In vitro and in vivo studies of the inhibitory effects of emodin isolated from Polygonum cuspidatum on Coxsakievirus B₄.
The lack of effective therapeutics for Coxsackievirus B₄ (CVB₄) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present study, the possibility of using emodin as a potential antiviral to treat CVB₄ infection was explored in vitro and in mice. Emodin reduced CVB₄ entry and replication on Hep-2 cells in a concentration- and time-dependent manner, with a 50% effective concentration (EC₅₀) of 12.06 μM and selectivity index (SI) of 5.08, respectively. The inhibitory effect of emodin for CVB₄ entry and replication was further confirmed by a quantitative real time PCR (qPCR) assay. The results further showed that the mice orally treated with different dosages of emodin displayed a dose dependent increase of survival rate, body weight and prolonged mean time of death (MTD), accompanied by significantly decreased myocardial virus titers and pathologic scores/lesions. Moreover, emodin could inhibit CVB₄-induced apoptosis in vitro and in vivo. Our results indicated that emodin could be used as potential antiviral in the post-exposure prophylaxis for CVB₄ infection.
State Key Laboratory of Virology, Institute of Medical Virology, School of Medicine, Wuhan 430071, China. zqyang@whu.edu.cn.
Zhao
Z
Liu
Fei
F
Wei
Liang-Jun
LJ
Chen
Hai-Rong
HR
Xiong
Yuan-Yuan
YY
Liu
Fan
F
Luo
Wei
W
Hou
Hong
H
Xiao
Zhan-Qiu
ZQ
Yang
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000821:virology; D004353:Drug Evaluation, Preclinical; D004642:Emodin / Q000302:isolation & purification / Q000494:pharmacology*; D029822:Enterovirus B, Human / Q000187:drug effects*; D045468:Fallopia japonica / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000821:virology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy / Q000821:virology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000998:Antiviral Agents; D051017:Apoptosis Regulatory Proteins; D010936:Plant Extracts; D004642:Emodin