Inhibitory effects of baicalein against herpes simplex virus type 1

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 presen...

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Main Authors: Zhuo Luo, Xiu-Ping Kuang, Qing-Qing Zhou, Chang-Yu Yan, Wen Li, Hai-Biao Gong, Hiroshi Kurihara, Wei-Xi Li, Yi-Fang Li, Rong-Rong He
Format: Article
Language:English
Published: Elsevier 2020-12-01
Series:Acta Pharmaceutica Sinica B
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211383520306171
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language English
format Article
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author Zhuo Luo
Xiu-Ping Kuang
Qing-Qing Zhou
Chang-Yu Yan
Wen Li
Hai-Biao Gong
Hiroshi Kurihara
Wei-Xi Li
Yi-Fang Li
Rong-Rong He
spellingShingle Zhuo Luo
Xiu-Ping Kuang
Qing-Qing Zhou
Chang-Yu Yan
Wen Li
Hai-Biao Gong
Hiroshi Kurihara
Wei-Xi Li
Yi-Fang Li
Rong-Rong He
Inhibitory effects of baicalein against herpes simplex virus type 1
Acta Pharmaceutica Sinica B
Anti-HSV-1
Baicalein
Viral inactivation
IKK-β phosphorylation
NF-κB activation
HSV-1 infection
author_facet Zhuo Luo
Xiu-Ping Kuang
Qing-Qing Zhou
Chang-Yu Yan
Wen Li
Hai-Biao Gong
Hiroshi Kurihara
Wei-Xi Li
Yi-Fang Li
Rong-Rong He
author_sort Zhuo Luo
title Inhibitory effects of baicalein against herpes simplex virus type 1
title_short Inhibitory effects of baicalein against herpes simplex virus type 1
title_full Inhibitory effects of baicalein against herpes simplex virus type 1
title_fullStr Inhibitory effects of baicalein against herpes simplex virus type 1
title_full_unstemmed Inhibitory effects of baicalein against herpes simplex virus type 1
title_sort inhibitory effects of baicalein against herpes simplex virus type 1
publisher Elsevier
series Acta Pharmaceutica Sinica B
issn 2211-3835
publishDate 2020-12-01
description 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 vitro. In the ocular inoculation mice model, baicalein markedly reduced in vivo 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 ex vivo 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 IκB kinase beta (IKK-β) 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.
topic Anti-HSV-1
Baicalein
Viral inactivation
IKK-β phosphorylation
NF-κB activation
HSV-1 infection
url http://www.sciencedirect.com/science/article/pii/S2211383520306171
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spelling doaj-abf265e50b414c178652de769beeb9d82020-12-17T04:48:14ZengElsevierActa Pharmaceutica Sinica B2211-38352020-12-01101223232338Inhibitory effects of baicalein against herpes simplex virus type 1Zhuo Luo0Xiu-Ping Kuang1Qing-Qing Zhou2Chang-Yu Yan3Wen Li4Hai-Biao Gong5Hiroshi Kurihara6Wei-Xi Li7Yi-Fang Li8Rong-Rong He9Guangdong 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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, ChinaGuangdong 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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, China; Yunnan University of Traditional Chinese Medicine, Kunming 650550, ChinaGuangdong 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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, ChinaGuangdong 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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, ChinaGuangdong 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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, ChinaGuangdong 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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, ChinaGuangdong 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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, ChinaYunnan University of Traditional Chinese Medicine, Kunming 650550, China; Corresponding authors.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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, China; Corresponding authors.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; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, China; Corresponding authors.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 vitro. In the ocular inoculation mice model, baicalein markedly reduced in vivo 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 ex vivo 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 IκB kinase beta (IKK-β) 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.http://www.sciencedirect.com/science/article/pii/S2211383520306171Anti-HSV-1BaicaleinViral inactivationIKK-β phosphorylationNF-κB activationHSV-1 infection