Table 1.

Representative flavonoids showing anti-obesity and anti-diabetic effects.

Name of Flavonoids	Structures	Plant Sources	Anti-Obesity and Anti-Diabetic Effect in in Vitro/in Vivo Model	Molecular Mechanism in Obesity and Diabetes	References
Quercetin		Apples, berries, red onions, cherries, broccoli, coriander, etc.	↑ Apoptosis in 3T3-L1 preadipocytes	↓ PARP, ↑ AMPK, ↑ Caspase 3 and 9	[45]
			↑ Glucose uptake in rat adipocyte, C2C12 muscle cells	↑ GLUT4	[46]
			↑ Glucose uptake, ↓ Fat accumulation in 3T3-L1 preadipocytes	↓ PPARγ1	[47]
			↓ Hyperglycemia, ↑ Insulin in STZ-induced diabetic rats, db/db mice	↓ NF-κB, ↓ Caspase 3, ↓ MDA levels, ↑ SOD and CAT	[48]
Rutin		Buckwheat, oranges, grapes, lemons, limes, peaches and berries	↓ Blood lipids, ↓ Fatty liver in DIO mice and rat	↓ PPAR and ↓ C/EBP, ↓ TNF-α, ↓ IL-6	[49]
			↑ Glucose uptake in the rat soleus muscle	↑ PI3K, ↑ MAPK	[50]
Isorhamnetin		Ginkgo biloba L., Hippophae rhamnoides L. and Oenanthe javanica (Blume)	↓ Hyperglycemia and oxidative stress in STZ-induced diabetic rat, Inhibition adipogenesis in 3 T3-L1 cells	↓ PPARγ, ↓ C/EBPα	[51]
			↑ Insulin secretion in HFD-induced C57BL/6 mice	↑ GLUT2, ↑ PPARγ	[52]
Kaempferol		Grapefruit, tea, cruciferous vegetables	↓ Hyperglycemia, ↑ Glucose uptake in rat soleus muscle	↓ Caspase 3	[53]
			↑ β-cell survival in INS-1E cells	↑ GLUT4, ↑ AMPK	[54]
			↑ Antioxidant defense and body weight gain in diabetic rats and HFD-obese mice	↓ PPARγ, ↓ SREBP-1c, ↓ TNF-α, ↓ IL-6	[55]
Resveratrol		Red grapes, red wine, peanuts, and ground nuts	↑ Glucose uptake	↑ GLUT4	[56]
			↓ Lipid accumulation 3T3-L1	↓ PPARγ	[57]
			↑ Lipolytic activity in adipocytes	↑ cAMP	[58]
Naringenin		Spreng, Grapefruits, oranges and tomatoes	↓ Blood lipids, ↓ Fatty liver in Hypercholesterolemic rats	↓ HMG-CoA, ↓ ACAT	[59]
			↓ Glucose uptake in 3T3-L1 adipocytes	↓ PI3K, ↓ AKT	[60]
			↓ Hyperglycemia in STZ-induced rat	↑ Antioxidant enzyme (SOD)	[61]
Naringin		Citrus fruits and Grapefruit	↓ Hyperglycemia, ↑ Plasma insulin, ↑ Leptin in STZ-induced diabetic mice and db/db mice	↑ GLUT4, ↑ PPARγ	[59]
			↓ Blood lipids, ↓ Fatty liver in db/db Mice	↓ HMG-CoA, ↓ ACAT	[62]
Hesperidin		Lemons and oranges	↓ Blood glucose level, ↓ Blood lipids in STZ-induced type 1 diabetic rats	↑ Glucokinase	[63]
			↓ Oxidative stress, apoptosis	↑ GLUT4, ↓ HMG-CoA, ↓ ACAT	[64]
Eriodictyol		Lemon fruits	↓ Adipocyte-specific fatty acid binding protein in differentiated 3 T3-L1 adipocytes	↑ PPARγ	[65]
			↑ Glucose uptake, ↑ Insulin resistance in HepG2 cells	↑ AKT	[65]
			↓ Diabetes-related lipid peroxidation	↓ TNFα, ↓ ICAM-1, ↓ VEGF	[66]
Genistein		Soy foods	↓ Plasma triglycerides in Sprague-Dawley rats	↑ GLUT4	[67,68,69]
			↑ Insulin-positive β cell in HG-induced diabetic mice	↑ cAMP signaling, ↑ PKA activation	[70]
			↓ Blood glucose, ↓ Blood HbA1c in STZ-induced diabetic mice, ↓ Adipocyte differentiation	↓ TNF-α, ↓ TGFβ1, ↓ NF-κB, ↑ AMPK, ↑ ACC	[71]
Daidzein		Soy foods and nuts	↓ Blood glucose, ↓ Urinary glucose	↓TNF-α, ↓ TGFβ1, ↓ NF-κB	[70]
			↓ Plasma triglycerides in Sprague-Dawley rats	↑ GLUT4, ↓ G6Pase, ↓ PEPCK	[67]
Apigenin		Passion flower and chamomile	↓ Hyperglycemia, ↓ Oxidative stress in STZ-induced diabetic rats and mice	↓ NF-κB, ↓ TNF-α, ↓ IL-1β	[72]
			↑ Glucose uptake, ↑ Insulin secretion in alloxan-induced diabetic mice and INS-1E cells, ↓ Lipid accumulation, ↓ Hyperglycemia in HepG2 hepatocytes	↓ G6Pase, ↑ GLUT4, ↑ AMPK, ↓ MCP-1, ↑ AMPK, ↑ ACC	[73]
Luteolin		Celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, apple skins, and chrysanthemum flowers	↑ Insulin secretion in 3T3-L1 hepatocyte	↑ GLUT4, ↑ Leptin	[74]
			↑ Insulin secretion in uric acid damaged pancreatic β-cells	↓ MAFA, ↓ NF-κB, ↓ CREB-B	[75]
Tangeretin		Citrus fruit rinds, mandarin orange	↑ Insulin secretion, ↑ Glycogen, ↓ Total cholesterol in HFD-induced obese mice	↓ TNF-α, ↓ IL-6, ↓ IL-1β	[76]
			↓ Plasma glucose level, ↓ Plasma HbA1c in diabetic rats	↑ AMPK	[77]
Epicatechin Gallate		Tea, grapes and seeds of certain leguminous plants	↓ Hepatic lipid accumulation in HepG2 cells	↓ Fatty acid synthase, ↓ ACC1	[78]
(−)-Catechin		Tea, grapes and seeds of certain leguminous plants	↓ Insulin-dependent glucose uptake, ↑ Adiponectin protein	↓ KLF7, ↓ PPARγ, ↓ C/EBPα	[79]
(−)-Epigallo catechin gallate		Tea, grapes and seeds of certain leguminous plants	↑ Insulin secretion, protect insulin-producing β-cells	↑ FOXO1, ↑ PDX-1, ↑ IRS2, ↑ AKT, ↑ NeuroD, ↑ MAFA	[80]
Cyanidin		Plants with purple corn color (PCC)	↓ White and brown adipose tissue weights, ↓ Hyperglycemia	↓ TNF-α, ↓ SREBP-1	[81]
Anthocyanins		Black soybean seed coats bilberries	↓ Hyperglycemia, ↑ Insulin sensitivity, ↑ GLUT4 (WAT and muscle) in T2DM mice	↑ AMPK, ↓ PEPCK, ↓ G6Pase, ↓ ACC1, ↓ PPARα, ↑ Acyl-CoA oxidase, ↑ CPT-1A, ↓ RBP4	[82]
Cyanidin-3-glucoside		Plant bayberry fruit	Protect hepatocytes ↓ HG-stimulated damage	↑ AKT, ↓ JNK, ↓ TNF-α, ↓ IL-6, ↓ MCP-1	[83]
			↑ Insulin secretion in oxidative stress-induced pancreatic β damage	↑ GLUT4, ↑ LPL, ↑ FAS, ↑ AMPK	[84]

(↓) Decrease, (↑) Increase.