Jianpi Qingchang decoction regulates intestinal motility of dextran sulfate sodium-induced colitis through reducing autophagy of interstitial cells of Cajal

AIM To investigate the underlying effect of Jianpi Qingchang decoction(JQD) regulating intestinal motility of dextran sulfate sodium(DSS)-induced colitis in mice. METHODS C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15^(th) day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of Cajal(ICC) were observed. The levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, IL-10 and interferon gamma(IFN-γ), the expression of nuclear factor-kappa B(NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3(LC3-Ⅱ) and Beclin-l m RNA, and the colonic smooth muscle tension were assessed. RESULTS Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1β, TNF-α, IL-10 and IFN-γ, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency increased(P < 0.05), the expression of c-kit m RNA and the colonic smooth muscle contractile amplitude decreased in the DSS group(P < 0.05). Compared with the DSS group, the levels of IL-10 and IFN-γ, the expression of c-kit m RNA, and the colonic smooth muscle contractile amplitude increased(P < 0.05), the levels of TNF-α and IL-1β, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency decreased in the JQD group(P < 0.05).CONCLUSION JQD can regulate the intestinal motility of DSS-induced colitis in mice through suppressing intestinal inflammatory cascade reaction, reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle cells.

Changes in Small Intestinal Motility and Related Hormones by Acupuncture Stimulation at Zusanli(ST 36) in Mice

Objective： To clarify the effects of acupuncture stimulation at Zusanli（ST 36） on the hormonal changes. Methods： Eight-week-old male C57BL/6 mice received acupuncture stimulation at acupoint ST 36 or Quchi（LI 11） once a day for 3 or 5 days in the acupuncture-stimulated groups, but not received in the normal group（n=6 in each group）. On day 3 or 5, animals were given 0.1 m L of charcoal orally with a bulbed steel needle, 30 min after the last acupuncture stimulation. Ten minutes later, mice were anesthetized, and the intestinal transit and the concentrations of vasoactive intestinal peptide（VIP）, motilin, ghrelin and gastrin in the serum were measured. Results： Compared to no acupuncture stimulation, acupuncture stimulation at ST 36 for 5 days increased the intestinal transit and down-regulated the concentration of VIP and up-regulated the concentrations of motilin, ghrelin and gastrin（P〈0.05 or 0.01）, whereas acupuncture stimulation at LI 11 did not change them significantly（P〉0.05）. Conclusion： Acupuncture stimulation at ST 36 for 5 days enhances the small intestinal motility and regulates the secretion of hormones related to small intestinal motility.

Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation

BACKGROUND Slow transit constipation(STC)is a disorder with delayed colonic transit.Cinnamic acid(CA)is an organic acid in natural plants,such as Radix Scrophulariae(Xuan Shen),with low toxicity and biological activities to modulate the intestinal microbiome.AIM To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids(SCFAs)and evaluate the therapeutic effects of CA in STC.METHODS Loperamide was applied to induce STC in mice.The treatment effects of CA on STC mice were assessed from the 24 h defecations,fecal moisture and intestinal transit rate.The enteric neurotransmitters:5-hydroxytryptamine(5-HT)and vasoactive intestinal peptide(VIP)were determined by the enzyme-linked immunosorbent assay.Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function.16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome.The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.RESULTS CA ameliorated the symptoms of STC and treated STC effectively.CA ameliorated the infiltration of neutrophils and lymphocytes,increased the number of goblet cells and acidic mucus secretion of the mucosa.In addition,CA significantly increased the concentration of 5-HT and reduced VIP.CA significantly improved the diversity and abundance of the beneficial microbiome.Furthermore,the production of SCFAs[including acetic acid(AA),butyric acid(BA),propionic acid(PA)and valeric acid(VA)]was significantly promoted by CA.The changed abundance of Firmicutes,Akkermansia,Lachnoclostridium,Monoglobus,UCG.005,Paenalcaligenes,Psychrobacter and Acinetobacter were involved in the production of AA,BA,PA and VA.CONCLUSION CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.

The Effect of Acupuncture on Intestinal Motility and Sero－Enzyme Activity in Perioperation

The authors studied 39 surgical patients suffering from abdominal illnesses. The patientswere divided into acupuncture and control groups. In the acupuncture group, needles were inserted atacupuncture points Zusanli (St 36) and Sanyinjiao (Sp.6) during the second 12 hours following the opera-tion. The patients were then observed to mark the time of the first passing of flatus. Sero-enzyme activityof glutamic pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT) and glutamyltranspeptidase ( -GT) was determined before the operation, and measured at two day intervals from the1st to 7th days after the operation. The results show the time of passing flatus in the acupuncture group(58. 78±23. 94 h) was obviously faster than that in the control group (86. 14±20. 43 h) , P<O. 001. Thissuggests acupuncture can promote intestinal activity. After operation, sero-enzyme activity was raised200 % - 300 % over the average pre-operation activity. This is evidence of trauma to the cells caused bythe surgical procedure. This trauma caused the cells, directly or indirectly, to release enzymes into theblood. However, in those patients who received acupuncture therapy, sero-enzyme activity reduced to anormal level much faster. There is a possibility that acupuncture may be used to regulate reactivity of or-ganisms experiencing trauma, and to promote repair of the damaged cells.

Effects of a Combination of Fu Zi and Rou Gui on Intestinal Neurotransmitters and Microflora in Rats with Slow Transit Constipation

[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae) and Rou Gui(Cortex Cinnamomi, the bark of Cinnamamunz cassia Presl of family Lauraceae) on intestinal neurotransmitters and microflora in rats with slow transit constipation(STC). [Methods] Experimental rats were given loperamide hydrochloride by gavage to induce STC, and then treated with Fu Zi alone, Rou Gui alone, a combination of Fu Zi and Rou Gui(2:1 w/w), and prucalopride, respectively, for 14 days. Meanwhile, the general condition, the time to first black stool and the rate of intestinal propulsion of rats in each group were observed after STC was induced and after drug treatment, and the pathological changes in rat colon were observed via hematoxylin-eosin(HE) staining, and the levels of colonic 5-hydroxytryptamine(HT), vasoactive intestinal peptide(VIP) and substance P(SP) were detected by ELISA, and the changes in intestinal flora were detected by 16S rRNA Real-time PCR. [Results] Compared with healthy rats, the time to first black stool and the rate of intestinal propulsion, colonic 5-HT and SP levels significantly decreased(p<0.01), while their colonic VIP level significantly increased(p<0.01). Compared with STC rats, the time to first black stool, the rate of intestinal propulsion, colonic 5-HT and SP levels in Fu Zi-Rou Gui(2:1) treated rats and prucalopride treated rats significantly increased(p<0.01), while their colonic VIP level significantly decreased(p<0.01). There was no significant difference in alpha diversity between healthy rats and STC rats. However, analysis on beta diversity revealed that there were differences in microflora structure and composition between them. Compared with healthy rats, the relative abundance of Firmicutes and Proteobacteria in STC rats significantly increased, while that of Bacteroidetes decreased. Compared with STC rats, the relative abundance of Proteobacteria decreased and that of Bacteroidetes and Firmicutes increased in Fu Zi-Rou Gui(2:1) treated rats;the relative abundance of Bacteroidetes and Proteobacteria decreased while that of Firmicutes increased in Fu Zi treated rats;the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased in Rou Gui treated rats;the relative abundance of Firmicutes and Proteobacteria decreased while that of Bacteroidetes increased in prucalopride treated rats. The intestinal flora in rats of all groups was dominated by Lactobacillus spp. and other genera of anaerobic bacteria. Compared with healthy rats, the relative abundance of Lactobacillus spp. and Clostridium spp. in STC rats decreased, while those of Blautia spp. and Ruminococcus spp. and Allobaculum spp. increased. Compared with STC rats, the relative abundance of Lactobacillus spp. in all rats treated with drugs increased. [Conclusions] The combination of Fu Zi and Rou Gui(2:1) can effectively improve intestinal motility in STC rats by regulating intestinal microbial community and the levels of colonic neurotransmitters.

Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study

AIM To identify a set of contributors, and weight and rank them on a pathophysiological basis.METHODS Patients who have undergone a lactulose or glucose hydrogen breath test to rule out small intestinal bacterial overgrowth(SIBO) for various clinical symptoms, including diarrhoea, weight loss, abdominal pain, cramping or bloating, were seen as eligible for inclusion in a retrospective single-centre study. Clinical data such as co-morbidities, medication, laboratory parameters and other possible risk factors have been identified from the electronic data system. Cases lacking or with substantially incomplete clinical data were excluded from the analysis. Suspected contributors were summarised under four different pathophysiological pathways(impaired gastric acid barrier, impaired intestinal clearance, immunosuppression and miscellaneous factors including thyroid gland variables) and investigated using the χ2 test, Student's t-test and logistic regression models.RESULTS A total of 1809 patients who had undergone hydrogen breath testing were analysed. Impairment of the gastric acid barrier(gastrectomy, odds ratio: OR = 3.5, PPI therapy OR = 1.4), impairment of intestinal clearance(any resecting gastric surgery OR = 2.6, any colonicresection OR = 1.9, stenosis OR = 3.4, gastroparesis OR = 3.4, neuropathy 2.2), immunological factors(any drug-induced immunosuppression OR = 1.8), altered thyroid gland metabolism(hypothyroidism OR = 2.6, levothyroxine therapy OR = 3.0) and diabetes mellitus(OR = 1.9) were associated significantly to SIBO. Any abdominal surgery, ileocecal resection, vagotomy or Ig A-deficiency did not have any influence, and a history of appendectomy decreased the risk of SIBO. Multivariate analysis revealed gastric surgery, stenoses, medical immunosuppression and levothyroxine to be the strongest predictors. Levothyroxine therapy was the strongest contributor in a simplified model(OR = 3.0).CONCLUSION The most important contributors for the development of SIBO in ascending order are immunosuppression, impairment of intestinal clearance and levothyroxine use, but they do not sufficiently explain its emergence.

Gastrointestinal problems in a valproic acid-induced rat model of autism: From maternal intestinal health to offspring intestinal function

BACKGROUND Autism spectrum disorder(ASD)is a developmental disorder characterized by social deficits and repetitive behavior.Gastrointestinal(GI)problems,such as constipation,diarrhea,and inflammatory bowel disease,commonly occur in patients with ASD.Previously,GI problems of ASD patients were attributed to intestinal inflammation and vertical mother-to-infant microbiome transmission.AIM To explore whether GI problems in ASD are related to maternal intestinal inflam-mation and gut microbiota abnormalities.METHODS An ASD rat model was developed using valproic acid(VPA).Enzyme-linked immunosorbent assay and fecal 16S rRNA sequencing were used to test GI changes.RESULTS VPA exposure during pregnancy led to pathological maternal intestinal changes,resulting in alterations in maternal gut microbiota.Additionally,the levels of inflammatory factors also increased.Moreover,prenatal exposure to VPA resulted in impaired duodenal motility in the offspring as well as increased levels of infla-mmatory factors.CONCLUSION GI problems in ASD may be associated with maternal intestinal inflammation and microbiota abnormality.Future research is required to find more evidence on the etiology and treatment of GI problems in ASD.

Histological and Morphological Study of the Intestines of Wistar Rat Fetuses in a Modified Gastroschisis Experimental Model

In gastroschisis (G), the lesion degree of exposed intestinal segments is related to the time of its contact with the amniotic fluid (AF) and exposure to meconium which is the cause of intestinal morphological and histological alterations. The outcome of these alterations is intestinal hypoperistalsis and nutrient absorption deficiency, which contribute to increased morbidity and high medical-hospital costs. In this study, morphological and histological intestine alterations were identified at two different contact occasions with AF. Experimental gastroschisis (G) was performed on Wistar rat fetuses at a single gestational age on day 18.5th. The fetuses were removed on the 20.5th (G-1) and 21.5th days (G-2). Fetuses of both groups were divided in 3 sub-groups: control (C), gastroschisis (G) and sham (S). Measurements were taken of the Whole Set including fetus, placenta and membranes with AF (WS), fetus body weight (BW), intestinal weight (IW) and their diameters (DI). The objective of the present study is to test a new gastroschisis experimental model and identify differences in morphological and histological alterations in these two gestational periods that may be directly related to intestinal motility disorders in G. The WS and BW presented no significant statistical difference when compared G1 and G2. The results of the intestine average weight of G2 fetuses were significantly higher when compared to G1 fetuses in all subgroups (C: p = 0.02;G: p = 0.01;S: p = 0.02, Mann Whitney). The results of the intestinal average diameters (D/d) in G1 and G2 presented significant statistical difference only in G subgroup (p Kruskal Wallis). When compared intestinal average diameters, there was significant statistical difference of G fetuses in G1 and G2 (p Mann Whitney). In conclusion, the present experimental G model was adequate to reproduce G in rat fetuses. All G fetuses presented significant statistical difference when compared to other group in their subgroup and when compared G1 and G2 (p < 0.05). These alterations can explain the difficulties in accomplishing adequate peristalsis in G neonate bearers.

Shouhui Tongbian Capsule in treatment of constipation: Treatment and mechanism development

Constipation is common in the diseases of the digestive system in clinics.With the change in diet structure and the increase in life pressure,the prevalence rate increases year by year.In traditional Chinese medicine(TCM),the location of the disease of constipation is in the large intestine,which is related to the dysfunction of lung,spleen,liver,kidney and other viscera.Its pathogenesis is conductive dysfunction of large intestine.Based on the theory,Shouhui Tongbian Capsule(SHTB)is composed of eight traditional Chinese medicines,including Polygoni multiflori Radix(Heshouwu in Chinese),Aloe(Luhui in Chinese),Cassiae Semen(Juemingzi in Chinese),Ginseng Radix et Rhizoma(Renshen in Chinese),Lycii Fructus(Gouqizi in Chinese),Asini Corii Colla(Ejiao in Chinese),Aurantii Fructus Immaturus(Zhishi in Chinese),and Atractylodis Macrocephalae Rhizoma(Baizhu in Chinese),which could help to release excessive turbid,and nourishing yin and supplementing qi in the treatment.This study has been carried out to review the latest advances of SHTB in the treatment of constipation.The results showed that significant effect of SHTB was found in the treatment of constipation,such as functional constipation,and constipation associated with tumor chemotherapy,colitis,type 2 diabetes and chronic cardiac failure.Besides,obvious adverse reactions were not observed.SHTB could effectively treat five types of constipation,provide direction for the future exploration of SHTB in the treatment of other types of constipation。

In vivo anti-diarrheal activity of jujube honey on castor oil-induced diarrhea in mice

OBJECTIVE:To evaluate the antidiarrheal effect of jujube honey on experimentally castor oil-induced diarrhea in mice by using different testing models(diarrhea,enteropooling and gastrointestinal motility).METHODS:The mice intragastric administration castor oil was post-treated after 30 min with jujube honey,diluted jujube honey and loperamide or vehicles in different experimental groups.The onset and number of wet defecation on the absorbent paper was recorded for each animal for 4 h.Plasma was examined for C-reactive protein(CRP)and nitric oxide(NO)for clinical inflammation evaluation.The oxidative stress was investigated by superoxide dismutase(SOD)and catalase levels.RESULTS:The diluted jujube honey exhibited an important antidiarrheal activity manifested by significant delay in onset of diarrhea(P<0.05),loss in number of wet stools(P<0.001),total number of stools(P<0.001)and total stool weight of fecal output(P<0.001)in 4 h in castor oil-induced diarrheal groups.The inhibition of intestinal transit of charcoal meal(P<0.01)is a most likely mechanism that may account for antidiarrheal effect of jujube honey.It also significantly increased SOD and catalase levels(P<0.001)and significantly decreased CRP and NO in plasma diarrheic mice(P<0.01).CONCLUSION:The results of this research reveal that the jujube honey contains pharmacologically active compounds with antidiarrheal properties.However,diluted honey is more effective in the treatment of diarrhea and imbalance of intestinal motility.In conclusion,these findings illustrated the antidiarrheal activity effect of jujube honey and which has the strongest evidence supporting its use in the treatment of diarrhea in traditional medicine.

Bioactive xanthones from whole plants of Gentianella acuta

Objective： To study the constituents from the whole plants of Gentianella acuta and their biological activities.Methods： The compounds were isolated by multiple chromatographic methods and the structures of mentioned isolates were determined by routine NMR experiments and chemical methods.Results： A phytochemical investigation to obtain intestine motility inhibitor resulted in the isolation of one new xanthone glycoside,gentixanthonoside A（1）,along with nine tetrahydroxanthones,1,3,5R,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone（2）,1,3,5S,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone（3）,amarellin E（4）,amarellin F（5）,swertiachoside B（6）,amarellin D（7）,amarellin C（8）,amarellin A（9）,and amarellin B（10）from the whole plants of G.acuta.Conclusion： Compounds 2 –10 showed significant reduce effects on contraction tension at 40 μM.