Table 5.

Antifibrotic activities of hyperoside (Hyp) in experimental models related to hepatic fibrosis.

Hyperoside/Source	Experimental Model	Dose	Results/Molecular Mechanisms	References
Hyp	LX-2 cells	2 mM/L	↓cell proliferation ↑cell apoptosis rate ↑proapoptotic genes (Bcl-Xs, DR4, Fas, FasL) ↓antiapoptotic genes (A20, c-IAP1, Bcl-XL, RIP1) ↓α-SMA, collagen I mRNA and protein ↓intracellular ROS ↓TNF-α-induced NFκB p65 DNA binding (by Hyp 1mM/L)	[85]
Hyp	CCl4-induced male Kunming mice	200, 400 mg/kg	↓serum MAO ↓hepatic MAO ↓fibrosis around central vein ↓hepatic MDA ↑hepatic SOD, GSH-Px, CAT ↑hepatic Nrf2	[35]
Hyp	High-fat diet-induced male C57BL/6 mice	50 mg/kg	↓hepatic fibrotic area ↓hepatic Col1A1, CTGF, TGF-β mRNA	[74]
Hyp	Heart failure-induced liver fibrosis in male Wistar rats	100, 200 mg/kg	↓hepatic hydroxyproline ↓hepatic fibrosis area ↓hepatic α-SMA, collagen I, CTGF mRNA and protein ↓hepatic MMP2, MMP9 mRNA and protein ↓hepatic TGFβ1, p-Smad 2,3 protein	[55]
Hyp	Heart failure-induced liver fibrosis in male Wistar rats	200 mg/kg	↓hepatic hydroxyproline ↓hepatic TGF-β1, CTGF, TIMP1, MMP1, MMP2, collagen III mRNA and protein ↓hepatic MDA ↑hepatic SOD, GSH-Px	[59]
Hyp	TGF-β1-induced LX-2 cells	2 mM	↓α-SMA mRNA and protein ↓collagen I mRNA and protein ↓p-Smad 2,3 protein	[55]

Bcl-2, B-cell lymphoma; DR, death receptor; FasL, Fas ligand; c-IAP1, cellular inhibitor of apoptosis protein1; RIP1, receptor interacting protein; α-SMA, α-smooth muscle actin; TNF-α, tumor necrosis factor-alpha; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; CCl₄, carbon tetrachloride; MAO, monoamine oxidase; MDA, malondialdehyde; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; CAT, catalase; Col1A1, collagen type 1 alpha 1; CTGF, connective tissue growth factor; TGF-β, transforming growth factor-beta; and MMP, matrix metalloproteinase. Upward pointing arrow (↑) and downward pointing arrow (↓) represent an increase and a decrease in gene/protein expression or numerical values, respectively.