Antiviral effects of sophoridine against coxsackievirus B3 and its pharmacokinetics in rats.
Coxsackievirus B3 (CVB3) is a major pathogen for acute and chronic viral myocarditis. The aim of this study was to investigate the antiviral effects of sophoridine, an alkaloid extracted from Chinese medicinal herb, Sophora flavescens, against CVB3, and the underlying pharmacokinetics. First, we determined the antiviral effects of sophoridine against CVB3 in in vitro (primarily cultured myocardial cells), in vivo (BALB/c mice) and serum pharmacological experiments. Then, we determined the pharmacokinetic behavior in serum samples of SD rats after oral administration by HPLC. Finally, we determined the effects of sophoridine on the production of cytokines in a murine viral myocarditis model by measuring mRNA expression of some important cytokines in hearts of infected BALB/c mice by RT-PCR. We found that sophoridine exhibited obvious antiviral effects both in vitro and in vivo, and serum samples obtained from rats with oral administration of sophoridine reduced the virus titers in infected myocardial cells. The serum concentration profile correlated closely with antiviral activity profile. Moreover, sophoridine significantly enhanced mRNA expression of IL-10 and IFN-gamma, but decreased TNF-alpha mRNA expression. In conclusion, sophoridine possesses antiviral activities against CVB3, by regulating cytokine expression, and it is likely that sophoridine itself, not its metabolites, is mainly responsible for the antiviral activities. Therefore, sophoridine may represent a potential therapeutic agent for viral myocarditis.
Zhang
Yuanyuan
Y
Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, No. 555 Zuchongzhi Road, Zhangjiang Pudong, Shanghai, China.
Zhu
Haiyan
H
Ye
Guan
G
Huang
Chenggang
C
Yang
Yingzhen
Y
Chen
Ruizhen
R
Yu
Yong
Y
Cui
Xiaolan
X
D000470:Alkaloids / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000401:mortality; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal; D029822:Enterovirus B, Human / Q000502:physiology*; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011807:Quinolizines / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014779:Virus Replication / Q000187:drug effects; D000093842:Matrines
D000470:Alkaloids; D000998:Antiviral Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D011807:Quinolizines; D012333:RNA, Messenger; D000093842:Matrines