Effects of Erchen Decoction on Oxidative Stress-Related Cytochrome P450 Metabolites of Arachidonic Acid in Dyslipidemic Mice with Phlegm-Dampness Retention Syndrome: A Randomized, Controlled Trial on the Correspondence between Prescription and Syndrome

Abstract

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.

Erchen Decoction Alleviates High-Fat Diet + AOM/DSS-Induced CRC by Ameliorating Cholesterol-Bile Acid Metabolism Disorder through Regulating FXR and the Gut Microbiota

“…ECD is a multicomponent traditional Chinese medicine formula that is commonly employed in clinical settings to treat ailments stemming from the accumulation of phlegm dampness, including obesity, diabetes, hypertension, hyperlipidemia, and fatty liver [31]. According to recent reports, ECD can effectively treat hyperlipidemia and is widely used in clinical and basic research to ameliorate the metabolic abnormalities of a high-fat diet [32,33]. Moreover, ECD can be combined with other decoctions, such as Huiyanzhuyu decoction to induce apoptosis of laryngeal squamous cell carcinoma cells, Linguizhugan decoction to ameliorate hepatic insulin resistance, and Sanziyangqin decoction for chronic obstructive pulmonary disease, to demonstrate cancer suppression [34][35][36][37][38].…”

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms

“…Phlegm is similar to the modern medical term hyperlipidaemia and hypercoagulable states, which are the most important risk factors for IS (Song et al, 2019). Lipids from the blood can seep through the endothelial spaces or damaged areas and remain in the various layers of the blood vessels, gradually forming lipid streaks and cholesterol crystals, which are equivalent to phlegm in TCM (Chen et al, 2023). The damage to the intima activates pro‐coagulant substances and inhibits anti‐coagulant substances, causing strong vasoconstriction and platelet aggregation, which is equivalent to blood stasis in TCM (Bi et al, 2019).…”

Study on the Mechanism of Huanglian Jiedu Decoction in Treating Dyslipidemia Based on Network Pharmacology

“…Many herbs such as Rhizoma Coptidis (Huanglian), Radix Scutellariae (Huangqin), Rheum officinale (Dahuang), red yeast rice (Hongqu), and Fructus Crataegi (Shanzha) are frequently used in the treatment of hyperlipidemia and achieve significant effects in regulating blood lipids [ 7 ]. Many herbal formulas such as Da Chaihu decoction [ 8 ], Erchen decoction [ 9 ], Gegen Qinlian decoction [ 10 ], and Wendan decoction [ 11 ] also regulate dyslipidemia. These data suggest that TCM medications have a good effect on treating dyslipidemia.…”