DIA-PRM Proteomic Analysis of Phlegm-Dampness Constitution with Glucolipid Metabolic Disorders by the Intervention of Hua Tan Qu Shi Recipe

Abstract

Background. Phlegm-dampness constitution as one of nine constitutions in traditional Chinese medicine (TCM) has been a high risk factor for glucolipid metabolic disorders (GLMD). Based on our previous findings, Hua Tan Qu Shi recipe (HTQSR) could effectively improve metabolic indicators of GLMD by targeting on phlegm-dampness constitution. However, the proteomic mechanisms of GLMD with the treatment of HTQSR targeting on phlegm-dampness constitution remain unknown. Methods. Clinical participants from phlegm-dampness constitution with the prediabetic state (T), phlegm-dampness constitution with marginally elevated blood lipids (Z), and phlegm-dampness constitution before sickness (W) were included in this study, who orally took HTQSR for 12 weeks and, respectively, marked AT, AZ, and AW. Data-independent acquisition (DIA) and parallel reaction monitoring (PRM) were performed to identify the differential proteins; then, Venn analysis was used to investigate coexpressed and coregulated proteins. In addition, ingenuity pathway analysis (IPA) software was utilized to explore the related pathways and diseases and biofunctions. Results. LXR/RXR activation, acute phase response signaling, and production of nitric oxide and reactive oxygen species in macrophages were obviously activated between the T and AT groups, as well as the Z and AZ groups. In contrast, these three pathways were inhibited between the W and AW groups. Importantly, one coexpressed and coregulated differential protein, B2MG, was validated by PRM among all groups. Conclusions. This work firstly reported the underlying proteomic mechanisms of GLMD with the treatment of HTQSR targeting on phlegm-dampness constitution, indicating that intervention of phlegm-dampness constitution might be a novel strategy for the preventive treatment of GLMD.