Ji Yao, Li Zhang, Zezhi Zhou, Jiqiang Liu, Jie Cheng, Fan Long and Ting Yuan* Pages 1 - 19 ( 19 )
Introduction: In this study, the molecular mechanisms through which Lascorbate (Vitamin C) potentially treats Chronic Obstructive Pulmonary Disease (COPD) were identified. A non-targeted metabolomics analysis revealed metabolic disorders and significantly reduced levels of L-ascorbate in COPD patients compared to healthy subjects.
Method: The COPD rat model was established by exposing them to Cigarette Smoke (CS). The L-ascorbate intervention reduced lung inflammation and histological damage in COPD rat models. Network pharmacology analysis revealed 280 common targets between L-ascorbic acid (drug) and COPD (disease), of which seven core targets were MMP3, MME, PCNA, GCLC, SOD2, EDN1, and EGF. According to molecular docking prediction, L-ascorbate had the highest affinity with EGF. Molecular dynamics simulation indicated relatively stable EGF and L-ascorbate complexes.
Results: The PI3K/AKT signaling pathway was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analysis.
Conclusion: Finally, the in vivo and in vitro experiments confirmed that L-ascorbate affected COPD by regulating the EGF/PI3K/AKT pathway. In summary, based on network pharmacology and molecular docking analyses, this study revealed that L-ascorbate affects COPD development by regulating the PI3K/AKT signaling pathway through EGF, and thus contributes to the understanding and clinical application of Lascorbate in the treatment of COPD.
Chronic obstructive pulmonary disease, L-ascorbate, non-targeted metabolism, network pharmacology, molecular docking.