The Protective Effect of Betulinicd Acid Alleviates CCl₄-Induced Acute Liver Injury in Mice and Its Related Mechanism

OBJECTIVE To observe the effect of betulinic acid on CCl₄ induced liver injury in mice and its possible molecular mechanisms. METHODS Male ICR mice were randomly divided into 5 groups: normal control group， CCl₄ group (20mg/kg)， CCl₄+Silibinin group (200 mg/kg)， CCl₄+betulinic acid group (20 mg/kg)， CCl₄+betulinic acid group (40mg/kg). Mice in the normal control group and CCl₄ group were given distilled water while other groups were given drugs in 7 days by gavage. 2h after the last administration， 0.1% CCl₄ with vegetable oil solution (10 mL/kg) by intraperitoneal injection， and the mice in normal control group were given the same volume of vegetable oil solution. 18 h after the model establishment， the blood and liver were collected. Hematoxylin (HE) staining was used to observe the changes of hepatic histopathology. Superoxide dismutase (SOD)， malonaldehyde (MDA)， interleukin-6 (IL-6)， interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α) were measured by corresponding kits. Western blot was used to demonstrate the expression levels of related protein. RESULTS Betulinic acid significantly reduced levels of pro-inflammatory cytokines including interleukin-6 (IL-6)， interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum. Besides， it also attenuated superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. In addition， betulinic acid regulated proteins levels of Nrf-2/HO-1/NF-κB pathway in liver. CONCLUSION Betulinic acid exhibited therapeutical effect on CCl₄ induced liver injury in mice which might be related to the regulation of Nrf-2/HO-1/NF-κB pathway.