Li Zhi-Jian, Guo Xin, Dawuti Gulina, Aibai Silafu
Department of Pharmacology and Toxicology Laboratory, Xinjiang Institute of Traditional Uighur Medicine, Urumqi, Xinjiang, 830049, China.
Xinjiang Hospital of Traditional Uighur Medicine, Urumqi, Xinjiang, 830049, China.
Phytother Res. 2015 Jul;29(7):1019-25. doi: 10.1002/ptr.5340. Epub 2015 Apr 28.
Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti-inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38-A and M27-A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33 µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0 µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC = 18.75 µg/ml). Studies on the mechanism of action using an HPLC-based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14α-demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0 mg/cm(2) ) significantly enhanced the cure rate in a guinea-pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent.
鞣花酸（EA）已被证明具有抗氧化、抗菌和抗炎活性。在维吾尔族传统医学中，地锦草用于治疗真菌疾病，最近的研究表明，其治疗效果归因于EA含量。然而，EA的抗真菌活性作用尚未见报道。本研究旨在探讨EA在体外和体内对真菌菌株的抑制作用。采用美国国家临床实验室标准委员会（M38 - A和M27 - A2）的标准方法在体外测定最低抑菌浓度（MIC）。EA具有广谱抗真菌活性，所有受试皮肤癣菌菌株的MIC在18.75至58.33μg/ml之间。EA对两种念珠菌菌株也有活性，MIC在25.0至75.0μg/ml之间。它对光滑念珠菌无活性。六种皮肤癣菌对EA的敏感性与商用抗真菌药氟康唑相当。最敏感的丝状菌是红色毛癣菌（MIC = 18.75μg/ml）。使用基于高效液相色谱的测定法和酶联免疫吸附测定法对作用机制的研究表明，EA分别抑制了红色毛癣菌膜中麦角甾醇的生物合成并降低了甾醇14α - 脱甲基酶P450（CYP51）的活性。体内试验表明，局部应用EA（4.0和8.0mg/cm²）可显著提高红色毛癣菌豚鼠感染模型的治愈率。结果表明，EA有潜力被开发为一种天然抗真菌剂。
