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This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1β(IL-1β) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.
Subject(s)
Animals , Rats , Diabetes Mellitus, Type 2/drug therapy , Gastrointestinal Microbiome , Inflammation/drug therapy , Insulin , PowdersABSTRACT
Objective: To explore the interrelation of "composition-target-disease" of Kaixinsan on treatment of Alzheimer's disease. Method: Through the integrated pharmacological platform of Chinese medicine V1.0,the active ingredients and potential targets of four Chinese herbs in Kaixinsan were collected,disease targets of Alzheimer's disease were searched,and enriched by the gene ontology database and the Kyoto encyclopedia of genes and genomes at hubs. Result: Among the 250 compounds of Kaixinsan,2 877 targets were associated with Alzheimer's disease.The key targets,such as mitochondrial trifunctional enzyme subunit alpha(HADHA),hydroxyacyl coenzyme A dehydrogenase(HADH),sterol-4-alpha-carboxylate 3-dehydrogenase(NSDHL) and others,played their pharmacological effects mainly through regulating purine and nucleotide metabolism,Huntington's disease,Alzheimer's disease,neurodegenerative diseases,oxidative phosphorylation,and endocrine and metabolic diseases in molecular reactions,such as cytoplasm,mitochondria,adenosine triphosphate binding,and mitochondrial matrix. Conclusion: The platform can predict the key targets and related pathways of Kaixinsan for treatment of Alzheimer's disease,which lays the foundation for further revealing material basis and mechanism of this formula,and plays an important role in digging and developing this classic and famous formula.
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<p><b>OBJECTIVE</b>To study the protection of Zibu Piyin Recipe (ZBPYR) on the insulin signal pathway in the hippocampus of Pi-yin deficiency diabetic encephalopathy rats and to explore its possible mechanisms.</p><p><b>METHODS</b>The type 2 diabetic model was established using high fat diet and intraperitoneal injection of small dose streptozotocin (STZ). The Pi-yin deficiency model was established referring to classic compound factors. The learning and memory capabilities were tested in rats by the behavioral changes. The protein expressions of hippocampal IRE1alpha, JNK, and IRS-1 were detected using Western blot.</p><p><b>RESULTS</b>There was statistical difference in the learning and memory capabilities of Pi-yin deficiency rats when compared with the blank control group (P<0.05). The learning and memory capabilities could be improved by ZBPYR. The protein expressions of hippocampal phospho-IRS-1, phospho-JNK, and total IRE1alpha were enhanced (P<0.05). But they were weakened after treatment of ZBPYR.</p><p><b>CONCLUSIONS</b>ZBPYR could significantly improve the learning and memory capabilities of Pi-yin deficiency diabetic rats. Its functions might be correlated with improving the endoplasmic reticulum stress to regulate the insulin signaling pathway.</p>
Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Endoplasmic Reticulum Stress , Endoribonucleases , Metabolism , Hippocampus , Metabolism , Insulin , Metabolism , Insulin Receptor Substrate Proteins , Metabolism , Insulin Resistance , JNK Mitogen-Activated Protein Kinases , Metabolism , Multienzyme Complexes , Metabolism , Protein Serine-Threonine Kinases , Metabolism , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between the excitotoxicity and serum-inducible kinase (SNK) and spine-associated Rap GTPase-activating protein (SPAR) pathway in primary hippocampal neuron injury induced by glutamate and furthermore, to explore the molecular mechanism of neuroprotection of Zibu Piyin Recipe (ZBPYR) and the relationship between ZBPYR and the morphological regulation of dendritic spines.</p><p><b>METHODS</b>The serum containing ZBPYR was prepared by seropharmacology. Reverse transcription and polymerase chain reaction (RT-PCR) was used to detect the expression of mRNA for SNK, SPAR, postsynaptic density protein 95 (PSD-95) and N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A and NR2B) in primary rat hippocampal neuron cultures after pretreatment with 10 micromol/L glutamate and ZBPYR serum.</p><p><b>RESULTS</b>ZBPYR serum pretreatment resulted in a significant down-regulation of glutamate-induced SNK mRNA expression (P<0.05). Significant up-regulation was seen on the mRNA expression of SPAR and PSD-95 (P<0.05). All these changes were dose-dependent. The mRNA expression of NR1, NR2A and NR2B was down-regulated to different degrees (P<0.05).</p><p><b>CONCLUSION</b>The mechanism of effect of ZBPYR on glutamate-induced excitotoxicity may be related to the regulation of SNK-SPAR signal pathway. ZBPYR may play a role in protecting and maintaining the normal morphology and structure of dendritic spines, which may be achieved by inhibiting the excessive activation of NMDA receptors.</p>
Subject(s)
Animals , Rats , Cells, Cultured , Disks Large Homolog 4 Protein , Drugs, Chinese Herbal , Pharmacology , GTPase-Activating Proteins , Genetics , Metabolism , Gene Expression Regulation , Glutamic Acid , Toxicity , Hippocampus , Pathology , Intracellular Signaling Peptides and Proteins , Genetics , Metabolism , Membrane Proteins , Genetics , Metabolism , Neurons , Pathology , Protein Kinases , Genetics , Metabolism , Protein Serine-Threonine Kinases , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , SerumABSTRACT
@#ObjectiveTo study the therapeutic effect and mechanisms of nourishing Piyin Remedy (nPR) on experimental rat spinal cord injury.MethodsThirty-two healthy SD rats were divided into 2 equal groups randomly: nPR group and injured group. Animal model of incomplete injury of spinal cord was made by Allen's equipment on rat's T8—T9 segment. The spinal nerve function,SEP,retrograde and label technique of horse radish peroxidase,gross observation,histological and morphometric analysis were taken as the observed indices.ResultsThe value of observed indices of nPR group were improved evidently compared with injured group.ConclusionNourishing Piyin Remede can hold back the secondary spinal cord injury and accelerate the recovery of spinal nerve function.
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<p><b>OBJECTIVE</b>To investigate the apoptosis effect induced by D-limonene on BGC-823 gastric cancer cells.</p><p><b>METHODS</b>The expression of p53, bc1-2 in BGC-823 cells and qualitative, quantitative index of cell apoptosis were detected with MTT, electron microscopy, flow cytometry and immunohistochemical method.</p><p><b>RESULTS</b>D-limonene could induce the formation of apoptotic bodies in a dose- and time-dependent manner. The expression of bcl-2 protein decreased and p53 protein increased in BGC-823 cells treated with D-limonene, compared with the control cells.</p><p><b>CONCLUSION</b>D-limonene exerts its cytotoxic effect on BGC-823 gastric cancer cells by inducing apoptosis.</p>