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西伯利亚落叶松中的黄酮类化合物二氢槲皮素在病毒性胰腺炎模型中对柯萨奇病毒B4的抗病毒活性。

Virus-inhibiting activity of dihydroquercetin, a flavonoid from Larix sibirica, against coxsackievirus B4 in a model of viral pancreatitis.

作者信息

Galochkina Anastasia V, Anikin Vadim B, Babkin Vasily A, Ostrouhova Liudmila A, Zarubaev Vladimir V

机构信息

Influenza Research Institute, St. Petersburg, Russia.

Irkutsk Institute of Chemistry, Irkutsk, Russia.

出版信息

Arch Virol. 2016 Apr;161(4):929-38. doi: 10.1007/s00705-016-2749-3. Epub 2016 Jan 18.

Abstract

Members of the family Picornaviridae, in particular, enteroviruses, represent a serious threat to human health. They are responsible for numerous pathologies ranging from mild disease to fatal outcome. Due to the limited number of safe and effective antivirals against enteroviruses, there is a need for search and development of novel drugs with various mechanisms of activity against enteroviruses-induced pathologies. We studied the effect of dihydroquercetin (DHQ), a flavonoid from larch wood, on the course of pancreatitis of white mice caused by coxsackievirus B4 (CVB4). DHQ was applied intraperitoneally at doses of 75 or 150 mg/kg/day once a day for 5 days postinfection (p.i.) starting on day 1 p.i., and its effect was compared to that of the reference compound ribavirin. The application of DHQ resulted in a dose-dependent decrease in the virus titer in pancreatic tissue, reaching, at the highest dose, 2.4 logs on day 5 p.i. Also, the application of DHQ led to restoration of antioxidant activity of pancreatic tissue that was impaired in the course of pancreatitis. Morphologically, pancreatic tissue of DHQ-treated animals demonstrated less infiltration with inflammatory cells and no signs of tissue destruction compared to placebo-treated mice. Both ribavirin- and DHQ-treated animals developed fewer foci of pancreatic inflammation per mouse, and these foci contained fewer infiltrating cells than those in placebo-treated mice. The effect of DHQ was comparable to or exceeded that of ribavirin. Taken together, our results suggest high antiviral activity of DHQ and its promising potential in complex treatment of viral pancreatitis.

摘要

小核糖核酸病毒科成员,尤其是肠道病毒,对人类健康构成严重威胁。它们可导致从轻度疾病到致命后果的多种病理状况。由于针对肠道病毒的安全有效抗病毒药物数量有限,因此需要寻找和开发针对肠道病毒引起的病理状况具有多种作用机制的新型药物。我们研究了落叶松木中的类黄酮二氢槲皮素(DHQ)对柯萨奇病毒B4(CVB4)引起的小白鼠胰腺炎病程的影响。从感染后第1天开始,于感染后(p.i.)每天腹腔注射一次剂量为75或150 mg/kg的DHQ,持续5天,并将其效果与参考化合物利巴韦林进行比较。DHQ的应用导致胰腺组织中病毒滴度呈剂量依赖性下降,在感染后第5天,最高剂量时下降了2.4个对数。此外,DHQ的应用使胰腺炎病程中受损的胰腺组织抗氧化活性得以恢复。形态学上,与安慰剂处理的小鼠相比,DHQ处理动物的胰腺组织炎症细胞浸润较少,且无组织破坏迹象。利巴韦林和DHQ处理的动物每只小鼠胰腺炎症灶均较少,且这些病灶中的浸润细胞比安慰剂处理的小鼠少。DHQ的效果与利巴韦林相当或超过利巴韦林。综上所述,我们的结果表明DHQ具有较高的抗病毒活性,在病毒性胰腺炎的综合治疗中具有广阔的应用前景。

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