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大黄素通过调控 NF-κB 信号通路促进细胞凋亡抑制非洲猪瘟病毒复制。

Aloe-emodin inhibits African swine fever virus replication by promoting apoptosis via regulating NF-κB signaling pathway.

机构信息

Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510462, China.

African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, 510642, China.

出版信息

Virol J. 2023 Jul 19;20(1):158. doi: 10.1186/s12985-023-02126-8.

Abstract

African swine fever (ASF) is an acute infectious haemorrhagic fever of pigs caused by African swine fever virus (ASFV). Aloe-emodin (Ae) is an active ingredient of Chinese herbs with antiviral, anticancer, and anti-inflammatory effects. We investigated the antiviral activity and mechanism of action of Ae against ASFV using Real-time quantitative PCR (qPCR), western blotting, and indirect immunofluorescence assays. Ae significantly inhibited ASFV replication. Furthermore, transcriptomic analysis revealed that ASFV infection activated the NF-κB signaling pathway in the early stage and the apoptosis pathway in the late stage. Ae significantly downregulated the expression levels of MyD88, phosphor-NF-κB p65, and pIκB proteins as well as the mRNA levels of IL-1β and IL-8 in porcine alveolar macrophages (PAMs) infected with ASFV, thereby inhibiting the activation of the NF-κB signaling pathway induced by ASFV. Flow cytometry and western blot analysis revealed that Ae significantly increased the percentage of ASFV-induced apoptotic cells. Additionally, Ae promoted apoptosis by upregulating the expression levels of cleaved-caspase3 and Bax proteins and downregulating the expression levels of Bcl-2 proteins. This suggests that Ae promotes apoptosis by inhibiting the NF-κB pathway, resulting in inhibition of ASFV replication. These findings have further improved therapeutic reserves for the prevention and treatment of ASF.

摘要

非洲猪瘟 (ASF) 是由非洲猪瘟病毒 (ASFV) 引起的猪的急性传染病。大黄素 (Ae) 是一种中药的有效成分,具有抗病毒、抗癌和抗炎作用。我们通过实时定量 PCR (qPCR)、western blot 和间接免疫荧光检测来研究 Ae 对 ASFV 的抗病毒活性和作用机制。Ae 显著抑制 ASFV 复制。此外,转录组分析表明,ASFV 感染在早期激活 NF-κB 信号通路,在晚期激活细胞凋亡通路。Ae 显著下调感染 ASFV 的猪肺泡巨噬细胞 (PAMs) 中 MyD88、磷酸化-NF-κB p65 和 pIκB 蛋白以及 IL-1β 和 IL-8 的 mRNA 水平,从而抑制 ASFV 诱导的 NF-κB 信号通路的激活。流式细胞术和 western blot 分析表明,Ae 显著增加了 ASFV 诱导的凋亡细胞的比例。此外,Ae 通过上调 cleaved-caspase3 和 Bax 蛋白的表达水平,下调 Bcl-2 蛋白的表达水平,促进细胞凋亡。这表明 Ae 通过抑制 NF-κB 通路促进细胞凋亡,从而抑制 ASFV 的复制。这些发现进一步提高了预防和治疗 ASF 的治疗储备。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2af6/10357809/a339a69bfc21/12985_2023_2126_Fig1_HTML.jpg

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