Oeanolic acid protects against the hepatotoxicity of D-galactosame plus endotoxin in mice

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

“…d ‐GalN/LPS‐induced activation of p‐JNK and NF‐κB p65 and protein overexpression of caspase‐3, caspase‐8 and COX2 were significantly suppressed by OA. These results clearly demonstrated that OA po is as effective as OA administered sc in protecting against d ‐GalN/LPS‐induced liver injury, and the protective mechanisms are related to the reduction in oxidative damage and suppression of TNF‐α‐triggered signalling through the NF‐κB and JNK pathways, thus reducing apoptosis and hepatocellular death …”

“…The dose and time of oral OA administration make a big difference between hepatoprotection and hepatotoxicity. Specifically, the OA po doses of less than 100 mg/ kg for 4 days in mice, 37 7-14 days in rats 38,44 or 10-60 mg/kg for 30 days in rats, 47,53 OA appeared to be safe, while the OA po doses above 225 mg/kg for 10 days, 18…”

“…Oral dose and time‐induced hepatoprotection and hepatotoxicity comparisons. The hepatoprotective studies are indicated by filled black circles, and the hepatotoxicity studies are indicated by open inverted triangles…”

“…In scenario A, OA is used as a drug for cholestasis and is effective against LCA‐ and BDL‐induced cholestasis . Low doses of OA are beneficial in protecting against d ‐GlaN/LPS‐induced liver injury, including cholestasis . In scenario B, high doses of OA, both orally and systemic administration for the long‐term, can produce cholestasis .…”

“… TRG 5 activation by OA could cause both hepatoprotection and hepatotoxicity. A, d ‐GlaN/ LPS ‐induced liver injury is associated with cholestasis, and low dose of OA (90 mg/kg, po × 4 d) showed hepatoprotection; B, high dose of OA (1000 μmoles, 451 mg/kg, po × 10 d) produced cholestatic liver injury as showed in arrows; C, OA (91 mg/kg, sc × 1 d) produced apparent cell proliferation, and mitotic cells are shown in arrows…”