Salvianic Acid A Sodium

Rosmarinic acid (RA) is a natural polyphenolic compound with various biological and pharmaceutical activities. Due to the limited availability in plant sources and the complexity of its chemical synthesis, the biosynthesis of RA shows great potential. However, few studies have investigated RA biosynthesis in S. cerevisiae, and inhibitory effects from its biosynthesis on intrinsic metabolic pathways remain unclear. In this study, RNA-seq technology was employed to investigate the stress response of S. cerevisiae to RA and its precursors (caffeic acid, CA and salvianic acid, SAA). The results revealed an increased inhibitory effect with a variation number of differentially expressed genes (DEGs): 338 for 200-mg/L SAA, 510 for 200-mg/L CA, and 934 for 200-mg/L RA. Furthermore, trends analysis of DEGs expression level uncovered similar stress response patterns of S. cerevisiae under RA and SAA, indicating a shared inhibition mechanism. Common response pathways, including ribosome biogenesis, RNA polymerase biosynthesis, and purine and pyrimidine metabolism, were elucidated. Additionally, common regulated genes (HSP12, PAU4, TIR3) and different regulated genes (UTP6, NAN1, IMP4) in aforementioned pathways were identified. Unique genes and pathways were also mapped to reveal the special response mechanism to different polyphenolic acids, such as oxidative phosphorylation for RA and amino acid metabolism for CA. Overall, this work provides a foundation for understanding transcriptomic response of yeast to RA and RA biosynthesis.

Senile osteoporosis (SOP) seriously disturbs the life of elder people. Inhibition of autophagy can contribute to the progression of SOP. Meanwhile, Salvianic acid A (SA) could inhibit the progression of SOP, and it could regulate the autophagy. However, the relationship between SA and autophagy in SOP remains to be further explored.

Bone marrow mesenchymal stem cells (BMSCs) were isolated from senescence-accelerated mouse propensity 6 (SAMP6) mice. Then, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were performed to analyze the osteogenesis in BMSCs. Meanwhile, protein levels were investigated using Western blot. The binding between Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) and Rubicon was investigated using Co-IP. ChIP and Dual-luciferase assay were used to explore the binding between bromodomain-containing protein 4 (BRD4) and ARIH1 promoter region.

The levels of BRD4, Rubicon and p62 were upregulated in BMSCs from SAMP6 mice, while ARIH1, Beclin1, ATG5 and the ratio of LC3II/LC3I were downregulated. SA could promote the osteogenesis of BMSCs through mediating the autophagy. In addition, SA dose-dependently upregulated the levels of OPN, OCN and Runx2 in BMSCs from SAMP6 mice. ARIH1 could degrade Rubicon through ubiquitination, and BRD4 could transcriptionally inhibit the expression of ARIH1. Meanwhile, SA obviously promoted the autophagy and osteogenesis in BMSCs through mediation of BRD4/ARIH1/Rubicon axis.

SA promoted osteogenic differentiation of BMSCs in senile osteoporosis through BRD4/ARIH1/Rubicon axis. Thus, our study might provide a new theoretical basis for developing the new strategies against SOP in clinic.