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⁻¹) 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⁻¹ BH was greater than that of 4 μg ml⁻¹ fluconazole (FLC). Furthermore, RT-PCR analysis showed that 256 and 64 μg ml⁻¹ 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 对白色念珠菌抑制作用的潜在机制，重点是高渗透压甘油丝裂原活化蛋白激酶 (HOG-MAPK) 通路，该通路调节多种生理功能。BH（256 和 64 μg ml ^-1）显着增加了白色念珠菌的细胞内甘油和 ROS 水平，抑制胚管和菌丝形成，并增加细胞壁上几丁质和 β-1,3-葡聚糖的暴露。BH的抑制作用与其浓度呈正相关，256 μg ml ^-1 BH的抑制作用大于4 μg ml ^-1氟康唑（FLC）。此外，RT-PCR 分析显示 256 和 64 μg ml ^-1 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 积累相关的关键下游因子的表达。ATP11和SOD2）、胚管和菌丝形成（HWP1）以及细胞壁完整性（CHS3和GSC1）。BH 影响白色念珠菌的多种生物过程；因此，它可以成为传统唑类抗真菌剂的有效替代品。