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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Format: | Article |
Language: | English |
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Elsevier
2020-12-01
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Series: | Acta Pharmaceutica Sinica B |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383520306171 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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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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 |