The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics
The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics
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DOI：
10.1007/s11306-019-1614-2
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发表时间：
2019-12-01
期刊：
影响因子：
3.6
通讯作者：
Gao, Wenyuan
中科院分区：
文献类型：
--
作者：
Luo, Liyu;Zhou, Junyi;Gao, Wenyuan
芒柄花素（MBHS）及其糖基化衍生物芒柄花素（MBHG）作为主要异黄酮，对脂多糖（LPS）诱导的炎症具有抗炎作用。尽管各种研究都集中在解释MBHG和MBHS的药物活性，但其在斑马鱼模型中的分子机制尚不清楚。目的基于脂质组学和靶向转录组学研究MGHG和MBHS抗炎作用的分子机制。方法采用UHPLC-MS进行脂质分析，RT-PCR进行mRNA分析，比较不同组的结果，探索脂质和mRNA的显著变化。结果脂质组学结果显示，在MBHG或MBHS处理的lps诱导炎症斑马鱼模型中，磷脂酰胆碱（PCs）显著下调。此外，MBHS还可以降低三酰基甘油（TAGs）的水平。在靶向转录组学分析中，MBHG或MBHS处理下，参与MAPK通路的4种细胞因子（tnf - α、IL-1 β、IL-6和ifn - γ）和3种mRNA （JNK1、ERK1和p38a）下调，IL-10上调。结论结合脂质组学和靶向转录组学结果，我们发现MBHG和MBHS通过MyD88或TRIF MAPK/ ERK和MAPK/JNK通路以及甘油磷脂、糖基磷脂酰肌醇（GPI）锚定生物合成和甘油脂代谢，对lps诱导的斑马鱼模型具有有效的抗炎作用。我们的研究结果为MBHG或MBHS的抗炎机制提供了新的见解，并为解释药物的药理机制提供了一种有效的方法。
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-alpha, IL-1 beta, IL-6 and IFN-gamma) 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.