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抗真菌番荔枝(刺果番荔枝)提取物靶向多药耐药白色念珠菌的细胞包膜。

Antifungal Annona muricata L. (soursop) extract targets the cell envelope of multi-drug resistant Candida albicans.

机构信息

Bioactive Natural Products Laboratory, Department of Biochemistry, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.

Laboratory of Cellular Biology, Department of Biology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.

出版信息

J Ethnopharmacol. 2023 Jan 30;301:115856. doi: 10.1016/j.jep.2022.115856. Epub 2022 Oct 22.

Abstract

ETNOPHARMACOLOGICAL RELEVANCE

Annona muricata L. (soursop) is traditionally used in the treatment of inflammatory diseases, cancer, and infections caused by fungi. The therapeutic activity explored by its medicinal use is generally associated with its phytoconstituents, such as acetogenins and alkaloids. However, its potential antifungal bioactivity as well as its mechanism of action remains to be established.

AIM OF THE STUDY

To evaluate the antifungal activity of the ethanolic extract of A. muricata leaves against multidrug-resistant Candida albicans (ATCC® 10231).

MATERIAL AND METHODS

Phytoconstituents were detected by UFLC-QTOF-MS. The minimum inhibitory concentration was determined, followed by the determination of the minimum fungicidal concentration. For planktonic cells, the growth curve and cell density were evaluated. Studies to understand the mechanism of action on the cell envelope involved crystal violet permeability, membrane extravasation, sorbitol protection, exogenous ergosterol binding assay, metabolic activity, and cell viability. Furthermore, mitochondrial membrane potential was assessed.

RESULTS

Our analyses demonstrated a significant inhibitory effect of A. muricata, with the ability to reduce fungal growth by 58% and cell density by 65%. The extract affected both the fungal plasma membrane and cell wall integrity, with significant reduction of the cell viability. Depolarization of the fungal mitochondrial membrane was observed after treatment with A. muricata. Rutin, xi-anomuricine, kaempferol-3O-rutinoside, nornuciferine, xylopine, atherosperminine, caffeic acid, asimilobine, s-norcorydine, loliolide, annohexocin, annomuricin, annopentocin, and sucrose were identified as extract bioactive components.

CONCLUSIONS

Our findings show that the A. muricata extract is a source of chemical diversity, which acts as a potential antifungal agent with promising application to the therapy of infections caused by C. albicans.

摘要

植物药理学相关性

番荔枝(soursop)传统上用于治疗炎症性疾病、癌症和真菌感染。其药用探索的治疗活性通常与其植物成分有关,如乙酰氧基生物和生物碱。然而,其潜在的抗真菌生物活性及其作用机制仍有待确定。

研究目的

评估番荔枝叶乙醇提取物对多药耐药白色念珠菌(ATCC®10231)的抗真菌活性。

材料和方法

采用 UFLC-QTOF-MS 检测植物成分。测定最小抑菌浓度,然后测定最小杀菌浓度。对于浮游细胞,评估生长曲线和细胞密度。了解细胞包膜作用机制的研究包括结晶紫通透性、膜外渗、山梨醇保护、外源性麦角固醇结合测定、代谢活性和细胞活力。此外,还评估了线粒体膜电位。

结果

我们的分析表明,番荔枝具有显著的抑制作用,能够使真菌生长减少 58%,细胞密度减少 65%。该提取物影响真菌的质膜和细胞壁完整性,显著降低细胞活力。用番荔枝处理后,观察到真菌线粒体膜去极化。鉴定出芦丁、xi-anomuricine、山奈酚-3O-鼠李糖苷、诺木啡林、木樨草素、atherosperminine、咖啡酸、asimilibine、s-norcorydine、loliolide、annohexocin、annomuricin、annopentocin 和蔗糖是提取物的生物活性成分。

结论

我们的研究结果表明,番荔枝提取物是一种化学多样性的来源,它作为一种有潜力的抗真菌剂,有望应用于治疗白色念珠菌引起的感染。

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