Antiviral effects of sophoridine against coxsackievirus B3 and its pharmacokinetics in rats
Antiviral effects of sophoridine against coxsackievirus B3 and its pharmacokinetics in rats
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DOI：
10.1016/j.lfs.2005.09.034
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发表时间：
2006-03-20
期刊：
影响因子：
6.1
通讯作者：
Cui, XL
中科院分区：
文献类型：
--
作者：
Zhang, YY;Zhu, HY;Cui, XL
柯萨奇病毒133（Coxsackievirus 133，CVB 3）是引起急、慢性病毒性心肌炎的主要病原。本研究的目的是研究从中草药苦参中提取的生物碱槐定碱对柯萨奇病毒B3的抗病毒作用及其药代动力学。首先，我们在体外（原代培养的心肌细胞），在体内（BALB/c小鼠）和血清药理学实验中测定槐定碱对CVB 3的抗病毒作用。采用高效液相色谱法测定SD大鼠口服给药后血清中的药代动力学行为。最后，我们确定槐定碱对小鼠病毒性心肌炎模型中细胞因子的产生的影响，通过检测感染的BALB/c小鼠心脏中的一些重要细胞因子的mRNA表达，通过RT-PCR。我们发现槐定碱在体外和体内都表现出明显的抗病毒作用，并且从口服槐定碱的大鼠获得的血清样品降低了感染的心肌细胞中的病毒滴度。血药浓度曲线与抗病毒活性曲线密切相关。槐定碱还能显著增强IL-10和IFN-γ的mRNA表达，但降低TNF-α的mRNA表达。总之，槐定碱通过调节细胞因子的表达而具有抗CVB 3的活性，并且槐定碱本身而不是其代谢产物可能是主要负责抗病毒活性的。因此，槐定碱可能是一种潜在的治疗病毒性心肌炎的药物。(c)2005年爱思唯尔公司All rights reserved.
Coxsackievirus 133 (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. (c) 2005 Elsevier Inc. All rights reserved.