Original articles
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[J]. Acta Pharmaceutica Sinica B, 2020, 10(12): 2323-2338

Inhibitory effects of baicalein against herpes simplex virus type 1
Zhuo Luoa,b,c, Xiu-Ping Kuanga,b,c,d, Qing-Qing Zhoua,b,c, Chang-Yu Yana,b,c, Wen Lia,b,c, Hai-Biao Gonga,b,c, Hiroshi Kuriharaa,b,c, Wei-Xi Lid, Yi-Fang Lia,b,c, Rong-Rong Hea,b,c
a Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility, College of Pharmacy, College of Pharmacy, Jinan University, Guangzhou 612505, China;
b 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;
c Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 612505, China;
d Yunnan University of Traditional Chinese Medicine, Kunming 650550, China
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 IkB 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.
Key words:    Anti-HSV-1    Baicalein    Viral inactivation    IKK-β phosphorylation    NF-кB activation    HSV-1 infection   
Received: 2020-03-05     Revised: 2020-04-10
DOI: 10.1016/j.apsb.2020.06.008
Funds: This study was partly supported by National Natural Science Foundation of China (Grant Nos. U1801284, 81573675, 81622050, 81873209 and 81673709), National Key Research and Development Program of China (Grant No. 2017YFC1700404), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (Grant No. 2017BT01Y036, China) and GDUPS (2019, China), the Guangdong Science and Technology Foundation (Grant No. 2017A030306004), the Program of Hong Kong Scholar (XJ2016017, China), Science and Technology Program of Guangzhou (Grant No. 201903010062, China), the Youth Top-notch Talent Support Program of Guangdong Province (Grant No. 2016TQ03R586, China).
Corresponding author: Wei-Xi Li, liweixi1001@163.com;Yi-Fang Li, liyifang706@jnu.edu.cn;Rong-Rong He, rongronghe@jnu.edu.cn     Email:liweixi1001@163.com;liyifang706@jnu.edu.cn;rongronghe@jnu.edu.cn
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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

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