背景:冬虫夏草(C.蝉),名为“陈华”,这是一种菊科的变形,是由寄生在蝉幼虫上的真菌形成的昆虫复合物,属于木耳科和Codceps属,传统上在中国民族药理学中占有重要地位,专门用于眼睛清晰度和作为与年龄相关的眼部疾病的补救措施。促进其视力增强和对年龄相关性黄斑变性(AMD)的潜在有效性的潜在机制仍未被探索。
目的:本研究旨在阐明蝉及其活性成分的保护作用,Myriocin(Myr),反对AMD。
方法:采用化学诱导剂在体外和体内对视网膜色素上皮(RPE)进行损伤。通过生物信息学分析和分子生物学方法研究了连翘的关键成分及其抗AMD的相关机制。
结果:通过高效液相色谱(HPLC)将Myr鉴定为C.cicadae中的活性成分,并证明了对RPE细胞的保护作用,减少碘酸钠(SI)诱导的结构损伤和细胞死亡。Further,Myr减少了AMD小鼠的眼睑分泌物,并恢复了其视网膜结构和功能。Myr治疗中的差异表达基因(DEGs)主要与TNF和坏死性凋亡信号通路相关。分子对接表明TNF和Myr之间有很强的亲和力。Myr抑制TNF信号通路从而降低ARPE-19细胞中炎症因子的表达。此外,Myr与坏死抑制剂Necrostatin-1(Nec-1)具有一致的作用,抑制RIPK1/RIPK3/MLKL通路,从而保护ARPE-19细胞。
结论:研究结果提出了Myr,作为对抗SI诱导的AMD的有效保护者,主要通过调节TNF-RIPK1/RIPK3/MLKL信号通路,提供了作为AMD治疗的可行候选药物的治疗方法的见解。
BACKGROUND: Cordyceps cicadae (C.cicadae), named \"Chan Hua\", an anamorph of Isaria cicadae Miquel, is an entomogenous complex formed by fungi parasitizing on the larvae of cicadas and belongs to the Claviciptaceae family and the genus Codyceps, which traditionally holds a significant place in Chinese ethnopharmacology, specifically for eye clarity and as a remedy for age-related ocular conditions. The underlying mechanisms contributing to its eyesight enhancement and potential effectiveness against Age-related macular degeneration (AMD) remain unexplored.
OBJECTIVE: This study aims to elucidate the protective role of C.cicadae and its active ingredient, Myriocin (Myr), against AMD.
METHODS: A chemical inducer was employed to make retinal pigment epithelium (RPE) damage in vitro and in vivo. The key ingredients of C.cicadae and their related mechanisms for anti-AMD were studied through bioinformatic analysis and molecular biological approaches.
RESULTS: Myr was identified through high-performance liquid chromatography (HPLC) as an active ingredient in C.cicadae, and demonstrated a protective effect on RPE cells, reducing the structural damage and cell death induced by sodium iodate (SI). Further, Myr reduced eyelid secretions in AMD mice and restored their retinal structure and function. The differentially expressed genes (DEGs) in Myr treatment are primarily associated with TNF and Necroptosis signaling pathways. Molecular docking indicated a strong affinity between TNF and Myr. Myr inhibited the TNF signaling pathway thereby reducing the expression of inflammatory factors in ARPE-19 cells. Additionally, Myr had consistent action with the necroptosis inhibitor Necrostatin-1 (Nec-1), inhibited the RIPK1/RIPK3/MLKL pathway thereby protecting ARPE-19 cells.
CONCLUSIONS: The findings present Myr, as a potent protector against SI-induced AMD, predominantly through modulation of the TNF-RIPK1/RIPK3/MLKL signaling pathway, offering the insights of therapeutic C.cicadae as viable candidates for AMD treatment.