Quzhou Aurantii Fructus (QAF) has a long history as a folk medicine and food for the treatment of liver diseases. While our earlier study provided evidence of hepatoprotective properties contained within the flavonoids and limonins constituents in QAF, the potential preventative effects afforded by essential oil components present within QAF remains enigmatic. In this study, we prepared Quzhou Aurantii Fructus essential oil (QAFEO) and confirmed its anti-inflammatory effects on liver inflammation through experimentation on lipopolysaccharide and D-galactosamine (LPS/D-GalN) induced acute liver failure (ALF) mouse models. Using RNA-sequence (RNA-seq) analysis, we found that QAFEO prevented ALF by systematically blunting the pathways involved in response to LPS and toll-like receptor signaling pathways. QAFEO effectively suppressed the phosphorylation of tank-binding kinase 1 (TBK1), TGF-beta activated kinase 1 (TAK1), interferon regulatory factor 3 (IRF3), and the activation of mitogen activated kinase-like protein (MAPK) and nuclear factor-kappa B (NF-κB) pathways in vivo and in vitro. Importantly, QAFEO substantially reduced myeloid differentiation primary response gene 88 (MyD88)- toll-like receptor 4 (TLR4) interaction levels. Moreover, 8 compounds from QAFEO could directly bind to REAL, TAK1, MyD88, TBK1, and IRF3. Taken together, the results of our study support the notion that QAFEO exerts a hepatoprotective effect through inhibiting LPS-mediated inflammatory response.

Graphical abstract

中文翻译：

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衢州枳壳提取精油通过抑制脂多糖介导的炎症反应预防急性肝衰竭

衢州枳壳（QAF）作为治疗肝病的民间药食，有着悠久的历史。虽然我们早期的研究提供了 QAF 中的类黄酮和柠檬苦素成分所含的保肝特性的证据，但 QAF 中存在的精油成分所提供的潜在预防作用仍然是个谜。在本研究中，我们制备了衢州枳壳精油（QAFEO），并通过脂多糖和D-半乳糖胺（LPS/D-GalN）诱导的急性肝衰竭（ALF）小鼠模型实验证实了其对肝脏炎症的抗炎作用。通过 RNA 序列 (RNA-seq) 分析，我们发现 QAFEO 通过系统地削弱参与 LPS 和 Toll 样受体信号通路响应的通路来预防 ALF。QAFEO有效抑制tank结合激酶1（TBK1）、TGF-β激活激酶1（TAK1）、干扰素调节因子3（IRF3）的磷酸化以及丝裂原激活激酶样蛋白（MAPK）和核因子的激活体内和体外 kappa B (NF-κB) 通路。重要的是，QAFEO 显着降低了骨髓分化初级反应基因 88 (MyD88)-toll 样受体 4 (TLR4) 相互作用水平。此外，QAFEO 中的 8 种化合物可以直接结合 REAL、TAK1、MyD88、TBK1 和 IRF3。综上所述，我们的研究结果支持 QAFEO 通过抑制 LPS 介导的炎症反应发挥保肝作用的观点。

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