ABSTRACT
OBJECTIVES@#To investigate the mechanism of comorbidity between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) based on metabolomics and network pharmacology.@*METHODS@#Six ApoE－/－ mice were fed with a high-fat diet for 16 weeks as a comorbid model of NAFLD and AS (model group). Normal diet was given to 6 wildtype C57BL/6J mice (control group). Serum samples were taken from both groups for a non-targeted metabolomics assay to identify differential metabolites. Network pharmacology was applied to explore the possible mechanistic effects of differential metabolites on AS and NAFLD. An in vitro comorbid cell model was constructed using NCTC1469 cells and RAW264.7 macrophage. Cellular lipid accumulation, cell viability, morphology and function of mitochondria were detected with oil red O staining, CCK-8 assay, transmission electron microscopy and JC-1 staining, respectively.@*RESULTS@#A total of 85 differential metabolites associated with comorbidity of NAFLD and AS were identified. The top 20 differential metabolites were subjected to network pharmacology analysis, which showed that the core targets of differential metabolites related to AS and NAFLD were STAT3, EGFR, MAPK14, PPARG, NFKB1, PTGS2, ESR1, PPARA, PTPN1 and SCD. The Kyoto Encyclopedia of Genes and Genomes showed the top 10 signaling pathways were PPAR signaling pathway, AGE-RAGE signaling pathway in diabetic complications, alcoholic liver disease, prolactin signaling pathway, insulin resistance, TNF signaling pathway, hepatitis B, the relax in signaling pathway, IL-17 signaling pathway and NAFLD. Experimental validation showed that lipid metabolism-related genes PPARG, PPARA, PTPN1, and SCD were significantly changed in hepatocyte models, and steatotic hepatocytes affected the expression of macrophage inflammation-related genes STAT3, NFKB1 and PTGS2; steatotic hepatocytes promoted the formation of foam cells and exacerbated the accumulation of lipids in foam cells; the disrupted morphology, impaired function, and increased reactive oxygen species production were observed in steatotic hepatocyte mitochondria, while the formation of foam cells aggravated mitochondrial damage.@*CONCLUSIONS@#Abnormal lipid metabolism and inflammatory response are distinctive features of comorbid AS and NAFLD. Hepatocyte steatosis causes mitochondrial damage, which leads to mitochondrial dysfunction, increased reactive oxygen species and activation of macrophage inflammatory response, resulting in the acceleration of AS development.
Subject(s)
Animals , Mice , Non-alcoholic Fatty Liver Disease/metabolism , Cyclooxygenase 2/metabolism , PPAR gamma/metabolism , Reactive Oxygen Species/metabolism , Mice, Inbred C57BL , Hepatocytes , Macrophages/metabolism , LiverABSTRACT
As one of the classic prescriptions of traditional Chinese medicine， Didangtang is an effective prescription for breaking and expelling blood stasis. It was considered that Didangtang damage the healthy qi and contained toxic Chinese medicinal materials such as leeches and gadflies， and thus it was rarely used. However， as the attention to classic prescriptions increases， Didangtang has been widely used in clinical practice and demonstrated definite efficacy in treating diabetes mellitus and its complications， malignant tumors， Alzheimer's disease， stroke， renal diseases， cardiovascular diseases， peripheral vascular diseases， gynecological disease， and male diseases according to the disease location， pathogenesis， symptoms， and pharmacological effects. Didangtang has the effects of mitigating insulin resistance， improving microvascular and peripheral vascular circulation， delaying diabetic macrovascular lesions， preventing vascular fibrosis， improving immunity， inhibiting tumor growth， protecting the brain tissue， nerve cells， vascular endothelial function， and kidney， reducing inflammation， and delaying aging. This paper summarizes the clinical application of Didangtang and initially explores the underlying mechanism.
ABSTRACT
Objective:To evaluate the clinical effect of Guanxin Tongmai plaster combined with conventional western medicine in the treatment of phlegm and blood stasis syndrome of coronary heart disease and angina pectoris.Methods:A total of 60 patients in the Department of Cardiology of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine (TCM) from February to August 2020 who met the inclusion criteria were randomly divided into two groups with 30 in each group. Both groups were treated with conventional western medicine. On this basis, Guanxin Tongmai plaster was applied at the acupoints in the treatment group and placebo plaster was applied in the control group. TCM syndrome score was performed before and after treatment, angina score was evaluated from three aspects of angina attack frequency, duration and pain degree, and blood lipid TG, TC, LDL-C and HDL-C were detected by enzyme quantitative method. The blood homocysteine (Hcy) was detected by enzyme circulation method, the ECG and the nitroglycerin reduction rate were recorded, and the safety index was detected according to the ECG changes.Results:In the treatment period, 2 patients in the treatment group fell off, 3 in the control group. A total of 28 patients in the treatment group and 27 in the control group were analyzed. The total effective rate of ECG efficacy in the treatment group was 67.9% (19/28) and the control group was 48.1% (13/27). There was significant difference between the two groups ( χ2=4.46, P=0.040). After treatment, the TCM syndrome score and angina score in the treatment group were significantly lower than those in the control group ( t values were 9.12 and 4.45, P values were 0.004 and 0.042, respectively). The reduction rate of nitroglycerin in the treatment group was 82.1% (23/28) and 55.6% (15/27) in the control group. There was significant difference between the two groups ( χ 2=4.72, P=0.030). After treatment, the plasma TG, TC, LDL-C in the treatment group were significantly lower than those in the control group ( t values were 4.17, 6.57 and 6.52, P<0.05 or P<0.01), the level of HDL-C was significantly higher than that of the control group ( t=7.07, P=0.010), and the level of plasma Hcy was significantly lower than that in the control group ( t=6.70, P=0.012). There was no significant difference in liver, kidney and coagulation function between the two groups. Conclusion:Guanxin Tongmai plaster combined with conventional western medicine can improve the clinical symptoms of patients with coronary heart disease and angina pectoris, reduce the level of blood lipid and Hcy, and improve the clinical curative effect.