Ferulic acid isolated from propolis inhibits porcine parvovirus replication potentially through Bid-mediate apoptosis
Ferulic acid isolated from propolis inhibits porcine parvovirus replication potentially through Bid-mediate apoptosis
复制标题
从蜂胶中分离出的阿魏酸可能通过 Bid 介导的细胞凋亡抑制猪细小病毒的复制
DOI：
10.1016/j.intimp.2020.106379
复制
发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Wang, Xuefei
中科院分区：
文献类型：
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作者：
Ma, Xia;Guo, Zhenhuan;Wang, Xuefei
蜂胶是一种传统中药，广泛应用于兽医临床。许多化合物已被鉴定和分离自甘草。阿魏酸（FA）是黄芪的主要成分之一，已有研究证明其具有抗病毒作用。为研究FA的抗病毒作用机制，本文介绍了免疫荧光、实时荧光定量PCR和免疫印迹等实验方法。在猪肾（PK-15）细胞中，PPV感染诱导了促凋亡基因Bid、Bad、Bim和巴克的表达，破坏了线粒体膜电位，促进了caspase介导的半胱天冬酶依赖性凋亡信号传导并诱导了细胞凋亡。此外，感染的PK-15细胞增加了细胞内活性氧（ROS）的产生。然而，FA处理逆转了这些作用并增加了细胞活力。FA处理还显著降低PPV诱导的Bid、Cyt-c和Apaf-1的表达，表明ROS参与了PPV介导的凋亡途径的激活。该体外研究表明，FA的抗病毒活性可能与通过阻断促凋亡因子如Bid、Bcl-2和Mcl-1来抑制PPV的复制，以及通过抑制Bid相关信号通路的激活来减弱PPV介导的反应有关。药理学抑制剂通过阻断Bid抑制PPV诱导的细胞凋亡，并抑制Caspase家族蛋白在PPV诱导的细胞凋亡中的表达。总之，我们的结果表明，PPV诱导PK-15细胞凋亡通过激活BID和BID相关的信号通路，线粒体作为这些途径的介质。FA有效地和广泛地减弱了PPV的这种作用，因此是一种潜在的抗PPV的抗病毒剂。
Propolis from honeybee hives, which is a traditional Chinese medicine, is widely used in veterinary clinics. Many compounds have been identified and isolated from propolis. Ferulic acid (FA), one of the propolis components, previous studies have proven that it has antiviral effects. To study the mechanism of FA antiviral effects, experiments such as immunofluorescence, quantitative real-time PCR and immunoblotting were introduced. In porcine kidney (PK-15) cells, PPV infection induced the expression of the proapoptotic genes Bid, Bad, Bim and Bak, disrupted mitochondrial membrane potential, promoted mitochondria-mediated, caspase-dependent apoptotic signaling and induced apoptosis. Furthermore, the infected PK-15 cells had increased intracellular reactive oxygen species (ROS) generation. FA treatment, however, reversed these effects and increased cell viability. FA treatment also significantly decreased the PPV-induced expression of Bid, Cyt-c and Apaf-1, suggesting that ROS were involved in the activation of the mitochondria-mediated apoptosis pathway. This in vitro study showed that the antiviral activity of FA was probably associated with inhibiting the replication of PPV by blocking proapoptotic factors such as Bid, Bcl-2 and Mcl-1, and attenuating the mitochondria-mediated response by inhibiting the activation of the Bid-related signaling pathway. Pharmacological inhibitors inhibited PPV-induced apoptosis by blocking Bid, and also suppressed the expression of Caspase family proteins in ppv-induced apoptosis. Taken together, our results suggested that PPV induced PK-15 cell apoptosis via activation of Bid and Bid-related signaling pathways and that the mitochondria act as the mediators of these pathways. FA effectively and extensively attenuated this PPV action, and thus is a potential antiviral agent against PPV.