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1.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5265-5272, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350244

RESUMO

The aim of this paper was to investigate the mechanism of the active peptide DP17 of Eupolyphaga steleophaga in the treatment of hyperlipidemia rats. HPLC and MADIL-TOF/TOF-MS were used for the amino acid sequence analysis and solid-phase synthesis on the active peptide of E. steleophaga which were obtained by biomimetic enzymatic hydrolysis, separation and purification. The hyperlipidemia model was established by feeding with high-fat diet.Twenty days later, the rats in the blank group and the model group were given the saline and the rats in remaining groups were given the corresponding drugs by oral administration. After administration for 4 weeks, the levels of triglyceride(TG), total cholesterol(TC) and low density lipoprotein(LDL) in serum, the levels of TG, TC, adenosine monophosphate(AMP), adenosine triphosphate(ATP) in liver tissues and TG in feces were detected, respectively. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of liver tissues. The Real-time fluorescence quantitative PCR method was used to detect the expression of acetyl coa carboxylase(ACC) and hydroxymethylglutaryl-coa reductase(HMGCR) mRNA in liver tissues. The expression of mammalian target of rapamycin(mTORC1) protein and adenosine 5'-monophosphate-activated protein kinase(AMPK) in liver tissues were detected by Western blot. The analysis showed that the amino acid sequence of active peptide from E. steleophaga was DAVPGAGPAGCHPGAGP(DP17). The results of pharmacological experiments showed that after oral administration of DP17 in rats, the levels of TG, TC and LDL in serum as well as TG and TC levels in liver tissues were significantly decreased(P<0.05), while the levels of AMP, ATP in liver tissues and TG content in feces were significantly increased(P<0.05); the liver steatosis of rats was significantly relieved; the expression of ACC, HMGCR mRNA and mTORC1 protein in liver tissues were significantly reduced, while the expression of AMPK phosphorylated protein was significantly increased(P<0.05). DP17, the active peptide of E. steleophag can significantly reduce lipid accumulation in liver tissues, and it may play a role in reducing blood lipids by regulating the energy metabolism balance in the body and activating AMPK/mTOR signaling pathway.


Assuntos
Hiperlipidemias , Animais , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Lipídeos , Fígado , Peptídeos , Ratos , Triglicerídeos
2.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4448-4454, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164375

RESUMO

To explore the mechanism of Scutellaria barbata-Hedyotis diffusa against breast cancer based on network pharmacological methods. The active components and corresponding target proteins of S. barbata and H. diffusa were screened by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and the targets of breast cancer were screened through the Genecards and OMIM databases. Venn online software was used to obtain the common targets of drugs and the disease, and then the "compound-target-disease" network diagram was constructed by using Cytoscape 3.7.2 software. The STRING database was used to draw the protein-protein interaction(PPI) network, and the David database was used to perform GO function and KEGG pathway enrichment analysis on effective targets. The results showed that 29 S. barbata compounds, 7 H. diffusa compounds, and 109 effective targets were screened. The 59 common targets for drugs and disease were obtained through Venn diagrams. The PPI network showed that MYC, CCND1, EGFR, ESR1, CASP3, VEGFA, etc. might be the key targets for "S. barbata-H. diffusa" in the treatment of breast cancer. In the GO function analysis, 88 entries were found, involving the regulation of transcription factor activity, receptor activity, cytokine activity, enzyme activity, and biosynthetic processes. In KEGG pathway analysis, 37 entries related to cancer, cell cycle, apoptosis, angioge-nesis and other pathways were found, including p53 signaling pathway, ErbB signaling pathway, nod like receptor signaling pathway, MAPK signaling pathway, VEGF signaling pathway, Wnt signaling pathway and mTOR signaling pathway and other classic signaling pathways. This study preliminarily revealed the key targets, biological processes and signal pathway of "S. barbata-H. diffusa" against breast cancer. It was found that its function was in a multi-target and multi-channel manner, which laid a foundation for future molecular biological experiments.


Assuntos
Neoplasias da Mama , Medicamentos de Ervas Chinesas , Hedyotis , Scutellaria , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa
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