Table 2.

Origins of flavonoids and their targeted signaling pathways that induce apoptosis and inhibit cell proliferation and angiogenesis.

Compound	Main Origin and Structure	Signaling Pathway	HCC Model	Reference
Luteolin	Celery, green pepper, parsley, thyme, dandelion	ROS-mediated pathway Caspase Activation	Hep G2 cells	[114]
Luteolin-7-O-glucoside	Dandelion, coffee and Cynara scolymus	Arrest G2/M phases of cell by JNK and Caspase activation	HepG2 cells	[115]
Isoorientin	Passion flower, Vitex negundo, Terminalia myriocarpa	Regulation of Cell cycle-related genes ROS-mediated pathway Caspase-3 and caspase-9 activation	Hep G2 cells	[116]
Chrysin	Honey, propolis, passion flowers, and Passiflora caerulea	Downregulation of Skp2 and LRP6 Activation of the p53/Bcl-2/caspase-9	Hep G2 cells	[117]
Oroxylin A	Scutellaria baicalensis and Oroxylum indicum	Suppression of PI3K-PTEN-Akt-mTOR signaling pathway Activation of the ERK-eIF2α-ATF4-CHOP branch of the UPR pathway	HepG2 cells	[118]
Wogonin	Scutellaria baicalensis	Activation of the UPR pathway and inactivation of Akt signaling	HepG2, SMMC7721, and Hep3B cells	[119]
Baicalein	Roots of Scutellaria baicalensis and Scutellaria lateriflora	Inhibition of the PKB/mTOR pathway Blocking MEK-ERK signaling	HepG2 cells Xenograft in mice	[120,121]
Eriodictyol	Eriodictyon californicum	Upregulation of Bax and PARP downregulation of Bcl-2	HepG2 cells	[122]
Hesperidin	Citrus fruits	Regulation of mitochondrial pathway Death receptor pathway; increases the levels of intracellular ROS, ATP, and Ca2+	HepG2 cells Xenograft in mice	[112,123]
Puerarin	Root of Pueraria	Regulation of MAPK pathways	SMMC-7721 cells	[51]
Galangin	Alpinia officinarum and Helichrysum aureonitens	Pro apoptotic Mitochondrial pathway mediated by Bax	HepG2, HepG2, Hep3B, and PLC/PRF/5 cells	[124,125]
Epigallocatechin gallate	Tea leaves	Inhibition of tyrosine kinase receptors Downregulation of PI3K/Akt activity; downregulating Bcl-2 alpha and Bcl-xl by inactivation of NF-κB Hypoxia	SMMC7721, SKhep1, HLE, HepG2, HuH-7, PLC/PRF/5 cells; Xenograft in mice	[110,126]
Dihydromyricetin	Ampelopsis japonica, Hovenia dulcis	Reduction of TGFβ via p53- dependent pathway	HepG2 cells	[127]
Kurarinol	Roots of Sophora flavescens	Suppressing STAT3 signaling	HepG2, Huh-7, and H22 cells; Xenograft in mice	[113]
Eriocitrin	Lemon fruits	Upregulation of p53, cyclin A, cyclin D3, and CDK6 through activation of mitochondrial pathway	HepG2 cells	[128]
Fisetin	Strawberries, apples, persimmons, onions, and cucumbers	Regulation of CDK5 signaling NRF2-mediated oxidative stress response Glucocorticoid signaling ERK/MAPK signaling	HepG2 cells	[129]
Kaempferol	kale, beans, tea, spinach, and broccoli.	Inhibition of MAPK and HIF-1	Huh7 cells	[130]
Theaflavins	Black tea	Activating the caspase pathwayBlockage of STAT3 pathway	HepG2 cells Xenograft in mice	[111]