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Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.
Assuntos
Animais , Ratos , Vasculite por IgA/tratamento farmacológico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , MetabolômicaRESUMO
Aim To explore the regulatory effect of Danggui-chuanxiong herb pair (GX) on JAK-STAT signaling pathway in rats with cerebral ischemia/reper-fusion injury (I/R). Methods The I/R injury rat model was constructed by modified suture occlusion method. After 24 hours of perfusion, Zea Longa scoring method was used to score the neurological function, TTC staining to detect the cerebral infarct volume of rats, HE staining to observe the pathological changes of brain tissues, the biochemical method to determine the MDA, SOD, GSH-Px expression, ELISA to detect the expression of NF-κB, VEGF, ICAM-1 and PAH in brain tissues, and immunohistochemical method to detect JAK2, p-STAT3, AKT And ERK1/2 expression of the brain tissue ischemic penumbra area. Results Compared with sham group, model rats had severe neurological damage, larger cerebral infarction, necrosis, edema, inflammation, disorder of nerve cell arrangement, abnormal cell enlargement, vacuole-like changes, neuron reduction and other pathologies in brain tissues. The expression JeveJs of MDA, NF-κB, VEGF, PAI-1 and ICAM-1 in brain tissues of model group significantly increased, and the expression levels of GSH-Px and SOD were significantly reduced. Compared with model group, the neurological scores of rats in GX
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Aim To study the effect of drug-containing serum of Schisandra Chinensis Fructus and compatible with Glycyrrhizae Radix Et Rhizoma -on lipid accumulation in hepatocytes and explore the related mechanism. Methods SD rats were given Schisandra Chinensis Fructus (SF, 3.9 g • kg"1), Schisandrae Chinensis Fructus-Glycyrrhizae Radix Et Rhizoma (SG, 1 : 1, 1 '• 1. 5, the extract 3. 9 g • kg"1 in crud of Schisandrae Chinensis Fructus), once per day, the drug-containing serum was prepared after seven days of continuous administration. Conventional cultivation of human normal hepatocytes (L02 cells) in vitro, cells were divided into blank control group, SF group, and SG(1 : 1 and 1 : 1.5) group. After 48 hours' treatment , lactate dehydrogenase ( LDH) release was detected by the kit, the levels of intracellular triglyceride (TG) and total cholesterol (TC) were detected by biochemical method. The mRNA expression levels of PPAR-a, PPAR-7, Fabpl/2, SREBPlc, ACCa and FAS were detected by the real-time reverse tran scrip- tion polymerase chain reaction ( RT-PCR ). Results The biochemical results showed that compared with the blank group, the content of TG and TC in SF group increased significantly (P < 0. 05 ) , the mRNA expres sion of PPAR-a and PPAR-7 in SF group was significantly reduced, and the mRNA expression of SREBPlc and ACCa markedly increased ( P < 0.05, P < 0.01). When compared with SF group, the levels of TG and TC in SG (1 : 1) group were significantly reduced (P <0. 05) , the mRNA expressions of Fabpl/2 and FAS in SG (1 : 1) group were significantly reduced, while the mRNA expression of SREBPlc significantly increased ( P < 0. 05, P < 0. 01 ). TC content in SG (1 : 1.5) group significantly decreased (P < 0.05 ) and the mRNA expression of PPAR-7, SREBP1 c in SG (1 : 1.5) significantly increased, but the Fabpl/2 and FAS markedly decreased (P <0. 05, P < 0. 01). Conclusions SF containing serum can significantly increase the content of TG and TC in hepatocytes , and the SG containing serum can significantly improve the elevated TG and TC contents and reduce lipid accumulation. The mechanism may be related to the regulation of mRNA expression of PPAR-a, PPAR- 7, Fabpl/2, SREBPlc, ACCa and FAS.
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Objective To construct a glioma targeting delivery system, PAMAM G5 were modified with the oligopeptide of blood brain barrier (BBB) targeting TGN and tumor targeting oligopeptide iRGD to solve the problem of non-specificity in distribution and difficulty in permeating BBB of ATO, in order to have better anti-glioma effect. Methods The physical and chemical properties of nanocarriers were investigated by 1H-NMR and transmission electron microscopy (TEM); The encapsulation efficiency and in vitro release were analyzed by inductively coupled plasma emission spectrum (ICP) and dialysis bag method; The effects of iRGD and TGN on cellular uptake of the carriers were analyzed by laser confocal and flow cytometry. The cytotoxicity of nanocarriers on brain microvascular endothelial cells (HBMEC) and glioma cells (U87), the inhibition effect on U87 cells of drug delivery systems after acrossing the BBB model in vitro were investigated by MTT method. Results The iRGD/TGN-PEG-PAMAM was synthesized successfully. The TEM results showed that iRGD/TGN-PEG-PAMAM was regular in shape and uniform in size. The particle size of iRGD/TGN-PEG-PAMAM/ATO was (24.87 ± 0.84) nm and the potential was (17.26 ± 1.64) mV. The synthesized carrier had less toxicity to HBMEC and U87 cells. The encapsulation efficiency of iRGD/TGN-PEG-PAMAM/ATO delivery system was (71.92 ± 1.17)%. The in vitro release showed that ATO had a slow release trend after entrapment, and it was more favorable for ATO release under acidic conditions. The cell uptake indicated that iRGD/TGN modification was more beneficial for U87 cell to uptake the drug delivery system. The in vitro inhibition effect on U87 cells after acrossing the BBB model showed iRGD/TGN-PEG-PAMAM/ATO had better inhibition effect on U87 cells. Conclusion The iRGD/TGN-PEG-PAMAM/ATO targeting drug delivery system has good inhibition effect on U87 cells effect after acrossing the BBB model in vitro, which provides a new strategy for the treatment of glioma.