ABSTRACT
In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)-based liver metabolomics approach was used to explore the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in improving atherosclerosis(AS) of mice with apolipoprotein E gene knockout(ApoE~(-/-)). AS mouse model was induced by high-fat diet. The pathological and biochemical indexes such as the histopathological changes, body weight, liver weight, blood lipid level and inflammatory factors in the liver of mice were determined. The metabolic profiling of mice liver samples was performed with UPLC-Q-TOF-MS. Multiple statistical analysis methods including partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to screen and identify biomarkers. The levels of related enzymes including LCAT, sPLA2, EPT1 and ACER1 were detected. The results showed that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" significantly reduced the areas of aortic plaque and fat vacuoles of liver in AS mice and decreased the accumulation of lipid droplets and liver coefficient. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" also regulated the levels of blood lipid and inflammatory injury in the liver. The metabolites of the control group, the model group and the "Trichosanthis Fructus-Allii Macrostemonis Bulbus" group could be distinguished significantly. Fifteen potential biomarkers related to AS were discovered and preliminarily identified, seven of which could be regulated by "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in a trend of returning to normal. Metabolic pathway analysis screened out two major metabolic pathways. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" obviously regulated the levels of LCAT, sPLA2, EPT1 and ACER1. It was inferred that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" could play a major role in AS treatment by regulating glycerophospholipid and sphingolipid metabolism disorders in the liver, with the mechanism probably relating to the intervention of the expression of LCAT, sPLA2, EPT1 and ACER1.
Subject(s)
Animals , Mice , Apolipoproteins E/genetics , Atherosclerosis/genetics , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Liver , MetabolomicsABSTRACT
Objective:Based on the hyperlipidemia rat model and network pharmacology technology, the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia was analyzed. Method:The levels of blood lipids and inflammatory factors were measured through prophylactic administration of low, medium and high-dose Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs in hyperlipidemia rats. The active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs were screened out through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and text mining. The targets of active ingredients screened through the Swiss Target Prediction, Similarity ensemble approach (SEA), DrugBank database. The disease targets were collected through Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), DrugBank, DisGeNET database. The targets of active ingredients and disease target were integrated, and screened through topological parameters to gain the main candidate targets of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the gene ontology (GO) functional enrichment analysis were conducted through ClueGO and Database for Annotation, Visualization and Integrated Discovery (DAVID), respectively. The traditional Chinese medicine-chemical ingredient-target network model, and the target-pathway network model were constructed through Cytoscape, and their crosstalk target and signal pathway were analyzed. Result:Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia, increased high-density lipoprotein (HDL-C) levels, and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). According to the findings, 27 active ingredients, such as mandenol, diosmetin and α-spinasterol, might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs, 16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways, main targeting apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL), low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism, bile secretion, peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level, targeting tumor necrosis factor (TNF), IL-6, interleukin-1β (IL-1β), mitogen-activated protein kinase 1 (MAPK1), C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway, interleukin-17 (IL-17) signaling pathway, and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level. The DAVID database for GO enrichment analysis showed that the hyperlipidemia was treated mainly through biological processes, such as inflammation, lipid localization, storage and lipid metabolism. Conclusion:These findings can predict the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia, and provide a theoretical basis for the material basis and clinical application of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs.
ABSTRACT
Objective To investigate the clinical efficacy of superficial needling therapy for early ankylosing spondylitis and its effect on tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6).Methods Eighty patients with early ankylosing spondylitis meeting the inclusion criteria were randomly allocated to treatment and control groups using random number card method with the ratio of 1:1, 40 cases each. The treatment group received superficial needling therapy alone and the control group, conventional treatment with celecoxib capsules, methotrexate tablets and sulfasalazine enteric-coated tablets. Treatment was given for a total of 24 weeks. Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), lumbago, TCM syndrome score, TNF-α, IL-1 and IL-6 were observed in the two groups before and after treatment.Results The BASDAI, BASFI, lumbago, TCM syndrome score, TNF-α, IL-1 and IL-6 improved in the two groups after treatment compared with those before the treatment (P<0.05). The BASDAI, BASFI, lumbago, TCM syndrome score, TNF-α, IL-1 and IL-6 in the treatment group superior to those in the control group after the treatment (P<0.05).Conclusions Superficial needling therapy can relieve the clinical symptoms in patients with early ankylosing spondylitis and improve spinal joint function with good safety. Its mechanism may be related to reducing inflammatory cytokines TNF-α, IL-1 and IL-6.
ABSTRACT
Objective To investigate the clinical efficacy of superficial needling therapy for early ankylosing spondylitis and its effect on tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6).Methods Eighty patients with early ankylosing spondylitis meeting the inclusion criteria were randomly allocated to treatment and control groups using random number card method with the ratio of 1:1, 40 cases each. The treatment group received superficial needling therapy alone and the control group, conventional treatment with celecoxib capsules, methotrexate tablets and sulfasalazine enteric-coated tablets. Treatment was given for a total of 24 weeks. Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), lumbago, TCM syndrome score, TNF-α, IL-1 and IL-6 were observed in the two groups before and after treatment.Results The BASDAI, BASFI, lumbago, TCM syndrome score, TNF-α, IL-1 and IL-6 improved in the two groups after treatment compared with those before the treatment (P<0.05). The BASDAI, BASFI, lumbago, TCM syndrome score, TNF-α, IL-1 and IL-6 in the treatment group superior to those in the control group after the treatment (P<0.05).Conclusions Superficial needling therapy can relieve the clinical symptoms in patients with early ankylosing spondylitis and improve spinal joint function with good safety. Its mechanism may be related to reducing inflammatory cytokines TNF-α, IL-1 and IL-6.