Flavonoids analysis in citrus peels by UPLC-Q-TOF-MS/MS and its antioxidant and anti-inflammation activity

• A total of 51 flavonoid metabolites in nine citrus peels were systematically quantified using UPLC-Q-TOF-MS/MS analysis. • HCA, PCA and OPLS-DA were used to study and characterize flavonoid compounds of nine citrus peels. • Citrus peel flavonoid metabolites remarkedly reducing the generation of ROS, and decreased IL-8, TNF-ɑ, MCP-1and IL-6 RNA transcription in A549 cells. • Gray correlation analysis confirmed (-)-Vestitone, dimefline, eupafolin, and trans-cinnamaldehyde strongly associated with inflammatory variables. Citrus is the world's largest fruit, developed a rich variety resources in a long history of cultivation. Flavonoid is a natural product found widely in citrus plants. In this study, the major flavonoids and relative activities of 9 citrus peels were investigated by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) analysis and antioxidant and anti-inflammatory assays in A549 cell. A total of 51 flavonoids were identified, comprising a variety of subclasses. Notably, Citrus Reticulata Blanco (MJ) and Bu Zhi Huo (CJ) demonstrated distinctive flavonoid profiles. Flavonoid extracts from MJ and Citrus maxima (HY) peels significantly reduced reactive oxygen species (ROS) generation and decreased the levels of cytokines (IL-8, TNF-α, MCP-1, and IL-6) in A549 cells. Furthermore, these extracts up-regulated the expression of Nrf2 and HO-1 and inhibited the phosphorylation of p65 and NF-κB activity. Gray correlation analysis identified (-)-vestitone, dimefline, eupafolin, and trans-cinnamaldehyde as strongly associated with inflammatory markers. The findings suggest that flavonoids extracted from citrus peels possess significant antioxidant and anti-inflammatory activities, highlighting their potential as natural therapeutic agents for combating inflammation.