Berberis kaschgarica Rupr. fruits (BKF) can reduce blood pressure, regulate blood lipid levels, and exert anti-inflammatory and anti-oxidative effects. Additionally, alkaloids are among the active components in BKF. Sensitive and selective high-performance liquid chromatography with mass spectrometry, network pharmacology, and bioinformatic analysis was conducted. We identified 544 metabolites and 105 secondary metabolites from BFK. Among the secondary metabolites, 24 were alkaloids. Moreover, there were 583 potential drug targets and 4,481 human anti-atherosclerosis targets. Finally, 366 intersecting targets of BFK against atherosclerosis were identified. These targets were enriched in 546 terms in biological processes, 48 terms in cell components, 121 terms in molecular functions, and 36 signaling pathways. Notably, 18 of the 24 alkaloids were fat-soluble alkaloids (FSA), and the remaining 6 were water-soluble alkaloids (WSA). Because oxyberberine (OBB) was predicted to have an ideal anti-atherosclerosis effect and was further studied. We established four intervention groups: FSA, WSA, total alkaloids (TA), and OBB. The effects of these alkaloids on caspase-11-induced pyroptosis and TLR4-induced inflammation in LPS-stimulated mouse macrophages in vitro were explored. The anti-pyroptosis results demonstrated significant evaluation in caspase-11, caspase-1, IL-1β, IL-18, and, GSDMD. Additionally, there were significant decreases in MMP3 and MMP9 in the supernatant, as well as the expression of TLR4 and pSTAT3. Conclusively, BKF contains numerous effective components, making it a valuable natural medicinal material with substantial developmental and utilitarian potential. In in vitro experiments, the alkaloids from BKF can reduce the LPS-induced expression of caspase-11 and GSDMD. Compared with previous studies on BKF, which had gaps in systematic identification of bioactive subtypes via basic colorimetry and unclear anti-AS mechanisms. our study advances research by using UPLC-MS/MS for the first time to identify 544 metabolitesin BKF, establishing a comprehensive metabolite profile and integrating network pharmacology and in vitro assays to first link BKF alkaloids to regulating caspase-11-mediated pyroptosis and TLR4-induced inflammation. Moreover, our findings contribute to compositional innovation, mechanistic breakthroughs, and translational value.
Ainiwaer et al. (Mon,) studied this question.