Department of Pharmacology and Toxicology Laboratory, Xinjiang Institute of Traditional Uighur Medicine, Xinjiang Laboratory of Uighur Medical Prescription, Urumqi, Xinjiang, 830049, China.
Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
Phytother Res. 2017 Jul;31(7):1039-1045. doi: 10.1002/ptr.5823. Epub 2017 May 19.
Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38-A and M27-A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC-based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α-demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.
没食子酸（GA）是一种多酚天然化合物，存在于许多药用植物物种中，包括石榴皮（Punica granatum L.），并已被证明具有抗炎和抗菌特性。石榴皮用于治疗维吾尔族和其他传统医学体系中的细菌和真菌病原体，但令人惊讶的是，GA 对抗真菌活性的影响尚未报道。在这项研究中，我们旨在研究 GA 在体外和体内对真菌菌株的抑制作用。最小抑菌浓度（MIC）通过 NCCLS（M38-A 和 M27-A2）标准方法在体外确定，结果表明 GA 具有广谱抗真菌活性，所有测试的皮肤真菌菌株的 MIC 均在 43.75 和 83.33μg/ml 之间。没食子酸对三种念珠菌菌株也具有活性，MIC 介于 12.5 和 100.0μg/ml 之间。最敏感的念珠菌物种是白色念珠菌（MIC=12.5μg/ml），最敏感的丝状物种是红色毛癣菌（MIC=43.75μg/ml），其效力与对照药物氟康唑相当。使用基于 HPLC 的测定法和酶联免疫吸附测定法研究了抑制麦角固醇生物合成的作用机制。没食子酸分别降低了 T. rubrum 膜中固醇 14α-去甲基化酶 P450（CYP51）和角鲨烯环氧化酶的活性。体内模型表明，腹腔注射 GA（80mg/kg/d）可显著提高系统性真菌感染小鼠感染模型的治愈率。总之，我们的研究结果证实了 GA 的抗真菌作用，并提出了一种作用机制，表明 GA 有可能进一步开发为临床用天然抗真菌药物。版权所有©2017 约翰威立父子公司
