Effect and mechanism of Jingqi Yukui Capsules on gastric ulcer mucosa healing quality: based on network pharmacology and animal experiment / 中国中药杂志

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term "gastric ulcer". The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.

Effect of Bletillae Rhizoma Polysaccharide on PI3K/Akt in Gastric Tissue of GU Model Rats / 中国实验方剂学杂志

Objective::To investigate the effect of Bletillae Rhizoma polysaccharide on the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) gene protein and its mediated cytokines interleukin-2 receptor (IL-2R) and interleukin-4 (IL-4) in gastric tissue of rats with gastric ulcer (GU). Method::Sixty SPF Wistar rats were randomly divided into blank group and model group.The GU model was replicated by direct acetic acid cauterization in model group.The GU model rats were randomly divided into five groups: model group, positive control group, and large, medium and small-dose Bletillae Rhizoma polysaccharide groups, with 10 rats in each group.Rats in blank group and GU model group were given 10 mL·kg-1·d-1 distilled water by gavage, rats in large, medium and small-dose groups were given 0.5, 0.25, 0.125 g·kg-1·d-1 Bletillae Rhizoma polysaccharide by gavage, while rats in positive control group were given 0.3 g·kg-1·d-1 ranitidine by gavage for 15 days.Serum nitric oxide (NO) content, pepsinase activity and cytokines IL-2R and IL-4 levels in rats of each group were measured by enzyme-linked immunosorbent assay (ELISA), PI3K and Akt mRNA expressions were detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and PI3K and Akt protein expressions were detected by Western blot. Result::Compared with the blank group, the contents and gene expressions of cytokines IL-2R and IL-4 in gastric tissue were significantly increased, and the PI3K and Akt genes and protein expressions were significantly increased, with statistical significance (P<0.01). Compared with GU model group, the content and gene expressions of IL-2R and IL-4 in large, medium and small-dose Bletillae Rhizoma polysaccharide groups were decreased significantly, and the PI3K and Akt gene and protein expressions were decreased significantly in large-dose Bletillae Rhizoma polysaccharide group, while those in large and medium-dose Bletillae Rhizoma polysaccharide groups were decreased significantly (P<0.05, P<0.01). Conclusion::Bletillae Rhizoma polysaccharide can protect gastric mucosa by down-regulating PI3K and Akt gene and protein expressions and inhibiting abnormal secretion of cytokines IL-2R and IL-4.

Effect of Hei Xiaoyaosan on Expression of CaMKⅡα Protein and Its Phosphorylation in Hippocampus and Cerebral Cortex of APP/PS1 Double Transgenic Mice / 中国实验方剂学杂志

Objective::To study the effect of Hei Xiaoyaosan on the expression of calcium calmodulin-dependent protein kinase Ⅱ alpha(CaMKⅡα) and its phosphorylation in hippocampus and cortex of mice with Alzheimer's disease. Method::After weighing, 30 APP/PSI transgenic male mice were divided into model group, donepezil hydrochloride group and Hei Xiaoyaosan group according to random principle and 10 in each group.At the same age, wild-type C57BL/6 10 mice of the same species were treated as blank group. Donepezil hydrochloride group (6 g·kg-1) and Hei Xiaoyaosan group (3.25 mg·kg-1) were administered for 90 days, then the behavior of all the mice were detected by Morris water maze, the expression of CaMKⅡα, p-CaMKⅡα proteins in hippocampus and cortex by immunohistochemical technique and Western blot. Result::After intervention 3 months, compared with blank group, the average escaping latency periods prolonged significantly and the number of cross-platform and effective areas were decreased distinctly in model group mice(P<0.01), CaMKⅡα protein relative expression decreased significantly(P<0.01), p-CaMKⅡα protein relative expression increased significantly(P<0.01). Compared with the model group, the escape latency of donepezil hydrochloride and Hei Xiaoyaosan group were significantly shortened, and the number of crossing platforms and effective areas was significantly increased (P<0.05, P<0.01), the expression of CaMKⅡα protein in the hippocampus and cortex of drug groups was significantly increased (P<0.01), p-CaMKⅡα protein in the hippocampus and cortex of drug groups was significantly decreased (P<0.05, P<0.01). Conclusion::Hei Xiaoyaosan can improve the learning and memory ability of AD mice by regulating the expression of CaMKⅡα and its phosphorylation, which are key proteins involved in the mechanism of cell memory formation in different brain regions of AD mice.

Effect of Huangqi Jianzhongtang on JAK2/STAT3 Signal Pathway in Rats with Spleen-Stomach Deficiency Cold Type Gastric Ulcer / 中国实验方剂学杂志

Objective:To investigate the effect of Huangqi Jianzhongtang on Janusprotein tyrosine kinase 2/signal transducers and transcriptional activator protein 3 (JAK2/STAT3) signal pathway in rats with spleen-stomach deficiency cold type gastric ulcer (GU). Method:A total of 60 SPF level Wistar rats were randomly divided into two groups: blank group and model group. Model rats were used to reconstruct the spleen-stomach deficiency cold type GU model by comprehensive modeling method. Model rats were divided into model group, Anweiyang group and high, medium and low-dose Huangqi Jianzhongtang groups according to the random number table, with 10 rats in each group. Rats in blank group and model group were given 10 mL·kg-1·d-1 distilled water, and 16, 8, 4 g·kg-1·d-1 Huangqi Jianzhongtang, respectively. Rats in the positive control group were given 0.14 g·kg-1·d-1 Anweiyang for 21 days. The gene expressions of JAK2 and STAT3 in the ulcer tissue were detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), the protein expressions and phosphorylation levels of JAK2 and STAT3 in the ulcer tissue were detected by Western blot, and the contents of interleukin-10（IL-10）and interleukin-17（IL-17）in the gastric tissue of each group were detected by enzyme-linked immunosorbent assay (ELISA). Result:Compared with the blank group, the general survival condition of the model group was worse, the content of IL-10 in gastric homogenate was significantly reduced, while the content of IL-17 was significantly increased (P<0.05), the protein expressions of JAK2 and STAT3 in gastric tissue was not significantly increased, whereas the gene expressions and phosphorylation levels of JAK2 and STAT3 were significantly increased (P<0.05). Compared with the model group, the content of IL-10 increased, but the content of IL-17 decreased, the gene expressions of JAK2 and STAT3 and the level of protein phosphorylation decreased in the treatment group, especially in the high-dose Huangqi Jianzhongtang group, with statistically significant differences (P<0.05). Conclusion:Huangqi Jianzhongtang can improve the survival condition of rats with spleen stomach deficiency cold type gastric ulcer, and its mechanism may be related to the intervention of gastric mucosal immune barrier dysfunction mediated by JAK2/STAT3 pathway activation.

Feasibility of Hei Xiaoyaosan in Preventing and Treating Alzheimer's Disease Based on Theory of 'Correlation of Liver and Kidney' Based on Ca2+-CaM/CaMKⅡ-CREB Signal Pathway / 中国实验方剂学杂志

Alzheimer's disease（AD） is an incipient aging neurodegenerative disease， which increases rapidly along with the development trend of social aging and seriously threatens the health of the people. In the absence of effective preventive measures， it will have an enormous impact on the socio-economic and healthcare system. The study found that abnormal cell signal transduction is a key link in many diseases. Cell signal transduction theory has been widely used to clarify the essence of traditional Chinese medicine visceral image and the mechanism of traditional Chinese medicine. 'Correlation of Liver and Kidney' is one of the core plates of the theory of 'Correlation of Five Organs'， which is suitable for explaining the pathogenesis of complex diseases and the correlation of multiple syndromes， and guiding the prescription of clinical syndrome. Hei Xiaoyaosan， as the first choice compound for the prevention and treatment of AD based on the theory of "Correlation of Liver and Kidney' in our team， can play the effects of prevention and treatment by soothing liver and nourishing blood， strengthening spleen and tonifying kidney， and promoting brain collaterals and dredging viscerab spirit. Based on the theory of 'Correlation of Liver and Kidney'， this paper expounds the pathogenesis of AD from the perspective of traditional Chinese medicine， and puts forward the methods and ideas of the preventing and treating of AD from Ca2+-calcium/calmodulin dependent protein （CaM）/calcium/calmodulin dependent protein kinaseⅡ（CaMKⅡ）-cyclic adenosine phosphate reactive element binding protein （CREB） cell signal transduction pathway by consulting literatures and previous studies.

Analysis on WANG Dao-kun's Experience in Using Wenzhong Zhixie Decoction for Treatment of Spleen Diarrhea / 中国中医药信息杂志

Spleen diarrhea is one of the common diarrhea diseases. Because it has long course, lingering and difficult to cure, and easy to occur, it is difficult to treat. Professor WANG Dao-kun believes that spleen-stomach yang deficiency, disorder of qi movement, and dampness and internal stagnation are the common etiology and pathogenesis of spleen diarrhea. The treatment should be warming middle Jiao and tonifying spleen, regulating qi, and promoting diarrhea. Professor WANG has prepared modified Wenzhong Zhixie Decoction for the treatment of spleen diuresis. This article expounded Professor WANG's experience in treating spleen diarrhea with Wenzhong Zhixie Decoction.

WANG Dao-kun's Experience in Application of Dunhuang Ancient Medical Prescription Dabupi Decoction into the Treatment of Gastric Stuffiness / 中国中医药信息杂志

Dunhuang medicine is a branch of Dunhuang studies, including the characteristics of Dunhuang ancient medical prescriptions and treatment technique.Dunhuang Dabupi Decoction has good efficacy in nourishing vitality and yin and promoting the production of body fluid. Professor WANG Dao-kun used the prescription to treat gastric stuffiness, gaining significant curative effect. This article summaried cases of using this prescription, to show the advantages of Dunhuang ancient medical prescription Dabupi Decoction for present use.

Study on interference effect of Sijunzi decoction on brain-gut CaM/CaMK II of spleen Qi deficiency syndrome rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the dynamic time-phase expressions of key genes of brain-gut CaM signal pathway of spleen Qi deficiency rats and the intervention effect of Sijunzi decoction.</p><p><b>METHOD</b>Male Wistar rats were randomly divided into the normal control group, model 14 d, 21 d, 28 d groups, and Sijunzi decoction 14 d, 21 d, 28 d groups. Except for the normal control group, the remaining groups were included into the spleen Qi deficiency model with the bitter cold breaking Qi method (ig 7.5 g · kg⁻¹ · d⁻¹ of Rheum officinale, Fructus aurantii immaturus, Magnolia officinalis preparation) and the exhaustive swimming method. On the 7th day after the modeling, the Sijunzi decoction groups were orally administered with Sijunzi decoction 20 g · kg⁻¹ · d⁻¹. The expressions of key genes CaM/CaMK II of CaM signaling pathway in hippocampus and intestine at different time points by immunohistochemical method and Western blot. At the same time, the intervention effect of Sijunzi decoction on spleen Qi deficiency rats and its mechanism were analyzed.</p><p><b>RESULT</b>Spleen Qi deficiency rats showed higher intestinal CaM/CaMK II expression and lower hippocampus CaM/CaMK II expression than normal rats (P < 0.05, P < 0.01). After the treatment of Sijunzi decoction, spleen Qi deficiency rats showed reduction in intestinal CaM/CaMK II expression and increase in hippocampus CaM/CaMK II expression (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>The formation of spleen Qi deficiency syndrome may be related to the high expression of CaM/CaMK II in small intestine tissues and its low expression in hippocampus tissues. Sijunzi decoction may achieve the therapeutic effect in spleen Qi deficiency syndrome by reducing the CaM/CaMK II expression in intestinal tissues and increasing it in hippocampus tissues.</p>

Relationship between Urine Albumin and Vascular Endothelial Growth Factor in Children with Henoch-Schonlein Purpura / 实用儿科临床杂志

0.05],but significant difference existed in children with HSPN compared with HSP and control group[(3.01?1.52) g/d vs (0.05?0.02) g/d or (0.04?0.02) g/d Pa

Effect of Endothelin-1 and C-Reactive Protein on Vascular Endothelial Cell Dysfunction in Simple Obese Children / 实用儿科临床杂志

Objective To explore the effect of endothelin-1(ET-1) and C-reactive protein(CPR) on vascular endothelial cell dysfunction in simple obese children.Methods Thirty-nine simple obese children in the First Hospital of Huangshi City were chosen from Jan.2006 to Jun.2008 as experimental group (obese group) and 21 healthy children as healthy control group with the same age and gender were enrolled in the study.The levels of plasma ET-1 and serum CRP were tested by radioimmunoassay.Data were analyzed with t test and linear correlation analysis.Results Compared with plasma ET-1 level in healthy control group[(43.5?10.2) ng?L-1],the level in obese group[(57.8?19.7) ng?L-1] had significant difference(t=3.704,P