Virus-inhibiting activity of dihydroquercetin, a flavonoid from Larix sibirica, against coxsackievirus B4 in a model of viral pancreatitis
Virus-inhibiting activity of dihydroquercetin, a flavonoid from Larix sibirica, against coxsackievirus B4 in a model of viral pancreatitis
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DOI：
10.1007/s00705-016-2749-3
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发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Zarubaev, Vladimir V.
中科院分区：
文献类型：
--
作者：
Galochkina, Anastasia V.;Anikin, Vadim B.;Zarubaev, Vladimir V.
小核糖核酸病毒科的成员，特别是肠道病毒，对人类健康构成严重威胁。它们导致从轻微疾病到致命结果的多种病理。由于针对肠道病毒的安全有效的抗病毒药的数量有限，因此需要寻找和开发具有针对肠道病毒诱导的病理的各种活性机制的新型药物。本文研究了落叶松黄酮类化合物二氢槲皮素（DHQ）对柯萨奇病毒B4（CVB 4）所致白色小鼠胰腺炎的影响。DHQ以75或150 mg/kg/天的剂量腹腔内施用，每天一次，持续感染后（p.i.）从感染后第1天开始，并将其效果与参比化合物利巴韦林的效果进行比较。DHQ的应用导致胰腺组织中病毒滴度的剂量依赖性降低，在最高剂量下，在感染后第5天达到2.4 log。此外，DHQ的应用导致胰腺炎过程中受损的胰腺组织的抗氧化活性恢复。在形态学上，与安慰剂治疗的小鼠相比，DHQ治疗的动物的胰腺组织表现出较少的炎性细胞浸润，并且没有组织破坏的迹象。利巴韦林和DHQ治疗的动物每只小鼠的胰腺炎症灶较少，并且这些病灶比安慰剂治疗的小鼠含有更少的浸润细胞。DHQ的效果与利巴韦林相当或超过利巴韦林。综上所述，我们的研究结果表明DHQ的高抗病毒活性及其在病毒性胰腺炎综合治疗中的潜力。
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.