TABLE 3.

Representative antidiabetic flavonoids.

Bioactive metabolites	Detail	Cell lines/model	Dose	Negative/positive control	Duration	References
Apigenin	Neutralized active oxygen and enhanced the activity of antioxidant enzymes to achieve anti-oxidation	Alloxan-induced diabetic mice	0.78 mg/kg	NC: saline (0.1 ml)	10 days	Panda and Kar, (2007)
Baicalein	Activated AMPK to achieve anti-inflammatory function and inhibit IR	HFD-induced mice	400 mg/kg	—	29 weeks	Pu et al. (2012)
	Downregulated related genes SREBP-1c, FAS, key enzymes for cholesterol and fatty acid synthesis to regulate lipid metabolism	HFD-induced Rats	80 mg/kg	NC: saline	18 weeks	Guo et al. (2009)
Puerarin	Inhibited NOX4, NOX2, and NF-κB	STZ-induced diabetic rats	18, 45 mg/kg	—	3 weeks	Li et al. (2016)
	Reduced ROS and renewed the activities of antioxidant enzymes	Lead-induced Rats	200 mg/kg	NC: saline (0.9% NaCl)	75 days	Liu et al. (2011)
	Upregulated the mRNA levels of endogenous antioxidant enzymes	Preadipocyte 3T3-L1 cell	100 μM	—	6 days	Lee K. M et al. (2010)
	Inhibitied NF-κB-driven liver inflammation and the TGF-β/smad signaling pathway	HFD-induced diabetic rats	100 mg/kg	—	8 weeks	Hou et al. (2018)
	lower blood glucose levels	STZ-induced diabetic rats	15 mg/kg	NC: saline	2 weeks	Hsu et al. (2003)
	Decreased the blood glucose level of T2DM by downregulating ADRP mRNA expression and depressing IR	HFD-induced Diabetic Rats	40, 80, and 160 mg/kg	NC: saline	6 weeks	Sun et al. (2008)
	Activated GLP-1R signaling	HFD-induced Diabetic Mice	150 mg/kg	—	35 days	Yang et al. (2016)
	Reduced pancreatic tissue damage and upregulated IRS-1 and IGF-1	STZ-induced diabetic mice	20, 40, and 80 mg/kg	PC: metformin (40 mg/kg)	14 days	Wu et al. (2013)
Quercetin	Inhibited the generation of free radicals, enhanced the activity of antioxidant enzymes, and reduced the content of MDA and NO	STZ-induced broilers	0.2, 0.4, and 0.6 g/kg	—	42 days	Ying et al. (2020)
	Promoted insulin secretion through the ERK1/2 pathway	INS-1 cells	20 μM	—	5 days	Youl et al. (2010)
	Inhibited COX and LOX	RLE cells	10, 20 μM	—	24 h	Lee O. H et al. (2010)
	Blocked the production of pro-inflammatory cytokines	Orbital fat tissues	100 μM	—	72 h	Yoon et al. (2012)
	Activated AMPK pathway to inhibit adipogenesis	3T3-L1 cells	0, 10, 50, and 100 μM	—	8 days	Ahn et al. (2008)
Quercitrin	Restored glycogen content and carbohydrate metabolic enzyme activities	STZ-induced diabetic rats	30 mg/kg	NC: carboxymethyl cellulose (1 ml/rat)	30 days	Babujanarthanam et al. (2010)
	Decreased fasting blood glucose, increased insulin levels, and improved the antioxidant status	STZ-induced diabetic rats	30 mg/kg	NC: carboxymethyl cellulose (1 ml/rat)	30 days	Babujanarthanam et al. (2011)
Hesperidin	Inhibited the generation of ROS and reduced the content of MDA	Exhausted exercise model in rats	200 mg/kg	—	52 days	Estruel-Amades et al. (2019)
	Inhibited cell apoptosis by reducing the levels of Caspase-9, Caspase-3, and Bax/Bcl-2	The retinal ganglion cell 5 (RGC-5) cells	12.5, 25, and 50 μM	—	48 h	Liu et al. (2017)
	Suppression of systemic levels of IL-6, MCP-1, and TBARS	HFD-induced C57BL/6J mice	100 mg/kg	—	4 weeks	Ferreira et al. (2016)
	Inhibited both amylose and amylopectin digestion	HepG2 cells	10, 50 μM	PC: Metformin (1,000 μM)	24 h	Shen et al. (2012)
	Inhibited hepatic gluconeogenesis	Rat liver	40, 80, 120, 160, and 200 μM	—	24 h	Zareei et al. (2017)
	Increased PPAR-γ activity or PPAR-γ mRNA expression	HEK293 cells	400 and 800 μg/ml EMS	—	9 weeks	Shin et al. (2013)
	Improved the impaired fasting glucose level and glucose tolerance	HFD-induced mice	1%, 5% EMS (ethanol extract of Prunus mume fruits)	—	9 weeks	Shin et al. (2013)
Myricetin	Increased GSH level and CAT activity	Adult female Wistar Albino mice	3 mg/kg	—	7 days	Hassana et al. (2017)
	Reduced MDA and oxidation protein	MC3T3-E1 cell	0.01–10 μM	—	2 days	Lee and Choi, (2008)
	Inhibition of NF-κB-mediated inflammatory responses	LPS-induced mice	120 mg/kg	PC: dexamethasone (0.5 mg/kg)	4 h	Qi et al. (2017)
	Inhibited α-Amylase (α-Amy) and α-Glucosidase (α-Glu) activity	Pancreatic α-Amylase, α-Glucosidase	0.5, 1 μg/ml	—	20 min	Meng et al. (2016)
Kaempferol	Inhibited the production of ROS, enhanced the activity of antioxidant enzymes, and scavenged free radicals	dRib-induced HIT-T15 cells	10 μM	—	30 min	Lee Y. Jet al. (2010)
	Inhibited the activation of AP-1	PC3 cells	50 μM	—	24 h	Gopalakrishnan et al. (2006)
	Ameliorated hyperglycemia as ligands of PPARγ	3T3-L1 adipocytes	5, 10, 20, and 50 μM	PC: Rosiglitazone (1 μM)	7 days	Fang et al. (2008)
	Reduced inflammation by downregulation of IKK and inhibition of NF-κB pathway activation	HFD-Induced Rats	50, 150 mg/kg	PC: Aspirin (100 mg/kg)	9 weeks	Luo et al. (2015)
	Protected pancreatic beta-cell survival and function	INS-1E beta-cells	10 μM	—	4 days	Zhang and Liu, (2011)
Luteolin	Reduced oxidative stress and enhanced activity in the NOS–NO pathway	STZ-induced diabetic rats	10, 50, 100 mg/kg	—	8 weeks	Qian et al. (2010)
	Attenuated IR through the activation of AMPKα1 signaling	HFD-induced diabetic mice	0.01% v/v	—	20 weeks	Zhang et al. (2016)
		RAW 264.7 cells	20 μM	—	24 h
	Reduced oxidative stress by elevating the enos expression, enhancing mnsod, and suppressing mptp in the downstream	STZ-induced diabetic rats	100 mg/kg	—	2 weeks	Zhou et al. (2021)
	Reduced oxidative stress by elevating the eNOS expression, enhancing MnSOD, and suppressing mPTP downstream	STZ-induced diabetic rats	50 mg/kg	—	2 weeks	Yang et al. (2015)
	Increased the antioxidant capacity such as GSH and gpx activity, and decreased MDA level	STZ-induced diabetic rats	25, 50, 100 mg/kg	NC: 0.5% CMC	12 weeks	Chen Y et al. (2017)
	Inhibited IL-1β, vascular endothelial growth factor, and NF-κB mRNA and protein expression
	Decreased the IL-1β mRNA expression and TNF-α mRNA expression to ameliorate inflammatory	STZ-induced diabetic rats	50, 100 mg/kg	—	8 weeks	Gu et al. (2018)