The differences in dryness between raw Aurantii Fructus Immaturus(AFI) and bran-fried products were investigated based on a slow-transit constipation(STC) model. Seventy healthy SPF-grade rats were randomly divided into a blank group(K), a positive drug group(Y), a model group(M), low-and high-dose raw AFI groups(SD and SG), and low-and high-dose bran-fried AFI groups(FD and FG). During the experiment, it was found that compared with the K group, the groups with drug treatment had little effect on the daily body weight of the STC rats. The first defecation time of black stool in the M group was significantly higher than that in the K group, and the 24-hour fecal output significantly decreased starting from the 13th day, indicating successful modeling. The SG group showed a significant increase in the first defecation time, fecal water content, urine output, and water intake than other groups with drug treatment. The FG group had the highest fecal output than other groups with drug treatment. The FD group had the highest salivary secretion than other groups with drug treatment. The levels of cAMP/cGMP, VIP, 5-HT, AQP1, and AQP5 were measured in each group with drug treatment, and the expression of c-Kit and SCF mRNA in gastric antrum tissue and AQP3 mRNA in the kidney and colon were detected by RT-PCR. The results showed that the SD and SG groups had a more significant impact on AQP1, AQP5, and other water channel indexes in STC rats than the FD and FG groups. The FD and FG groups had a more significant impact on c-Kit, SCF, VIP, 5-HT, and other gastrointestinal motility indicators than the SD and SG groups. This study, through in vitro biological observations, immunological detection, and gene expression analysis, found that raw AFI had strong dryness property, while bran-fried AFI could alleviate its dryness property.
Rats ; Animals ; Serotonin ; Constipation/drug therapy* ; Drugs, Chinese Herbal ; RNA, Messenger

OBJECTIVE: To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC). METHODS: A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot. RESULTS: Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01). CONCLUSION ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.
Mice ; Animals ; Sirtuin 1/genetics* ; Antioxidants ; Occludin ; Lipopolysaccharides ; Claudin-1 ; Mannose ; Mice, Inbred C57BL ; Constipation/drug therapy* ; Inflammation ; Signal Transduction

BACKGROUND: Constipation is a common chronic bowel disorder with an incidence of more than 50% in the elderly population. Complementary and alternative medicine is a cost-effective and satisfactory treatment for constipation used widely by the elderly. OBJECTIVE: This study evaluates the efficacy of an herbal formula made from Foeniculum vulgare Mill. and Rosa damascena for the treatment of constipation in an elderly population and consequent changes to their quality of life. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This double-blind randomized active controlled clinical trial, with parallel group allocation ratio of 1:1, was conducted in a referral clinic in Afzalipour Hospital, affiliated to Kerman University of Medical Sciences in Kerman, Southeastern Iran. Individuals over 60 years of age, diagnosed with functional constipation (based on the Rome IV criteria), were included in this study. Participants received a sachet of 10 g F. vulgare and R. damascena (herbal formula group) or polyethylene glycol 4000 (PEG 4000 group) with a glass of warm water two times a day for 4 weeks and were followed up for 4 additional weeks. MAIN OUTCOME MEASURES: Constipation severity, stool consistency, and the quality of life were used as the primary outcomes. Drug side effects were used as a secondary outcome. The outcomes were assessed using the Constipation Assessment Scale, the Bristol Stool Form Scale, and the Patient Assessment of Constipation Quality of Life questionnaire. RESULTS: A total of 25 participants in each group completed the four-week treatment cycle and the eight-week follow-up. At the end of the four-week treatment cycle, all clinical outcomes had significant improvements in both groups (P < 0.05). The analysis of constipation severity (P < 0.001), stool consistency (P < 0.001), and the quality of life (P < 0.001) showed significant improvements with fewer side effects (mild diarrhea) and a longer duration of symptom relief in the herbal formula group compared to the PEG 4000 group. CONCLUSION: Although both interventions significantly improved the treatment outcomes, constipation severity, stool consistency and the quality of life were improved more effectively by the herbal formula than by PEG 4000; however, the mechanism of action is not yet understood. TRIAL REGISTRATION This trial was registered in the Iranian Registry of Clinical Trials (IRCTID: IRCT20200108046056N1).
Aged ; Constipation/drug therapy* ; Double-Blind Method ; Foeniculum ; Humans ; Iran ; Middle Aged ; Quality of Life ; Rosa ; Treatment Outcome

OBJECTIVES: To study the clinical efficacy, advantages, and disadvantages of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation (OOC). METHODS: A total of 168 children with OOC were enrolled in this prospective study. All the subjects were randomly divided into a test group and a control group based on the order of visiting time, 84 in each group. The test group was treated with adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder, and the control group was treated with oral administration of compound polyethylene glycol 4000-electrolyte powder alone. Eleven children in the test group and two children in the control group withdrew from the study since they could not finish the whole treatment course. Finally, 73 children in the test group and 82 children in the control group were included in this analysis. As clinical outcomes, the total score of clinical symptoms and overall response rate were compared between the two groups at weeks 4 and 8 of treatment. RESULTS: There was no significant difference in the total score of clinical symptoms between the two groups at beginning of treatment and at week 4 (P>0.05), while the test group had a significantly lower total score of clinical symptoms than the control group at week 8 (P<0.05). At week 4, there was no significant difference in overall response rate between the two groups (P>0.05), while the test group had a significantly higher overall response rate than the control group at week 8 (P<0.05). CONCLUSIONS Adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder is significantly associated with improvement of clinical outcomes in the treatment of children with OOC.
Administration, Oral ; Biofeedback, Psychology ; Child ; Constipation/drug therapy* ; Electrolytes/therapeutic use* ; Humans ; Polyethylene Glycols/therapeutic use* ; Powders/therapeutic use* ; Prospective Studies ; Treatment Outcome

OBJECTIVE: To analyze the rules of acupoint and medication selection of acupoint application therapy for functional constipation (FC) by data mining technology. METHODS: The clinical research literature regarding acupoint application therapy for FC from published to February 26, 2020 was searched in CNKI, VIP, Wanfang, SinoMed and PubMed. The prescriptions were extracted, and by using SPSS24.0 and SPSS Modeler14.0 software, the use of high-frequency acupoints and medication was summarized. The association rule analysis, cluster analysis and core prescription analysis of acupoints and medication were analyzed. RESULTS: A total of 122 prescriptions of acupoint application therapy were included, involving 32 acupoints. The core prescription of acupoints was Tianshu (ST 25), Dachangshu (BL 25), Shenque (CV 8) and Guanyuan (CV 4). The high-frequency meridians mainly included conception vessel, CONCLUSION The use of local acupoint and regulating-
Acupuncture Points ; Acupuncture Therapy ; Constipation/drug therapy* ; Data Mining ; Humans ; Meridians

Shouhui Tongbian Capsules was used to explore the therapeutic effect and potential mechanism on slow transit constipation model mice induced by loperamide hydrochloride. In the experiment, loperamide hydrochloride-induced ICR mice were used as the model of slow transit constipation. Fifty ICR mice were divided into the blank group, model group and high, medium and low dose groups of Shouhui Tongbian Capsules extract(100, 200 and 400 mg·kg~(-1)). The model group and the administration groups were then modeled using loperamide hydrochloride intragastrically to obtain slow transit constipation. After successful modeling, high, medium and low doses of drugs were given to each drug group by intragastric administration. After 14 days of administration, the first defecation time, 6 h defecation grain number, 6 h defecation wet weight and dry weight, black feces discharged within 6 h and the fecal water content were measured. Intestinal tissues were taken for c-Kit and SCF immunohistochemical sections to detect the expression of c-Kit and SCF in the blank group, model group and high, medium and low dose groups of the medicinal extract of Shouhui Tongbian Capsules. The tissue changes in the intestinal wall of mice were detected by HE staining. At the same time, partial intestinal tissues were taken to test the activity of ATP synthase and isocitrate dehydrogenase in intestinal tissues of mice. RESULTS:: showed that Shouhui Tongbian Capsules effectively improved the symptoms of slow transit constipation in ICR mice and promoted intestinal movement. Shouhui Tongbian Capsules obviously shortened the time of discharging black stool for the first time, improved the intestinal propulsion rate, increased the water content and amount of feces, and improved the constipation symptoms. Mechanism study revealed that Shouhui Tongbian Capsules increased ATP synthase activity and mitochondrial isocitrate dehydrogenase activity in intestinal tissue, and up-regulated c-Kit/SCF signaling pathway to promote interstitial Cajal cells proliferation, intestinal nerve transmission, intestinal motility and transport capacity.
Animals ; Capsules ; Constipation/drug therapy* ; Gastrointestinal Transit ; Loperamide ; Mice ; Mice, Inbred ICR

The effect of Shouhui Tongbian Capsules(SHTB) on the endogenous metabolites of colon tissue in mice with slow transit constipation was analyzed by metabolomics methods to explore its mechanism in the treatment of constipation. ICR mice were randomly divided into normal group, model group and SHTB group according to the body weight. The mice were given diphenoxylate to establish the slow transit constipation model. Mouse carbon ink pushing rate, first defecation time and the number of defecation particles in 12 h were observed. The mouse colon tissue was separated and the mucous cells were detected by Periodic acid Schiff and Alcian blue(AB-PAS) staining. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry(UPLC-ESI-Orbitrap-MS/MS) technology was used to characterize the differences in tissue metabolism to screen out the potential different metabolites and possible metabolic pathways in colon tissue. The results indicated that SHTB could significantly shorten the first defecation time and the number of defecations, and increase the number of intestinal peristalsis and mucous cells in the colonic mucosa compared to the model mice. Metabolomics results showed that, compared with the normal group, a total of 17 potential biomarkers, including L-kynurenine, N6,N6,N6-trimethyl-L-lysine, L-formylkynurenine, N6-acetyl-L-lysine, L-phenylalanine, phenylacetaldehyde, xanthoxin, thymidine, glycyl-L-leucine, cystathionine,(R)-1-aminopropan-2-ol, deoxycytidine, gamma-glutamyl-gamma-aminobutyraldehyde, D-galactose, L-arginine, L-proline and pyruvate, were found and identified in colon tissue. Treated with SHTB, these metabolic differences tended to return to normal levels. Therefore, it could be made a conclusion that the therapeutic effect of SHTB on chronic transit constipation may be related to regulating phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, tyrosine metabolism, arginine biosynthesis, pyruvate metabolism, glycolysis, pyrimidine metabolism, tricarboxylic acid cycle and galactose metabolism.
Animals ; Biomarkers ; Capsules ; Chromatography, High Pressure Liquid ; Constipation/drug therapy* ; Metabolomics ; Mice ; Mice, Inbred ICR ; Tandem Mass Spectrometry

Dendrobium officinale is a sacred product for nourishing Yin and has a clear "thick gastrointestinal" effect. Modern pharmacological studies had found that it could improve gastrointestinal function. This study observed the improvement effect of D. officinale on constipation model mice with Yin deficiency caused by warm-drying medicine. It provided experimental basis for the treatment of Yin deficiency constipation. The male and female ICR mice were randomly divided into normal group, model group, D. officinale high, medium and low dose groups(0.6, 0.4, 0.2 g·kg~(-1)), and phenolphthalein tablets group. The model mice of Yin deficiency constipation were established by gavage with warm-drying medicine. The overall state and body temperature of the mice were observed and recorded. The number of feces, feces weight, fecal moisture content and intestinal propulsion were measured. The morphological damage of colon tissue was observed by hematoxylin-eosin(HE) staining. The expression of inducible nitric oxide synthase(iNOS) in the colon was detected by Western blot and immunohistochemical method. The expression of iNOS mRNA in the colon was detected by Real-time fluorescence quantitative PCR, and the serum cyclic guanosine phosphate(cGMP) level was detected the enzyme-linked immunosorbent assay(ELISA). The results showed that D. candidum could reduce the body temperature of mice with Yin deficiency constipation, increase the number of feces, wet feces, dry feces and intestinal propulsion ability, reduce the expression of iNOS protein and mRNA in the colon, and reduce the content of cGMP in the serum. It showed that D. candidum could improve the symptoms of Yin deficiency constipation mice caused by warm-drying medicine, and the mechanism may be related to reducing the expression of iNOS in the colon and increasing intestinal motility.
Animals ; Colon ; Constipation/drug therapy* ; Dendrobium ; Female ; Male ; Mice ; Mice, Inbred ICR ; Yin Deficiency/genetics*

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic

Books on Chinese herbal medicines have shown that Dendrobium has the effect of nourishing Yin and reinforcing Yin,usually used for constipation induced by spleen Yin deficiency in clinical application. D. huoshanense,as an independent species among many species of Dendrobium,has no experimental studies about its effects on spleen Yin deficiency-type constipation. The purpose of this experiment was to illustrate the therapeutic effect of D. huoshanense on the constipation of spleen Yin deficiency type in rats,investigate its preliminary mechanism,and compare it with the D. officinale and D. nobile contained in the Chinese Pharmacopoeia to clarify its characteristics. The spleen Yin deficiency model was replicated in 70 rats by the composite factor method,and then the model rats were randomly divided into 7 groups: model group,Liuwei Dihuang Pills group( LWDHP),D. huoshanense high( DHS-H),medium( DHS-M),low( DHS-L) dose groups,D. nobile group( DNS),and D. officinale group( DOS),and another 10 rats were used as normal group( Normal). After 7 continuous days of administration,the fecal water content and intestine propulsion rate of each group were detected. HE staining was used to observe the pathological damage of ileum and colon in each group. Immunohistochemistry and Western blot were used to detect aquaporin 3( AQP3) expressions,while the expression levels of the somatostatin( SS) and motilin( MTL) in the ileum of each group were detected by enzyme-linked immunosorbent assay. The results showed that as compared with the model group,the rats in each drug-administered group had increased number of fecal pellets,increased fecal water content,and the increased intestinal propulsion rate( P<0. 01),while the pathological damage of the ileum and colon was significantly reduced; the expression of AQP3 protein was significantly decreased( P<0. 01); the level of MTL was significantly increased and the level of SS was decreased( P<0. 01). All DHS groups showed a good dose-effect relationship,and the same dose treatment effect was equivalent to that of DOS,but it was superior to DNS. Therefore,DHS has a significant therapeutic effect on constipation of spleen Yin deficiency type,and its mechanism may be related to intestinal motility and water-liquid metabolism,with a good therapeutic effect.
Animals ; Constipation ; drug therapy ; Dendrobium ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Intestines ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Spleen ; Yin Deficiency ; drug therapy