Network pharmacology and untargeted metabolomic-based investigation of anti-osteoporotic effects of viscozyme-assisted polysaccharide from Portulaca oleracea L.

Osteoporosis is a metabolic bone disease closely associated with oxidative stress. We had previously confirmed that the Viscozyme-assisted polysaccharide from Portulaca oleracea L (VPOP1) protects against antioxidant stress and evaluated the structure of VPOP1. In this study, we aimed to explore the anti-osteoporotic effects of VPOP1 on H2O2-induced osteoblast apoptosis. In addition, untargeted zebrafish metabolomics based on UPLC-Q-Orbitrap-HRMS was used to investigate the potential anti-osteoporotic mechanisms of VPOP1. The levels of Bcl-2 decreased significantly and those of caspase-3, Bax, and cytochrome C increased after treatment with H2O2. VPOP1 inhibited apoptosis in H2O2-induced MC3T3 cells. Metabolomic analyses showed that 28 potential biomarkers were gradually restored to normal levels after treatment with VPOP1 compared with that in the model group. Among them, leukotrienes D4 and A4, L-dopa, and L-tyrosine are important biomarkers and therapeutic targets. Pathway analysis revealed that arachidonic acid, tyrosine, phenylalanine, and sphingolipid metabolism were the major intervening pathways. Collectively, these results help us understand the protective activity of large molecular weight compounds, such as VPOP1, against osteoporosis.