Biomarkers based on multiplatform comprehensive analysis: A systematic analysis of Geng‐Nian‐Shu in perimenopausal syndrome

Abstract

Although Geng‐Nian‐Shu has been shown to be clinically effective in perimenopausal syndrome, its active components and mechanism have not yet been elucidated. To demonstrate the mechanism‐based biomarkers of Geng‐Nian‐Shu in treating perimenopausal syndrome, a total of 135 chemical constituents including 52 prototype blood constituents were identified via high‐performance liquid chromatography‐quadrupole‐time of flight/mass spectrometry. Then, network pharmacology showed significant enrichment for the PhosphoInositide‐3 Kinase/Akt pathway, suggesting that it may be the main regulatory pathway for the Geng‐Nian‐Shu treatment of the perimenopausal syndrome. Subsequently, multivariate analysis was performed between the Geng‐Nian‐Shu sham‐treated and Geng‐Nian‐Shu ovariectomy‐treated groups and further screened out 18 prototype blood constituents by correlation analysis with plasma estrogen levels to identify potential biomarkers associated with Geng‐Nian‐Shu treat the ovariectomy‐induced perimenopausal syndrome. Finally, the results of pharmacological experimental verification and Pearson correlation analysis indicated that catalpol, ligustilide, paeoniflorin, and gallic acid were selected as biomarkers of Geng‐Nian‐Shu which were strongly and positively correlated with PhosphoInositide‐3 Kinase/Akt signaling pathway. In this study, based on high‐performance liquid chromatography‐quadrupole‐time of flight/mass spectrometry combined with pharmacodynamics, network pharmacology, pharmacology, and other disciplines, we explored the effects and mechanisms of Geng‐Nian‐Shu in the treatment of perimenopausal syndrome at multiple levels. Using multiplatform technology to investigate the role of Geng‐Nian‐Shu represents a new strategy for the selection and verification of biomarkers of Geng‐Nian‐Shu and provides a basis for further development and utilization of Geng‐Nian‐Shu.