Ginsenoside Compound K Assisted G-Quadruplex Folding and Regulated G-Quadruplex-Containing Transcription

Ginsenoside compound K (CK) is one of the major metabolites of the bioactive ingredients in Panax ginseng, which presents excellent bioactivity and regulates the expression of important proteins. In this work, the effects of CK on G-quadruplexes (G4s) were quantitatively analyzed in the presence and absence of their complementary sequences. CK was demonstrated to facilitate the formation of G4s, and increase the quantity of G4s in the competition with duplex. Thermodynamic experiments suggested that the electrostatic interactions were important for G4 stabilization by CK. CK was further found to regulate the transcription of G4-containing templates, reduce full-length transcripts, and decrease the transcription efficiency. Our results provide new evidence for the pharmacological study of ginsenosides at the gene level.

Biochemical Targets and Molecular Mechanism of Ginsenoside Compound K for Treating Osteoporosis Based on Network Pharmacology

Ginsenosides have been proven to be potential beneficial in treatment of osteoporosis. To investigate the potential of ginsenosides in osteoporosis, ginsenoside compound K (GCK) was selected to explore the potential therapy targets and mechanism based on network pharmacology (NP). 206 and 6590 targets were obtained for GCK and osteoporosis, respectively, in which 138 targets were identified as co-targets of GCK and osteoporosis based on intersection analysis. Five central gene clusters and hub genes (STAT3, PIK3R1, VEGFA, JAK2 and MAP2K1) were identified through protein-protein interaction network analysis. Gene Ontology (GO) enrichment implied that phosphatidylinositol-related biological process, molecular modification and function may play an important role for GCK in treatment and prevention of osteoporosis. Functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that 16 targets were enriched in the osteoclast differentiation. Also, except for being identified as hub targets, MAPK and phosphatidylinositol-related proteins were enriched in the downstream signaling of c-Fms in the osteoclast differentiation pathway. Molecular docking further confirmed that GCK could interact with active cavity on the surface of c-Fms (osteoclast differentiation-related membrane receptor), and their complex could be stabilized by three H-bonds with residues including Glu 664 (3.19 Å), Glu 664 (2.62 Å) and Cys 666 (2.78 Å). Summarily, GCK could interfere the occurrence and progress of osteoporosis through c-Fms-mediated MAPK and phosphatidylinositol-related signaling regulating osteoclast differentiation.