College of Veterinary Medicine, Shandong Agricultural University, Tai`an, Shandong 271018, China.
Ninth People's Hospital of Zhengzhou, Zhengzhou 450053, PR China.
Phytomedicine. 2022 Aug;103:154212. doi: 10.1016/j.phymed.2022.154212. Epub 2022 May 27.
Fumonisin B1 is categorised as possible carcinogenic to humans which commonly contaminate maize and maize-based products worldwide, FB1, like other environmental pollutants, may activate apoptosis, autophagy, the inflammatory response and oxidative stress. Platycodon grandiflorus polysaccharide (PGPS) is prepared from a traditional herbal medicine in Asia with tremendous pharmacological activities. However, whether PGPS could relieve FB1-induced apoptosis has not been elucidated. The study aimed to evaluate the surface morphology of PGPS and its protective effect on fumonisin B1-induced apoptosis.
The surface morphology of PGPS was evaluated by SEM and AFM. Expressions of proteins involved in autophagy and apoptosis were detected by western blot analysis. Western blot, transient transfection, JC-1 and Annexin V-FITC/PI staining, CCK8, Live-cell imaging and autophagy inhibitor were used to observe the effect and explore the mechanism of PGPS on FB1-induced apoptosis of 3D4/21 cells.
PGPS had triple helix conformation, and had the characteristics of compact, polyporous and agglomerated morphology. PGPS promoted the expression of LC3-II and Beclin1, reduced the expression of p62, and significantly activated autophagy. PGPS inhibited the Akt/mTOR signaling pathway at 24 h. Besides, PGPS increased the expression of Bcl-2 and decreased the expression of Cleaved Caspase-3. PGPS-mediated autophagy was inhibited by 3-MA, accompanied by the upregulation of Caspase-3 and Cleaved Caspase-3, suggesting that enhanced autophagy inhibited apoptosis.
PGPS can activate autophagy, which in turn protects FB1-induced apoptosis. Targeting autophagy may provide a new way to improve the health of humans or animals in FB1 contaminated areas.
伏马菌素 B1 被归类为可能对人类致癌的物质,它普遍存在于全世界的玉米及其制品中。FB1 与其他环境污染物一样,可能会激活细胞凋亡、自噬、炎症反应和氧化应激。桔梗多糖(PGPS)是从亚洲传统草药中提取的,具有巨大的药理活性。然而,PGPS 是否可以缓解 FB1 诱导的细胞凋亡尚未阐明。本研究旨在评估 PGPS 的表面形态及其对伏马菌素 B1 诱导的细胞凋亡的保护作用。
通过 SEM 和 AFM 评估 PGPS 的表面形态。通过 Western blot 分析检测自噬和细胞凋亡相关蛋白的表达。Western blot、瞬时转染、JC-1 和 Annexin V-FITC/PI 染色、CCK8、活细胞成像和自噬抑制剂用于观察 PGPS 对 3D4/21 细胞 FB1 诱导的细胞凋亡的影响并探讨其机制。
PGPS 具有三螺旋构象,具有紧密、多孔和聚集的形态特征。PGPS 促进 LC3-II 和 Beclin1 的表达,降低 p62 的表达,显著激活自噬。PGPS 在 24 小时内抑制 Akt/mTOR 信号通路。此外,PGPS 增加了 Bcl-2 的表达,降低了 Cleaved Caspase-3 的表达。PGPS 介导的自噬被 3-MA 抑制,伴随着 Caspase-3 和 Cleaved Caspase-3 的上调,表明增强的自噬抑制了细胞凋亡。
PGPS 可以激活自噬,进而保护 FB1 诱导的细胞凋亡。靶向自噬可能为改善 FB1 污染地区人类或动物的健康提供新途径。