ABSTRACT
ObjectiveTo study the effect of Huazhuo Jiedu Huoxue Tongluo （HJHT） prescription on the intestinal flora in rats with cerebral ischemia-reperfusion injury， and to explore the mechanism of Chinese medicinal prescription regulating intestinal flora to restore the balance of brain-gut axis. MethodFifty male SPF SD rats were randomly assigned into sham group， model group， high-dose HJHT group （25.0 g·kg-1）， medium-dose HJHT group （12.5 g·kg-1）， and low-dose HJHT group （6.25 g·kg-1）， with 10 rats in each group. The rat model of permanent middle cerebral artery infarction was established according to Longa method and previous research experience， and reperfusion was performed 2 h after ischemia. The recovery of neurological function deficit and the percentage of cerebral infarction area were detected 72 h after administration. Real-time PCR was performed to detect the mRNA levels of Occludin and zonula occludens-1 （ZO-1） in rat colon. Hematoxylin-eosin （HE） staining was conducted to reveal the intestinal damage. The feces of 6 rats in each group were collected for 16S rRNA sequencing. The expression of Treg and Th17 in intestinal tissue， peripheral blood， and brain tissue were detected. ResultCompared with the sham group， the model group showed obvious neurological deficit （P<0.05） and large cerebral infarction area （P<0.05）. High-dose and medium-doses HJHT alleviated the symptoms of neurological impairment （P<0.05） and reduce the cerebral infarction area （P<0.05） compared with the model group. Compared with the sham group， the model group showed destroyed structure of colonic mucosa and incomplete epithelial cells and goblet cells， while high-dose and medium-doses HJHT alleviated such changes. The mRNA levels of Occludin and ZO-1 in the model group were lower than those in the sham group （P<0.05），and the high-dose HJHT groups were higher than the model group （P<0.05）. The intestinal flora structure was significantly different between the model group and the sham group while similar between the high-dose HJHT group and sham group. Compared with the sham group， the model group showed down-regulated expression of Treg and up-regulated expression of Th17 in the intestinal tissue， peripheral blood， and brain tissue， and high-dose and medium-dose HJHT alleviated the changes in the expression of Treg and Th17 in the model group （P<0.05）. ConclusionHuazhuo Jiedu Huoxue Tongluo prescription may improve the permeability of intestinal wall by adjusting the abundance and diversity of intestinal microorganisms to reduce the migration of intestinal Th17 cells toward the ischemic lateral brain tissue， mitigate the inflammatory response， and thus alleviate the cerebral ischemia-reperfusion injury in rats.
ABSTRACT
In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.
Subject(s)
Animals , Rats , Drugs, Chinese Herbal/pharmacology , Molecular Docking Simulation , Network Pharmacology , PC12 Cells , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Saponins , Signal Transduction , TriterpenesABSTRACT
Traditional Chinese medicines(TCMs) have certain limitations in the clinical research design in their post-marketing evaluation, so that randomized controlled programs cannot be strictly implemented in some studies, while the objective performance criteria is a reasonable external controlled research method that has been gradually recognized at home and abroad in recent years in addition to randomized controlled trial(RCT) method. It is more mature in medical devices, surgery and other research fields, but there is no relevant report in the field of post-marketing evaluation of Chinese patent medicines. In this paper, the application prospect of the objective performance criteria and the problems were discussed in the field of post-marketing evaluation of TCM. The characteristics of as TCM are more consistent with the scope of the objective performance criteria, the application of the objective performance criteria in post-marketing evaluation of Chinese patent medicines, especially in single arm research, can break through the limitations of existing conventional clinical research methods, and improve the level of evidence, with good feasibility and advantages. However, in the application process, we should pay attention to the key issues such as the selection of index, research population, follow-up period and the reference selection, to ensure the quality of research. This research group has carried out some exploration and practice in the field of post-marketing evaluation of TCM injections by using single arm combined with the objective performance criteria, hoping to establish the key technology in this field, and provide certain research and design reference for the secondary development of Chinese patent medicines.
Subject(s)
Drugs, Chinese Herbal , Marketing , Medicine, Chinese Traditional , Nonprescription Drugs , Product Surveillance, Postmarketing , Randomized Controlled Trials as TopicABSTRACT
Objective To analyze the clinical value of vitamin D supplementation combined with standard secondary prevention and treatment in patients with coronary heart disease(CHD).Methods 120 patients with CHD were divided into the control group and the observation group,60 cases in each group.Both groups were given the standard secondary prevention and treatment and the observation group were additionally given vitamin D supplementation.The changes of glucose and lipid metabolism and carotid plaque before and after treatment were compared between the two groups,and the incidence of readmission in the two groups was sta-tistically analyzed.Results After 6 and 12 months of treatment,the fasting blood glucose(FPG),2 h post-prandial blood glucose(2 h PG),carotid intima-media thickness(IM T),coronary plaque integral and high-sen-sitivity C reactive protein(hs-CRP)in the observation group were lower than those in the control group,while glycosylated hemoglobin(HbA1c),serum calcium and 25(OH)D3were higher than those in the control group (P<0.05);There were no significant differences between the two groups in the incidence rates of adverse car-diovascular events and readmission(P>0.05).Conclusion In the treatment of patients with CHD,vitamin D supplementation combined with standard secondary prevention and treatment can regulate glucose and lipid metabolism,delay the progression of carotid atherosclerosis and reduce the incidence of adverse cardiovascular events.
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In order to conceal the unpleasant smell of pharmaceutical raw materials of penicillin V potassium, we use Beta-cyclodextrin [Beta-CD] as a drug carrier. The Penicillin V potassium Beta-CD inclusion complex was prepared by saturated aqueous solution method; the characterization of penicillin V potassium Beta-CD inclusion complex is determined by scanning electron microscopy, Differential Scanning Calorimeter [DSC] and X-ray Diffraction [XRD], the formation constants of the complexes were determined by UV spectrophotometry; based on the results obtained from the orthogonal experimental design, the optimum preparation process are summarized as follow: Beta-CD: Penicillin V potassium = 4: 1 [molar ratio], stirring temperature 50 centigrade, strirring time 12h, the encapsulation efficiency is 29.40%
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Objective To measure the values of quantitative ultrasound(QUS) of different gestational age preterm infants at birth in Guangzhou area,and compare them with the values of Caucasian preterm infants in order to get insight into the bone development status of preterm infants in Guangzhou area and to evaluate the practicability of QUS.Methods The Omnisense quantitative ultrasound produced by Israel Sunlight company was used to measure the bone speed of sound(SOS) of left tibia of preterm infants born between Jun.2010 and Jun.2012 in Maternity and Children Health Hospital of Huadu District in Guangzhou,and the values of SOS of Caucasian preterm infants was compared.Results There were totally 1039 preterm infants born in Guangzhou area involved in this study,and they were divided into group A,B,C,D by gestational ages:≤ 30 weeks,30 + 1 ～ 32 weeks,32 + 1 ～ 34 weeks,34 + 1 ～ 36 + 6 weeks.The values of SOS of each group at birth were(2892.05 ± 139.17) m/s,(2936.84 ± 137.87) m/s,(2966.65 ± 116.60) m/s and (2988.63 ± 120.74) m/s,separately,and with the increase of gestational age,and there was significant difference of SOS between different gestational age groups(F =15.758,P =0.000).But there was no significant difference of SOS between male and female (F =2.665,P =0.103).Compared with Caucasian preterm infants,the SOS value gap (defined as the Z value) of preterm infants of different gestational age in Guangzhou area was no significant difference(P =0.117),and there was no significant difference between male and female (F =3.494,P =0.062).Conclusions The value of SOS of preterm infants was higher with the increase of maturity of preterm infants.There was no significant difference of SOS between Guangzhou preterm infants and Caucasian preterm infants.And QUS is suitable for clinical evaluation of bone development status of preterm infants.