厚朴酚作为一种有效的抗真菌剂，抑制了 PKC 和 Cek1 MAPK 信号通路等毒力因子。
Magnolol as a potent antifungal agent inhibits virulence factors the PKC and Cek1 MAPK signaling pathways.
机构信息
Department of Oral Medicine, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
出版信息
Front Cell Infect Microbiol. 2022 Jul 22;12:935322. doi: 10.3389/fcimb.2022.935322. eCollection 2022.
Magnolol, a lignin compound extracted from Cortex, has been found to have prominent antifungal effects against . However, the specific mechanism still remains unclear. Therefore, this study aimed to further explore the inhibition mechanism of magnolol against virulence factors and the related signaling pathways. By an XTT reduction assay, a hyphal formation assay, confocal laser scanning microscopy, transmission electron microscopy, a calcofluor white staining assay, and a cell wall β-glucan quantitative detection assay, we evaluated the inhibitory effects of magnolol against the adhesion, hyphal formation, biofilm viability, biofilm spatial structure, and cell wall ultrastructure of . Moreover, by RNA sequencing and qRT-PCR, we confirmed the effects of magnolol in inhibiting the gene expression of virulence factors and the related signaling pathways. The results revealed that the adhesion and hyphal formation of were inhibited significantly by magnolol. The viability and spatial structures of biofilms were further weakened. ultrastructure showed partial thinning of cell walls and even rupture, with cytoplasmic leakage. The cell wall intergrity and β-glucan content were also radically reduced. Moreover, magnolol caused significant inhibition of the expression of adhesion, invasion, hyphal formation, biofilm formation, β-1,3-glucan synthesis, and hydrolase secretion-related genes, including , , , , , , , and . Furthermore, the PKC pathway-related genes (, , , , ) and Cek1 pathway-related genes (, , , ) were also significantly downregulated, indicating that the inhibition of magnolol against virulence factors might be related to PKC and Cek1 MAPK signaling pathways. In conclusion, the findings of this study confirmed the inhibition mechanism of magnolol against virulence factors, which might be related to PKC and Cek1 MAPK pathways, thus laying the theoretical foundation for its clinical antifungal applications.
厚朴酚是从厚朴树皮中提取的一种木质素化合物，已被发现对具有显著的抗真菌作用。然而，其具体机制尚不清楚。因此，本研究旨在进一步探讨厚朴酚抑制粘质沙雷氏菌毒力因子及相关信号通路的机制。通过 XTT 还原试验、菌丝形成试验、激光共聚焦扫描显微镜、透射电子显微镜、钙荧光白染色试验和细胞壁β-葡聚糖定量检测试验，评估了厚朴酚对粘质沙雷氏菌黏附、菌丝形成、生物膜活力、生物膜空间结构和细胞壁超微结构的抑制作用。此外，通过 RNA 测序和 qRT-PCR，我们证实了厚朴酚抑制粘质沙雷氏菌毒力因子及其相关信号通路基因表达的作用。结果表明，厚朴酚显著抑制粘质沙雷氏菌的黏附和菌丝形成。生物膜的活力和空间结构进一步减弱。超微结构显示细胞壁部分变薄，甚至破裂，细胞质渗漏。细胞壁完整性和β-葡聚糖含量也明显降低。此外，厚朴酚还导致与粘质沙雷氏菌黏附、侵袭、菌丝形成、生物膜形成、β-1,3-葡聚糖合成和水解酶分泌相关的基因（包括,,,,,,,,, 和 ）的表达显著抑制。此外，PKC 途径相关基因（,,,,, ）和 Cek1 途径相关基因（,,,,, ）也显著下调，表明厚朴酚抑制粘质沙雷氏菌毒力因子的作用可能与 PKC 和 Cek1 MAPK 信号通路有关。综上所述，本研究结果证实了厚朴酚抑制粘质沙雷氏菌毒力因子的机制可能与 PKC 和 Cek1 MAPK 通路有关，为其临床抗真菌应用奠定了理论基础。
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