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紫色土瓜(Harv)通过减少黄曲霉中麦角固醇的产生来发挥其抗真菌活性。

Tulbaghia violacea (Harv) Exerts its Antifungal Activity by Reducing Ergosterol Production in Aspergillus flavus.

机构信息

Department of Biochemistry & Microbiology, Nelson Mandela University, University Way, Summerstrand, P.O. Box 77000, Port Elizabeth, Eastern Cape, South Africa.

出版信息

Curr Microbiol. 2021 Aug;78(8):2989-2997. doi: 10.1007/s00284-021-02546-1. Epub 2021 Jun 8.

Abstract

Opportunistic infections in immunosuppressed patients have led to an increase in fungal infections, with Aspergillus being one of the main causative agents. Medicinal plants exhibiting antifungal activity have the potential to be used as chemotherapeutic agents. However, often their mechanisms of action are not fully researched. Tulbaghia violacea exhibits antifungal activity towards Candida, Aspergillus flavus and Aspergillus parasiticus but its mode of action has only recently begun to be investigated. This study aimed to ascertain the effect of T. violacea rhizome extracts on ergosterol production in A. flavus and the mechanism of inhibition. The MIC of a T. violacea rhizome extract against A. flavus was first determined, using a broth dilution assay, to be 15 mg/ml. Thereafter, the culture was subjected to sub-inhibitory concentrations of the extract before sterol intermediates of the ergosterol biosynthetic pathway were isolated and analysed for dose-dependent accumulation. Analysis by reverse-phase HPLC displayed a decline in ergosterol production in a dose-dependent manner when exposed to increasing concentrations of T. violacea extract. Quantification of the sterol intermediates of the ergosterol pathway indicated a definite accumulation of 2,3-oxidosqualene. The results prove that the plant extract affected ergosterol synthesis by inhibiting oxidosqualene cyclase. This prevented the formation of downstream intermediates of the ergosterol pathway ultimately resulting in inhibition of ergosterol production.

摘要

免疫抑制患者的机会性感染导致真菌感染增加,其中曲霉菌是主要病原体之一。具有抗真菌活性的药用植物有可能被用作化疗药物。然而,它们的作用机制通常未得到充分研究。Tulbaghia violacea 对念珠菌、黄曲霉和寄生曲霉表现出抗真菌活性,但它的作用模式最近才开始被研究。本研究旨在确定 T. violacea 根茎提取物对黄曲霉中麦角固醇产生的影响及其抑制机制。首先,通过肉汤稀释法测定 T. violacea 根茎提取物对黄曲霉的 MIC,结果为 15mg/ml。此后,在亚抑菌浓度下培养物,然后分离和分析麦角固醇生物合成途径中的甾醇中间体,并进行剂量依赖性积累分析。反相 HPLC 分析显示,当暴露于越来越高浓度的 T. violacea 提取物时,麦角固醇的产生呈剂量依赖性下降。麦角固醇途径的甾醇中间体的定量分析表明 2,3-氧化鲨烯确实有积累。结果证明植物提取物通过抑制角鲨烯环化酶来影响麦角固醇的合成。这阻止了麦角固醇途径下游中间体的形成,最终导致麦角固醇产生的抑制。

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