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柚皮素通过抑制 ROS 介导的内质网应激和细胞凋亡抑制牛病毒性腹泻病毒复制。

Bergamottin Inhibits Bovine Viral Diarrhea Virus Replication by Suppressing ROS-Mediated Endoplasmic Reticulum Stress and Apoptosis.

机构信息

College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

College of Animal Science and Technology, Tarim University, Alar 843300, China.

出版信息

Viruses. 2024 Aug 13;16(8):1287. doi: 10.3390/v16081287.

DOI:10.3390/v16081287
PMID:39205261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11360249/
Abstract

Bovine viral diarrhea virus (BVDV) is one of the most important etiological agents that causes serious economic losses to the global livestock industry. Vaccines usually provide limited efficacy against BVDV due to the emergence of mutant strains. Therefore, developing novel strategies to combat BVDV infection is urgently needed. Bergamottin (Berg), a natural furanocoumarin compound, possesses various pharmaceutical bioactivities, but its effect on BVDV infection remains unknown. The present study aimed to investigate the antiviral effect and underlying mechanism of Berg against BVDV infection. The results showed that Berg exhibited an inhibitory effect on BVDV replication in MDBK cells by disrupting the viral replication and release, rather than directly inactivating virus particles. Mechanistically, Berg inhibits BVDV replication by suppressing endoplasmic reticulum (ER) stress-mediated apoptosis via reducing reactive oxygen species (ROS) generation. Studies in vivo demonstrated that oral gavage of Berg at doses of 50 mg/kg and 75 mg/kg significantly reduced the viral load within the intestines and spleen in BVDV-challenged mice. Furthermore, histopathological damage and oxidative stress caused by BVDV were also mitigated with Berg treatment. Our data indicated that Berg suppressed BVDV propagation both in vitro and in vivo, suggesting it as a promising antiviral option against BVDV.

摘要

牛病毒性腹泻病毒(BVDV)是导致全球畜牧业严重经济损失的最重要病因之一。由于突变株的出现,疫苗通常对 BVDV 的疗效有限。因此,迫切需要开发新的策略来对抗 BVDV 感染。佛手柑素(Berg)是一种天然呋喃香豆素化合物,具有多种药物生物活性,但它对 BVDV 感染的影响尚不清楚。本研究旨在探讨 Berg 对 BVDV 感染的抗病毒作用及其机制。结果表明,Berg 通过破坏病毒复制和释放而不是直接使病毒失活来抑制 MDBK 细胞中的 BVDV 复制。在机制上,Berg 通过减少活性氧(ROS)的产生来抑制内质网(ER)应激介导的凋亡来抑制 BVDV 的复制。体内研究表明,在 BVDV 攻毒的小鼠中,以 50mg/kg 和 75mg/kg 的剂量口服 Berg 可显著降低肠道和脾脏中的病毒载量。此外,Berg 处理还减轻了 BVDV 引起的组织病理学损伤和氧化应激。我们的数据表明,Berg 既能在体外又能在体内抑制 BVDV 的增殖,提示其是一种有前途的抗 BVDV 药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/78c4bddbead2/viruses-16-01287-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/1b8fdf365d1c/viruses-16-01287-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/e6d56591da56/viruses-16-01287-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/404e51323ce7/viruses-16-01287-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/df9c742dae4c/viruses-16-01287-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/7262d64e0366/viruses-16-01287-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/79f16b0c3d48/viruses-16-01287-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/c47c1c7c145a/viruses-16-01287-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/ad4ff541270c/viruses-16-01287-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/78c4bddbead2/viruses-16-01287-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/1b8fdf365d1c/viruses-16-01287-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/e6d56591da56/viruses-16-01287-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/404e51323ce7/viruses-16-01287-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/df9c742dae4c/viruses-16-01287-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/7262d64e0366/viruses-16-01287-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/79f16b0c3d48/viruses-16-01287-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/c47c1c7c145a/viruses-16-01287-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/ad4ff541270c/viruses-16-01287-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea93/11360249/78c4bddbead2/viruses-16-01287-g009.jpg

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