Sun Yaogui, Niu Li, Song Meiqin, Zhao Xin, Sun Na, He Junping, Wu Caihong, Jiang Junbing, Bai Yuansheng, Guo Jianhua, Li Hongquan
College of Animal Science and Veterinary Medicine, Shanxi Agricultural University , Taigu, Shanxi , PR China .
Pharm Biol. 2014 Jul;52(7):841-7. doi: 10.3109/13880209.2013.871639. Epub 2014 Feb 7.
Marek's disease (MD) seriously threatens the world poultry industry and has resulted in great economic losses. Chinese medicinal herbs are a rich source for lead compounds and drug candidates for antiviral treatments.
To investigate the anti-MDV activity and mechanism of 20 compounds extracted from Chinese medicinal herbs.
Antiviral assay, time of addition experiments, and virucidal assay were performed on chicken embryo fibroblast cells. The 50% cytotoxic concentration and 50% effective concentration were determined and, accordingly, selectivity index and inhibition ratio were calculated.
Antiviral assay showed dipotassium glycyrrhizinate (DG) and sodium tanshinone IIA sulfonate (STS) exhibited significantly inhibitory activity against MDV in a dose-dependent manner. EC50 of DG and STS were 893.5 ± 36.99 µg/mL and 54.82 ± 2.99 µg/mL, and selective index (SI) were >3.36 and >9.12, respectively. Time of addition experiment and virucidal assay demonstrated DG inhibited viral replication in the full replication cycle and inactivated MDV particles in non-time-dependent manner, but STS interfered with the early stage of MDV replication and inactivated MDV particles in a time-dependent manner. Moreover, both DG and STS promoted apoptosis of cells infected by MDV.
DG and STS have great potential for developing new anti-MDV drugs for clinic application.
马立克氏病(MD)严重威胁着世界家禽业,并已造成巨大经济损失。中草药是先导化合物和抗病毒治疗候选药物的丰富来源。
研究从中草药中提取的20种化合物的抗马立克氏病病毒(MDV)活性及作用机制。
在鸡胚成纤维细胞上进行抗病毒试验、加药时间实验和杀病毒试验。测定50%细胞毒性浓度和50%有效浓度,并据此计算选择性指数和抑制率。
抗病毒试验表明,甘草酸二钾(DG)和丹参酮IIA磺酸钠(STS)对MDV具有显著的剂量依赖性抑制活性。DG和STS的半数有效浓度(EC50)分别为893.5±36.99μg/mL和54.82±2.99μg/mL,选择性指数(SI)分别>3.36和>9.12。加药时间实验和杀病毒试验表明,DG在整个复制周期抑制病毒复制,以非时间依赖性方式灭活MDV颗粒,但STS干扰MDV复制的早期阶段,并以时间依赖性方式灭活MDV颗粒。此外,DG和STS均促进MDV感染细胞的凋亡。
DG和STS在开发用于临床的新型抗MDV药物方面具有巨大潜力。