Phlegm-dampness retention (PDR) syndrome is one of the main syndromes of dyslipidemia. This study investigated the effects of Erchen decoction (ECD) on concentrations of two oxidative stress-related cytochrome P450 (CYP450) metabolites of arachidonic acid—14,15-dihydroxyeicosatrienoic acid (14,15-DHET) and 20-hydroxyeicosatetraenoic acid (20-HETE)—in mice with dyslipidemia and phlegm-dampness retention (PDR) syndrome (n = 5 C57BL/6J mice and n = 30 apolipoprotein E knockout mice). Murine models of the disease and syndrome were established using multifactor stimulation. Then, all mice were assigned to normal, model, low- (L-), medium- (M-), or high- (H-) dose ECD groups or to a control or an unmatched prescription-syndrome (unmatched P-S) group; five mice were included in each group. Dose formulations were administered by oral gavage for 30 days to animals in the corresponding groups. We detected and analyzed hematoxylin and eosin (HE) staining characteristics of the mouse aorta and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), peroxynitrite (ONOO-), 14,15-DHET, and 20-HETE concentrations in each group. TC and LDL-C concentrations significantly decreased in the M-ECD versus control group ( P < 0.05 ); however, the TC and LDL-C concentrations were not significantly different in the unmatched P-S versus model group ( P > 0.05 ). After treatment in the P-S correspondence groups (L-ECD, M-ECD, and H-ECD groups), the concentration of ONOO- decreased to different degrees in each group. Among these groups, the concentration of ONOO- significantly decreased in the L-ECD, M-ECD, and H-ECD groups versus the model group ( P < 0.05 ). However, the concentration of ONOO- was not significantly different in the unmatched P-S versus the model group ( P > 0.05 ). From the perspective of aortic HE staining, the P-S group experienced an improved endothelium structure after treatment. 14,15-DHET concentrations significantly increased in the normal, M-ECD, and H-ECD groups versus the model group; in the H-ECD versus the L-ECD group; and in the H-ECD versus the control group (all P < 0.05 ) to various extents after different doses of the prescription. 20-HETE concentrations pronouncedly decreased in the M-ECD versus normal group; in the M- and H-ECD groups versus the model group; in the M-ECD versus the L-ECD group; in the M-ECD versus the control group; and in the M-ECD versus the unmatched P-S ( P < 0.05 ). However, the concentrations of 14,15-DHET and 20-HETE in the model group were not significantly different from those of the unmatched P-S ( P > 0.05 ). In this study, ECD reversed blood lipid indexes and ameliorated oxidative stress-related metabolites, elevating serum 14,15-DHET and lowering serum 20-HETE in mice with dyslipidemia and PDR syndrome via CYP450 pathways of arachidonic acid metabolism. The efficacy of ECD relies on correspondence between the prescription and the syndrome. These findings scientifically validate the treatment according to traditional Chinese medicine syndrome differentiation. ECD can strengthen the protective effect on the vascular endothelium by driving out pathogenic factors and strengthening healthy resistance. Its efficacy may be related to the adjustment of the polarization state of macrophages.

Background: ‘Treating the same disease with different methods’ is a Traditional Chinese Medicine (TCM) therapeutic concept. That means although patients are diagnosed with the same disease, they may have different syndromes that require distinct drug administrations. This study aimed to identify the differentially expressed genes and related biological processes in dyslipidemia with the Phlegm-Dampness Retention (PDR) syndrome and the Spleen and Kidney Yang Deficiency (SKYD) syndrome using transcriptomic analysis.Methods: Ten ApoE knockout (ApoE-/-) mice were used for the establishment of dyslipidemic disease-syndrome models via multifactor-hybrid modeling, with 5 in the the PDR group and 5 in the SKYD group. Five C57BL/6J mice were employed as normal controls (NC) group. Test model quality. Aortic endothelial macrophages in mice were screened using flow cytometry. Transcriptomic analysis was performed for macrophages using RNA-Seq.Results: ①The quality assessment of the disease-syndrome model showed that TG, TC, and LDL-C levels significantly increased in the PDR and SKYD groups versus the NC group (P < 0.05). Combined with HE staining of aorta, the disease model was successfully established. ②The quality assessment of the syndrome models showed that mice in the PDR group presented with typical manifestations of the PDR syndrome, and mice in the SKYD group had the related manifestations of the SKYD syndrome, indicating that the syndrome models were successfully constructed. ③After comparing the differentially expressed gene (DEG) expressions in macrophages in dyslipidemia mice with different syndromes, 4142 genes were identified with statistical significance (P < 0.05). The Gene Ontology (GO) analysis for the DEGs showed that biological process of difference between PDR group and SKYD group include both adverse and protective processes were included.Conclusion: The DEGs between the PDR syndrome and the SKYD syndrome indicate different biological mechanisms between the onset of the two syndromes. They have distinctive biological processes, including adverse and protective processes, corresponding to the invasion of pathogenic factors into the body and the fight of healthy qi against pathogenic factors, respectively, in the TCM theory. Our results have demonstrated the biological evidence behind ‘treating the same disease with different treatments’ in TCM.