Institute for Chinese Materia Medica, School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
Tianjin Key Laboratory of Pulp & Paper, Tianjin University of Science & Technology, Tianjin, 300457, China.
J Ethnopharmacol. 2022 Jan 10;282:114659. doi: 10.1016/j.jep.2021.114659. Epub 2021 Sep 17.
Senkyunolide H (SNH) is a bioactive phthalide isolated from Ligusticum chuanxiong Hort rhizome and was reported to have multiple pharmacological effects.
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.
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.
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.
The present study indicated that SNH protected PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway.
川芎嗪 H（SNH）是从川芎根茎中分离得到的一种具有生物活性的苯酞类化合物，据报道具有多种药理作用。
本研究旨在验证 SNH 对 PC12 细胞在氧葡萄糖剥夺/再灌注（OGD/R）损伤中的保护作用，并阐明其潜在机制。
在 PC12 细胞中建立 OGD/R 模型，通过 MTT 法测定细胞活力。用扫描电子显微镜（SEM）观察细胞形态。筛选 SNH 的潜在靶点和 OGD/R 的相关靶点，并基于网络药理学分析构建 SNH 和 OGD/R 的合并蛋白-蛋白相互作用（PPI）网络。京都基因与基因组百科全书（KEGG）数据库用于通路分析。测定细胞内 cAMP 水平和蛋白表达水平，以阐明潜在机制。
SNH 预处理可防止 PC12 细胞免受 OGD/R 诱导的细胞死亡。SNH 还显著保护细胞突起。构建了一个合并的 PPI 网络，共享的候选靶点显著富集在 cAMP 信号通路中。与 OGD/R 建模相比，SNH 处理后细胞内 cAMP 水平和 p-CREB、p-AKT、p-PDK1 和 PKA 蛋白的蛋白水平升高。
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。
