TABLE 2.

Experiment designs and effects of apigenin on diabetes (in vivo and in vitro).

Study design	Experiment models	Dose	Duration	Administration route	Source	Mechanisms	Reference
In vivo experiment	miRNA103 transgenic mice	40 mg/kg	14 days	Intraperitoneal injection (after modeling)	Commercial	Inhibition of miRNA103 maturation	Ohno et al. (60)
	Wistar rats	10, 20, and 40 mg/kg	21 days	Intraperitoneal injection (after modeling)	Commercial	decrease of MDA content, increase of SOD activity and GSH level	Mao et al. (67)
	Sprague–Dawley rats	50 and 100 mg/kg	6 weeks	Oral gavage (after modeling)	Commercial	Inhibition of NF-κB activation and ICAM-1 mRNA expression	Ren et al. (97)
	C57BL/6J mice (high fat diet)	0.005% (w/w)	16 weeks	Food intake (during modeling)	Commercial	Upregulated expression of genes regulating fatty acid oxidation, TCA cycle and cholesterol homeostasis, downregulated expression of lipogenic genes in the liver	Jung et al. (29)
	C57BL/6J mice (high fructose diet)	50 mg/kg	4 weeks	oral gavage (during modeling)	Commercial	Inhibition of binding of Keap1 to Nrf2 to in increase the expressions of anti-oxidative genes	Yang et al. (126)
In vitro experiment	Huh7 cells	10 μM	24 h	−	Commercial	Inhibition of miRNA103 maturation	Ohno et al. (60)
	Hep3B cells, U-2 OS cells	30 μM	16 h	−	Commercial	Rapid intracellular translocation of FOXO1, downregulation of PEPCK, G6Pc, FASN and ACC, inhibition of the PKB/AKT-signaling pathway	Bumke-Vogt et al. (134)
	HepG2 cells	20 μM
	HEK cells	20 μM
	RINm5F rat pancreatic β cells	5 μM	1 h	−	Commercial	Reduction of intracellular ROS production, alleviation of DNA damage, lipid peroxidation, cell apoptosis of pancreatic beta cells, the loss of antioxidant enzymes	Wang et al. (71)
	Inhibition of apigenin against pancreatic α-Amylase	400 μM	10 min	−	Commercial	Inhibition against α-Amylase	Zhang et al. (64)
	H9c2 cells	1, 3, and 10 μM	20 h	−	Commercial	Inhibition of HIF-1α to improve abnormal glucolipid metabolism	Zhu et al. (105)
	Detection of Tyr phosphorylation: KK-1	40 μM	6 h	−	Commercial	Inhibition of tyrosine nitration of the insulin receptor kinase domain to alleviate insulin resistance	Fang et al. (58)

Keap1, Kelch-like ECH-associated protein 1; Nrf2, nuclear factor erythroid 2–related factor 2; 2-NBDG, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose; ROS, reactive oxygen species; PKCβII, protein kinase C βII; HIF-1α, hypoxia-inducible factor 1 alpha.