Zhi Yupeng, Ren Yupeng, Xia Xuemei, Tian Qiao, Meng Yingshi, Tao Siyu
Key Laboratory of Veterinary Medicine in Universities of Sichuan Province, Southwest Minzu University, Chengdu, 610041, China.
Microb Pathog. 2025 Nov;208:107957. doi: 10.1016/j.micpath.2025.107957. Epub 2025 Aug 6.
Porcine epidemic diarrhea virus (PEDV) remains a significant threat to global swine industry, with immunization strategies limited by viral genome variation and a lack of effective therapeutic drugs. The flavonoid compound chrysin has shown potential anti-PEDV activity, but its specific antiviral mechanisms remain unclear. This study validated the inhibitory effect of chrysin on PEDV using IFA and qPCR. Additionally, Transcriptome sequencing was conducted on PEDV-infected Vero cells with and without chrysin treatment to reveal its antiviral mechanism. The results showed that 5813 DEGs at 12 hpi and 3374 DEGs at 24 hpi, with enrichment in pathways related to transcription, translation, metabolism, innate immunity, and apoptosis. Notably, KEGG analysis indicated that Chrysin regulate PEDV-induced apoptosis by modulating the TNF, MAPK, and p53 signaling pathways, which might antagonize PEDV infection. Subsequent results confirmed that chrysin can significantly downregulate the reactive ROS levels and cell apoptosis rate induced by PEDV infection (P<0.05), and inhibit the activation of the JNK and p53 pathways, including the phosphorylation of ASK1, JNK, and p53. Chrysin also significantly reduced cleaved caspase 3/8/9 levels and Bax/Bcl-2 ratios, thereby affecting PEDV N protein expression (P < 0.05). Moreover, similar inhibitory effects on PEDV can also be achieved through the JNK inhibitor SP600125 and the p53 inhibitor PFT-α. These findings revealed that chrysin can antagonize PEDV-induced apoptosis through the ROS/JNK/p53 signaling axis, thereby inhibiting viral replication. This study provides a scientific basis for developing chrysin as a novel anti-PEDV drug and offers insights into the screening and research of antiviral drug targets.
猪流行性腹泻病毒（PEDV）仍然是全球养猪业的重大威胁，其免疫策略受到病毒基因组变异和缺乏有效治疗药物的限制。黄酮类化合物白杨素已显示出潜在的抗PEDV活性，但其具体的抗病毒机制仍不清楚。本研究使用免疫荧光分析（IFA）和定量聚合酶链反应（qPCR）验证了白杨素对PEDV的抑制作用。此外，对经白杨素处理和未经处理的PEDV感染的Vero细胞进行转录组测序，以揭示其抗病毒机制。结果显示，在感染后12小时有5813个差异表达基因（DEG），在24小时有3374个DEG，这些基因在与转录、翻译、代谢、固有免疫和细胞凋亡相关的通路中富集。值得注意的是，京都基因与基因组百科全书（KEGG）分析表明，白杨素通过调节肿瘤坏死因子（TNF）、丝裂原活化蛋白激酶（MAPK）和p53信号通路来调节PEDV诱导的细胞凋亡，这可能拮抗PEDV感染。随后的结果证实，白杨素可显著下调PEDV感染诱导的活性氧（ROS）水平和细胞凋亡率（P<0.05），并抑制JNK和p53通路的激活，包括凋亡信号调节激酶1（ASK1）、JNK和p53的磷酸化。白杨素还显著降低了裂解的半胱天冬酶3/8/9水平和Bax/Bcl-2比值，从而影响PEDV N蛋白表达（P < 0.05）。此外，通过JNK抑制剂SP600125和p53抑制剂PFT-α也可对PEDV产生类似的抑制作用。这些发现揭示了白杨素可通过ROS/JNK/p53信号轴拮抗PEDV诱导的细胞凋亡，从而抑制病毒复制。本研究为将白杨素开发为新型抗PEDV药物提供了科学依据，并为抗病毒药物靶点的筛选和研究提供了见解。
