Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy

Table 1 Antioxidant and anti-inflammatory agents for the treatment of hepatocellular carcinoma

Molecules	Model	Function	Ref.
β-sitosterol	HepG2 cells; Rat HCC	Treatment of β-sitosterol niosomes displays direct cytotoxicity to HepG2 cells in vitro and anti-HCC ability in rats	[182]
Curcumin	HepG2 and SK-Hep-1 cells. A nude mouse xenograft model bearing HepG2 cells	It can inhibit cell proliferation and increase cell apoptosis and cell cycle arrest at the G0/G1 phase of cancer cells by downregulating the expression of BCLAF1 and inhibiting the activation of the PI3K/AKT/GSK-3β pathway	[183]
Empagliflozin	DENA-induced HCC in mice	It shows a synergistic effect on the control of angiogenesis, invasion, and metastasis of tumor cells in mice with DENA-induced HCC by inhibiting the expression of MAPKs and reducing liver injury enzymes	[184]
Gastrodin	Subcutaneous H22 cells-induced tumor in mice	It can specifically increase the expression of NF-κB downstream genes such as Bcl-xL, Bcl-2, and IL-2 in CD4 but not CD8 T cells	[185]
Genistein	TAA-induced HCC in rats	It displays antioxidant and anti-HCC effects by suppressing the versican/PDGF bidirectional axis and protein expression of PKC and ERK-1	[186]
Lactoferrin	DEN-induced HCC in rats	It shows a chemopreventive effect against DEN-induced HCC in rats in a dose-dependent manner by suppressing the expression and activation of AKT	[187]
Selenium	TAA-induced HCC in rats	Selenium nanoparticles improve the tumor suppressive effect of sorafenib and overcome drug resistance in rat HCC by inducing apoptosis and targeting AKT/mTOR and NF-κB signaling pathways, as well as epigenetic regulation	[188]
Silymarin	DEN/AAF/CCl4 induced HCC in rats	It suppresses cancer cell growth in rats with DEN/AAF/CCl4-induced tumors by inhibiting the expression of Ki-67 and HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways	[189]
Taraxasterol	HepG2 and Huh7H22 bearing mice	It can suppress tumor cell growth by suppressing Ki67 expression and inducing cell apoptosis via suppressing IL-6/STAT3 signaling pathway, as well as promoting T cell infiltration in tumor tissue	[190]
Telmisartan	NDEA-induced HCC in mice	It exerts an anti-HCC effect and increases tumor cell sensitivity to sorafenib treatment by suppressing phosphorylation-induced activation of TAK1 and the ERK1/2 and NF-кB signaling pathways	[191]
Delta-tocotrienol	HCC cell lines SK Hep-1 and Huh7	It promotes the anti-HCC cell activity of IFN-α by increasing ROS and increasing cell apoptosis together with an increased Bax/Bcl-xL ratio. In addition, it can activate Notch1 signaling pathway	[192]

AKT: Protein kinase B; Bax: Bcl-2-like protein 4; Bcl-2: B-cell lymphoma 2; Bcl-xL: B-cell lymphoma extra-large; BCLAF1: BCL-2-associated transcription factor 1; CD4: Cluster of differentiation 4; c-Met: Tyrosine-protein kinase Met; ERK-1/2: Extracellular signal-regulated kinases 1/2; GSK-3β: Glycogen synthase kinase-3β; HCC: Hepatocellular carcinoma; HGF: Hepatocyte growth factor; IL-2: Interleukin 2; Ki-67: Marker of proliferation Ki-67; MAPK: Mitogen-activated protein kinase; mTOR: Mammalian target of rapamycin; NF-κB: Nuclear factor κB; PI3K: Phosphatidylinositol-3-kinase; PDGF: Platelet-derived growth factor; SIRT1: Sirtuin 1; SREBP-1c: Sterol regulatory element binding protein 1c; STAT3: Signal transducer and activator of transcription 3; DENA Diethylnitrosamine; TAA: Thioacetamide; ROS: Reactive oxygen species; NDEA: N-Nitrosodiethylamine; AAF: 2-acetylaminofluorene; CCl₄: Carbon tetrachloride.