Polygalacin D inhibits the growth of hepatocellular carcinoma cells through BNIP3L-mediated mitophagy and endogenous apoptosis pathways

Platycodon grandiflorum(Jacq.)A.DC.is a famous medicinal plant commonly used in East Asia.Triterpene saponins isolated from P.grandiflorum are the main biologically active compounds,among which polygalacin D(PGD)has been reported to be an anti-tumor agent.However,its anti-tumor mechanism against hepatocellular carcinoma is unknown.This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action.We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy.Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways.Subsequently,using specific inhibitors,we found that apoptosis and autophagy had mutually reinforcing effects.In addition,further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like(BNIP3L)levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors.Overall,our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways.Therefore,PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.

Polygalacin D对糖尿病慢性炎性脱髓鞘性多发性神经根神经病小鼠神经炎症的改善作用及机制

目的 探究Polygalacin D对糖尿病慢性炎性脱髓鞘性多发性神经根神经病小鼠神经炎症的改善作用及机制。方法 选择敲除共刺激蛋白CD86非肥胖糖尿病背景的小鼠作为糖尿病慢性炎性脱髓鞘性多发性神经根神经病模型,对小鼠进行神经评分;HE染色检测小鼠坐骨神经病理损伤;流式细胞术检测小鼠脾脏CD4^(+)IFN-γ^(+)细胞、CD4^(+)IL-17^(+)细胞、CD4^(+)IL-4^(+)细胞和CD4^(+)CD25^(+)FOXP3^(+)细胞比例;qRT-PCR检测小鼠脾脏单个核细胞IFN-γ、TNF-α、IL-17和IL-10 mRNA表达水平;Western blot检测小鼠脾脏单个核细胞PI3K和p-AKT蛋白表达水平。结果 Polygalacin D降低糖尿病慢性炎性脱髓鞘性多发性神经根神经病小鼠坐骨神经炎症细胞浸润,降低小鼠脾脏CD4^(+)IFN-γ^(+)细胞和CD4^(+)IL-17^(+)细胞比例,增加CD4^(+)IL-4^(+)细胞和CD4^(+)CD25^(+)FOXP3^(+)细胞比例,降低脾脏单个核细胞IFN-γ、TNF-α和IL-17 mRNA表达水平及PI3K和p-AKT蛋白表达水平,增加IL-10 mRNA表达水平。结论 Polygalacin D通过抑制PI3K/AKT信号通路改善糖尿病慢性炎性脱髓鞘性多发性神经根神经病神经炎症。

远志皂苷D通过Wnt/β-catenin信号通路抑制结直肠癌的生长和转移

目的探究远志皂苷D(PGD)对结直肠癌(CRC)的生长和转移的抑制作用,并探究其可能机制。方法不同浓度PGD处理结直肠癌SW620细胞,通过CCK-8检测细胞增殖活性,通过Transwell实验检测细胞迁移和侵袭,通过Western blot检测细胞Wnt/β-catenin信号通路相关蛋白表达;将结肠癌细胞皮下注射于裸鼠并给予PGD,测量肿瘤体积及瘤重,通过免疫荧光检测肿瘤Ki-67表达;β-catenin过表达质粒转染PGD处理后的结直肠癌SW620细胞,通过CCK-8检测细胞增殖活性,通过Transwell实验检测细胞迁移和侵袭。结果PGD剂量依赖地抑制结直肠癌SW620细胞增殖、迁移和侵袭,降低Wnt/β-catenin信号通路相关蛋白p-GSK3β、β-catenin、cyclinD1和c-Myc表达水平;PGD降低结直肠癌SW620细胞肿瘤体积、瘤重及肿瘤组织Ki-67表达;过表达β-catenin促进PGD处理结直肠癌SW620细胞增殖、迁移和侵袭。结论PGD在体外抑制CRC细胞增殖、迁移和侵袭,且在体内抑制CRC细胞移植瘤肿瘤生长,这可能与其抑制GSK-3β磷酸化,从而抑制Wnt/β-catenin信号通路激活有关。