Table 1.
Pharmacological Activities of Rg3 in the Treatment of Liver Diseases
| Disease | Model | Types | Dosage | Effects and related mechanisms | References |
|---|---|---|---|---|---|
| Hepatitis B virus | HepG2.2.15 | In vitro | 100 μM | Downregulation: JNK, AP-1, HBsAg and HBeAg Upregulation: TRAF6, TAK1, IL-8 and TNF-α |
[20] |
| Hepatitis C virus | Huh7 Huh7.5.1 | In vitro | 100 μM | Downregulation: CDK1 and Drp1 Upregulation: p21 |
[24] |
| Liver injury | HepG2 t-BHP-induced male ICR Mice |
In vitro In vivo |
1-10 μM 25, 50 mg/kg |
Downregulation: ALT and AST | [42] |
| Liver injury | LPS-induced liver injury in Male Wistar rats | In vivo | 5, 10 mg/kg | Downregulation: GOT, GPT, NF-kB, COX-2 and iNOS Upregulation: HO-1 |
[43] |
| Liver injury | Cisplatin-induced liver injury in Male BALB/c mice | In vivo | 5, 10 mg/kg | Downregulation: BUN, ALT, AST, NO, MDA, ROS and 3-NT Upregulation: GSH-Px, SOD and CAT |
[40] |
| Liver injury | EtOH induced TIB-73 | In vitro | 1-30 μM | Downregulation: LDH, AST, ROS, ERK and JNK | [41] |
| Liver injury | NAPQI induced H4IIE | In vitro | 1-10μg/mL | Downregulation: ALT, AST, Mrp2 and Mrp4 Upregulation: GSH, Nrf2, Mrp1, Mrp3, GCLC and GCLM |
[29] |
| Liver injury | Human primary hepatocytes CLP induced-C57BL/6 mice |
In vitro In vivo |
6.25, 12.5, 25μM 10, 20 mg/kg |
Downregulation: ROS, GST Upregulation: OCR, GSH, OPA1, Complex I, and Complex II, PGC1-α, NRF-1, Tfam-1, LC3B II/LC3B I, Beclin-1, AMPK and ACC |
[34] |
| Liver injury | APAP-induced liver injury in Male ICR mice | In vivo | 10, 20 mg/kg | Downregulation: ALT, AST, MDA, 4-HNE, CYP2E1, Bax, TNF-α, IL-1β, IKKα, IKKβ, IκBα and NF-κB Upregulation: GSH, PI3K, AKT and Bcl-2 |
[30] |
| Liver injury | D-Galactose Male ICR mice |
In vivo | 10, 20 mg/kg | Downregulation: ALT, BUN, AGEs, MDA, 4-HNE, CYP2E1, Bax, p53 and cleaved-caspase3 Upregulation: CAT, SOD, PI3K, AKT and Bcl-2 |
[37] |
| Liver injury | Human primary hepatocytes CLP induced-C57BL/6 mice |
In vitro In vivo |
25 μM 20 mg/kg |
Upregulation: OPA, Complex I, and Complex II, PGC1-α, NRF-1, Tfam-1, LC3B II, LC3B I, Beclin-1, TUG1, SIRT1, AMPK and ACC | [35] |
| NAFLD | HepG2 | In vitro | 1-100 μM | Downregulation: TC, TG, SREBP-2 and HMGCR Upregulation: AMPK |
[48] |
| NAFLD | 3T3-L1 HFD-induced C57BL/6 male mice |
In vitro In vivo |
5-50 μM 1mg/kg |
Downregulation: TC, TG, ALT, AST, STAT5, PPARγ, TNF-α, IL-1β, Fabp4, Scd1 and CPT-1α Upregulation: p-AKT, IL-6 and IL-10, |
[49] |
| NAFLD | HFD-induced C57BL/6 mouse, db/db mice | In vivo | - | Downregulation: pro-inflammatory cytokine secretion | [53] |
| NAFLD | HFD-induced C57BL/6 mouse | In vivo | - | Downregulation: TC, LDL, TG and AST | [50] |
| NAFLD | Primary hepatocytes Raw264.7 cells |
In vitro | 5 μM | Downregulation: mTORC1, Ccl2, Ccl5, IL-1β, IL-6, iNos and TNF-α Upregulation: Hmgcs2, CD163 and IL-10 |
[54] |
| NASH | Macrophage-induced THP-1 Male C57BL/6J mice |
In vitro In vivo |
0.001–1 μg/mL 15, 30 mg/kg |
Downregulation: F4/80 and p–NF–κB | [55] |
| Liver fibrosis | LPS-induced HSC-T6 TAA-induced liver injury in Male ICR mice |
In vitro In vivo |
0-16 μM 5, 10 mg/kg |
Downregulation: AST, ALT, CAT, MDA, TGF-β1 and α-SMA, LC3b/LC3a, p62, ATG5 and ATG7 Upregulation: SOD, GSH, PI3K, AKT and mTOR |
[63] |
| HCC | SMMC-7721 | In vitro | 15 μg/ml | Downregulation: PCNA and cyclin D1 | [74] |
| HCC | Hep3B | In vitro | 1-30 μM | Downregulation: Bcl-2 Upregulation: LDH, ROS, Bax, caspase-3 and cytosolic cytochrome c |
[68] |
| HCC | Hep1-6 HepG2 C57BL/6 mice |
In vitro In vivo |
0-200 μg/ml 3.0 mg/kg |
Downregulation: Bcl-2, Bcl-XL and Cytochrome c in the mitochondrial fraction Upregulation: Bax and Cytochrome c in the cytosolic fraction. |
[69] |
| HCC | SMMC-7721 HepG2 |
In vitro | 25-100 μg/ml | Downregulation: Bcl-2 Upregulation: caspase-3 and Bax |
[67] |
| HCC | Primary rat hepatocytes HepG2 |
In vitro | 10-100 μM | Downregulation: OPA-1, Bcl-2 Upregulation: UCP-2, cleaved PARP, Fas and LC3 II |
[70] |
| HCC | KM mice | In vivo | 3.0 mg/kg | Upregulation: IL-2 and IFN-γ | [71] |
| HCC | HepG2 | In vitro | 7.81-500 μg/ml | Downregulation: Bcl-2, VEGF, DNMT3a and DNMT3b Upregulation: P53 |
[72] |
| HCC | Bel-7402 HCCLM3 Male BALB/c nude mice |
In vitro In vivo |
0-100 μM 10 mg/kg |
Downregulation: NHE1, EGF, EGFR, ERK1/2, HIF-1α and Ki67 Upregulation: cleaved-caspase-3 |
[73] |
| HCC | Female C57BL/6 mice | In vivo | 10 mg/kg | Downregulation: Angiogenesis quantification | [80] |
| HCC | HepG2 MHCC-97L BALB/c nude mice |
In vitro In vivo |
1.25-5 μg/ml 2.5-10 mg/kg |
Upregulation: ARHGAP9 | [79] |
| HCC | SMMC-7721 SK-Hep-1 |
In vitro | 1- 16 μg/ml | Downregulation: lncRNA-HOTAIR, MMP2, MMP9, PI3K and AKT | [77] |