Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103/287, 41125 Modena, Italy.
Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/A, 70126 Bari, Italy.
Int J Mol Sci. 2021 Apr 17;22(8):4175. doi: 10.3390/ijms22084175.
L. (pomegranate) fruit is known to be an important source of bioactive phenolic compounds belonging to hydrolysable tannins. Pomegranate extracts have shown antifungal activity, but the compounds responsible for this activity and their mechanism/s of action have not been completely elucidated up to now. The aim of the present study was the investigation of the inhibition ability of a selection of pomegranate phenolic compounds (i.e., punicalagin, punicalin, ellagic acid, gallic acid) on both plant and human fungal pathogens. In addition, the biological target of punicalagin was identified here for the first time. The antifungal activity of pomegranate phenolics was evaluated by means of Agar Disk Diffusion Assay and minimum inhibitory concentration (MIC) evaluation. A chemoinformatic analysis predicted for the first time topoisomerases I and II as potential biological targets of punicalagin, and this prediction was confirmed by in vitro inhibition assays. Concerning phytopathogens, all the tested compounds were effective, often similarly to the fungicide imazalil at the label dose. Particularly, punicalagin showed the lowest MIC for and , whereas punicalin was the most active compound in terms of growth control extent. As for human pathogens, punicalagin was the most active compound among the tested ones against reference strains, as well as against the clinically isolates. UHPLC coupled with HRMS indicated that , similarly to the phytopathogen , is able to hydrolyze both punicalagin and punicalin as a response to the fungal attack. Punicalagin showed a strong inhibitory activity, with IC values of 9.0 and 4.6 µM against topoisomerases I and II, respectively. Altogether, the results provide evidence that punicalagin is a valuable candidate to be further exploited as an antifungal agent in particular against human fungal infections.
石榴果实是众所周知的生物活性酚类化合物的重要来源，属于可水解单宁。石榴提取物具有抗真菌活性，但负责这种活性的化合物及其作用机制尚未完全阐明。本研究的目的是研究选择的石榴酚类化合物（即安石榴甙、安石榴林、鞣花酸、没食子酸）对植物和人类真菌病原体的抑制能力。此外，石榴素的生物靶标也首次在这里被鉴定出来。采用琼脂圆盘扩散法和最小抑菌浓度（MIC）评价法评估石榴酚类化合物的抗真菌活性。化学信息分析首次预测拓扑异构酶 I 和 II 是石榴素的潜在生物靶标，并通过体外抑制试验证实了这一预测。对于植物病原体，所有测试的化合物都有效，通常与标签剂量的杀真菌剂咪鲜胺相似。特别是，安石榴素对 和 的 MIC 最低，而安石榴林在生长控制程度方面是最有效的化合物。对于人类病原体，安石榴素是测试化合物中对 参考菌株以及临床分离株最有效的化合物之一。UHPLC 与 HRMS 联用表明，与植物病原体 一样，能够水解安石榴素和安石榴林，作为对真菌攻击的反应。安石榴素对拓扑异构酶 I 和 II 的 IC 值分别为 9.0 和 4.6µM，具有很强的抑制活性。总之，这些结果表明，安石榴素是一种有价值的候选物，可以进一步开发为抗真菌剂，特别是针对人类真菌感染。
