TABLE 3.

Progress in the research regarding flavonoids for the treatment of iron overload.

Classification	Compound	Model	Mechanism	Results	References
Flavones	Baicalein	Male Wistar rats	Scavenged radical	Decreased the level of lipid and protein iron overload-induced oxidation	Czapski et al. (2012)
		A mouse model of aplastic anemia with iron overload complication	Up-regulated hepcidin and its regulators (BMP-6, SMAD, and TfR2) at the protein and mRNA levels	Protected iron overload-induced apoptosis and reduced iron deposition	Dijiong et al. (2019)
		A model of UV/Visible spectroscopic studies	Modulation of metal homeostasis and the inhibition of Fenton chemistry	Ameliorated iron status and decreased iron overload-induced oxidation	Perez et al. (2009)
	Baicalin	Male Kunming mice	Be capable of the antioxidant and iron chelation activities	Protected the liver of iron overload	Zhao et al. (2005)
		Hepatocytes CYP2E1	Chelated iron	Decreased iron overload-induced oxidation	Xu et al. (2012)
		A model of Electron Spin Resonance spectra	Facilitated the transfer of electrons from Fe(2+) to dissolved oxygen	Decreased iron overload-induced oxidation	Nishizaki and Iwahashi (2015)
		C6 cells	Positively regulated divalent metal transporter 1 expression and negatively regulated ferroportin 1 expression	Down-regulated iron concentration and decreased iron deposition	Guo et al. (2014)
		Male Wistar rats	Chelated iron and educed the loss of tyrosine hydroxylase-positive cells	Reduced iron deposition in different brain regions and protected dopaminergic neurons	Xiong et al. (2012)
	Apigenin	A375 human melanoma cell line and	Chelated iron, scavenged radical and inhibited lipoxygenase	Decreased iron overload-induced oxidative damage	Danciu et al. (2018)
	Luteolin	A model evaluated the pH effect on the lipid oxidation and polyphenols	Chelated iron and scavenged radical	Decreased iron overload-induced lipid oxidation	Kim and Choe (2018)
Flavonols	Quercetin	MDCK cells	Facilitated chelatable iron shuttling via glucose transport proteins in either direction across the cell membrane	Ameliorated iron status	Vlachodimitropoulou et al. (2011)
		Male Wistar rats	Be capable of the antioxidant and iron chelation activities	Decreased iron overload-induced oxidative damage, hepatotoxicity and nephrotoxicity	Gholampour and Saki (2019)
		Human colon carcinoma cell line HT29 clone 19A	Protected iron overload-induced DNA breaks and oxidized bases	Decreased iron overload-induced oxidative damage	Glei et al. (2002)
		Male specific-pathogen-free C57BL/6J mice	Lowered the iron level particularly in the islet in T2DM mice and abolished partially oxidative stress in pancreatic tissue	Decreased iron overload-induced oxidative damage	Li et al. (2020)
		β-thalassemia major patients	Reduced high sensitivity C-reactive protein, iron, ferritin, and transferrin saturation and increased transferrin	Ameliorated iron status	Sajadi Hezaveh et al. (2019)
		HUVECs	Protected iron overload-induced mitochondrial dysfunction via ROS/ADMA/DDAHII/eNOS/NO pathway	Decreased iron overload-induced cell damage	Chen et al. (2020)
		Male Kunming mice	Inhibited iron overload-induced lipid peroxidation and protein oxidation of liver, decreased hepatic iron and hepatic collagen content, increased the serum non-heme iron level, released iron from liver and finally excrete it through feces	Decreased iron overload-induced oxidative damage, ameliorated iron status, and reduced iron deposition by excreting iron through feces	Kim and Choe (2018)
	Rutin	Male albino rats	Be capable of the antioxidant and iron chelation activities	Decreased iron overload-induced oxidative damage	Aziza et al. (2014)
	Kaempferol	HepG2 cells	Protected arachidonic acid and iron induced ROS	Decreased arachidonic acid and iron overload-induced oxidative damage	Cho et al. (2019)
	Myricetin	SH-SY5Y cells	Reduce iron contents may via inhibiting transferrin receptor 1 (TfR1) expression	Ameliorated iron status	Wang et al. (2017)
		Sprague Dawley male animals rat hepatocytes	Prevented both lipid peroxidation and accumulation of oxidation products in DNA via stimulation of DNA repair processes	Decreased iron overload-induced genotoxicity	Abalea et al. (1999)
Flavanones	Naringenin	Male Wistar rats	Improved antioxidant enzyme activities	Decreased iron overload-induced oxidative damage	Chtourou et al. (2014)
		Male Wistar rats	Scavenged radical	Restores iron overload-induced brain dysfunction	Chtourou et al. (2015)
Flavanols	Catechin	Male ICR mice	Chelated iron and Scavenged reactive oxygen active nitrogen	Decreased arachidonic acid and iron overload-induced oxidative damage	Yang et al. (2019)
		Male Swiss albino mice	Chelated iron and scavenged radical	Decreased iron overload-induced oxidative damage	Chaudhuri et al. (2015)
Isoflavones	Purerarin	Male Kunming mice and ARPE-19 cells	Be associated with regulation of iron-handling proteins, enhancement of the antioxidant capacity, and the inhibition of MAPK and STAT3 activation and the apoptotic pathways under iron overload condition	Decreased iron overload-induced retinal oxidative damage and reduced retinal iron deposition	Song et al. (2020)
		APPswe/PS1ΔE9 transgenic mice	Decreased iron levels and malondialdehyde content, increased glutathione peroxidase and superoxide and reduced inflammatory response markers	Decreased iron overload-induced oxidative damage and inflammatory response markers	Zhang et al. (2018)
	Genistein	HepG2 cells	Be related to the BMP response element or the STAT3-binding site in the Hepcidin promoter	Increased Hepcidin transcript levels and promoter activity	Zhen et al. (2013)