Table 1.
Hepatoprotective activities of hyperoside (Hyp) in experimental models related to various liver diseases.
| Hyperoside/Source | Experimental Model | Dose | Results/Molecular Mechanisms | References |
|---|---|---|---|---|
| Hyp/Artemisia capillaris |
CCl4-induced liver injury in mice | 50, 100, 200 mg/kg | ↓serum AST, ALT ↓centrizonal necrosis ↓hepatic MDA ↑hepatic GSH ↑hepatic Nrf2 protein ↑hepatic HO-1 mRNA and protein |
[34] |
| Hyp | CCl4-induced male Kunming mice | 200, 400 mg/kg | ↓serum AST, ALT ↓hepatocellular necrosis ↓hepatic MDA, SOD, GSH-Px ↑hepatic CAT ↑hepatic Nrf2 |
[35] |
| Hyp | CCl4-induced male Sprague-Dawley rats | 60 mg/kg | ↓serum AST, ALT ↓liver cell edema, nuclear condensation, hepatocellular vacuolization ↓hepatic MDA ↑hepatic SOD ↑hepatic p-AKT, p-GSK-3β ↑hepatic nuclear Nrf2 ↑hepatic HO-1 ↓hepatic p-Fyn ↓hepatic PHLPP2 |
[36] |
| Hyp | CCl4-induced male BALB/c mice | 50, 100 mg/kg | ↓serum AST, ALT ↓hepatocellular vacuolization ↓hepatic MDA, SOD ↑hepatic GSH |
[37] |
| Hyp | CCl4-induced C57BL/6J mice | 200 mg/kg | ↓serum AST, ALT ↓hepatocyte destruction ↓hepatic p-p38, p-Erk protein |
[38] |
| Hyp | CCl4-induced rats | 30, 60 mg/kg | ↓hepatic focal necrosis ↓hepatic MDA ↑hepatic SOD, GSH |
[40] |
| Hyp/Zanthoxylum schinifolium | CCl4-induced mice | 10, 20 mg/kg | ↓serum AST, ALT ↓hepatic TBARS |
[41] |
| Hyp/Canarium album and Euphorbia nematocypha |
CCl4-induced primary cultured rat hepatocytes | 1, 10 µM | ↓MDA | [42] |
| Hyp/Zanthoxylum bungeanum leaves | High-carbohydrate/high-fat diet and alloxan-induced male Kunming mice | 200 mg/kg | ↓hepatic AST, ALT ↑hepatic Na+/K+ ATPase ↓hepatic focal necrosis ↑hepatic SOD, GSH, CAT ↓hepatic MDA ↓hepatic ATF3 ↓hepatic p-p65 ↓hepatic p-p38, p-Erk1/2, p-JNK ↓hepatic Bax ↑hepatic Bcl-2 ↓hepatic caspase 3,9 ↓hepatic cytochrome c |
[53] |
| Hyp | ApoE−/− mice fed high-fat diet | 200 mg/kg | ↓serum AST, ALT ↓hepatic MDA ↑hepatic SOD, GSH-Px |
[61] |
| Hyp | Kunming mice given 50% alcohol | 25, 50 mg/kg | ↓serum AST, ALT ↓hepatocellular necrosis and edema ↓hepatic MDA ↑hepatic SOD, GSH |
[39] |
| Hyp/Abelmoschus manihot | Ducklings inoculated with HBV-DNA | 0.1 g/kg/day | ↓hepatocellular necrosis ↓hepatocellular vacuolation |
[54] |
| Hyp | Ducklings inoculated with duck HBV DNA | 60 mg/kg | ↓hepatic ALT ↓hepatic cord derangement |
[58] |
| Hyp | Heart failure-induced liver fibrosis in male Wistar rats | 100, 200 mg/kg | ↓serum AST, ALT ↓serum ALP |
[55] |
| Hyp | Heart failure-induced liver fibrosis in male Wistar rats | 100, 200 mg/kg | ↓serum AST, ALT ↓hepatic MDA ↑hepatic SOD, GSH-Px |
[59] |
| Hyp | Diabetes-induced rats | 10 mg/kg | ↓serum AST, ALT | [60] |
| Hyp | Pneumonia-induced liver injury in BALB/c mice | 12.5, 50 mg/kg | ↓serum AST, ALT | [56] |
| Hyp | Cisplatin-induced liver injury in male ICR mice | 50 mg/kg | ↓serum AST, ALT, GGT ↓hepatocellular vacuolation ↓hepatic MDA ↑hepatic T-AOC, SOD, CAT, GSH, GSH-Px, GST |
[48] |
| Hyp | H2O2-induced LO2 liver cells | 100 µM | ↑cell survival rate, ↓LDH leakage ↑GSH ↑HO-1 mRNA and protein ↑nuclear Nrf-2 mRNA and protein ↑ARE, p-GSK-3β |
[43] |
| Hyp | H2O2-induced LO2 liver cells | 100, 200 µM | ↓MDA, ROS ↑HO-1 ↑ARE ↑nuclear Nrf-2 ↓nuclear Bach1 ↑Crm1 ↑Erk1/2 |
[37] |
| Hyp | H2O2-induced HepG2 cells | 1, 10 µM | ↓ROS | [44] |
| Hyp | t-BHP-induced LO2 liver cells | 100 µM | ↑HO-1 ↑nuclear Nrf-2 ↓p-Fyn ↑p- GSK-3β ↑p-Akt ↓PHLPP2 |
[36] |
| Hyp | Concanavalin A-induced Kunming mice | 25, 50 mg/kg | ↓serum AST, ALT ↓hepatocellular necrosis ↓hepatic MDA ↑hepatic SOD |
[62] |
| Hyp/Apocynum venetum | D-GalN/TNF-α-induced primary cultured mouse hepatocytes | 20, 40, 80 µM | ↑cell survival rate | [63] |
| Hyp/Canarium album and Euphorbia nematocypha | D-GalN-induced primary cultured rat hepatocytes | 3, 10, 30 µM | ↓ALT | [42] |
| Hyp | Acetaminophen-induced LO2 liver cells | 10, 20 µM | ↑cell survival rate ↓LDH ↓ALT ↑nuclear Nrf2 ↑HO-1, GCLC, NQO1 |
[49] |
| Hyp | Acetaminophen-induced male Kunming mice |
100 mg/kg | ↓serum AST, ALT ↓liver congestion, centrilobular necrosis ↑hepatic UGTs ↑hepatic SULTs ↓hepatic CYP2E1 ↑nuclear Nrf-2 mRNA and protein |
[50] |
| Hyp | Acetaminophen-induced male C57BL/6 mice | 25, 50, 100 mg/kg | ↓serum AST, ALT, ALP ↓hepatic MDA ↑hepatic GSH, SOD, GST, GSH-Px ↑hepatic nuclear Nrf2 ↑hepatic HO-1, GCLC, NQO1 |
[49] |
| Hyp | Acetaminophen-induced male C57BL/6 mice | 60 mg/kg | ↓serum AST, ALT ↓hepatocellular vacuolation, lintrahepatic hemorrhage, lymphocyte infiltration ↓hepatic ROS, MDA ↑hepatic GSH, GST, GSH-Px ↓hepatic CYP2E1 mRNA and protein |
[51] |
| Hyp | Hepatic ischemia-reperfusion injury male Wistar rats | 50 mg/kg | ↓serum AST, ALT ↓Suzuki score ↓hepatic MDA ↑hepatic SOD, GSH-Px ↑hepatic HO-1, NQO1 protein ↓apoptotic cells in liver ↑hepatic Bcl-2 protein ↓hepatic Bax, caspase-3 protein |
[57] |
CCl4, carbon tetrachloride; AST, aspartate aminotransferase; ALT, alanine aminotransferase; MDA, malondialdehyde; GSH, glutathione; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, heme oxygenase-1; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; CAT, catalase; AKT, protein kinase B; GSK-3β, glycogen synthase kinase-3β; PHLPP2, PH domain and leucine rich repeat protein phosphatase 2; Erk, extracellular signal-regulated kinase; TBARS, thiobarbituric acid reactive substance; ATF3, cyclic AMP-dependent transcription factor; JNK, c-Jun N-terminal kinase; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; ALP, alkaline phosphatase; GGT, gamma glutamyl peptidase; LDH, lactate dehydrogenase; ARE, antioxidant response element; Bach1, BTB domain and CNC homolog 1; Crm1, chromosome region maintenance 1; NQO1, NAD(P)H quinone dehydrogenase 1; UGTs, UDP-glucuronosyltransferases; SULTs, sulfotransferases; and CYP, cytochrome P450. Upward pointing arrow (↑) and downward pointing arrow (↓) represent an increase and a decrease in gene/protein expression or numerical values, respectively.