Research progress in the treatment of slow transit constipation by traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Slow transit constipation (STC) is a common gastrointestinal disorder seriously impacting patients' quality of life. At present, although conventional chemical drugs effectively control STC symptoms in the short term, the long-term effects are poor, and the side effects are significant. In this regard, traditional Chinese medicine (TCM) offers an opportunity for STC treatment. Many pharmacological and clinical studies have confirmed this efficacy of TCM with multiple targets and mechanisms. AIM OF THE STUDY: This review attempted to summarize the characteristics of TCM (compound prescriptions, single Chinese herbs, and active ingredients) for STC treatment and discussed their efficacy based on analyzing the pathogenesis of STC. MATERIALS AND METHODS: The information was acquired from different databases, including PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases. We then focused on the recent research progress in STC treatment by TCM. Finally, the future challenges and trends are proposed. RESULTS: TCM has good clinical efficacy in the treatment of STC with multi-mechanisms. Based on the theory of syndrome differentiation, five kinds of dialectical treatment for STC by compound TCM prescriptions were introduced, namely: Nourishing Yin and moistening the intestines; Promoting blood circulation and removing blood stasis; Warming Yang and benefiting Qi; Soothing the liver and regulating Qi; and Benefiting Qi and strengthening the spleen. In addition, six single Chinese herbs and eight active ingredients also show good efficacy in STC treatment. CONCLUSIONS: TCM, especially compound prescriptions, has bright prospects in treating STC attributed to its various holistic effects.

Bamboo shavings derived O-acetylated xylan alleviates loperamide-induced constipation in mice.

BSH-1 is an O-acetylated xylan obtained from bamboo shavings. This study determined the protective effects of BSH-1 against loperamide (Lop)-induced constipation in mice. Mice received BSH-1 by gavage daily for 14 days. In constipated mice, BSH-1 significantly shortened the defecation time and raised the gastrointestinal (GI) transit rate, stool production, and cecal concentration of short-chain fatty acids (SCFAs). BSH-1 regulated the serum levels of gut hormones and neurotransmitters. BSH-1 also significantly altered the cecal microbiota of the constipated mice by increasing the abundance of potentially beneficial bacteria (e.g., Lactobacillus, Roseburia, and Bacteroidales_S24-7) and decreasing potentially pathogenic bacteria (e.g., Alloprevotella and Staphylococcus). Furthermore, colonic transcriptome analysis revealed that BSH-1 significantly reversed the expression changes of genes related to intestinal motility, water and ion transport, inflammation and cancer in constipated mice. Our findings indicated that BSH-1 effectively relieved Lop-induced constipation in mice and could be potentially used for constipation treatment.

Effects of probiotics on loperamide-induced constipation in rats.

The role of probiotics in mitigating constipation, gut immunity, and gut microbiota has not been well studied. We aimed to evaluate the effects of probiotics on loperamide (LP)-induced constipation in Sprague-Dawley rats. Altogether, 150 male Sprague-Dawley rats (age 8 weeks) were used in the experiments following a 12-day acclimatisation period and were randomly divided into three treatment groups (groups 1, 2, and 3). Spastic constipation was induced via oral LP administration (3 mg/kg) for 6 days, 1 h before administering each test compound in groups 1 and 2. A probiotic solution (4 mL/kg body weight) was orally administered once a day for 6 days in group 2. In group 1, a phosphate buffer solution was orally administered once a day for 6 days, 1 h after each LP administration. In group 3, a phosphate buffer solution was orally administered once a day for 6 days. In the probiotic group, faecal parameters improved; faecal n-butyric acid, acetic acid, and IgA concentrations were increased; intestinal transit time was shortened; and disturbance of intestinal microbiota was inhibited. Our findings suggest that this probiotic was useful in improving various symptoms caused by constipation.

The Short-Term Effects and Tolerability of Low-Viscosity Soluble Fibre on Gastroparesis Patients: A Pilot Clinical Intervention Study.

Gastroparesis is a motility disorder that causes severe gastric symptoms and delayed gastric emptying, where the majority of sufferers are females (80%), with 29% of sufferers also diagnosed with Type-1 or Type-2 diabetes. Current clinical recommendations involve stringent dietary restriction and includes the avoidance and minimization of dietary fibre. Dietary fibre lowers the glycaemic index of food, reduces inflammation and provides laxation. Lack of dietary fibre in the diet can affect long-term gastrointestinal health. Our previously published rheological study demonstrated that "low-viscosity" soluble fibres could be a potentially tolerable source of fibre for the gastroparetic population. A randomised controlled crossover pilot clinical study was designed to compare Partially-hydrolysed guar gum or PHGG (test fibre 1), gum Arabic (test fibre 2), psyllium husk (positive control) and water (negative control) in mild-to-moderate symptomatic gastroparesis patients (requiring no enteral tube feeding). The principal aim of the study was to determine the short-term physiological effects and tolerability of the test fibres. In n = 10 female participants, post-prandial blood glucose, gastroparesis symptoms, and breath test measurements were recorded. Normalized clinical data revealed that test fibres PHGG and gum Arabic were able to regulate blood glucose comparable to psyllium husk, while causing far fewer symptoms, equivalent to negative control. The test fibres did not greatly delay mouth-to-caecum transit, though more data is needed. The study data looks promising, and a longer-term study investigating these test fibres is being planned.

Novel Cyclic Endomorphin Analogues with Multiple Modifications and Oligoarginine Vector Exhibit Potent Antinociception with Reduced Opioid-like Side Effects.

Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent µ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.

The Use of a PEG/Ascorbate Booster Following Standard Bowel Preparation Improves Visualization for Capsule Endoscopy in a Randomized, Controlled Study.

BACKGROUND/AIMS: The increasing use of capsule endoscopy (CE) to examine the gastrointestinal tract highlights the need to establish intestinal preparations that ensure optimal visualization while maximizing patient adherence. Thus, we assessed whether bowel preparation involving dietary restriction and a booster regimen produces adequate CE visualization in a real-world clinical setting. METHODS: We conducted a randomized, double-blind, prospective study of CE procedures at 2 tertiary-care centers. Patients were allocated to 3 groups: group 1 followed a clear liquid diet and fasting-based bowel preparation for the exploration (n = 55); group 2 followed the same procedure as group 1 and then ingested 1 L of a polyethylene glycol (PEG)/ascorbic acid booster solution when the capsule reached the small intestine (n = 55); and group 3 followed the same procedure but ingesting only 0.5 L of the booster solution (n = 56). The quality of visualization and the average gastric, orocecal and small-bowel transit times were evaluated. RESULTS: A total of 166 patients participated in the study. Significantly higher quality of visualization (Park score) was obtained in group 3 (2.28 ± 0.59) than in group 1 (1.84 ± 0.54, P < .001), while there were no significant differences in the average gastric (range: 36.58- 48.32 min, P = .277), orocecal (range: 322.58-289.45 min, P = .072), and small-bowel transit time (range: 280.71-249.95 min, P = .286) between the 3 groups. CONCLUSIONS: Following a clear liquid diet and fasting-based bowel preparation for CE exploration, administering a booster solution of PEG/ascorbic acid after the capsule had reached the small intestine improves mucosal visualization and cleansing without affecting capsule transit times.

The protective effects of yellow tea extract against loperamide-induced constipation in mice.

Yellow tea, a rare type tea from China, has a rich breadth of functional ingredients and benefits the gastrointestinal tract. However, it is not clear whether the yellow tea extract can alleviate constipation. Therefore, we used loperamide-induced constipation in mice to evaluate the effects of yellow tea extract. Fifty Kunming mice were randomly divided into five groups: normal, model, low-dose yellow tea extract, low-dose yellow tea extract prevention group, and high-dose yellow tea extract prevention group. Mice were administered yellow tea extract for 5 weeks followed by loperamide-induced constipation for the final 2 weeks. The results showed that yellow tea extract alleviated constipation symptoms by improving the fecal water content, defecation weight, and gastrointestinal transit rate. Yellow tea extract intervention also protected colon tissue, regulated serum neurotransmitters, and decreased the vasoactive intestinal peptide level. Furthermore, qRT-PCR indicated that yellow tea extract regulated genes associated with the constipation state, raised 5-HT3 and 5-HT4 and reduced AQP3 and AQP4 mRNA expression. Moreover, we found that yellow tea extract changed the gut microbiota composition. Community diversity and richness were increased and principal co-ordinate analysis demonstrated that the yellow tea extract prophylaxis groups differed from the model group. Difference analysis indicated that yellow tea extract increased Roseburia, Lachnospiraceae_UCG-006, and Bifidobacterium and decreased norank_f_Clostridiales_vadinBB60_group, unclassified_o_Bacteroidales, and Bacteroides, which are correlated with constipation. Based on these results, we believe that regular yellow tea consumption can effectively alleviate constipation.

Heat-inactivated Lactobacillus plantarum nF1 promotes intestinal health in Loperamide-induced constipation rats.

Constipation is a common condition that affects individuals of all ages, and prolonged constipation needs to be prevented to avoid potential complications and reduce the additional stress on individuals with pre-medical conditions. This study aimed to evaluate the effects of heat-inactivated Lactobacillus plantarum (HLp-nF1) on loperamide-induced constipation in rats. Constipation-induced male rats were treated orally with low to high doses of HLp-nF1 and an anti-constipation medication Dulcolax for five weeks. Study has 8 groups, control group; loperamide-treated group; Dulcolax-treated group; treatment with 3.2 × 1010, 8 × 1010 and 1.6 × 1011, cells/mL HLp-nF1; Loperamide + Dulcolax treated group. HLp-nF1 treated rats showed improvements in fecal pellet number, weight, water content, intestinal transit length, and contractility compared to the constipation-induced rats. Also, an increase in the intestine mucosal layer thickness and the number of mucin-producing crypt epithelial cells were observed in HLp-nF1-treated groups. Further, the levels of inflammatory cytokines levels were significantly downregulated by treatment with HLp-nF1 and Dulcolax. Notably, the metagenomics sequencing analysis demonstrated a similar genus pattern to the pre-preparation group and control with HLp-nF1 treatment. In conclusion, the administration of >3.2 × 1010 cells/mL HLp-nF1 has a positive impact on the constipated rats overall health.

Inhibitory Effects of Dexmedetomidine and Propofol on Gastrointestinal Tract Motility Involving Impaired Enteric Glia Ca2+ Response in Mice.

Propofol and dexmedetomidine are popular used for sedation in ICU, however, inadequate attention has been paid to their effect on gastrointestinal tract (GIT) motility. Present study aimed to compare the effect of propofol and dexmedetomidine on GIT motility at parallel level of sedation and explore the possible mechanism. Male C57BL/6 mice (8-10 weeks) were randomly divided into control, propofol and dexmedetomidine group. After intraperitoneal injection of propofol or dexmedetomidine, comparable sedative level was confirmed by sedative score, physiological parameters and electroencephalogram (EEG). Different segments of GIT motility in vivo (gastric emptying, small intestine transit, distal colon bead expulsion, stool weight and number of fecal pellets, gastrointestinal transit and whole gut transit time) and colonic migrating motor complexes (CMMCs) pattern in vitro were evaluated. The Ca2+ response of primary enteric glia was examined under the treatment of propofol or dexmedetomidine. There is little difference in physiological parameters and composite permutation entropy index (CPEI) between administration of 50 mg/kg propofol and 40 µg/kg dexmedetomidine, indicated that parallel level of sedation was reached. Data showed that propofol and dexmedetomidine had significantly inhibitory effect on GIT motility while dexmedetomidine was stronger. Also, the amplitude (ΔF/F0) of Ca2+ response in primary enteric glia was attenuated after treated with the sedatives while the effect of dexmedetomidine was greater than propofol. These findings demonstrated that dexmedetomidine caused stronger inhibitory effects on GIT motility in sedative mice, which may involve impaired Ca2+ response in enteric glia. Hence, dexmedetomidine should be carefully applied especially for potential GIT dysmotility patient.

Effects of Cisapride, Buprenorphine, and Their Combination on Gastrointestinal Transit in New Zealand White Rabbits.

Due to their effective analgesic properties, opioids are worthy of consideration for pain management in rabbits. However, this class of drugs causes undesirable effects including reduced gastrointestinal (GI) motility, reduced fecal output, and delays GI transit times and thus increases the risk of GI stasis. The risk of stasis discourages the use of opioids in rabbits, which could affect animal welfare. Gastroprokinetic agents such as cisapride are effective in promoting gastric emptying in many species, but whether this effect occurs in rabbits is unknown. This study assessed the efficacy of cisapride when administered as a single agent and in combination with buprenorphine in rabbits; efficacy was assessed by measuring GI transit times, fecal output, body weight, and food and water intake. Female New Zealand White rabbits (n = 10) were studied in a crossover, randomized design and received either vehicle and buprenorphine, cisapride and saline, cisapride and buprenorphine, or vehicle and saline (control) every 8 h for 2 d. Rabbits were anesthetized and administered radio-opaque, barium-filled spheres via orogastric tube. Feces was assessed via radiography for detection of the barium-spheres to determine GI transit time. GI transit time was significantly longer in buprenorphine groups than in control groups, regardless of the use of cisapride. Fecal output and food and water intake were lower for buprenorphine groups than control groups. Cisapride did not significantly alter GI transit, fecal output, or food and water intake. In addition, treatment group did not significantly affect body weight. In conclusion, buprenorphine treatment (0.03 mg/kg TID) prolonged GI transit time and reduced fecal output and food and water consumption in rabbits. Coadministration of buprenorphine and cisapride (0.5 mg/kg) did not ameliorate these effects, and the administration of cisapride at this dose did not appear to affect GI motility in female rabbits.

Antioxidant activity and laxative effects of tannin-enriched extract of Ecklonia cava in loperamide-induced constipation of SD rats.

To investigate the role of tannin-enriched extracts of Ecklonia cava (TEE) on the regulation of oxidative balance and laxative activity in chronic constipation, we investigated alterations after exposure to TEE, on constipation phenotypes, muscarinic cholinergic regulation, and oxidative stress responses in the transverse colons of SD rats with loperamide (Lop)-induced constipation. This extract contains high levels of total condensed tannin content (326.5 mg/g), and exhibited high inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. TEE treatment induced significant improvements in reactive oxygen species (ROS) production, superoxide dismutase (SOD) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation in primary smooth muscles of rat intestine cells (pRISMCs) and transverse colon of constipation model. Also, Lop+TEE treated groups showed alleviated outcomes for the following: most stool parameters, gastrointestinal transit, and intestine length were remarkably recovered; a similar recovery pattern was observed in the histopathological structure, mucin secretion, water channel expression and gastrointestinal hormones secretion in the transverse colon; expressions of muscarinic acetylcholine receptors M2/M3 (mAChR M2/M3) and their mediators on muscarinic cholinergic regulation were significantly recovered. Taken together, these results provide the first evidence that TEE stimulates oxidative stress modulation and muscarinic cholinergic regulation when exerting its laxative effects in chronic constipation models.

Effects of fiber intake on intestinal pH, transit, and predicted oral mesalamine delivery in patients with ulcerative colitis.

BACKGROUND AND AIM: Limited data are available on the effects of fermentable fiber in altering intestinal pH and transit to predict efficacy-based delivery profiles of pH-dependent mesalamine coatings in ulcerative colitis (UC). This study aimed to examine regional pH and transit after acute changes in fermentable fiber intake in quiescent UC patients and their effects on drug release systems. METHODS: In a randomized, double-blind study, 18 patients with quiescent UC and 10 healthy controls were supplied meals high (13 g) or low (≤ 2 g) in fermentable fiber and subsequently ingested a wireless pH-motility capsule. After a ≥ 3-day washout, they crossed over to the other diet. Measurements of intestinal pH and transit were used to predict drug release for the various pH-dependent coatings. RESULTS: Increasing fermentable fiber intake lowered overall (median 6.2 [6.1-6.7] vs low: 6.9 [range or interquartile range: 6.4-7.4]; P = 0.01) and distal pH (7.8 [7.3-8.1] vs 8.2 [8.0-8.5]; P = 0.04) in controls. In UC patients, only cecal pH was decreased (high: 5.1 [4.8-5.5] vs low: 5.5 [5.3-5.7]; P < 0.01). Colonic transit in the UC cohort varied widely after a low-fiber intake but tended to normalize after the high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients, with a multi-matrix delayed release system having the highest likelihood of patients (20-40%) with incomplete dissolution, and predominant small intestinal dissolution predicted for Eudragit L (94% patients) and S (44-69%). CONCLUSIONS: Patients with quiescent UC have abnormalities in intestinal pH and transit in response to acute changes in fermentable fiber intake. These have potentially detrimental effects on predicted luminal release patterns of pH-dependent 5-aminosalicylic acid release systems.

Laxative effect and mechanism of Tiantian Capsule on loperamide-induced constipation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiantian capsule (TTC), as a functional food, which consists of four herb medicines, including Aloe vera Burm.f. (25%), leaf juices, dried; Cucurbita moschata Duch. (25%), fructus, dried; Poria cocos (Schw.) Wolf. (12.5%), sclerotium, dried; Tremella fuciformis Berk. (12.5%), fruiting bodies, dried, and one extract xylooligosaccharides (25%) from Maize Cob by enzymolysis, has been commonly used in China to ameliorate constipation. AIM OF THE STUDY: The aim of the work is to elucidate the potential laxative mechanisms of TTC in loperamide-induced constipated rats. MATERIALS AND METHODS: LC-MS/MS was employed for analyzing the TTC extract. The gastrointestinal transit was evaluated by X-ray. The H&E and Alcian-Blue stain were applied to determine the changes of goblet cells and mucus layer, respectively. Meanwhile, levels of neurotransmitters were evaluated by enzyme-linked immunosorbent assay. The protein expressions were also measured by immunohistochemistry and Western blot. RESULTS: Our results showed that TTC administration attenuated constipation responses in aspects of fecal pellets number, water content of feces, stomach emptying and gastrointestinal transit. Further investigations revealed that TTC treatment not only induced the recovery of neurotransmitters, such as motilin, substance P, somatostatin, endothelin and vasoactive intestinal peptide, but also up-regulated the expressions of c-kit and stem cell factor (SCF). Additionally, the number of goblet cells and thickness of the mucus layer were elevated, and the guanylate cyclase C-cGMP signal pathway was also up-regulated after TTC treatment. CONCLUSION: Our findings demonstrated that the laxative effect of TTC in constipation rats is probably due to the regulation of bowel movement and intestinal fluid secretion.

Effect of glutamine on the growth performance, digestive enzyme activity, absorption function, and mRNA expression of intestinal transporters in heat-stressed chickens.

To explore the effect of glutamine (Gln) on the growth performance, digestive enzyme activity, absorption function and mRNA expression of intestinal transporters in heat-stressed chickens, 540 21-day-old Arbor Acres broilers were randomly assigned to a control group (no stress, NS), Gln group (Chickens were administered 0.5% and 1.0% Gln, respectively), heat stress group (HT), and Gln + HT group (Chickens were administered 0.5% and 1.0% Gln, respectively). The chickens in the HT and Gln + HT groups were reared under HT (36 ± 1 °C for 10 h/d and 22 ± 1 °C for 14 h/d), for 21 days. In contrast to the NS group, heat stress caused a reduction in the body weight gain (BWG); feed intake (FI); activity of trypsin, lipase, alkaline phosphatases, Ca2+ and Mg2+ adenosine triphosphatases, and Na+-K+-ATPase; and content of glutathione and d-xylose (P < 0.05) in the other groups. In addition, compared to the F:G and expression levels in the NS group, the heat stress increased the feed intake:body weight gain (F:G) and mRNA expression levels of SGLT1, CaBP-D28k, and L-GSBP (P < 0.05). Furthermore, HT-challenged birds were pretreated with Gln, the BWG; FI; activity of trypsin, lipase, alkaline phosphatase, Ca2+ and Mg2+ adenosine triphosphatases, and Na+-K+-ATPase; and content of glutathione and d-xylose (P < 0.05) were dramatically increased, but it decreased the F:G and mRNA expression levels of SGLT1, CaBP-D28k, and L-GSBP (P < 0.05) in the HT group. In summary, Gln can effectively improve growth performance and may promote digestion and absorption in the gastrointestinal tract by mediating the mRNA expression level of nutrient transporters and Gln metabolism in heat-stressed broilers.

Dexamethasone programs lower fatty acid absorption and reduced PPAR-γ and fat/CD36 expression in the jejunum of the adult rat offspring.

The progeny of rats born and breastfed by mothers receiving dexamethasone (DEX) during pregnancy exhibits permanent reduction in body weight and adiposity but the precise mechanisms related to this programming are not fully understood. In order to clarify this issue, the present study investigated key aspects of lipoprotein production and lipid metabolism by the liver and the intestine that would explain the reduced adiposity seen in the adult offspring exposed to DEX in utero. Female Wistar rats were treated with DEX (0.1 mg/kg/day) between the 15th and the 21st days of pregnancy, while control mothers were treated with vehicle. Male offspring born to control mothers were nursed by either adoptive control mothers (CTL/CTL) or DEX-treated mothers (CTL/DEX). Male offspring born to DEX-treated mothers were nursed by either control mothers (DEX/CTL) or adoptive DEX-treated mothers (DEX/DEX). We found that only the male DEX/DEX offspring had reduced adiposity. Additionally, male DEX/DEX progeny had lower circulating triacylglycerol (TAG) levels only in fed-state. The four groups of offspring presented similar energy expenditure, respiratory quotient and very low-density lipoprotein (VLDL) production. On the other hand, DEX/DEX rats displayed reduced TAG levels after gavage with olive oil and reduced expression of fatty acid translocase Cd36 (Fat/Cd36) and peroxisome proliferator-activated receptor γ (Pparg) in the jejunum. Altogether, our study supports the notion that reduced fat absorption by the jejunum may contribute to the lower adiposity of the adult offspring born and breastfed by mothers treated with DEX during pregnancy.

Hydrogen and methane breath test results are negatively associated with IBS and may reflect transit time in post-surgical patients.

BACKGROUND: Contention surrounds hydrogen and methane breath tests as putative measures of small intestinal bacterial overgrowth. We aimed to explore the clinical characteristics associated with positive and negative results to help clarify their role. METHODS: 525 glucose hydrogen/methane breath tests completed over 3 years were analyzed to look for positively and negatively associated predictive factors. Characteristics such as height and weight and underlying medical conditions, medications, and surgical history were collated. KEY RESULTS: There were 85 and 42 positive hydrogen and methane tests, respectively. Patients with irritable bowel syndrome (IBS) (HR = 0.17, p = 0.004) and those with a higher body mass index (HR = 0.93, p = 0.004) were significantly less likely to have a positive test. Patients who underwent the test post-surgically were significantly more likely to have a positive test (HR = 2.76, p = 0.001). A sub-analysis of post-surgical patients by type and region of surgical resection demonstrated that none were statistically more likely than the next to have a positive test. However, for the surgical group as a whole the number of motility-depressing drugs taken (such as opioids) was associated with a significantly decreased likelihood of a positive test (HR = 0.752, p = 0.045). CONCLUSION: Our data suggest that patients with a diagnosis of IBS are statistically less likely to have a positive test and it is of limited utility in this group. Post-surgical patients are more likely to have a positive test, possibly secondary to fast transit rather than bacterial overgrowth, as suggested by a significantly negative association with motility-suppressing drugs in this sub-group.

The role of autonomic pathways in peripheral apelin-induced gastrointestinal dysmotility: involvement of the circumventricular organs.

NEW FINDINGS: What is the central question of this study? Are central autonomic pathways and circumventricular organs involved in apelin-induced inhibition of gut motility? What is the main finding and its importance? Peripherally administered apelin-13 inhibits gastric and colonic motor functions through sympathetic and parasympathetic autonomic pathways, which seems to be partly mediated by the apelin receptor in circumventricular organs. ABSTRACT: Peripheral administration of apelin-13 has been shown to inhibit gastrointestinal (GI) motility, but the relevant mechanisms are incompletely understood. This study aimed to investigate (i) whether the apelin receptor (APJ) is expressed in circumventricular structures involved in autonomic functions, (ii) whether they are activated by peripherally administered apelin, (iii) the role of autonomic pathways in peripheral exogenous apelin-induced GI dysmotility, and (iv) the changes in apelin levels in the extracellular environment of the brain following its peripheral application. Ninety minutes after apelin-13 administration (300 µg kg-1 , i.p.), gastric emptying (GE) and colon transit (CT) were measured in rats that underwent parasympathectomy and/or sympathectomy. Plasma and cerebrospinal fluid (CSF) samples were also collected from another group of rats that received apelin-13 or vehicle injection. The immunoreactivities for APJ and c-Fos in circumventricular organs (CVOs) were evaluated by immunohistochemistry. Compared with vehicle-treated rats, GE and CT were inhibited significantly by apelin-13 treatment, and were completely restored in animals that underwent the combination of parasympathectomy and sympathectomy and sympathectomy alone, respectively. Apelin concentrations were elevated in both plasma and CSF following peripheral administration of apelin-13. APJ expression was detected in area postrema (AP), subfornical organ and organum vasculosum of lamina terminalis, and c-Fos expression was observed in response to apelin injection. Apelin-induced c-Fos expression in AP was partially attenuated by pretreatment with the cholecystokinin-1 receptor antagonist lorglumide, whereas it was completely abolished in vagotomized rats. The present data suggest that APJ in CVOs could indirectly contribute to the inhibitory action of peripheral apelin on GI motor functions.

Aster tataricus alleviates constipation by antagonizing the binding of acetylcholine to muscarinic receptor and inhibiting Ca2+ influx.

BACKGROUND: The dried root and rhizome of Aster tataricus (RA), is a traditional Chinese medicine has been used for more than 2000 years with the function of antitussive, expectorant and antiasthmatic. Ancient books and modern pharmacological researches demonstrated that RA may have the function of moistening intestines and relieving constipation, but there was a lack of systematic evidence. The aim of this study was to comprehensively evaluate the efficacy and possible mechanisms of ethanol extract of Aster tataricus (ATE) in treating constipation from in vivo to in vitro. METHODS: In vivo, the ATE was studied in loperamide-induced constipation of mice. In vitro, different concentrations of ATE was tested separately or cumulatively on spontaneous and agonists-induced contractions of isolated rat duodenum strips. RESULTS: In vivo, at doses of 0.16, 0.8 g/mL, ATE showed significantly promotion of the small intestinal charcoal transit, decrease of the amount of remnant fecal, and increase of the content of fecal water in colon. In addition, ATE could effectively relieve colonic pathological damage caused by loperamide as well. In vitro, with the cumulative concentration increase of ATE from 0.8 to 6.4 mg/mL, it could significantly decrease the contraction caused by KCl or Ach, and gradually restore to near base tension value.Meanwhile, it could also partially but significantly inhibit the contractions induced by Ach and CaCl2 on rat duodenum in a concentration related manner. CONCLUSIONS: Taking all these findings together, it could be speculated that ATE may attenuate constipation mainly through antagonizing the binding of acetylcholine to muscarinic receptor, inhibiting Ca2+ influx and anti-inflammation.

Mildly Pasteurized Whey Protein Promotes Gut Tolerance in Immature Piglets Compared with Extensively Heated Whey Protein.

Human milk is the optimal diet for infant development, but infant milk formula (IMF) must be available as an alternative. To develop high-quality IMF, bovine milk processing is required to ensure microbial safety and to obtain a protein composition that mimics human milk. However, processing can impact the quality of milk proteins, which can influence gastro-intestinal (GI) tolerance by changing digestion, transit time and/or absorption. The aim of this study was to evaluate the impact of structural changes of proteins due to thermal processing on gastro-intestinal tolerance in the immature GI tract. Preterm and near-term piglets received enteral nutrition based on whey protein concentrate (WPC) either mildly pasteurized (MP-WPC) or extensively heated (EH-WPC). Clinical symptoms, transit time and gastric residuals were evaluated. In addition, protein coagulation and protein composition of coagulates formed during in vitro digestion were analyzed in more detail. Characterization of MP-WPC and EH-WPC revealed that mild pasteurization maintained protein nativity and reduced aggregation of ß-lactoglobulin and α-lactalbumin, relative to EH-WPC. Mild pasteurization reduced the formation of coagulates during digestion, resulting in reduced gastric residual volume and increased intestinal tract content. In addition, preterm piglets receiving MP-WPC showed reduced mucosal bacterial adherence in the proximal small intestine. Finally, in vitro digestion studies revealed less protein coagulation and lower levels of ß-lactoglobulin and α-lactalbumin in the coagulates of MP-WPC compared with EH-WPC. In conclusion, minimal heat treatment of WPC compared with extensive heating promoted GI tolerance in immature piglets, implying that minimal heated WPC could improve the GI tolerance of milk formulas in infants.