Discover the Active Constituents and Mechanism of Yiqi Qubai Decoction (YQD) in Treating Vitiligo based on Serum Pharmacochemistry Combining Network Pharmacology, Molecular Docking and Zebrafish Experiment

Abstract

Yiqi Qubai Decoction (YQD) is composed of four herbs, namely, Astragalus propinquus Schischkin, Akebiae Fructu, Leonuri Fructus, and Caragana Sinica Roots. For decades, the decoction has been utilized in the form of granules for the treatment of vitiligo in China, with a remarkable curative result and widespread recognition among patients. However, the chemical contents and active substances of YQD absorption into the plasma, as well as its mechanism of vitiligo treatment, remain unknown. This problem was solved based on serum pharmacochemistry combining network pharmacology, molecular docking, and zebrafish experiments. First, the chemical components of YQD in vitro and the absorption components in rat plasma were identified using UPLC-Q-TOF/MS. Second, network pharmacology was integrated with molecular docking analysis to reveal the active ingredients and a putative mechanism for YQD vitiligo treatment. Finally, an in vivo zebrafish experiment validated the impact of enhancing melanin synthesis. A total of 44 chemical constituents and 36 absorption compounds, consisting of 4 prototype components and 32 metabolites were identified. Network pharmacology studies demonstrated that apigenin, astraisoflavan, akebia saponin D, genkwanin glucuronidation metabolites, and apigenin-glucuronidation metabolites might be the key active components of YQD for the treatment of vitiligo, while AKT1, mTOR, and MAPK1 may serve as the key targets. The main functional pathways involving these key targets include PI3K-AKT-mTOR, PI3K-AKT-FoxO, and MAPK signaling pathways. Molecular docking analysis found that the active components have a high affinity for AKT1, MAPK1, and mTOR. YQD could accelerate the new generation of melanin in zebrafish, which is of great significance for treating vitiligo. Our research not only looked at the absorptive and possibly useful ingredients and mechanisms of YQD for treating vitiligo, but it also confirmed the anti-vitiligo impact and served as a reference for further research, development, and application of YQD.