol 115:711–717
Liu H, Wang J, Liu M et al (2018b) Antiobesity effects of ginsenoside Rg1 on 3T3-L1 preadipocytes and high fat diet-induced obese mice mediated by AMPK. Nutrients 10:830
Liu L, Du X, Zhang Z et al (2018c) Trigonelline inhibits caspase 3 to protect β-cells apoptosis in streptozotocin-induced type 1 diabetic mice. Eur J Pharmacol 836:115–121
Liu Z, Han Y, Zhao F et al (2018d) Nobiletin suppresses high-glucose-induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF-κB pathway. J Cell Biochem 2018:1–7
Liu R, Zhang Y, Yao X et al (2020) ε-Viniferin, a promising natural oligostilbene, ameliorates hyperglycemia and hyperlipidemia by activating AMPK in vivo. Food Funct 11:10084–10093
Liu Y, Fu X, Chen Z et al (2021) The protective effects of sulforaphane on high-fat diet-induced obesity in mice through browning of white fat. Front Pharmacol 12:665894
Lopez-Lazaro M (2009) Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 9:31–59
Lorenz M, Wessler S, Follmann E et al (2004) A constituent of green tea, epigallocatechin-3- gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J Biol Chem 279:6190–6195
Lu C, Zhang F, Xu W et al (2015) Curcumin attenuates ethanol-induced hepatic steatosis through modulating Nrf2/FXR signaling in hepatocytes. IUBMB Life 67:645–658
Lu YL, Lin SY, Fang SU et al (2017) Hot-water extracts from roots of Vitis thunbergii var. taiwaniana and identified ε-viniferin improve obesity in high-fat diet-induced mice. J Agric Food Chem 65:2521–2529
Luo C, Yang H, Tang C et al (2015) Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats. Int Immunopharmacol 28:744–750
Luo H, Liu J, Ouyang Q et al (2017) The effects of oleanolic acid on atherosclerosis in different animal models. Acta Biochim Biophys Sin 49:349–354
Ma X, Xu L, Alberobello AT et al (2015) Celastrol protects against obesity and metabolic dysfunction through activation of a HSF1-PGC1α transcriptional axis. Cell Metab 22:695–708
Ma B, Zhu Z, Zhang J et al (2020) Aucubin alleviates diabetic nephropathy by inhibiting NF-κB activation and inducing SIRT1/SIRT3-FoxO3a signaling pathway in high-fat diet/streptozotocin-induced diabetic mice. J Funct Foods 64:103702
Man AWC, Xia N, Li H (2020) Circadian rhythm in adipose tissue: novel antioxidant target for metabolic and cardiovascular diseases. Antioxidants 9:968
Maneesai P, Bunbupha S, Kukongviriyapan U et al (2016) Asiatic acid attenuates renin-angiotensin system activation and improves vascular function in high-carbohydrate, high-fat diet fed rats. BMC Complement Altern Med 16:123
Masumoto S, Terao A, Yamamoto Y et al (2016) Non-absorbable apple polycyanidins prevent obesity associated with gut microbial and metabolomic changes. Sci Rep 6:31208
Matsukawa T, Inaguma T, Han J et al (2015) Cyanidin-3-glucoside derived from black soybeans ameliorate type 2 diabetes through induction of differentiation of preadipocytes into smaller and insulin-sensitive adipocytes. J Nutr Biochem 26:860–867
Matsukawa T, Villareal MO, Motojima H et al (2017) Increasing cAMP levels of preadipocytes by cyanidin-3-glucoside treatment induces the formation of beige phenotypes in 3T3-L1 adipocytes. J Nutr Biochem 40:77–85
Matsuo Y, Kusano R, Ogawa S et al (2016) Characterization of the α-amylase inhibitory activity of oligomeric proanthocyanidins from Acacia mearnsii bark extract. Nat Prod Commun 11:1851–1854
Mazimba O (2017) Umbelliferone: sources, chemistry and bioactivities review. Bull Fac Pharm, Cairo Univ 55:223–232
Mein JR, Dolnikowski GG,Ernst H et al (2011) Enzymatic formation of apo-carotenoids from xanthophylls carotenoids lutein, zeaxanthin and β-cryptoxanthin by ferret carotene-9′-10′-monooxygenase. Arch Biochem Biophys 506:109–121
Min W, Wu M, Fang P et al (2018) Effect of baicalein on GLUT4 translocation in adipocytes of diet-induced obese mice. Cell Physiol Biochem 50:426–436
Minakawa M, Miura Y, Yagasaki K (2012) Piceatannol, a resveratrol derivative, promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myotubes and suppresses blood glucose levels in type 2 diabetic model db/db mice. Biochem Biophys Res Commun 422:469–475
Mnafgui K, Kaanich F, Derbali A et al (2013) Inhibition of key enzymes related to diabetes and hypertension by eugenol in vitro and in alloxan-induced diabetic rats. Arch Physiol Biochem 119:225–233
Mo FF, Liu HX, Zhang Y et al (2019) Anti-diabetic effect of loganin by inhibiting FOXO1 nuclear translocation via PI3K/Akt signaling pathway in INS-1 cell. Iran J Basic Med Sci 22:262–266
Monagas M, Quintanilla-Lopez JE, Gomez-Cordoves C et al (2010) MALDI-TOF MS analysis of plant proanthocyanidins. J Pharm Biomed Anal 51:358–372
Moree SS, Kavishankar GB, Rajesha J (2013) Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin-induced diabetic rats. Phytomedicine 20:237–245
Morrow NM, Burke AC, Samsoondar JP et al (2020) The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK. J Lipid Res 61:387–402
Mosqueda-Solis A, Sanchez J, Reynes B et al (2018) Hesperidin and capsaicin, but not the combination, prevent hepatic steatosis and other metabolic syndrome-related alternations in Western diet-fed rats. Sci Rep 8:15100
Mouly P, Gaydou EM, Auffray A (1998) Simultaneous separation of flavanone glycosides and polymethoxylated flavones in citrus juices using liquid chromatography. J Chromatogr A 800:171–179
Mulvihill EE, Assini JM, Lee JK et al (2011) Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance. Diabetes 60:1446–1457
Murali R, Srinivasan S, Ashokkumar N (2013) Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Biochimie 95:1848–1854
Murari R, Saravanan R (2012) Antidiabetic effect of D-limonene, a monoterpene in streptozotocin-induced diabetic rats. Biomed Prev Nutr 2:269–275
Muruganandan S, Srinivasan K, Gupta S et al (2005) Effect of mangiferin on hyperglycemia and atherogenicity in streptozotocin diabetic rats. J Ethnopharmacol 97:497–501
Na B, Nguyen PH, Zhao BT et al (2015) Protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and glucosidase inhibitory activity of compounds isolated from Agrimonia pilosa. Pharm Biol 54:474–480
Nagata N, Xu L, Kohno S et al (2017) Glucoraphanin ameliorates obesity and insulin resistance through adipose tissue browning and reduction of metabolic endotoxemia in mice. Diabetes 66:1222–1236
Nakai M, Fukui Y, Asami S et al (2005) Inhibitory effects of oolong tea polyphenols on pancreatic lipase in vitro. J Agric Food Chem 53:4593–4598
Nakajima A, Ohizumi Y (2019) Potential benefits of nobiletin, a citrus flavonoid, against Alzheimer’s disease and Parkinson’s disease. Int J Mol Sci 20:3380
Nakajima K, Maeda N, Oiso S et al (2019) Decreased plasma octanoylated ghrelin levels in mice by oleanolic acid. J Oleo Sci 68:103–109
Nam D, Guo B, Chatterjee S et al (2015) The adipocyte clock controls brown adipogenesis through the TGF-β and BMP signaling pathways. J Cell Sci 128:1835–1847
Naowaboot J, Somparn N, Saenthaweesuk S et al (2015) Umbelliferone improves an impaired glucose and lipid metabolism in high-fat diet/streptozotocin-induced type 2 diabetic rats. Phytother Res 29:1388–1395
Naowaboot J, Piyabhan P, Munkong N et al (2016) Ferulic acid improves lipid and glucose homeostasis in high-fat diet-induced obese mice. Clin Exp Pharmacol Physiol 43:242–250
Naowaboot J, Somparn N, Saenthaweesuk S (2020) Renoprotective effect of umbelliferone in high-fat diet/streptozotocin-induced type 2 diabetic rats. Asian Pac J Trop Med 10:11–17
Narasimhan A, Chinnaiyan M, Kurundevi B (2015) Ferulic acid exerts its antidiabetic effect by modulating insulin-signaling molecules in the liver of high-fat diet and fructose-induced type 2 diabetic adult male rats. Appl Physiol Nutr Metab 40:769–781
Ni Y, Nagashimada M, Zhuge F et al (2015) Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: a comparison with vitamin E. Sci Rep 5:17192
Nie XQ, Chen HH, Zhang JY et al (2016) Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating the IRS-1/PI3K/Akt and AMPK/ACC2 signaling pathways. Acta Pharmacol Sin 37:483–496
Nie J, Chang Y, Li Y et al (2017a) Caffeic acid phenethyl ester (Propolis extract) ameliorates insulin resistance by inhibiting JNK and NF-κB inflammatory pathways in diabetic mice and HepG2 cell models. J Agric Food Chem 65:9041–9053
Nie Y, Luo F, Wang L et al (2017b) Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Funct 8:4028–4041
Ninomiya K, Matsuda H, Shimoda H et al (2004) Carnosic acid, a new class of lipid absorption inhibitor from sage. Bioorg Med Chem Lett 14:1943–1946
Niu Y, Li S, Na L et al (2012) Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK. PLoS One 7:e30782
Nizamutdinova IT, Jin YC, Chung JI et al (2009) The anti-diabetic effect of anthocyanins in streptozotocin-induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis. Mol Nutr Food Res 53:1419–1429
Nogara L, Naber N, Pate E et al (2016) Piperine’s mitigation of obesity and diabetes can be explained by its up-regulation of the metabolic rate of resting muscle. Proc Natl Acad Sci USA 113:13009–13014
Oberg AI, Yassin K, Csikasz RI et al (2011) Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats. PLOS One 6:e22510
Oguntibeju OO, Aboua Y, Goboza M (2019) Vindoline-a natural product from Catharanthus roseus reduces hyperlipidemia and renal pathophysiology in experimental type 2 diabetes. Biomedicines 7:59
Ogura K, Ogura M, Shoji T et al (2016) Oral administration of apple procyanidins ameliorates insulin resistance via suppression of pro-inflammatory cytokines expression in liver of diabetic ob/ob mice. J Agric Food Chem 64:8857–8865
Ohara K, Kusano K, Kitao S et al (2015) ε-Viniferin, a resveratrol dimer, prevents diet-induced obesity in mice. Biochem Biophys Res Commun 468:877–882
Ohta M, Fujinami A, Kobayashi N et al (2015) Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes. Nutr Res 35:618–625
Onda K, Horike N, Suzuki TI et al (2013) Polymethoxyflavonoids tangeretin and nobiletin increase glucose uptake in murine adipocytes. Phytother Res 27:312–316
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
Ono M, Fujimori K (2011) Antiadipogenic effect of dietary apigenin through activation of AMPK in 3T3-L1 cells. J Agric Food Chem 59:13346–13352
Oza MJ, Kulkarni YA (2018a) Biochanin A improves insulin sensitivity and controls hyperglycemia in type 2 diabetes. Biomed Pharmacother 107:1119–1127
Oza MJ, Kulkarni YA (2018b) Formononetin treatment in type 2 diabetic rats reduces insulin resistance and hyperglycemia. Front Pharmacol 9:739
Oza MJ, Kulkarni YA (2019) Formononetin attenuates kidney damage in type 2 diabetic rats. Life Sci 219:109–121
Oza MJ, Kulkarni YA (2020) Formononetin alleviates diabetic cardiomyopathy by inhibiting oxidative stress and upregulating SIRT1 in rats. Asian Pac J Trop Biomed 10:254–262
Pakdeechote P, Bunbupha S, Kukongviriyapan U et al (2014) Asiatic acid alleviates hemodynamic and metabolic alternations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats. Nutrients 6:355–370
Pan Y, Zhao W, Zhao D et al (2018) Salvianolic acid B improves mitochondrial function in 3T3-L1 adipocytes through a pathway involving PPARγ coactivator-1α (PGC-1α). Front Pharmacol 9:671
Park MY, Mun ST (2013) Dietary carnosic acid suppresses hepatic steatosis formation via regulation of hepatic fatty acid metabolism in high-fat diet-fed mice. Nutr Res Pract 7:294–301
Park SA, Choi MS, Cho SY et al (2006) Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice. Life Sci 79:1207–1213
Park CH, Tanaka T, Kim JH et al (2011a) Hepatoprotective effects of loganin, iridoid glucoside from Corni Fructus, against hyperglycemia-activated signaling pathway in liver of type 2 diabetic db/db mice. Toxicology 290:14–21
Park CH, Noh JS, Kim JH et al (2011b) Evaluation of morroniside, iridoid glucoside from Corni Fructus, on diabetes-induced alternations such as oxidative stress, inflammation, and apoptosis in the liver of type 2 diabetic db/db mice. Biol Pharm Bull 34:1559–1565
Park S, Choi Y, Um SJ et al (2011c) Oleuropein attenuates hepatic steatosis induced by high-fat diet in mice. J Hepatol 54:984–993
Park J, Kim HL, Jung Y et al (2019) Bitter orange (Citrus aurantium Linn) improves obesity by regulating adipogenesis and thermogenesis through AMPK activation. Nutrients 11:1988
Parnas M, Peters M, Dadon D et al (2009) Carvacrol is a novel inhibitor of Drosophila TRPL and mammalian TRPM 7 channels. Cell Calcium 45:300–309
Pascual-Serrano A, Arola-Arnal A, Suarez-Garcia S et al (2017) Grape seed proanthocyanidin supplementation reduces adipocyte size and increases adipocyte number in obese rats. Int J Obes 41:1246–1255
Patel MI, Gupta A, Dey CS (2011) Potentiation of neuronal insulin signaling and glucose uptake by resveratrol: the involement of AMPK. Pharmacol Rep 63:1162–1168
Patel OPS, Mishra A, Maurya R et al (2016a) Naturally occurring carbazole alkaloids from Murraya koenigii as potential antidiabetic agents. J Nat Prod 79:1276–1284
Patel TP, Rawal K, Soni S et al (2016b) Swertiamarin ameliorates oleic acid induced lipid accumulation and oxidative stress by attenuating gluconeogenesis and lipogenesis in hepatic steatosis. Biomed Pharmacother 83:785–791
Peng L, Yang J, Ning C et al (2012) Rhein inhibits integrin-linked kinase expression and regulates matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio in high glucose-induced epithelial-mesenchymal transition of renal tubular cell. Biol Pharm Bull 35:1676–1685
Pengzhan Y, Ning L, Xiguang L et al (2003) Antihyperlipidemic effects of different molecular weight sulphated polysaccharides from Ulva pertusa (Chlorophyta). Pharmacol Res 48:543–549
Pinent M, Blay M, Blade MC et al (2004) Grape seed-derived procyanidins have an antihyperglycemic effect in streptozotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines. Endocrinology 145:4985–4990
Polce SA, Burke C, Franca LM et al (2018) Ellagic acid alleviates hepatic oxidative stress and insulin resistance in diabetic female rats. Nutrients 10:531
Poudel B, Lim SW, Ki HH et al (2014) Dioscin inhibits adipogenesis through the AMPK/MAPK pathway in 3T3-L1 cells and modulates fat accumulation in obese mice. Int J Mol Med 43:1401–1408
Prabakaran D, Ashokkumar N (2013) Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats. Biochimie 95:366–373
Prabhakar PK, Doble M (2011) Interaction of phytochemicals with hypoglycemic drugs on glucose uptake in L6 myotubes. Phytomedicine 18:285–291
Prior RL, Lazarus SA, Cao G et al (2001) Identification of procyanidins and anthocyanins in blueberries and cranberries (Vaccinium spp) using high-performance liquid chromatography/mass spectrometry. J Agric Food Chem 49:1270–1276
Pu P, Wang XA, Salim M et al (2012a) Baicalein, a natural product, selectively activating AMPKα2 and ameliorates metabolic disorder in diet-induced mice. Mol Cell Endocrinol 236:128–138
Pu P, Gao DM, Mohamed S et al (2012b) Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet. Arch Biochem Biophys 518:61–70
Rahman N, Jeon M, Song HY et al (2016) Cryptotanshinone, a compound of Salvia miltiorrhiza inhibits pre-adipocytes differentiation by regulation of adipogenesis-related genes expression via STAT3 signaling. Phytomedicine 23:58–67
Ramadori G, Gautron L, Fujikawa T et al (2009) Central administration of resveratrol improves diet-induced diabetes. Endocrinology 150:5326–5333
Ramalingam S, Karuppiah M, Thiruppathi M (2020) Antihyperglycaemic potential of rosmarinic acid attenuates glycoprotein moiety in high-fat diet and streptozotocin-induced diabetic rats. Front Life Sci 13:120–130
Ramesh B, Pugalendi KV (2006) Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats. J Med Food 9:562–566
Rameshreddy P, Sathibabu Uddandrao VV, Brahmnaidu P et al (2018) Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese Sprague-Dawley rats. Mol Cell Biochem 442:143–154
Rashwan AS, El-Beltagy MA, Saleh SY et al (2019) Potential role of cinnamaldehyde and costunolide to counteract metabolic syndrome induced by excessive fructose consumption. Beni-Suef Univ J Basic Appl Sci 8:17
Rebello C, Greenway FL, Lau FH et al (2019) Naringenin promotes thermogenic gene expression in human white adipose tissue. Obesity 27:103–111
Reiter CEN, Kim J, Quon MJ (2010) Green tea polyphenol epigallocatechin gallate reduces endothelin-1 expression and secretion in vascular endothelial cells: roles for AMP-activated protein kinase, Akt, and FoxO1. Endocrinology 151:103–114
Rizza S, Muniyappa R, Lantorno M et al (2011) Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome. J Clin Endocrinol Metab 96:E782–E792
Rodriguez-Daza MC, Daoust L, Boutkrabt L et al (2020) Wild blueberry proanthocyanidins shape distinct gut microbiota profile and influence glucose homeostasis and intestinal phenotypes in high-fat high-sucrose fed mice. Sci Rep 10:2217
Rouseff R, Ting S (1979) Tangeretin content of Florida citrus peel as determined by HPLC. Proc Fla State Hort Soc 92:145–148
Ruan CT, Lam SH, Chi TC et al (2012) Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice. Phytomedicine 19:719–724
Ruan CT, Lam SH, Lee SS et al (2013) Hypoglycemic action of borapetoside A from the plant Tinospora crispa in mice. Phytomedicine 20:667–675
Runtuwene J, Cheng KC, Asakawa A et al (2016) Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4. Drug Des Devel Ther 10:2193–2202
Sae-Tan S, Grove KA, Kennett MJ et al (2011) (-)-Epigallocatechin-3-gallate increases the expression of genes related to fat oxidation in the skeletal muscle of high fat-fed mice. Food Funct 2:111–116
Saito K, Davis KC, Morgan DA et al (2019) Celastrol reduces obesity in MC4R deficiency and stimulates sympathetic nerve activity affecting metabolic and cardiovascular functions. Diabetes 68:1210–1220
Salemi Z, Ghasemi H, Morovati A et al (2018) Effects of biochanin A on resistin, adiponectin and some stress oxidative markers in normal and STZ-induced diabetic rats. Arch Med Lab Sci 4:9–16
Samad MB, Mohsin MNAB, Razu BA et al (2017) [6]-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathway in pancreatic β-cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemia in Lepr db/db type 2 diabetic mice. BMC Complement Altern Med 17:395
Samarghandian S, Borji A, Farkhondeh T (2017) Evaluation of antidiabetic activity of carnosol (phenolic diterpene in rosemary) in streptozotocin-induced diabetic rats. Cardiovasc Hematol Disord Drug Targets 17:11–17
Sandoval V, Femenias A, Martinez-Garza U et al (2019) Lyophilized maqui (Aristotelia chilensis) berry induces browning in the subcutaneous white adipose tissue and ameliorates the insulin resistance in high fat diet-induced obese mice. Antioxidants 8:360
Santini SJ, Porcu C, Tarantino G et al (2020) Oleuropein overrides liver damage in steatotic mice. J Funct Foods 65:103756
Saravanan S, Pari L (2015) Role of thymol on hyperglycemia and hyperlipidemia in high fat diet induced type 2 diabetic C57BL/6J mice. Eur J Pharmacol 761:279–287
Saravanan S, Pari L (2016) Protective effect of thymol on high fat diet-induced diabetic nephropathy in C57BL/6J mice. Chem Biol Interact 245:1–11
Saravanan G, Ponmurugan P, Deepa MA et al (2014) Anti-obesity action of gingerol: effect on lipid profile, insulin, leptin, amylase and lipase in male obese rats induced by a high-fat diet. J Sci Food Agric 94:2972–2977
Sarkar P, Nath K, Banu S (2019) Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats. Braz J Pharm Sci 55:e18201
Sasaki R, Nishimura N, Hoshino H et al (2007) Cyanidin-3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol 74:1619–1627
Sasikumar P, Prabha B, Reshmitha TR et al (2016) Comparison of antidiabetic potential of (+)- and (-)-hopeaphenol, a pair of enantiomers isolated from Ampelocissus indica (L.) and Vateria indica Linn., with respect to inhibition of digestive enzymes and induction of glucose uptake in L6 myotubes. RSC Adv 6:77075–77082
Sathibabu Uddandrao VV, Rameshreddy P, Brahmanaidu P et al (2020) Antiobesity efficacy of asiatic acid: down-regulation of adipogenic and inflammatory processes in high fat diet induced obese rats. Arch Physiol Biochem 126:453–462
Sattanathan K, Dhanapal CK, Umarani R et al (2011) Beneficial health effects of rutin supplementation in patients with diabetes mellitus. J Appl Pharm Sci 1:227–231
Schmieder RE, Hilgers KF, Schlaich MP et al (2007) Renin-angiotensin system and cardiovascular risk. Lancet 369:1208–1219
Schwarz EJ, Reginato MJ, Shao D et al (1997) Retinoic acid blocks adipogenesis by inhibiting C/EBPβ-mediated transcription. Mol Cell Biol 17:1552–1561
Seo MJ, Lee YJ, Hwang JH et al (2015) The inhibitory effects of quercetin on obesity and obesity-induced inflammation by regulation of MAPK signaling. J Nutr Biochem 26:1308–1316
Shah SS, Shah GB, Singh SD et al (2011) Effect of piperine in the regulation of obesity-induced dyslipidemia in high-fat diet rats. Ind J Pharmacol 43:296–299
Shan Q, Zheng Y, Lu J et al (2014) Purple sweet potato color ameliorates kidney damage via inhibiting oxidative stress mediated NLRP3 inflammasome activation in high fat diet mice. Food Chem Toxicol 69:339–346
Shao W, Yu Z, Chiang Y et al (2012) Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS One 7:e28784
Shen L, Xiong Y, Wang DQH et al (2013) Ginsenoside Rb1 reduces fatty liver by activating AMP-activated protein kinase in obese rats. J Lipid Res 54:1430–1438
Shen L, Haas M, Wang DQH et al (2015) Ginsenoside Rb1 increases insulin sensitivity by activating AMP-activated protein kinase in male rats. Physiol Rep 3:e12543
Shi L, Zhang W, Zhou YY et al (2008) Corosolic acid stimulates glucose uptake via enhancing insulin receptor phosphorylation. Eur J Pharmacol 584:21–29
Shi L, Shi L, Zhang H et al (2013) Oxymatrine ameliorates non-alcoholic fatty liver disease in rats through peroxisome proliferator-activated receptor-α activation. Mol Med Rep 8:439–445
Shi ZL, Liu YD, Yuan YY et al (2017) In vitro and in vivo effects of norathyriol and mangiferin on α-glucosidase. Biochem Res Int 2017:1206015
Shi X, Zhou X, Chu X et al (2019) Allicin improves metabolism in high-fat diet-induced obese mice by modulating the gut microbiota. Nutrients 11:2909
Shimba S, Ishii N, Ohta Y et al (2005) Brain and muscle Arnt-like protein-1 (Bmal1), a component of the molecular clock, regulates adipogenesis. PNAS 102:12071–12076
Shukla S, Gupta S (2010) Apigenin: a promising molecule for cancer prevention. Pharm Res 27:962–978
Sim MO, Ham JR, Lee HI et al (2014) Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice. Chem Biol Interact 216:9–16
Sim MO, Lee HI, Ham JR et al (2015) Long-term supplementation of esculetin ameliorates hepatosteatosis and insulin resistance partly by activating Adipo R2-AMPK pathway in diet-induced obese mice. J Funct Foods 15:160–171
Slavin J (2013) Fiber and prebiotics: mechanisms and health benefits. Nutrients 5:1417–1435
Son MJ, Miura Y, Yagasaki K (2015) Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice. Cytotechnology 67:641–652
Sonawane RD, Vishwakarma SL, Lakshmi S et al (2010) Amelioration of STZ-induced type 1 diabetic nephropathy by aqueous extract of Enicostemma littorale Blume and swertiamarin in rats. Mol Cell Biochem 340:1–6
Song F, Xie ML, Zhu LJ et al (2006) Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals. World J Gastroenterol 12:4359–4363
Song P, Kim JH, Ghim J et al (2013) Emodin regulates glucose utilization by activating AMP-activated protein kinase. J Biol Chem 288:5732–5742
Song HM, Li X, Liu YY et al (2018) Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS. Int J Mol Med 42:193–207
Sorrenti V, Raffaele M, Vanella L et al (2019) Protective effect of caffeic acid phenethyl ester (CAPE) and novel cape analogue as inducers of heme oxygenase-1 in streptozotocin- induced type 1 diabetic rats. Int J Mol Sci 20:2441
Srinivasan S, Sathish G, Jayanthi M et al (2014) Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats. Mol Cell Biochem 385:159–168
Stone B, Morell MK (2009) Carbohydrates. In: Khan K, Shewry PR (eds) Wheat: chemistry and technology, 4th edn. American Association of Cereal Chemists, St Paul, MN, pp 299–362
Su HM, Feng LN, Zheng XD et al (2016a) Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice. Biomed Biotechnol 17:437–446
Su ML, He Y, Li QS et al (2016b) Efficacy of acetylshikonin in preventing obesity and hepatic steatosis in db/db mice. Molecules 21:976
Su M, Huang W, Zhu B (2016c) Acetylshikonin from Zicao prevents obesity in rats on a high-fat diet by inhibiting lipid accumulation and inducing lipolysis. PLoS One 11:e0146884
Sun J, Fu X, Liu Y et al (2015) Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice. Drug Des Devel Ther 9:6327–6342
Sundaram R, Shanthi P, Sachdanandan P (2014) Effect of tangeretin, a polymethoxylated flavones on glucose metabolism in streptozotocin-induced diabetic rats. Phytomedicine 21:793–799
Sundaram R, Shanthi P, Sachdanandan P (2015) Tangeretin, a polymethoxylated flavone, modulates lipid homeostasis and decreases oxidative stress by inhibiting NF-κB activation and proinflammatory cytokines in cardiac tissues of streptozotocin-induced diabetic rats. J Funct Foods 16:315–333
Sung J, Lee J (2016) Capsicoside G, a furostanol saponin from pepper (Capsicum annum L.) seeds, suppresses adipogenesis through activation of AMP-activated protein kinase in 3T3-L1 cells. J Funct Foods 20:148–158
Sung J, Jeong HS, Lee J (2016) Effect of the capsicoside G-rich fraction from pepper (Capsicum annuum L.) seeds on high-fat diet-induced obesity in mice. Phytother Res 30:1848–1855
Takayanagi K (2011) Prevention of adiposity by the oral administration of β-cryptoxanthin. Front Neurol 2:67
Takii H, Kometani T, Nishimura T et al (2001) Antidiabetic effect of glycyrrhizin in genetically diabetic KK-Ay mice. Biol Pharm Bull 24:484–487
Takikawa M, Inoue S, Horio F et al (2010) Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. J Nutr 140:527–533
Tan MJ, Ye JM, Turner N et al (2008) Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol 15:263–273
Tay KC, Tan LTH, Chan CK et al (2019) Formononetin: a review of its anticancer potentials and mechanisms. Front Pharmacol 10:820
Tharaheswari M, Jayachandra Reddy N, Kumar R et al (2014) Trigonelline and diosgenin attenuate ER stress, oxidative stress-mediated damage in pancreas and enhance adipose tissue PPARγ activity in type 2 diabetic rats. Mol Cell Biochem 396:161–174
Tikellis C, Thomas MC (2012) Angiotensin-converting enzyme 2(ACE2) is a key modulator of the rennin angiotensin system in health and disease. Int J Peptides 2012:256294
Tilg H, Zmora N, Adolph TE et al (2020) The intestinal microbiota fuelling metabolic inflammation. Nat Rev Immunol 20:40–54
Tong Q, Tsai J, Tan G et al (2005) Interaction between GATA and the C/EBP family of transcription factors is critical for GATA-mediated suppression of adipocyte differentiation. Mol Cell Biol 25:706–715
Tsuduki T, Nakamura Y, Honma T et al (2009) Intake of 1-deoxynojirimycin suppresses lipid accumulation through activation of the β-oxidation system in rat liver. J Agric Food Chem 57:11024–11029
Tung YC, Lin YH, Chen HJ et al (2016) Piceatannol exerts anti-obesity effects in C57BL/6 mice through modulating adipogenic proteins and gut microbiota. Molecules 21:1419
Tzeng TF, Liou SS, Liu IM (2011) Myricetin ameliorates defective post-receptor insulin signalling via β-endorphin signalling in skeletal muscles of fructose-fed rats. Evid Based Complement Altern Med 2011:150752
Tzeng TF, Liou SS, Chang CJ et al (2013) Zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, attenuates non-alcoholic fatty liver disease in hamsters fed on high-fat diet. Evid Based Complement Altern Med 2013:303061
Uchida-Maruki H, Inagaki H, Ito R et al (2015) Piceatannol lowers the blood glucose level in diabetic mice. Biol Pharm Bull 38:629–633
Ueda M, Nishiumi S, Nagayasu H et al (2008) Epigallocatechin gallate promotes GLUT4 translocation in skeletal muscle. Biochem Biophys Res Commun 377:286–290
Uemura T, Goto T, Kang MS et al (2011) Diosgenin, the main aglycone of fenugreek, inhibits LXRα activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice. J Nutr 141:17–23
Um JH, Park SJ, Kang H et al (2010) AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 59:554–563
USDA (2020) US, Department of Agriculture, Food database-2020
Ushiroda C, Naito Y, Takagi T et al (2019) Green tea polyphenol (epigallocatechin-3-gallate) improves gut dysbiosis and serum bile acids dysregulation in high-fat diet-fed mice. J Clin Biochem Nutr 65:34–46
Varshney S, Shankar K, Beg M et al (2014) Rohitukine inhibits in vitro adipogenesis arresting mitotic clonal expansion and improves dyslipidemia in vivo. J Lipid Res 55:1019–1032
Varshney R, Mishra R, Das N et al (2019) A comparative analysis of various flavonoids in the regulation of obesity and diabetes: an in vitro and in vivo study. J Funct Foods 59:194–205
Venkadeswaran K, Muralidharan AR, Annadurai T et al (2014) Antihypercholesterolemic and antioxidant potential of an extract of the plant, Piper betle, and its active constituent eugenol, in triton WR-1339-induced hypercholesterolemia in experimental rats. Evid Based Complement Altern Med 2014:478973
Venkadeswaran K, Thomas PA, Geraldine P (2016) An experimental evaluation of the anti-atherogenic potential of the plant, Piper betle, and its active constituent, eugenol, in rats fed on atherogenic diet. Biomed Pharmacother 80:276–288
Vitale DC, Piazza C, Melilli B et al (2013) Isoflavones: estrogenic activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet 38:15–25
Vlavcheski F, Baron D, Vlachogiannis IA et al (2018) Carnosol increases skeletal muscle cell glucose uptake via AMPK-dependent GLUT4 glucose transporter translocation. Int J Mol Sci 19:1321
Von Lintig J (2010) Colors with functions: elucidating the biochemical and molecular basis of carotenoid mechanism. Annu Rev Nutr 30:35–56
Waltner-Law ME, Wang XL, Law BK et al (2002) Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem 277:34933–34940
Wan QF, Dong Y, Yang H et al (2004) Protein kinase activation increases insulin secretion by sensitizing the secretory machinery to Ca2+. J Gen Physiol 124:653–662
Wang J, He J (2019) Swertiamarin decreases lipid accumulation dependent on 3-ketoacyl-CoA-thiolase. Biomed Pharmacother 112:108668
Wang T, Wang Y, Kontani Y et al (2008) Evodiamine improves diet-induced obesity in a uncoupling protein-1-independent manner: involvement of antiadipogenic mechanism and extracellularly regulated kinase/mitogen activated protein kinase signaling. Endocrinology 149:358–366
Wang T, Wang Y, Yamashita H (2009a) Evodiamine inhibits adipogenesis via the EGFR-PKCalpha-ERK signalling pathway. FEBS Lett 583:3655–3659
Wang Y, Huang Y, Lam KSL et al (2009b) Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res 82:484–492
Wang P, Yan Z, Zhong J et al (2012a) Transient receptor potential vanilloid 1 activation enhances gut glucagon-like peptide-1 secretion and glucose homeostasis. Diabetes 61:2155–2165
Wang T, Takikawa Y, Tabuchi T et al (2012b) Carnosic acid (CA) prevents lipid accumulation in hepatocytes through the EGFR/MAPK pathway. J Gastroenterol 47:805–813
Wang T, Kusado T, Takeuchi T et al (2013a) Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice. PLoS One 8:e83264
Wang X, Liu R, Zhang W et al (2013b) Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects. Mol Cell Endocrinol 376:70–80
Wang F, Yan J, Niu Y et al (2014a) Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase. Pharm Biol 52:68–73
Wang HL, Li CY, Zhang B et al (2014b) Mangiferin facilitates islet regeneration and β-cell proliferation through upregulation of cell cycle and β-cell regeneration regulators. Int J Mol Sci 15:9016–9035
Wang P, Xu S, Li W et al (2014c) Salvianolic acid B inhibited PPARγ expression and attenuated weight gain in mice with high-fat diet-induced obesity. Cell Physiol Biochem 34:288–298
Wang Y, Fofana B, Roy M et al (2015a) Flaxseed lignan secoisolariciresinol diglucoside improves insulin sensitivity through upregulation of GLUT4 expression in diet-induced obese mice. J Funct Foods 18A:1–9
Wang YH, Liu YH, He GR et al (2015b) Esculin improves dyslipidemia, inflammation, and renal damage in streptozotocin-induced diabetic rats. BMC Complement Altern Med 15:402
Wang X, Lu Q, Yu DS et al (2015c) Asiatic acid mitigates hyperglycemia and reduces islet fibrosis in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model. Chin J Nat Med 13:529–534
Wang M, Luo L, Yao L et al (2016a) Salidroside improves glucose homeostasis in obese mice by repressing inflammation in white adipose tissues and improving leptin sensitivity in hypothalamus. Sci Rep 6:25399
Wang X, Zhao S, Su M et al (2016b) Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice. Biochem Biophys Res Commun 474:182–187
Wang B, Fu X, Liang X et al (2017a) Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα+ adipose progenitors. Cell Discov 3:17036
Wang S, Lu A, Zhang L et al (2017b) Extraction and purification of pumpkin polysaccharides and their hypoglycemic effect. Int J Biol Macromol 98:182–187
Wang XT, Gong Y, Zhou B et al (2018) Ursolic acid ameliorates oxidative stress, inflammation and fibrosis in diabetic cardiomyopathy rats. Biomed Pharmacother 97:1461–1467
Wang B, Gao X, Liu B et al (2019a) Protective effects of curcumin against chronic alcohol-induced liver injury in mice through modulating mitochondrial dysfunction and inhibiting endoplasmic reticulum stress. Food Nutr Res 63:3567
Wang HQ, Wang SS, Chiufai K et al (2019b) Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway. Chin J Nat Med 17:346–354
Wang L, Wei Y, Ning C et al (2019c) Ellagic acid promotes browning of white adipose tissues in high-fat diet-induced obesity in rats through suppressing white adipocyte maintaining genes. Endocrine J 66:923–936
Wang L, Wu Y, Zhuang L et al (2019d) Puerarin prevents high-fat diet-induced obesity by enriching Akkermansia muciniphila in the gut microbiota of mice. PLoS One 14:e0218490
Wang Q, Wu X, Shi F et al (2019e) Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice. Biomed Pharmacother 109:744–750
Weidner C, Wowro SJ, Freiwald A et al (2013) Amorfrutin B is an efficient natural peroxisome proliferator-activated receptor gamma (PPARγ) agonist with potent glucose lowering properties. Diabetologia 56:1802–1812
Weisberg SP, Leibel R, Tortoriello DV (2008) Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology 149:3549–3558
Wen L, Zhang Y, Sun-Waterhouse D et al (2017) Advantages of the polysaccharides from Gracilaria lemaneiformis over metformin in antidiabetic effects on streptozotocin-induced diabetic mice. RSC Adv 7:9141–9151
Westerheide SD, Bosman JD, Mbadugha BNA et al (2004) Celastrols as inducers of the heat shock response and cytoprotection. J Biol Chem 279:56053–56060
Wong KH, Li GQ, Li KM et al (2011) Kudzu root: traditional uses and potential medicinal benefits in diabetes and cardiovascular diseases. J Ethnopharmacol 134:584–607
Woo MN, Jeon SM, Kim HJ et al (2010) Fucoxanthin supplementation improves plasma and hepatic lipid metabolism and blood glucose concentration in high-fat fed C57BL/6N mice. Chem Biol Interact 186:316–322
Wu X, Beecher GR, Holden JM et al (2006) Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J Agric Food Chem 54:4069–4075
Wu T, Tang Q, Gao Z et al (2013) Blueberry and mulberry juice prevent obesity development in C57BL/6 mice. PLoS One 8:e77585
Wu JB, Kuo YH, Lin CH et al (2014a) Tormetic acid, a major component of suspension cells of Eriobotrya japonica, suppresses high-fat diet-induced diabetes and hyperlipidemia by glucose transporter 4 and AMP-activated protein kinase phosphorylation. J Agric Food Chem 62:10717–10726
Wu Y, Yu Y, Szabo A et al (2014b) Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet. PLoS One 9:e92618
Wu Z, Chen Q, Ke D et al (2014c) Emodin protects against diabetic cardiomyopathy by regulating the Akt/GSK-3β signaling pathway in the rat model. Molecules 19:14782–14793
Wu J, Shi S, Wang H et al (2016) Mechanisms underlying the effect of polysaccharides in the treatment of type 2 diabetes: a review. Carbohydr Polym 144:474–494
Wu TR, Lin CS, Chang CJ et al (2019) Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut 68:248–262
Xiao C, Wu QP, Cai W et al (2012) Hypoglycemic effects of Ganoderma lucidum polysaccharides in type 2 diabetic mice. Arch Pharm Res 35:1793–1801
Xiao H, Xie G, Wang J et al (2013) Chicoric acid prevents obesity by attenuating hepatic steatosis, inflammation and oxidative stress in high-fat diet-fed mice. Food Res Int 54:345–353
Xie W, Gu D, Li J et al (2011) Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS One 6:e24520
Xiong Y, Shen L, Liu KJ et al (2010) Antiobesity and antihyperglycemic effects of ginsenoside Rb1 in rats. Diabetes 59:2505–2512
Xu N, Zhang L, Deng J et al (2014) Low-dose diet supplementation of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice. Mol Nutr Food Res 58:1258–1268
Xu F, Wang F, Wang Z et al (2016) Glucose uptake activities of bis (2,3-dibromo-4,5-dihydroxybenzyl) ether, a novel marine natural product from red alga Odonthalia corymbifera with protein tyrosine phosphatase 1B inhibition, in vitro and in vivo. PLoS One 11:e0147748
Xu Y, Niu Y, Gao Y et al (2017) Borapetoside E, a clerodane diterpenoid extracted from Tinospora crispa, improves hyperglycemia and hyperlipidemia in high-fat-diet-induced type 2 diabetes mice. J Nat Prod 80:2319–2327
Xu G, Sun W, Guo X et al (2018a) Asiatic acid promotes liver fatty acid metabolism in diabetic models. Int J Clin Exp Med 11:11837–11845
Xu Q, Luo J, Wu N et al (2018b) BPN, a marine-derived PTP1B inhibitor, activates insulin signaling and improves insulin resistance in C2C12 myotubes. Int J Biol Macromol 106:379–386
Xu S, Wang G, Peng W et al (2019) Corosolic acid isolated from Eriobotrya japonica leaves reduces glucose level in human hepatocellular carcinoma cells, zebrafish and rats. Sci Rep 9:4388
Xu LN, Yin LH, Jin Y et al (2020a) Effect and possible mechanisms of dioscin on ameliorating metabolic glycolipid metabolic disorder in type 2 diabetes. Phytomedicine 67:153139
Xu X, Dai M, Lao F et al (2020b) Effect of glucoraphanin from broccoli seeds on lipid levels and gut microbiota in high-fat diet-fed mice. J Funct Foods 68:103858
Xue H, Li P, Luo Y et al (2019) Salidroside stimulates the Sirt1/PGC-1α axis and ameliorates diabetic nephropathy in mice. Phytomedicine 54:240–247
Yamada K, Hosokawa M, Yamada C et al (2008) Dietary corosolic acid ameliorates obesity and hepatic steatosis in KK-Ay mice. Biol Pharm Bull 31:651–655
Yan F, Hao H (2016) Effects of Laminaria japonica polysaccharides on exercise endurance and oxidative stress in forced swimming mouse model. J Biol Res (Thessalon) 23:7
Yang D, Luo Z, Ma S et al (2010) Activation of TRPV-1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension. Cell Metab 12:130–141
Yang J, Leng J, Li JJ et al (2016a) Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice. Phytomedicine 23:181–190
Yang L, Yao D, Yang H et al (2016b) Puerarin protects pancreatic β-cells in obese diabetic mice via activation of GLP-1R signaling. Mol Endocrinol 30:361–371
Yang Z, Li J, Xiong F et al (2016c) Berberine attenuates high glucose-induced fibrosis by activating the G-protein-coupled bile acid receptor TGR5 and repressing the S1P2/MAPK signaling pathway in glomerular mesangial cells. Exp Cell Res 346:241–247
Yang J, Kim CS, Tu TH et al (2017) Quercetin protects obesity-induced hypothalamic inflammation by reducing microglia-mediated inflammatory responses via HO-1 induction. Nutrients 9:650
Yao XG, Chen F, Li P et al (2013) Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models. J Ethnopharmacol 150:285–297
Yoo MY, Oh KS, Lee JW et al (2007) Vasorelaxant effect of stilbenes from rhizome extract of rhubarb (Rheum undulatum) on the contractility of rat aorta. Phytother Res 21:186–189
Yoon JJ, Lee YJ, Han BH et al (2017) Protective effect of betulinic acid on early atherosclerosis in diabetic apolipoprotein E gene knockout mice. Eur J Pharmacol 796:224–232
Yoshimura Y, Nishii S, Zaima N et al (2013) Ellagic acid improves hepatic steatosis and serum lipid composition through reduction of serum resistin levels and transcriptional activation of hepatic PPARα in obese, diabetic KK-Ay mice. Biochem Biophys Res Commun 434:486–491
Youssef DA, El-Fayoumi HM, Mahmoud MF (2019) Beta-caryophyllene protects against diet-induced dyslipidemia and vascular inflammation in rats: involvement of CB2 and PPARγ receptors. Chem Biol Interact 297:16–24
Yu YM, Chao TY, Chang WC et al (2016) Thymol reduces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyperlipidemic rabbits. J Food Drug Anal 24:556–563
Yuan X, Wei G, You Y et al (2017) Rutin ameliorates obesity through brown fat activation. FASEB J 31:333–345
Yuan Y, Liu Q, Zhao F et al (2019) Holothuria leucospilota polysaccharides ameliorate hyperlipidemia in high-fat diet-induced rats via short-chain fatty acids production and lipid metabolism regulation. Int j Mol Sci 20:4738
Zang Y, Zhang L, Igarashi K et al (2015) The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe soybean leaves in high-fat-diet mice. Food Funct 6:834–841
Zang Y, Igarashi K, Li Y (2016) Anti-diabetic effects of luteolin and luteolin-7-O-glucoside on KK-Ay mice. Biosci Biotechnol Biochem 80:1580–1586
Zeng XY, Wang H, Bai F et al (2015) Identification of matrine as a promising novel drug for hepatic steatosis and glucose intolerance with HSP72 as an upstream target. Br J Pharmacol 172:4303–4318
Zghonda N, Yoshida S, Ezaki S et al (2012) ε-Viniferin is more efficient than its monomer resveratrol in improving the functions of vascular endothelial cells and the heart. Biosci Biotechnol Biochem 76:954–960
Zhai B, Zhang C, Sheng Y et al (2018) Hypoglycemic and hypolipidemic effect of S-allyl-cysteine-sulfoxide (alliin) in DIO mice. Sci Rep 8:3527
Zhang WY, Lee JJ, Kim Y et al (2010a) Amelioration of insulin resistance by scopoletin in high-glucose induced, insulin resistant HepG2 cells. Horm Metab Res 42:930–935
Zhang ZF, Li Q, Liang J et al (2010b) Epigallocatechin-3-O-gallate (EGCG) protects insulin sensitivity in rat L6 muscle cells exposed to dexamethasone condition. Phytomedicine 17:14–18
Zhang Y, Fan S, Hu N et al (2012) Rhein reduces fat weight in db/db mouse and prevents diet-induced obesity in C57BI/6 mouse through inhibition of PPARγ signalling. PPAR Res 2012:374936
Zhang T, Yamamoto N, Ashida H (2014a) Chalcones suppress fatty acid-induced lipid accumulation through a LKB1/AMPK signaling pathway in HepG2 cells. Food Funct 5:1134–1141
Zhang Z, Wang S, Zhou S et al (2014b) Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway. J Mol Cell Cardiol 77:42–52
Zhang L, Han YJ, Zhang X et al (2016a) Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signaling in adipose tissue macrophages. Diabetologia 59:2219–2228
Zhang N, Yang Z, Xiang SZ et al (2016b) Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy. Mol Cell Biochem 417:87–96
Zhang R, Yu Y, Deng J et al (2016c) Sesamin ameliorates high-fat diet-induced dyslipidemia and kidney injury by reducing oxidative stress. Nutrients 8:276
Zhang R, Yu Y, Hu S et al (2016d) Sesamin ameliorates hepatic steatosis and inflammation in rats on a high-fat diet via LXRα and PPARα. Nutr Res 36:1022–1030
Zhang Y, Hu T, Zhou H et al (2016e) Antidiabetic effect of polysaccharides from Pleurotus ostreatus in streptozotocin induced diabetic rats. Int J Biol Macromol 83:126–132
Zhang T, Zhu Q, Shao Y et al (2017) Paeoniflorin prevents TLR2/4-mediated inflammation in type 2 diabetic nephropathy. Biosci Trends 11:308–318
Zhang B, Sun W, Yu N et al (2018a) Anti-diabetic effect of baicalein is associated with the modulation of gut microbiota in streptozotocin and high-fat-diet induced diabetic rats. J Funct Foods 46:256–267
Zhang C, Chen H, Bai W (2018b) Characterization of Momordica charantia L. polysaccharide and its protective effects on pancreatic cells injury in STZ-induced diabetic mice. Int J Biol Macromol 115:45–52
Zhang J, Celli GB, Brooks MS (2019a) Natural sources of anthocyanins. In: Brooks MS, Celli GB (eds) Anthocyanins from natural sources: exploiting targeted delivery for improved health, 1st edn. Royal Soc Chem, Cambridge, UK, pp 154–196
Zhang S, Guo S, Gao XB et al (2019b) Matrine attenuates high-fat diet-induced in vivo and ox-LDL-induced in vitro vascular injury by regulating the PKCα/eNOS and PI3K/Akt/eNOS pathways. J Cell Mol Med 23:2731–2743
Zhao D, Luan Z (2020) Oleanolic acid attenuates renal fibrosis through TGF-β/Smad pathway in a rat model of unilateral ureteral obstruction. Evid Based Complement Altern Med 2020:2085303
Zhao L, Sun LN, Nie HB et al (2014) Berberine improves kidney function in diabetic mice via AMPK activation. PLoS One 9: e113398; Idem. PLoS One 12:e0190562
Zhao M, Zheng S, Yang J et al (2015) Suppression of TGF-β1/Smad signalling pathway by sesamin contributes to the attenuation of myocardial fibrosis in spontaneously hypertensive rats. PLoS One 10:e0121312
Zheng JM, Zhu JM, Li LS et al (2008) Rhein reverses the diabetic phenotype of mesangial cells over-expressing the glucose transporter (GLUT1) by inhibiting the hexosamine pathway. Br J Pharmacol 153:1456–1464
Zheng T, Yang X, Wu D et al (2015) Salidroside ameliorates insulin resistance through activation of a mitochondria-associated AMPK/PI3K/akt/GSK-3β pathway. Br J Pharmacol 172:3284–3301
Zheng Z, Yin Y, Lu R et al (2019) Lycopene ameliorated oxidative stress and inflammation in type 2 diabetic rats. J Food Sci 84:1194–1200
Zhou JY, Zhou SW (2012) Protection of trigonelline on experimental diabetic peripheral neuropathy. Evid Based Complement Altern Med 2012:164219
Zhou J, Xu G, Ma S et al (2015) Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways. Biochem Biophys Res Commun 467:853–858
Zhou L, Xiao X, Zhang Q et al (2019) Dietary genistein could modulate hypothalamic circadian entrainment, reduce body weight, and improve glucose and lipid metabolism in female mice. Int J Endocrinol 2019:2163838
Zhu D, Zhang N, Zhou X et al (2017) Cichoric acid regulates the hepatic glucose homeostasis via AMPK pathway and activates the antioxidant response in high glucose-induced hepatocyte injury. RSC Adv 7:1363–1375
Zhu Z, Zhu B, Sun Y et al (2018) Sulfated polysaccharide from sea cucumber and its depolymerised derivative prevent obesity in association with modification of gut microbiota in high-fat diet-fed mice. Mol Nutr Food Res 62:e1800446
Zhu Z, Han Y, Ding Y et al (2021) Health effects of dietary sulphated polysaccharides from seafoods and their interaction with gut microbiota. Compr Rev Food Sci Food Saf 20:2882–2913
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Dinda, B., Dinda, S., Chakraborty, M. (2022). Pharmacology of Anti-obesity and Antidiabetic Phytochemicals Isolated from Various Natural Sources (Plants, Seaweeds, Mushrooms, Marine Animals, and Microorganisms). In: Dinda, B. (eds) Natural Products in Obesity and Diabetes. Springer, Cham. https://doi.org/10.1007/978-3-030-92196-5_5
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