Therapeutic effect of Cistanche deserticola on defecation in senile constipation rat model through stem cell factor/C-kit signaling pathway

BACKGROUND Constipation is one of the chronic gastrointestinal functional diseases.It seriously affects the quality of life.Cistanche deserticola(C.deserticola)can treat constipation obviously,but its mechanism has not been clarified.We supposed that mechanism of it improved the intestinal motility by stimulating interstitial Cajal cells(ICC).Activation of the C-kit receptor on the surface of ICC is closely related to ICC function,and the stem cell factor(SCF)/C-kit signaling pathways plays an important role on it.To investigate the mechanism of how C.deserticola treats constipation,this study aimed to establish a constipation model in rats and explore the role of SCF/C-kit signaling pathway in the treatment.AIM To explore the SCF/C-kit signaling pathways in the role of C.deserticola for treatment of constipation by a constipation rat model.METHODS Forty-eight 8-mo-old Sprague–Dawley rats were divided into 4 groups by random weight method:Normal group(n=12),model group(n=12),C.deserticola group(n=12)and blocker group(n=12).The normal group received normal saline by gavage;the model group received loperamide by gavage;the blocker group received loperamide and C.deserticola by gavage,and STI571 was injected by intraperitoneally.During treatment,the weight,fecal granules and fecal quality were recorded every 10 d.On day 20 after model induction,the colon tissues of each group were removed.Hematoxylin and eosin staining was used to observe pathological changes.Expression levels of SCF,C-kit and Aquaporin genes were detected by immunohistochemistry,western blotting,and real-time-quantitative polymerase chain reaction.The colonic epithelial mitochondria and goblet cells were observed by transmission electron microscopy.RESULTS Compared with the normal group,as treatment progressed,the weight of rats in the model and blocker groups decreased significantly,the stool weight decreased,and the stool quality was dry(P<0.05).C.deserticola reversed the decrease in body weight and stool weight and improved stool quality.Histopathological analysis indicated that the colonic mucosal epithelium in the model group was incomplete,and the arrangement of the glands was irregular or damaged.Treatment with C.deserticola improved the integrity and continuity of the epithelial cells and regular arrangement of the glands.The blocking agents inhibited the effects of C.deserticola Immunohistochemistry and real-timequantitative polymerase chain reaction showed that expression of SCF and C-kit protein or genes in the colonic tissue of the model group was decreased(P<0.05),while treatment with C.deserticola increased protein or gene expression(P<0.05).Western blotting showed that expression of aquaporin APQ3 was increased,while the expression of Cx43 decreased in the model group.Treatment with C.deserticola inhibited expression of APQ3 and promoted expression of Cx43.Transmission electron microscopy showed that the mitochondria of the colonic epithelium in the model group were swollen and arranged disorderly,and microvilli were sparse.The condition was better in the C.deserticola group.Mice treated with STI571 blocker confirmed that blocking the SCF/C-kit pathway inhibited the improvement of constipation by C.deserticola.CONCLUSION C.deserticola improved defecation in rats with constipation,and the SCF/C-kit signaling pathway,which is a key link of ICC function,played an important role of the treatment.

Systematic Evaluation of Maren Runchang Pill(麻仁润肠丸)in the Treatment of Patients with Senile Constipation

To systematically evaluate the clinical efficacy and safety of Maren Runchang Pill(麻仁润肠丸)in the treatment of senile constipation.Randomized controlled trials(RCT)on the treatment of senile constipation with Maren Runchang Pill(麻仁润肠丸)were searched by computer in CNKI,CBM,WanFang,VIP,PubMed,EMbase and the Cochrane Library databases.The retrieval time limit was from the establishment of the database to May 2019.A total of 2 researchers independently screened literature and extracted data according to the inclusion criteria,and Meta-analyzed the RCT that met the standards by applying RevMan5.3 software.A total of 5 randomized controlled trials were included,including 395 patients with senile constipation,199 in the experimental group and 196 in the control group.The treatment group was treated with Maren Runchang Pill(麻仁润肠丸),while the control group was treated with other Western medicine,including fruit guide tablets,lactulose oral liquid or kaisailu,etc.The results of Meta-analysis showed that there was no significant difference in the total clinical efficacy between Maren Runchang Pill(麻仁润肠丸)and other Western medicines[RR=1.02,95%CI(0.88,1.17),P=0.83].In terms of improvement of abdominal distension and inappetence,there was no significant difference between the treatment with Maren Runchang Pill(麻仁润肠丸)and other Western medicine[RR=1.03,95%CI(0.85,1.24),P=0.78].Maren Runchang Pill(麻仁润肠丸).This study showed that the efficacy of Maren Runchang Pill(麻仁润肠丸)in the treatment of senile constipation was not significantly different from that of conventional Western medicine,and was safe,and effective,with few adverse reactions.Maren Runchang Pill(麻仁润肠丸),as a traditional Chinese patent medicine,can play the role of regulating qi and replenishing blood,and regulating bowel and bowel laxative,with fewer cost.It is more suitable for the elderly to use,with good compliance,and clinically it should be used with syndrome differentiation.However,due to the quantity and quality of the original study,multi-center,high-quality randomized controlled trials are still needed to further confirm it.

Analysis of mechanism of Buzhong Yiqi Decoction in treating senile functional constipation via network pharmacology

Objective:To explore the molecular mechanism of buzhong yiqi decoction in the treatment of senile functional constipation based on network pharmacology.Methods:Chemical compositions and selected targets related to the eight traditional Chinese medicine herbs were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Through GeneCards database and OMIM database,disease targets of senile functional constipation were searched.R language was used to screen the common targets between drugs and disease,and then the interaction network diagram of the targets was constructed by String.Cytoscape3.7.0 was applied to construct the traditional Chinese medicines-chemical compositions-disease targets network.GO enrichment analysis and KEGG enrichment analysis of the targets were based on DAVID.Results:Five main chemical compositions including quercetin,kaempferol,nobiletin,naringenin and formononetin were screened,and five key targets including PTGS2,ESR1,AR,NOS2 and PPARG were identified.622 GO functional entries and 125 pathways were yielded by gene enrichment analysis.Conclusion:Buzhong yiqi decoction may play the role of anti-inflammatory and anti-oxidation through multi-component,multi-target and multi-channel,so as to improve senile functional constipation.