INTRODUCTION Formononetin (MBHS) and its glycosylated derivative ononin (MBHG), as the major isoflavones, have exhibited the anti-inflammatory impacts on the lipopolysaccharide (LPS)-induced inflammation. Although various researches have focused on interpreting the pharmaceutical activities of MBHG and MBHS, the molecular mechanisms in zebrafish models are still unclear. OBJECTIVE The purpose of the present work is to investigate the molecular mechanisms of the anti-inflammatory effects of MGHG and MBHS based on lipidomics and targeted transcriptomics. METHODS UHPLC-MS was applied for the lipid analyses and RT-PCR was adopted for the mRNA analyses, and the results of different groups were compared for exploring the significantly changed lipids and mRNAs. RESULTS The results of lipidomics revealed that phosphatidylcholines (PCs) were drastically down-regulated in the MBHG or MBHS treated LPS-induced inflammatory zebrafish models. Besides, MBHS can also decrease the levels of triacylglycerols (TAGs). For the targeted transcriptomics analyses, 4 cytokines (TNF-α, IL-1β, IL-6 and IFN-γ) and 3 mRNA (JNK1, ERK1 and p38a) involved in the MAPK pathway were down-regulated and IL-10 was up-regulated under the treatment of MBHG or MBHS. CONCLUSION Combining the results of lipidomics and targeted transcriptomics, we indicated that MBHG and MBHS exerted potent anti-inflammatory effects on the LPS-induced zebrafish models through the MyD88 or TRIF MAPK/ERK and MAPK/JNK pathways and the glycerophospholipid, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerolipid metabolisms. Our results provided new insights into the anti-inflammatory mechanisms of MBHG or MBHS and supplied an effective method to interpret the pharmacological mechanisms of drugs.

中文翻译：

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Formononetin和ononin对基于脂类组学和靶向转录组学的脂多糖诱导的斑马鱼模型的抗炎作用。

简介莫诺菌素（MBHS）及其糖基化衍生物ononin（MBHG）作为主要的异黄酮，已对脂多糖（LPS）诱导的炎症表现出抗炎作用。尽管各种研究集中于解释MBHG和MBHS的药物活性，但斑马鱼模型中的分子机制仍不清楚。目的本研究的目的是基于脂质组学和靶向转录组学研究MGHG和MBHS的抗炎作用的分子机制。方法采用UHPLC-MS进行脂质分析，采用RT-PCR进行mRNA分析，比较不同组的结果，探讨脂质和mRNA的显着变化。结果脂质组学的结果表明，在MBHG或MBHS处理的LPS诱导的炎性斑马鱼模型中，磷脂酰胆碱（PCs）显着下调。此外，MBHS还可以降低三酰甘油（TAGs）的水平。对于靶向转录组学分析，参与MAPK途径的4种细胞因子（TNF-α，IL-1β，IL-6和IFN-γ）和3种mRNA（JNK1，ERK1和p38a）被下调，IL-10升高-在MBHG或MBHS的处理下进行调节。结论结合脂质组学和靶向转录组学的结果，我们表明MBHG和MBHS通过MyD88或TRIF MAPK / ERK和MAPK / JNK途径以及甘油磷脂，糖基磷脂酰肌醇（GPI）对LPS诱导的斑马鱼模型发挥了有效的消炎作用。锚生物合成和甘油脂代谢。