Table 3.

Representative flavones and their underlying anti-diabetic effects.

Flavonoid Subclass	Name of Flavonoid	Structure of Flavonoid	Dietary Source	Metabolites Produced from Flavonoids	Function of Flavonoids	Mechanism of Action	Model Used		References
							In Vivo	In Vitro
Flavones	10. Baicalein		Scutellaria lateriflora L, and Scutellaria baicalensis Georgi	In Intestine: Baicalin will be converted into Baicalein and then absorbed rapidly. In the circulation: Baicalein will be converted to Baicalin	(A) Antihyperglycmeic effect: (B) Hypolipemic effect	Reduce the level of level of hemoglobin A1C (HbA1c) Suppress the activation of NF-κB Improve glucose tolerance and insulin secretion from pancreatic cells Improve viability of clonal β-cells which improves the production of NADH and NADPH Protect against β cells apoptosis Increase hexokinase activity in liver Activate MAPKs signaling pathway which reduce the effect of insulin resistance by phosphorylating Akt and IRS-1 and dephosphorylate NF-κB Suppress fatty acid synthesis	Obese diabetic mice Type 2 diabetic rats	CA1 hippocampal neurons	[187,190]
	11. Luteolin		Parsley, broccoli, onoins leaves, celery, cabbages, apple skins, carrots, and peppers	Metabolization is medicated by UGTs and COMTs to produce: (A) Luteolin-7-glucuronide (Glucuronidated) (B) Luteolin-4-glucuronide (C) Chrysoeriol/diosmetic (Methylated) (D) Luteolin monoglucuronide (Major form in human serum	(A) Antihyperglycmeic effect: (B) Hypolipemic effect	Reduce cAMP response element binding protein and histone acetyl transferase activity of CBP/p300 (NF-κB coactivator) Reduce apoptosis Up-regulate the espression of synaptic protein which target brain cells Improve insulin secretion by supressing Maf A through NF-κB signiling pathway Activate PPAR-γ which targets adiponectin, leptin and GLUT4 genes	Obese mice Streptozotocin induced diabetic rats Diabetic rats	Endothelium cells Human monocytes cells	[155,157]
	12. Diosmin		Citrus fruites, and Scrophularia nodosa L.	(A) Diosmin (Not excreted in urine) (B) Diosmetin (Not excreted in urine) (C) Minor metabolites in the form of glucuronic acid conjugate (Excreted in urine)	(A) Antihyperglycmeic effect: (B) Hypolipemic effect:	Reduce the level of hemoglobin A1C (HbA1c) due to increase in glutathione peroxidase (GPx) Decrease G6Pase, PEPCK, and fructose-1,6-bisphosphatase enzymes Reduce plasma glucose and increase plasma insulin by activating anti-oxidant enzymes Reduce hyperglycemia by inducing β-endorphin Increase hexokinase and glucose-6-phosphate dehydrogenase activity Reduce lipid peroxidation	Streptozotocin nicotinamide induced diabetic rats		[179,180]
	13. Apigenin		Onion, oranges, tea, parsley, chamomile, Hypericum perforatum L, wheat sprouts	Metabolization occurs through two phases: Phase (1): Apigenin produce three monohydroxylated: a) Luteolin b) Scutellarien c) iso-scutellarein Phase(2): Luteolin produce: a) Four monoglucuroconjugates b) Two Sulfoconjugate c) One methyl conjugate	(A) Antihyperglycmeic effect: (B) Hypolipemic effect:	Reduce cellular antioxidants Attenuate cell damage in pancreatic β-cells Improve the morphology of the cells Improve GLUT4 translocation which lowers glucose level Increase serum cholesterol Increase lipid peroxidation	Streptozotocin induced diabetic rats (0.2%)	HepG2 cells Differentiated3T3-L1 cells	[147,149]
	14.Tangeretin		Poncirus trifoliate L, citrus fruit rinds, and mandarin orange	Metabolization is medicated by CYP1A1 and CYP1A2 to produce: (A) 4′ hydroxy - 5, 6, 7, 8 tetramethoxyflavone (4′-OH-TMF)	(A) Antihyperglycmeic effect: (B) Hypolipemic effect:	Reduce blood glucose and HbA1c level Reduce the secretion of insulin resistance factor Increase the secretion level of insulin and insulin sensitizing factor Enhances glycolytic enzyme in the liver Reduce total cholesterol and adipocytokines level	Rats Streptozotocin (STZ)-induced diabetic rats High fat diet mice	Pancreatic β-cells	[160,162]
	15. Wogonin		Scutellaria baicalensis Georgi	(A) Wogonin-7-beta-D-glucuronide (Major metabolites) (B) Wogonin-5-beta-D-glucuronide	(A) Antihyperglycmeic effect: (B) Hypolipemic effect:	Reduce hyperglycemia and lipid droplets accumulation in the liver Increase vascular permeability and the expression of cell adhesion molecules Activate NF-κB and AMPK pathways Activate PPARα which has a beneficial effect on lipid metabolism	db/db mice	3T3-L1 cells	[173,175]
	16. Chrysin		passiflora caerulea (L,), honey, Tilia tomentosa Moench, and Pelargonium crispum (Berg.)	(A) Chrysin glucuronides (M1) (B) Chrysin sulfates (M2)	(A) Antihyperglycmeic effect: (B) Hypolipemic effect:	Reduce the level of pro-inflammatory cytokines that helps in the prevention of diabetic neuropathy Reduce blood glucose Improve renal pathology with the suppression of TGF-β, collagen-IV, and fibronectin Improve insulin level Reduce lipid peroxidation		INS-1E cells	[167,169]