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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.
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Animals , Humans , Rats , Animal Experimentation , Capsules , Gastric Mucosa/metabolism , Network Pharmacology , Stomach Ulcer/geneticsABSTRACT
Objective To explore the mucosal healing quality of hydrotalcite combined with esomeprazole in gastric ulcer.Methods Forty-two patients visiting from June 2014 to December 2015 and diagnosed with gastric ulcer were selected and divided into combination therapy group and single therapy group with 21 patients in each group.The patients of combination therapy group received esomeprazole combined with hydrotalcite,and the patients of single therapy group received esomeprazole alone.The total therapeutic course was eight weeks.At the same period,21 health check-up participants were enrolled as normal control group.The healing of gastric ulcer was observed under white light endoscopy.The morphological changes of gastric pits and microvessel of mucosal at peripheral mucosa around ulcer and normal gastric mucosal were observed under narrow band imaging magnifying endoscopy.The gastric mucosa tissues of the two groups before and after treatment,and normal gastric mucosa of healthy control group were taken.The amount of deposition and composition of collagen fibers,the expression level of factor Ⅷ,the level of transforming growth factor (TGF)-beta1 and the content of hydroxyproline were analyzed by Masson,immunofluorescent and immunohistochemistry staining as well as enzyme linked immunosorbent assay.Chi square test,one-way analysis of variance (ANOVA),least significant difference (LSD) method,Dunnett's T3 and Kruskal-Wallis test and other method were used for comparison.Results After treatment,18 patients of combination therapy group (21 patients) had regular microvessel nets (85.7％),which was significantly more than those of single therapy group (12 cases,57.1％) and healthy control group (10 cases,47.6 ％),and the differences were statistically significant (x2 =4.200,P=0.040).In the comparison of maturity of regenerative mucosa between combination therapy group and single therapy group after treatment,the ration between collagen type Ⅰ and Ⅱ,deposition of collagen fibers,the number of factor Ⅷ positive cells,the level of TGF-beta1 and the content of hydroxyproline were 36.05 and 23.14;269 375.63.± 171 608.63 and 137 693.14±98 330.93;34.91±8.40 and 28.24±6.93;104 498.71±40 487.96 and 70 757.11±19 323.95;(1 897.80±879.35) and (1 230.57±536.05) μg/L,respectively;while in healthy control group,the above parameters were 36.81,245 696.90 ± 224 687.00,23.10 ± 8.40,94 048.04 ±41 306.55 and 1 681.20 ± 423.61 μg/L,and the differences were statitically significant among these three groups (H=7.375,F=3.465,11.680,5.190,5.160;all P＜0.05).Those parameters of combination therapy group were significantly higher than those of single therapy group (H=2.416,LSD method;all P＜0.05).Conclusion Hydrotalcite combined with esomeprazole in the treatment of gastric ulcer could significantly improve microvessel morphology,maturity degree of regenerative mucosal structure and function,and the mucosal healing quality was also superior to single esomeprazole group.
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Background:Hydrotalcite has been used in the treatment of gastric ulcer,but its mechanism is not clear. Aims:To investigate the efficacy and mechanism of hydrotalcite on experimental gastric ulcer in rats. Methods:Experimental acetic acid-induced gastric ulcer model was established in rats. Model rats were randomly assigned into control group,low and high dose hydrotalcite groups,and 0. 9% NaCl solution,880 mg·kg - 1 ·d - 1 ,1 230 mg·kg - 1 ·d - 1 hydrotalcite were intragastrically administrated,respectively. After 14 days,macroscopic examination was performed;and HE staining, CD31 staining and VG staining were used to evaluate the histological maturity,AB-PAS staining,level of hexosamine, immunohistochemical staining,serum levels of epidermal growth factor( EGF),prostaglandin E2( PGE2 )were used to evaluate the functional maturity. Results:Compared with control group,ulcer index(UI)was significantly decreased in high dose hydrotalcite group(P < 0. 05). Thickness of restored mucosa was significantly increased(P < 0. 05),number of cystically dilated gland was significantly decreased(P < 0. 01),microvessel density(MVD),collagen fiber,secretion of mucus,level of hexosamine,expressions of EGF,EGR receptor(EGFR)and PGE2 ,serum levels of EGF and PGE2 were significantly increased in low and high hydrotalcite groups( P < 0. 05,P < 0. 01). Conclusions:Hydrotalcite could obviously improve the histological and functional maturity of regenerative mucosa,as well as the quality of ulcer healing. The mechanism might be related to the neutralization of gastric acid,enhancement of mucus-HCO3 - barrier and up-regulation of expressions of EGF and PGE2 .
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Objective To investigate the effect of modified Huangqi-Jianzhong decoction on healing quality of gastric ulcer in rats and to explore its mechanism. Methods 40 Wistar rats were randomly divided into a normal group, a model group, a modified Huangqi-Jianzhong decoction group and a omeprazole group (n=10) according to the random number table method. These rats were used to model of chronic gastric ulcer induced by acetic acid 100%. On third day after surgery, the rats in the modified Huangqi-Jianzhong decoction group were treated with 10% of the modified Huangqi-Jianzhong decoction according to the dose of 20 ml per kilogram of body weight. The rats in the omeprazole group were treated with a 3% omeprazole suspension according to the of 20 ml per kilogram of body weight. The rats in the normal group and the model group were treated with the same volume of saline. After treated with corresponding treatment for 16 days, the gastric mucosa pathology, ulcer index, regenerative mucosal thickness, mucosal surface mucus thickness, muscularis mucosal layer width of the defect, cystically dilated glands number and level of serum prostaglandin (6-K-PGF1α), epidermal growth factor (EGF), nitric oxide (NO) were observed. Results Compared with the model group, the rat ulcer index (8.95 ± 2.78 mm2 vs. 20.82 ± 5.12 mm2), mucosal muscularis defect width (123.56 ± 32.89 μm vs. 229.32 ± 49.69 μm), cystic glandular expansion (1.65 ± 0.76 vs. 6.12 ± 1.23) were lower in the modified Huangqi-Jianzhong decoction group (P<0.01). Thickness of regenerated mucosa (329.55 ± 32.22 μm vs. 198.22 ± 5.83 μm), the surface thickness of mucus (44.3 ± 2.8 μm vs. 24.5 ± 7.8 μm), serum 6-K-PGF1α (93.7 ± 8.9 pg/ml vs. 58.5 ± 5.8 pg/ml), EGF (2.11 ± 0.29 ng/L vs. 0.82 ± 0.20 ng/L) , NO (0.51 ± 0.03 μmol/L vs. 0.22 ± 0.05 μmol/L) was higher (P<0.01). In addition to the ulcer index, other each target improvement flavored were better in the modified Huangqi-Jianzhong decoction group than in the omeprazole group (P<0.05). Conclusion Modified Huangqi-Jianzhong decoction can improve the quality of ulcer healing by promoting gastric mucosa ulcer repair, reducimg ulcer index, mucous muscularis layer defect width and cystic glandular expansion and improving the thickness of regenerative mucosa, mucosal surface mucus thickness and cyst, EGF, NO level and thus improve the experimental gastric ulcer healing quality.
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Objective To investigate the effect and mechanism of invigorating spleen,eliminating stasis, heat-clearing drugs(milk veteh,root of red rooted salvia,Chinese goldthread)on quality of ulcer healing (QOUH).Methods The rat models of chronic gastric ulcer was induced by acetic acid,the effects of QOUH of milk veteh,root of red rooted salvia and Chinese goldthread on the model of gastric Ulcer were observed, the expression of EGFR mRNA of mucosa were measured by in situ hybridization.Results Milk veteh,root of red rooted salvia and Chinese goldthread could improve the injury of gastric mucosa.Milk veteh,root of red rooted salvia increased the expression of EGFR mRNA in the tissue around peptic ulcer(PU). Conclusion Invigorating spleen,eliminating stasis,heat-clearing drugs can improve QOUH,it is one of possible mechanisms that the drugs increased the expression of EGFR mRNA in the tissue around PU.
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Quality of ulcer healing (QUH) was applied to explore the mechanism of the recurrence of peptic ulcer. The relationship of QUH and epidermal growth factor, prostaglandins, heat shock proteins, immune function and Helico-bacter pylori was assayed. Mechanism of Chinese herbal medicine for the recurrence of peptic ulcer was presented as follows: improving blood circulation and barrier function of gastric mucosa, eliminating Helicobacter pylori and increas ing QUH.
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AIM To study the effects of rh bFGF on healing quality of chronic gastric ulcer in rats. METHODS Ulcer model induced by acetic acid was established. Rats were treated with rh bFGF ig until ulcer healing and then continually treated for 10 days(30 total treatment days). The effects of rh bFGF on healing quality of chronic gastric ulcer was evaluated not only from gastric mucoal barrier tissue structure but also from gastric mucus barrier. RESULTS rh bFGF( 5 000 ～ 10 000 AU?kg -1 ) increased the thickness of regenerated gastric mucosa, lowed its abnormity degree and made its align state near to normal. rh bFGF( 2 500 ～ 10 000 AU?kg -1 ) increased collagen and capillary density in scar tissue, added mucus quantity, mucopolysaccharide layer's thickness and PGE 2 content on the surface of regenerated gastric mucosa. CONCLUSION rh bFGF has effects of promoting gastric mucosal barrier to mature, increasing the function of gastric mucus barrier and increasing the quality of ulcer healing.