Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2021-09-17 , DOI: 10.1016/j.jep.2021.114659 Yunyao Jiang 1 , Yanyan Luo 2 , Xinyi Chen 1 , Nan Liu 3 , Jincai Hou 4 , Jingpei Piao 5 , Chao Song 6 , Chuanling Si 2 , Weicheng Hu 6 , Xueqin Li 7
Ethnopharmacological relevance
Senkyunolide H (SNH) is a bioactive phthalide isolated from Ligusticum chuanxiong Hort rhizome and was reported to have multiple pharmacological effects.
Aim of the study
The study was performed to verify the potency of SNH protecting PC12 cells from oxygen glucose deprivation/reperfusion (OGD/R)-induced injury and to elucidate the underlying mechanisms.
Materials and methods
OGD/R model was established in PC12 cells and the cell viability was measured by MTT assay. The cell morphology was observed using scanning electron microscope (SEM). The potential targets of SNH and related targets of OGD/R were screened, and a merged protein-protein interaction (PPI) network of SNH and OGD/R was constructed based on the network pharmacology analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for pathway analysis. Intracellular cAMP level and the protein expression levels were measured to elucidate the underlying mechanisms.
Results
SNH pretreatment protected PC12 cells against OGD/R-induced cell death. SNH also significantly protected the cell protrusion. A merged PPI network was constructed and the shared candidate targets significantly enriched in cAMP signaling pathway. The level of intracellular cAMP and the protein level of p-CREB, p-AKT, p-PDK1 and PKA protein were up-regulated after the treatment of SNH compared with OGD/R modeling.
Conclusions
The present study indicated that SNH protected PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway.
中文翻译:
Senkyunolide H通过cAMP-PI3K/AKT信号通路保护PC12细胞免受OGD/R诱导的损伤
民族药理学相关性
Senkyunolide H (SNH) 是一种从川芎根茎中分离出的生物活性苯酞,据报道具有多种药理作用。
研究目的
该研究旨在验证 SNH 保护 PC12 细胞免受氧葡萄糖剥夺/再灌注 (OGD/R) 诱导的损伤的效力,并阐明其潜在机制。
材料和方法
PC12细胞建立OGD/R模型,MTT法测定细胞活力。使用扫描电子显微镜(SEM)观察细胞形态。筛选出SNH的潜在靶点和OGD/R的相关靶点,基于网络药理学分析构建了SNH和OGD/R的融合蛋白-蛋白相互作用(PPI)网络。京都基因和基因组百科全书(KEGG)数据库用于通路分析。测量细胞内 cAMP 水平和蛋白质表达水平以阐明潜在机制。
结果
SNH 预处理保护 PC12 细胞免受 OGD/R 诱导的细胞死亡。SNH 还显着保护了细胞突出。构建了一个合并的 PPI 网络,共享的候选靶点在 cAMP 信号通路中显着富集。与 OGD/R 模型相比,SNH 处理后细胞内 cAMP 水平和 p-CREB、p-AKT、p-PDK1 和 PKA 蛋白水平上调。
结论
本研究表明,SNH 通过 cAMP-PI3K/AKT 信号通路保护 PC12 细胞免受 OGD/R 诱导的损伤。