Protective Effect of Water Extracts of Orychophragmus violaceus Seeds on Acetaminophen-induced Acute Liver Injury in Mice: Roles of Activating Hepatic AMPK/AKT/GSK-3β Signaling
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Abstract:
The antioxidant capacity of water extracts of Orychophragmus violaceus Seeds and the protective effects on liver injury induced by acetaminophen in mice were investigated. C57BL/6J male mice were randomly divided into seven groups: normal group, model group, bicycle control group (200 mg/kg), Kuihua Hugan tablets control group (350 mg/kg), water extracts of Orychophragmus violaceus seeds low-dose group (125 mg/kg), water extracts of Orychophragmus violaceus seeds middle-dose group (250 mg/kg), and water extracts of Orychophragmus violaceus seeds high-dose group (500 mg/kg). The mice were intragastrically administered with drugs or distilled water according to the body weight once a day. Four days later, all of the groups except for the normal group were treated with APAP (450 mg/kg) through intraperitioneal injection to establish the acute liver injury model. The mice were killed. The levels of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase and total bilirubin in serum were detected. What’s more, the activities of superoxide dismutase and the level of glutathione and malondiadehyde in liver tissue were detected. HE staining was used to observe the pathological changes of liver tissue in mice. Western blot was used to detect the expressions of p-AMPK, p-AKT, p-GSK-3β, p-JNK, Bcl-2, Bax, Caspase-9 and Caspase-3. Compared with the model group, water extracts of Orychophragmus violaceus seeds could significantly improve the pathological conditions of liver, and the ALT and AST activities in the middle-dose group were reduced by 48.73% and 59.11%, respectively; and the high-dose group were reduced by 71.38% and 59.33%, respectively, in serum of APAP induced liver injury mice. The activities of SOD and GSH were increased by 45.05% and 219.45% respectively in the middle dose group and 48.68% and 232.80% respectively in the high dose group. Meanwhile, water extracts of Orychophragmus violaceus seeds down-regulated the expressions of p-JNK, Bax, Caspase-3, and Caspase-9 (p<0.05) and up-regulated the expressions of Bcl-2, p-AMPK, p-AKT and p-GSK-3β (p<0.05). It suggested that water extracts of Orychophragmus violaceus seeds has protective effect against APAP induced hepatocyte apoptosis by up-regulating the AMPK/AKT/GSK-3β signaling pathway.
