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从……中分离出的血根碱通过抑制麦角甾醇合成对……表现出强大的抗真菌功效。

Sanguinarine, Isolated From , Exhibits Potent Antifungal Efficacy Against Through Inhibiting Ergosterol Synthesis.

作者信息

Hu Ziwei, Hu Hao, Hu Zhili, Zhong Xiaojun, Guan Yifu, Zhao Yunshi, Wang Lu, Ye Liang, Ming Liliang, Riaz Rajoka Muhammad Shahid, He Zhendan, Wang Yan, Song Xun

机构信息

School of Basic Medicine, School of Pharmaceutical Sciences, Respiratory Medicine Department, Shenzhen University General Hospital, Health Science Center, Shenzhen University, Shenzhen, China.

Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.

出版信息

Front Microbiol. 2022 Jun 15;13:908461. doi: 10.3389/fmicb.2022.908461. eCollection 2022.

Abstract

In recent decades, infections caused by the opportunistic fungus have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against both and . SAN exhibited antifungal activity against clinical isolates, with MICs in the range of 112.8-150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.

摘要

近几十年来,由机会性真菌引起的感染有所增加,尤其是在免疫缺陷患者中。在本研究中,我们研究了血根碱(SAN)对[具体两种真菌名称缺失]的作用机制。SAN对[具体真菌名称缺失]临床分离株表现出抗真菌活性,MIC范围为112.8 - 150.5μM。此外,扫描电子显微镜和透射电子显微镜显示,SAN诱导[具体真菌名称缺失]细胞发生形态变化以及结构破坏,包括细胞碎片团块、细胞壁破裂和膜变形。流式细胞术显示,SAN可导致细胞膜损伤,麦角固醇含量分析表明,SAN可使麦角固醇含量降低超过90%。此外,我们在小鼠模型中验证了SAN对[具体真菌名称缺失]引起的念珠菌病的疗效,与载体相比,SAN显著提高了生存率并减少了体重减轻。1.5和2.5mg/kg/d的SAN治疗明显降低了肾脏中的真菌负荷。此外,组织病理学检查表明,SAN治疗后在肺和肾组织中未观察到真菌细胞。因此,本研究表明SAN是一种有前景的植物源化合物,可用于开发有效的抗念珠菌剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d889/9240711/105c9416ae7b/fmicb-13-908461-g0001.jpg

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