Alleviation of Hepatic Ischemia Reperfusion Injury by Oleanolic Acid Pretreating via Reducing HMGB1 Release and Inhibiting Apoptosis and Autophagy

Abstract

Hepatic ischemia reperfusion (IR) injury (IRI) occurs during liver transplantation, hepatectomy, and hemorrhagic shock. Oleanolic acid (OA) is a natural compound with antioxidant and anti-inflammatory activity that has been used to treat liver disorders in clinical practice for several years. Here, we investigated the effects and underlying mechanisms of OA in hepatic IRI. A 60-minute partial (70%) hepatic, warm, ischemic reperfusion model was established in BALB/c mice, and two doses (30 and 60 mg/kg) of OA were administered intragastrically for 7 consecutive days prior to hepatic IR. Orbital blood and liver specimens were collected at 2, 8, and 24 h after IR. The results showed that OA preconditioning significantly alleviated hepatic injury, as evidenced by decreased alanine aminotransferase and aspartate aminotransferase levels; improved histology, inhibition of JNK phosphorylation, and high mobility group box 1 (HMGB1); and tumor necrosis factor-α downregulation in hepatic IR mice. OA upregulated Bcl-2 and downregulated caspase-3, caspase-9, Bax, Beclin 1, and LC3, which play crucial roles in the regulation of apoptosis and autophagy. These findings highlighted the protective effects of OA against hepatic IRI mediated by the inhibition of apoptosis and autophagy and the release of HMGB1, which acted as a late inflammatory mediator in hepatic IRI.

Therapeutic potential of PPARγ natural agonists in liver diseases

“…The protective effects of many Chinese herbal medicines, such as quercetin, [51][52][53] oleanolic acid, 54 proanthocyanidin B2, 55 epigallocatechin-3-gallate, 56 isorhamnetin 57 and genistein, 58 in liver diseases have been confirmed by our studies.…”

“…We also have published some reports on the effects of PPARs in liver diseases. The protective effects of many Chinese herbal medicines, such as quercetin, oleanolic acid, proanthocyanidin B2, epigallocatechin‐3‐gallate, isorhamnetin and genistein, in liver diseases have been confirmed by our studies.…”

Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation

“…A model of segmental (70%) hepatic warm IR was used, as previously described [ 6 ]. Food was withheld for a period of 12 h before surgery, but mice had free access to water.…”

“…Proinflammatory cytokine-mediated apoptosis and reactive oxygen species- (ROS-) induced necrosis is the leading cause of hepatocyte death in IRI [ 5 ]. Autophagy is an intracellular self-digestive lysosomal recycling pathway, and its role in hepatic IR injury has been widely studied [ 4 , 6 ].…”

Interferon Type I Regulates Inflammasome Activation and High Mobility Group Box 1 Translocation in Hepatocytes During Ehrlichia -Induced Acute Liver Injury

“…Understanding the role of hepatic IFN-I responses during infection with LPS-negative Ehrlichia IOE will greatly enhance our knowledge of the mechanisms of liver dysfunction in patients with HME. Similar to other disease models, (43,44) targeting HMGB1 and the IFN-I pathway may provide a novel approach for treatment of Ehrlichia-induced liver injury and sepsis.…”