Inhibitory effects of baicalein against herpes simplex virus type 1.
Acta Pharm Sin B
; 10(12): 2323-2338, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33354504
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 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-ß) 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.
Anti-HSV-1; Baicalein; CC50, 50% cytotoxic concentration; DCFH-DA, 2',7'-dichlorofluorescin diacetate; EC50, 50% effective concentration; GB, glycoprotein B; HSV-1 infection; HSV-1, herpes simplex virus types 1; ICP, infected cell polypeptide; IKK-ß phosphorylation; IKK-ß, IκB kinase beta; IL-1ß, interleukin 1 beta; IL-6, interleukin 6; IκB-α, inhibitor of NF-κB alpha; LPS, lipopolysaccharides; MOI, multiplicity of infection; NAC, N-acetyl-l-cysteine; NF-κB activation; NF-κB, nuclear factor kappa-B; PFU, plaque-forming units; PGA1, prostaglandin A1; ROS, reactive oxygen species; SI, selectivity index; TG, trigeminal ganglia; TNF-α, tumor necrosis factor alpha; Viral inactivation; dpi, days post-infection; p-IKK-ß, phosphorylated-IKK beta; p-IκB-α, phosphorylated-IκB alpha
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Acta Pharm Sin B
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China