Herb-Derived Compounds From Radix Salviae Decoction (RSD) Modulated Cell Death Of Vascular Smooth Muscle Cells
Description
Research Hypothesis The study hypothesized that herb-derived compounds from Radix Salviae Decoction (RSD) could modulate cell death of vascular smooth muscle cells (VSMC) through specific mechanisms. Specifically, it was hypothesized that these compounds might influence various forms of cell death, including pyroptosis, autophagy, and apoptosis, thereby affecting the function and survival of VSMC. Data Description and Collection The data was collected through a combination of network pharmacological analysis and in vitro experiments. The network pharmacological analysis involved identifying targets for three compounds from RSD (Tanshinone ⅡA (DST), Santalol (TXC), and Bornyl ester (LNZ)) and three types of cell death (pyroptosis, autophagy, and apoptosis) using literature and databases. A protein-protein interaction network was constructed using String, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore pathways affecting vascular smooth muscle cell death. In vitro experiments were conducted on VSMC in serum-free medium (SFM) conditions. The effects of RSD-derived compounds on cell death were assessed using various methods, including measuring mRNA levels of specific genes (GSDMD, GSDME, IL-1β, ATG12), determining the LC3-II/I ratio, and using flow cytometry to assess early apoptotic cells. Additionally, the levels of cytokines (IL-6 and TNF-α) were measured, and the activity of cell signaling pathways (PI3K-AKT and NF-κB) was evaluated. Data Interpretation The data showed that treatment with RSD-derived compounds significantly promoted pyroptosis of VSMC, as evidenced by increased mRNA levels of GSDMD and GSDME, as well as increased IL-1β mRNA levels. These compounds also inhibited autophagy by reducing ATG12 expression and decreasing the LC3-II/I ratio. Furthermore, they decreased the proportion of early apoptotic cells and notably inhibited the production of IL-6 and TNF-α. In terms of cell signaling, the compounds suppressed the PI3K-AKT pathway while activating the NF-κB signaling pathway. Notable Findings The notable findings include the identification of key proteins (CASP8, CASP3, TP53, JUN, and BAX) that play central roles in the protein interaction networks related to cell death modulation by RSD-derived compounds. These proteins are involved in various pathways affecting VSMC death, suggesting potential therapeutic targets for cardiovascular diseases.