Lan Tian, Wang Wen, Huang De-Lian, Zeng Xi-Xi, Wang Xiao-Xiao, Wang Jian, Tong Yu-Hua, Mao Zhu-Jun, Wang Si-Wei
The Joint Innovation Center for Health and Medicine, Quzhou People's Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, No. 100 Minjiang Road, Quzhou, 324000, China.
Preventive Treatment Center, Zhejiang Chinese Medical University Affiliated Four-provinces Marginal Hospital of Traditional Chinese Medicine, Quzhou Hospital of Traditional Chinese Medicine, Quzhou, 324000, China.
Nat Prod Bioprospect. 2023 Oct 7;13(1):36. doi: 10.1007/s13659-023-00398-9.
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.
枳壳作为一种治疗肝病的民间药物和食物有着悠久的历史。虽然我们早期的研究证明了枳壳中黄酮类和柠檬苦素成分具有保肝特性，但枳壳中精油成分的潜在预防作用仍然未知。在本研究中，我们制备了枳壳精油（QAFEO），并通过对脂多糖和D-半乳糖胺（LPS/D-GalN）诱导的急性肝衰竭（ALF）小鼠模型进行实验，证实了其对肝脏炎症的抗炎作用。通过RNA测序（RNA-seq）分析，我们发现QAFEO通过系统性地减弱参与LPS反应的途径和Toll样受体信号通路来预防ALF。QAFEO在体内和体外均能有效抑制衔接蛋白激酶1（TBK1）、转化生长因子-β激活激酶1（TAK1）、干扰素调节因子3（IRF3）的磷酸化，以及丝裂原活化激酶样蛋白（MAPK）和核因子-κB（NF-κB）通路的激活。重要的是，QAFEO显著降低了髓样分化初级反应基因88（MyD88）-Toll样受体4（TLR4）的相互作用水平。此外，QAFEO中的8种化合物可以直接与REAL、TAK1、MyD88、TBK1和IRF3结合。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这一观点。
