Table 4.
In vivo hepatoprotective effects and related mechanisms of action of oleanolic acid and its natural and synthetic derivatives (2014-2020)
| Disease model/ physiology | Effect |
Mechanism |
Compound | Dosei | Ref. | |
| ↑↑↑ | ↓↓↓ | |||||
| Hepatic injury (mice, EtOH) | Prevents ethanol induced liver injury, hepatoxicity | nNRF-2, HO-1, SOD-1, CAT, GR, hepatic GSH, ATP | sALT, sAST, CYP2E, ADH, TNF-α, IL-6, sTG, sLDH | OA | 10 mg/kg·d, 30 d | [60] |
| Hepatic injury (rats, CCl4) | Hepatoprotective | SOD, GPX | ALT, AST, LDH | OA, OA-Xs | 15 mg/kg | [61] |
| Hepatic fibrosis (HSCs, HEPG2, BEL-7402, LO-2; mice, CCl4) | Hepatoprotection | Apoptosis, Ca2+ | MitMP, sALT, sAST | OA-amino acids | 20 mg/kg, IC50 > 50 µmol/L | [62] |
| Hepatic fibrosis (rast, CCl4) | Anti-hepatic fibrosis | - | sALT, sAST, Liver indices | OA-Xs | 14-28 mg/kg·3 d, 9 wk | [63] |
| Hepatic injury (mice) | Hepatoprotective | NQO1 | mKC, MIP-2, OATP-1B2, GADD-45, CHOP-10, sALT, sMDA, pJNK, HO-1. | OA | 22.5 mg/kg·d, 3 d | [64] |
| Cholestasis (HEPG2) | Obstructive cholestasis | urinary BA, MRP-3, MRP-4, MRP-2, NRF-2 | sBA, sBil, sAST, sALT, sALP, nNRF-2, BSEP, | OA | 20 mg/kg, i.p, 1-50 µmol/L | [65] |
| Cholestasis (mice, LCA) | Cholestasis | MRP-2, MRP-3, MRP-4, NRF-2 | sALT, sALP, sAST, tBA, tBIL, SULT-2A1 | OA | 5-20 µg/kg | [66] |
| Hepatic NAFLD (rats, HFD) | Anti-NAFLD via AMPK-related pathways | HGF, ICAM, IGF-1, IGFBP-3, IGFBP-5, IGFBP-6, lipocalin-2, MCP-1, M-CSF, PREF-1, RAGE, GLUT-2, LDLR, pAMPK, pAKT, pGSK-3β, | TC, TG, LDL-C | OA-Xs | 60 mg/kg·d, 4 wk | [67] |
| Hepatic IRI (mice) | HO-1/Sesn2 signaling pathway | PI3K, HO-1, pAKT | sAST, sALT | OA | 30 mg/kg·d, 7 d | [68] |
| Hepatic IRI (rat) | Protects agaist hepatic IRI | pPI3K, pAKT, pGSK-3β | SALT, IL-1β | OA | 100 mg/kg·d, 7 d before IRI | [69] |
| Hepatic IRI, (mice) | Alleviate hepatic IRI | BCL-2 | apoptosis and autophagy, ALT, AST, CASP-3, CAPS-9, BAX, Beclin 1, LC3, TNF-α, HMG-B1, TLR-4, pJNK | OA | 30-60 mg/kg, 7 d | [70] |
OA: Oleanolic acid; OA-Xs: Natural derivatives of oleanolic acid; IRI: Ischemia-reperfusion injury; NRF-2: Nuclear factor erythroid-2-related factor 2; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; IL: Interleukin; TNF-α: Tumor necrosis factor-α; NAFLD: Non-alcoholic fatty liver disease; HFD: High-fat diet; LDH: Lactic dehydrogenase; MRPs: Multidrug resistance-associated proteins; JNK: cJUN NH2-terminal kinase.