Transcriptome analysis following Apigenin and Chrysin treatment of Mouse Embryonic Fibroblasts

There is no known single therapeutic drug for treating hypercholesterolemia that comes with negligible systemic side effects. In the current study, using next generation RNA sequencing approach in mouse embryonic fibroblasts we discovered that two structurally related flavonoid compounds, Apigenin and Chrysin exhibited moderate blocking ability of multiple transcripts that regulate rate limiting enzymes in the cholesterol biosynthetic pathway. The observed decrease in cholesterol biosynthesis pathway correlated well with an increase in transcripts involved in generation and trafficking of ketone bodies as evident by the upregulation of Bdh1 and Slc16a6 transcripts. Impact statement - The hypocholesterolemic potential of Apigenin and Chrysin at higher concentrations along with their ability to generate ketogenic substrate especially during embryonic stage is useful or detrimental for embryonic health is not clear and still debatable. Our findings will set the stage for translating this information to whole animal and clinical studies that could shed light to the existing information regarding safe use of Apigenin and Chrysin, specifically to embryonic health. Evaluation of the effects of two different flavonoids- Apigenin and Chrysin using RNA Seq analysis on Mouse Embryonic Fibroblast cells- in Mus Musculus transcriptome and mm9 genome and files or contents expressed as log 2

目前尚无已知的治疗高胆固醇血症(hypercholesterolemia)且全身副作用可忽略的单一治疗药物。本研究采用下一代RNA测序(next generation RNA sequencing)技术分析小鼠胚胎成纤维细胞(mouse embryonic fibroblasts)，发现两种结构相关的类黄酮化合物(flavonoid compounds)——芹菜素(Apigenin)与白杨素(Chrysin)，对调控胆固醇生物合成通路中限速酶的多个转录本(transcripts)展现出中等程度的阻断活性。观察到的胆固醇生物合成通路活性降低，与参与酮体(ketone bodies)生成与转运的转录本表达上调高度相关，这一点可通过Bdh1与Slc16a6转录本的上调得到验证。研究亮点(Impact statement)：高浓度下芹菜素与白杨素的降胆固醇活性(hypocholesterolemic potential)，及其尤其是在胚胎阶段生成生酮底物(ketogenic substrate)的能力，对胚胎健康究竟有益还是有害，目前尚不明确且仍存在争议。本研究结果为将该发现转化至整体动物实验与临床研究奠定了基础，此类后续研究可进一步阐明现有关于芹菜素与白杨素安全使用(尤其是针对胚胎健康)的相关信息。本研究基于RNA测序(RNA Seq)分析，对小家鼠(Mus musculus)转录组与mm9基因组(mm9 genome)背景下的小鼠胚胎成纤维细胞中两种不同类黄酮——芹菜素与白杨素的作用效果进行了评估，相关文件及数据以log₂(以2为底的对数)形式呈现。