Comprehensive Metabolomics and Network Pharmacology Reveal the Mechanism of Antioxidant Activities of Chimonanthus Praecox Chemical Components

Chimonanthus praecox (Linn.) has long been used in traditional Chinese medicine, yet there remains uncertainty regarding its specific antioxidant components and their functional mechanisms. Using broad-target metabolomics technology with ultra-performance liquid chromatography coupled with tandem mass spectrometry, this research comprehensively characterizes the chemical constituents of C. praecox and assesses its antioxidant potential through in vitro experiments. Through the integration of network pharmacology, we explored the mechanisms of action of the antioxidant components of C. praecox, and further validated the network predictions through molecular docking. The findings identified 2,176 secondary metabolites across three varieties of C. praecox, with significant differences in flavonoids, phenolic acids, and lignans among them. In vitro antioxidant tests revealed strong antioxidant capacities in C. praecox flowers. Network pharmacology analysis identified 384 chemical components from traditional Chinese medicine, along with 148 active substances and 761 corresponding targets. These targets encompassed 2,148 disease targets, with 342 intersection targets and 18 core targets identified. This analysis involved 319 gene function entries and 136 pathways (P<0.05). Topological analysis identified core components such as secoisolariciresinol, isolariciresinol, 3-methylkaempferol, targeting estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC), RAC-alpha serine/threonine-protein kinase (AKT1), and mitogen-activated protein kinase 3 (MAPK3). The antioxidant mechanism of C. praecox secondary metabolites involves multiple components, targets, and pathways. It potentially entails the upregulation of AKT1 and ESR1 antioxidant-related protein expression, downregulation of EGFR, MAPK3, and SRC oxidative stress-related protein expression, and activation of signal pathways associated with EGFR tyrosine kinase inhibitor resistance, estrogen signaling pathway, chemical carcinogenesis-receptor activation, lipid and atherosclerosis, prostate cancer, among others, to achieve antioxidant effects. These findings present a theoretical basis for further exploration and application of the antioxidant properties exhibited by C. praecox.