The present study aimed to investigate the protective effects of kamebakaurin (KA) and 1O, 20O-diacetyl kamebakaurin (Ac2KA) on acetaminophen (APAP)-induced hepatotoxicity and compare the hepatoprotective mechanisms of the two chemicals. Seven-week-old male C57BL/6J mice were orally administered KA, Ac2KA, or an ethanol/olive oil emulsion once per day for 7-days. Twenty-four hours after the final administration, the mice were fasted and then intraperitoneally injected with 450 mg/kg APAP or saline. At 16 h after injection, the mice were euthanized and blood samples were collected for plasma analysis. Pretreatment with KA and Ac2KA significantly attenuated APAP-induced hepatic injury. The protective effect of Ac2KA was stronger than that of KA. These two chemicals attenuated oxidative stress, inflammatory cytokine production, c-jun N-terminal kinase activation, and receptor-interacting protein (RIP)-3 activation. Ac2KA also decreased APAP-induced RIP-1 activation and nuclear factor kappa B (NF-κB) p65 translocation. Moreover, Ac2KA repressed mRNA expression of Cyp1a2/2e1 in the liver. Our results showed that KA and Ac2KA exerted protective effects against APAP-induced hepatotoxicity. The responsible mechanisms may be related to the chemicals' antioxidant activity and the inhibition of c-jun N-terminal kinase activation and RIP-3 activation. The effects of Ac2KA included those of KA, as well as RIP-1 inactivation, NF-κB inhibition, and Cyp inhibition.

中文翻译：

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1O，20O-二乙酰基kamebakaurin可防止对乙酰氨基酚引起的小鼠肝毒性。

本研究旨在调查kamebakaurin（KA）和1O，20O-二乙酰基kamebakaurin（Ac2KA）对对乙酰氨基酚（APAP）诱导的肝毒性的保护作用，并比较两种化学药品的保肝作用。每天一次给7周大的雄性C57BL / 6J小鼠口服KA，Ac2KA或乙醇/橄榄油乳液，持续7天。最后一次给药后24小时，将小鼠禁食，然后腹膜内注射450mg / kg APAP或盐水。注射后16小时，对小鼠实施安乐死并收集血样用于血浆分析。KA和Ac2KA预处理可显着减轻APAP诱导的肝损伤。Ac2KA的保护作用强于KA。这两种化学物质减弱了氧化应激，炎性细胞因子的产生，c-jun N末端激酶激活和受体相互作用蛋白（RIP）-3激活。Ac2KA还降低了APAP诱导的RIP-1激活和核因子κB（NF-κB）p65易位。此外，Ac2KA抑制肝脏中Cyp1a2 / 2e1的mRNA表达。我们的结果表明，KA和Ac2KA对APAP诱导的肝毒性具有保护作用。可能的机制可能与化学品的抗氧化活性以及c-jun N末端激酶激活和RIP-3激活的抑制有关。Ac2KA的作用包括KA的作用，以及RIP-1失活，NF-κB抑制和Cyp抑制。Ac2KA抑制肝脏中Cyp1a2 / 2e1的mRNA表达。我们的结果表明，KA和Ac2KA对APAP诱导的肝毒性具有保护作用。可能的机制可能与化学品的抗氧化活性以及c-jun N末端激酶激活和RIP-3激活的抑制有关。Ac2KA的作用包括KA的作用，以及RIP-1失活，NF-κB抑制和Cyp抑制。Ac2KA抑制肝脏中Cyp1a2 / 2e1的mRNA表达。我们的结果表明，KA和Ac2KA对APAP诱导的肝毒性具有保护作用。可能的机制可能与化学品的抗氧化活性以及c-jun N末端激酶激活和RIP-3激活的抑制有关。Ac2KA的作用包括KA的作用，以及RIP-1失活，NF-κB抑制和Cyp抑制。