Acquadro Stefano, Civra Andrea, Cagliero Cecilia, Marengo Arianna, Rittà Massimo, Francese Rachele, Sanna Cinzia, Bertea Cinzia, Sgorbini Barbara, Lembo David, Donalisio Manuela, Rubiolo Patrizia
Department of Drug Science and Technology, University of Turin, Turin, Italy.
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Planta Med. 2020 Dec;86(18):1363-1374. doi: 10.1055/a-1232-5705. Epub 2020 Sep 16.
Zika virus, an arthropod-borne flavivirus, is an emerging healthcare threat worldwide. Zika virus is responsible for severe neurological effects, such as paralytic Guillain-Barrè syndrome, in adults, and also congenital malformations, especially microcephaly. No specific antiviral drugs and vaccines are currently available, and treatments are palliative, but medicinal plants show great potential as natural sources of anti-Zika phytochemicals. This study deals with the investigation of the composition, cytotoxicity, and anti-Zika activity of leaf ethanolic extract, fractions, and phytoconstituents. leaves were collected from different areas in Italy and Greece in different seasons. Crude extracts were analyzed and fractionated, and the pure compounds were isolated. The phytochemical and biomolecular fingerprint of the pomegranate leaves was determined. The antiviral activities of the leaf extract, fractions, and compounds were investigated against the MR766 and HPF2013 Zika virus strains . Both the extract and its fractions were found to be active against Zika virus infection. Of the compounds isolated, ellagic acid showed particular anti-Zika activities, with EC values of 30.86 µM for MR766 and 46.23 µM for HPF2013. The mechanism of action was investigated using specific antiviral assays, and it was demonstrated that ellagic acid was primarily active as it prevented Zika virus infection and was able to significantly reduce Zika virus progeny production. Our data demonstrate the anti-Zika activity of pomegranate leaf extract and ellagic acid for the first time. These findings identify ellagic acid as a possible anti-Zika candidate compound that can be used for preventive and therapeutic interventions.
寨卡病毒是一种节肢动物传播的黄病毒，是全球新兴的医疗健康威胁。寨卡病毒会导致成年人出现严重的神经效应，如麻痹性格林-巴利综合征，还会导致先天性畸形，尤其是小头畸形。目前尚无特效抗病毒药物和疫苗，治疗手段只是缓解症状，但药用植物作为抗寨卡植物化学物质的天然来源具有巨大潜力。本研究对石榴叶乙醇提取物、馏分和植物成分的组成、细胞毒性及抗寨卡活性进行了研究。在不同季节从意大利和希腊的不同地区采集了石榴叶。对粗提物进行分析和分离，分离出纯化合物。确定了石榴叶的植物化学和生物分子指纹图谱。研究了叶提取物、馏分和化合物对MR766和HPF2013寨卡病毒株的抗病毒活性。发现提取物及其馏分均对寨卡病毒感染有活性。在分离出的化合物中，鞣花酸表现出特别的抗寨卡活性，对MR766的半数有效浓度（EC）值为30.86 μM，对HPF2013为46.23 μM。使用特定的抗病毒试验研究了其作用机制，结果表明鞣花酸主要通过预防寨卡病毒感染并能显著减少寨卡病毒子代产生而发挥活性。我们的数据首次证明了石榴叶提取物和鞣花酸的抗寨卡活性。这些发现确定鞣花酸是一种可能用于预防和治疗干预的抗寨卡候选化合物。
