Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, China.
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, China.
J Cell Mol Med. 2024 May;28(9):e18354. doi: 10.1111/jcmm.18354.
Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis-benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 μg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH-DA staining suggested its anti-Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N-acetyl-cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti-Candida therapies.
念珠菌属物种（尤其是白念珠菌）引起的感染威胁着公众健康并造成了经济负担。抗真菌药物的短缺和耐药性的出现呼吁开发新的抗真菌疗法，而天然产物是开发新药的有吸引力的来源。在我们的研究中，来源于中国草药Stephania tetrandra S. Moore 的双苄基异喹啉生物碱粉防己碱对包括白念珠菌在内的几种念珠菌属物种的浮游生长具有抗真菌作用，其 MIC 不超过 50μg/mL。此外，显微镜、MTT 和 XTT 还原测定的结果表明，粉防己碱对念珠菌的多种毒力因子具有抑制活性，如黏附、菌丝生长和生物膜形成。此外，该化合物还可以抑制已形成的白念珠菌生物膜的代谢活性。PI 染色后，通过共聚焦激光扫描显微镜（CLSM）分析显示粉防己碱可以增加细胞膜的通透性。DCFH-DA 染色表明其抗念珠菌机制还涉及细胞内 ROS 的过度产生，这通过 N-乙酰半胱氨酸（N-acetyl-cysteine）拯救试验得到进一步证实。此外，粉防己碱与三种抗真菌药物（两性霉素 B、氟康唑和卡泊芬净）表现出协同作用，进一步表明其在治疗白念珠菌感染方面的潜在用途。因此，这些结果表明粉防己碱可能是开发抗念珠菌疗法的潜在候选药物。
