Catalpol protects mice against Lipopolysaccharide/D-galactosamine-induced acute liver injury through inhibiting inflammatory and oxidative response

Abstract

The purpose of this study was to investigate the protective effect of catalpol on Lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced acute liver injury in mice. The mouse model was established by injection of LPS and D-gal. Catalpol (2.5, 5, 10 mg/kg) were pretreated intraperitoneally 1 h before LPS and D-gal. The survival rate, AST, ALT, MDA, MPO activity, hepatic tissue histology, TNF-α level, and NF-κB activation were assayed. The results revealed that catalpol dose-dependently elevated the survival rate. Furthermore, catalpol reduced the activities of AST, ALT, MDA, and MPO. The production of TNF-α was also inhibited by treatment of catalpol. In addition, catalpol inhibited LPS/D-gal-induced NF-κB activation. The expression of Nrf2 and HO-1 were up-regulated by treatment of catalpol. These results indicated that pretreatment with catalpol could attenuate LPS/D-gal-induced acute liver injury in mice and the underlying mechanism may due to the inhibition of NF-κB signaling pathway and the activation of Nrf2 signaling pathway.

Multiple Biological Effects of an Iridoid Glucoside, Catalpol, and Its Underlying Molecular Mechanisms

“…This protection was accompanied by reductions in MDA, MPO, and TNF-α and a reduction in activation of NF-κB activation. The expressions of Nrf2 and hemoxygenase-1 were up-regulated by catalpol treatment, suggesting that catalpol's effects were due to the activation of the Nrf2 signaling pathway and inhibition of NF-κB signaling [97]. The hepatoprotective effect of catalpol was supported by the in vitro studies of Feng and colleagues, who showed that catalpol (2-250 µg/mL) protected human normal hepatocytes (L-02 cells) against triptolide (TP) induced hepatotoxicity.…”

“…Pre-treatment with catalpol (2.5-10 mg/kg) significantly reduced liver damage and prolonged survival time in mice with acute liver injury produced by lipopolysaccharide (LPS)/d-galactosamine (d-gal) [97]; the reduced liver damage was evidenced by reductions in serum AST and ALT concentrations and by protection of the liver against the severe hemorrhagic necrosis, destruction of hepatic architecture, and massive infiltration of inflammatory cells. This protection was accompanied by reductions in MDA, MPO, and TNF-α and a reduction in activation of NF-κB activation.…”

“…This protective effect of catalpol was relative to its anti-oxidative effect through by activation of Nrf2, NAD(P) H: quinine oxidoreductase 1 (NQO1), HO-1 expression and glutathione (GSH) activity [98]. Both these studies suggested that the hepatoprotective effect of catalpol was mediated by the nuclear factor erythroid-2-related factor-2 (Nrf2)/antioxidant response element (ARE) pathway [97,98].…”

Catalpol‑mediated microRNA‑34a suppresses autophagy and malignancy by regulating SIRT1 in colorectal cancer

“…At the end of the experiment, euthanasia by anesthesia overdose with intraperitoneal injection of sodium pentobarbital (Nembutal; 200 mg/kg body weight) was perfomed. Then colon tissue samples were obtained from each rat after decapitation was performed to confirm euthanasia (6,18).…”

“…Several studies indicated that catalpol has inhibitory effects on proliferation and induced apoptosis in several cancer types including human CRC (3)(4)(5). Our previous study also focused on the therapeutic effect of catalpol against acute liver injury via alleviation of inflammatory response (6). However, the underlying mechanisms of catalpol in CRC treatment are still unclear, which limits the application of catalpol in CRC treatment.…”