College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
J Antibiot (Tokyo). 2021 Nov;74(11):807-816. doi: 10.1038/s41429-021-00463-w. Epub 2021 Aug 19.
Berberine hydrochloride (BH), an active component of Coptis chinensis and other plant taxa, has broad antimicrobial activity and may be useful for the treatment of Candida infections. In this study, the mechanisms underlying the inhibitory effect of BH against Candida albicans were evaluated, with a focus on the high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway, which regulates multiple physiological functions. BH (256 and 64 μg ml) significantly increased intracellular glycerol and ROS levels in C. albicans, inhibited germ tube and hyphal formation, and increased chitin and β-1,3-glucan exposure on the cell wall. The inhibitory effect of BH was positively correlated with its concentration, and the inhibitory effect of 256 μg ml BH was greater than that of 4 μg ml fluconazole (FLC). Furthermore, RT-PCR analysis showed that 256 and 64 μg ml BH altered the HOG-MAPK pathway in C. albicans. In particular, the upregulation of the core genes, SLN1, SSK2, HOG1, and PBS2 may affect the expression of key downstream factors related to glycerol synthesis and osmotic pressure (GPD1), ROS accumulation (ATP11 and SOD2), germ tube and hyphal formation (HWP1), and cell wall integrity (CHS3 and GSC1). BH affects multiple biological processes in C. albicans; thus, it can be an effective alternative to conventional azole antifungal agents.
盐酸小檗碱（BH）是黄连和其他植物类群的一种活性成分，具有广泛的抗菌活性，可用于治疗念珠菌感染。在这项研究中，评估了 BH 抑制白色念珠菌的作用机制，重点是高渗透压甘油 MAPK（HOG-MAPK）途径，该途径调节多种生理功能。BH（256 和 64μg/ml）显著增加了白色念珠菌细胞内甘油和 ROS 水平，抑制了芽管和菌丝形成，并增加了细胞壁上的壳聚糖和β-1,3-葡聚糖暴露。BH 的抑制作用与浓度呈正相关，256μg/ml BH 的抑制作用大于 4μg/ml 氟康唑（FLC）。此外，RT-PCR 分析表明，256 和 64μg/ml BH 改变了白色念珠菌中的 HOG-MAPK 途径。特别是，核心基因 SLN1、SSK2、HOG1 和 PBS2 的上调可能影响与甘油合成和渗透压（GPD1）、ROS 积累（ATP11 和 SOD2）、芽管和菌丝形成（HWP1）以及细胞壁完整性（CHS3 和 GSC1）相关的关键下游因子的表达。BH 影响白色念珠菌中的多个生物学过程；因此，它可以作为传统唑类抗真菌药物的有效替代品。
