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黄芩素对1型单纯疱疹病毒的抑制作用。

Inhibitory effects of baicalein against herpes simplex virus type 1.

作者信息

Luo Zhuo, Kuang Xiu-Ping, Zhou Qing-Qing, Yan Chang-Yu, Li Wen, Gong Hai-Biao, Kurihara Hiroshi, Li Wei-Xi, Li Yi-Fang, He Rong-Rong

机构信息

Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, College of Pharmacy, College of Pharmacy, Jinan University, Guangzhou 612505, China.

International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou 612505, China.

出版信息

Acta Pharm Sin B. 2020 Dec;10(12):2323-2338. doi: 10.1016/j.apsb.2020.06.008. Epub 2020 Jun 25.

Abstract

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain) . In the ocular inoculation mice model, baicalein markedly reduced HSV-1/F replication, receded inflammatory storm and attenuated histological changes in the cornea. Consistently, baicalein was found to reduce the mortality of mice, viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection model. Moreover, an HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 replication. Further investigations unraveled that dual mechanisms, inactivating viral particles and inhibiting IB kinase beta (IKK-) phosphorylation, were involved in the anti-HSV-1 effect of baicalein. Collectively, our findings identified baicalein as a promising therapy candidate against the infection of HSV-1, especially acyclovir-resistant strain.

摘要

单纯疱疹病毒1型(HSV-1)是一种普遍存在且广泛传播的人类病原体,可引发一系列疾病,包括唇疱疹、角膜盲和脑炎。目前,使用核苷类似物,如阿昔洛韦和喷昔洛韦,治疗HSV-1感染时,由于其副作用以及对耐药菌株疗效较低,常常存在局限性。因此,迫切需要开发新的抗疱疹药物和策略。在此,我们报告了黄芩素,一种在亚洲国家广泛使用的天然衍生化合物,在多种模型中强烈抑制HSV-1复制。黄芩素对HSV-1/F和HSV-1/Blue(一种阿昔洛韦耐药菌株)的复制均有效。在眼内接种小鼠模型中,黄芩素显著降低了HSV-1/F的复制,减轻了炎症风暴,并减轻了角膜的组织学变化。同样,在HSV-1鼻内感染模型中,发现黄芩素可降低小鼠死亡率、鼻腔和三叉神经节中的病毒载量。此外,在分离的小鼠表皮片中建立的HSV-1-EGFP感染模型证实黄芩素可抑制HSV-1复制。进一步研究表明,黄芩素的抗HSV-1作用涉及双重机制,即灭活病毒颗粒和抑制IB激酶β(IKK-β)磷酸化。总体而言,我们的研究结果表明黄芩素是一种有前景的抗HSV-1感染治疗候选药物,尤其是针对阿昔洛韦耐药菌株。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f35f/7745058/328bd5031bae/fx1.jpg

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