Study on Inhibitory Effect of the Swainsonine from Alkaloid of Astragalus strictus Grah. Ex Bend on Bovine Viral Diarrhea Virus
HAO Bao-cheng;WU Fan-lin;XING Xiao-yong;XIANG Hai-tao;WEN Feng-qin;WANG Xue-hong;QUAN Xiao-di;HU Yong-hao;LIANG Jian-ping;Key Laboratory of New Animal Drug Project,Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery,Ministry of Agriculture /Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences;College of Veterinary Medicine,Gansu Agricultural University;
【Objective】 Locoweed is one of the poisonous weeds in western China that influences the healthy development of grassland and animal husbandry. Locoweeds mainly belong to Astragalus and Oxytropis genera. As a serious lack of forage in winter season, livestock such as cattle and sheep are forced to feed them. Locoweed can decrease the production performance, toxicity and death of animals, and the direct economic loss of the grassland ecological and animal husbandry is about billions of dollars, which is the most serious poisonous weed. At present, the economic losses of animal death caused by locoweed poisoning continues to soar. Swainsonine is the main toxic component and believed to be the cause of animal locoweed poisoning. Locoweed is widely distributed and is rich in resources, and how to improve the grassland ecology and use of locoweed is becoming the topic of research subject and direction. In recent years, with the study and expansion of locoweed, people have found that swainsonine not only has a good anti-tumor effect, also it can be used as an immunomodulator, anti HIV and anti proliferation inhibitor, anti viral and cell protective agent and other drugs. At present, the domestic research on swainsonine anti-tumor and regulation of immunity is hot, However, no research reports are found in antiviral activity and mechanism of action of swainsonine up to the present. This experiment was designed to investigate the anti-virus mechanism of the swainsonine from alkaloid of Astragalus on bovine viral diarrhea virus(BVDV), and to make clear of the antiviral effect in vitro, it will provide references for the screening of anti BVDV drugs. 【Method】 Using cell culture techniques, and combined with CPE observation method and MTT colorimetric method, different concentrations SW toxicity with bovine kidney primary cells(Madin-Darby Bovine Kidney Cells, MDBK) were detected, the concentration of the drug's safety and TD50 was determined. They were measured by four administration routes of virus before swainsonine, virus after swainsonine, virus-and-swainsonine after 2 hours, and virus-and-swainsonine after swainsonine, which are the effect of different concentrations of SW against blocking effect on BVDV invasion, replicatting inhibition, directly killing effect and combining effects, respectively. The treatment indexes under different interaction modes were also calculated.【Result】It was found that the TCID50 of BVDV-MDV is 10-4.7. SW was not toxic to MDBK when its concentration was below 0.256 μg·mL-1, and TD50 is 2.512 μg·mL-1. Under the way of virus after SW, IC50 is 2.399 μg·mL-1, TI is 1.05. Under the way of SW after virus, IC50 is 1.018 μg·mL-1, TI is 2.47. Under the way of 2 h after mixed virus with SW, IC50 is 1.205 μg·mL-1, TI is 2.08. Under the way of synthetic action, IC50 is 0.782 μg·mL-1,TI is 3.21. After the TI of different modes of action was compared, it showed that the comprehensive effect on BVDV of SW(65.29%,P0.01) and the inhibition effect of SW on the reproduction of BVDV(65.05%, P0.01) were better, and SW had a certain direct killing effect on BVDV, but the blocking effect of SW on the invasion of BVDV was poor.【Conclusion】The effect of swainsonine(SW)-anti-BVDV activity in vitro was better, and the authors infered that the antiviral mechanism of SW might be that it could enter into the cells and inhibit the reproduction of BVDV, or it could play a role by killing the uncombined BVDV.
【Fund】： 国家高新技术研究发展计划(“863”计划)(2011AA10A214);; 中央级公益性科研院所基本科研业务费专项资金(1610322012001);; 西藏农牧厅委托项目(2012-2014)
【CateGory Index】： S852.65
【CateGory Index】： S852.65