Constipation In Rats Research Articles

Houpo Paiqi Mixture Promotes Intestinal Motility in Constipated Rats by Modulating Gut Microbiota and Activating 5-HT-cAMP-PKA Signal Pathway.

Constipation is a common functional gastrointestinal disorder which needs more effective treatment approaches. Houpo Paiqi Mixture (HPPQM) is a type of Chinese patent medicine developed from a classical formula that has been widely applied to the treatment of intestinal motility disorder. Here we aim to assess the effectiveness of HPPQM in the treatment of constipation in rat models and its potential mechanism. UPLC-MS/MS was performed to investigate the chemical component of HPPQM. Rats were randomly divided into normal control, constipation model (CM), HPPQM (low, middle and high dose) and mosapride groups. Loperamide 8mg/kg was given orally to induce constipation model. The small intestine motility, colonic contraction, rectum propulsion and histological feature of the colon were significantly improved in HPPQM group, compared with CM group (P<0.05). Results of 16S rRNA sequencing revealed that HPPQM treatment strikingly restructured intestinal microbiota in constipated rats by increasing the relative abundances of Bacteroides and Akkermansia and decreasing the relative abundances of Prevotella and Lactobacillus. The levels of GPR43, 5-HT, 5-HT4R, cAMP, PKA were decreased while SERT was increased in constipated rats (P<0.05), which could be restored to normal levels by treatment with HPPQM (P<0.05). Differences in amplitude between experimental CLSMs (with HPPQM added) and control CLSMs were discovered, starting at the concentration of 40 nL/mL (P<0.05). It was found that GLPG0974 and GR113808 could significantly reduce this reactivity (P<0.05). HPPQM manifested a curative effect in constipated rats by promoting intestinal motility. The underlying mechanisms might be related to modulating gut microbiota and activating 5-HT-cAMP-PKA signal pathway.

Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats.

Sacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats. Experiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB). (1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p < 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p < 0.01); yet SNS normalized vagal activity. SNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRACT.

The Effect of Polysaccharide Extracted from Raw Atractylodes Macrocephala on Loperamide-Induced Constipation in Rats

Objective: To explore the effect and mechanism of Polysaccharide extracted from raw Atractylodes Macrocephala on Loperamide-induced constipation in rats.

Defatted hempseed meal altered the metabolic profile of fermented yogurt and enhanced the ability to alleviate constipation in rats.

Hempseeds (Cannabis sativa L.) are rich in easily digestible proteins, fats, polyunsaturated fatty acids, and insoluble fiber and are of high nutritional value. Probiotics have been found to relieve constipation, which solves a health problem that constantly troubles a lot of people. Therefore, the changes in the metabolites of fermented yogurt with or without 10% defatted hempseed meal (10% SHY or 0% SHY respectively) were studied and their laxative effects were examined through animal experiments. Amino acids and peptides, terpene glycosides, carbohydrates, lineolic acids, and fatty acids were found to be the major contributors to the discrimination of the metabolic profile between 0% SHY and 10% SHY. The differentially accumulated metabolites may lead to the discrepancy in the yogurt's functionality. Animal experiments showed that the 10% SHY treatment prevented constipation by increasing feces number, fecal water content, and small intestinal transit rate and reducing inflammatory injury in loperamide-induced constipated rats. Further analysis of the gut microbiota revealed that 10% SHY gavage increased the relative abundances of the Lactobacillus, Allobaculum, Turicibacter, Oscillibacter, Ruminococcus, and Phascolarctobacterium genera in the constipated rats, whereas Akkermansia, Clostridium_XIVa, Bacteroides, Staphylococcus, and Clostridium_IV were decreased. The combination of defatted hempseed meal and probiotics was found to be effective in relieving constipation, probably due to the enriched amino acids and peptides, such as Thr-Leu and lysinoalanine through correlation analysis. Our findings indicated that defatted hempseed meal in yogurt altered the metabolic profile and effectively alleviated constipation in rats, which is a promising therapeutic candidate for constipation. © 2023 Society of Chemical Industry.

Exploring the Dose–Effect Relationship of Bifidobacterium longum in Relieving Loperamide Hydrochloride-Induced Constipation in Rats through Colon-Released Capsules

Constipation is a common disease affecting humans. Bifidobacterium longum is reportedly effective in relieving constipation. Current studies generally focus on the dose-response relationship of oral doses; however, the dose-effect relationship of B. longum in the colon, which is the primary site where B. longum exerts constipation-relieving effects, to treat constipation has not been studied. Herein, three strains of B. longum (FGSZY6M4, FJSWXJ10M2, and FSDJN6M3) were packaged in colon-released capsules to explore the dose-effect relationship in the colon. For each strain, three groups of capsules (104, 106, and 108 CFU/capsule, respectively) and one group of free probiotics (108 CFU/mL) were used to explore the colonic dose effect of B. longum. The results showed that the three strains of B. longum improved fecal water content and promoted intestinal motility by regulating gastrointestinal peptide (MTL, GAS, and VIP), aquaporin-3, and 5-hydroxytryptamine levels while promoting gastrointestinal motility and relieving constipation by regulating the intestinal flora composition of constipated rats and changing their metabolite content (short-chain fatty acids). Among the three free bacterial solution groups (108 CFU/mL), FGSZY6M4 was the most effective in relieving constipation caused by loperamide hydrochloride in rats. The optimal effective dose of each strain was 6M4 (104 CFU/day), 10M2 (106 CFU/day), and S3 (108 CFU/day) of the colon-released capsules. Therefore, for some effective strains, the dose of oral probiotics can be reduced by colon-released capsules, and constipation can be relieved without administering a great number of bacterial solutions. Therefore, investigating the most effective dose of B. longum at the colon site can help to improve the efficiency of relieving constipation.

Sanay Leaves Treatment in Constipation Rats Restores Defence System in Red Blood Cells

Sanay Leaves Treatment in Constipation Rats Restores Defence System in Red Blood Cells

English

The leaves of Crossepteryx febrifuga (Euphorbiaceae) are commonly used in the Republic of Congo in traditional medicine as a laxative. The present study aims to justify the traditional use of C. febrifuga in the treatment of constipation. The acute toxicity of the aqueous extract was evaluated at the doses of 2000 and 5000 mg/kg in mice in accordance with the OECD (2001) guideline no. 423. The laxative activity of the aqueous extract&nbsp;&nbsp; at doses of 100, 200 and 400 mg/kg was evaluated in normal rats, in rats made constipated rats by loperamide hydrochloride as well as on the accumulation of liquid intestinal. The results obtained showed that the aqueous extract at a dose of 2000 mg/kg does not modify the general behavior of mice and does not cause mortality. However, sedation and mortality were observed at the dose of 5000 mg/kg of the aqueous extract. Thus, the aqueous extract would be weakly toxic, with an LD50 &gt; 4000 mg/kg. Furthermore, it appears from this study that loperamide caused constipation in all normal rats during the three days of treatment, which resulted in a significant decrease (p?0.01 and p?0.001) in fecal parameters except the body weight of the animals which increased significantly (p ?0.01) compared to the control group. In addition, Normacol* and aqueous extract (100, 200 and 400 mg/kg) significantly (p?0.001) increase faecal parameters compared to control group. In addition, the aqueous extract significantly increases (p&lt;0.001) the accumulation of intestinal fluid and stimulates the excessive secretion of Na+ ions. These results show that C. febrifuga has laxative properties which could be justified by the presence of anthraquinones, flavonoids, alkaloids and saponosides highlighted in this plant. Key words: Crossopteryx febrifuga, aqueous extract, acute toxicity, laxative activity.

Microbiome and metabolome reveal the metabolic and microbial variations induced by depression and constipation

Depressed patients are often accompaniedwith constipation symptoms, and vice versa. However, the underlying mechanisms of such a bidirectional correlation have remained elusive. We aim to reveal the possible correlations between depression and constipation from the perspectives of gut microbiome and plasma metabolome. We constructed the depressed model and the constipatedmodel of rats, respectively. First, we measured the locomotor activity status and the gastrointestinal functions of rats. And then, nuclear magnetic resonance plasma metabolomics was applied to reveal the shared and the unique metabolites of depression and constipation. In addition, 16 S ribosomal RNA gene sequencing was used to detect the impacts of constipation and depression on gut microbiota of rats. Finally, a multiscale and multifactorial network, that is, the 'phenotypes - differential metabolites - microbial biomarkers' integrated network, was constructed to visualise the mechanisms of connections between depression and constipation. We found that spontaneous locomotor activity and gastrointestinal functions of both depressed rats and constipated rats significantly decreased. Further, eight metabolites and 14 metabolites were associated depression and constipation, respectively. Among them, seven metabolites and four metabolic pathways were shared by constipation and depression, mainly perturbing energy metabolism and amino acid metabolism. Additionally, depression and constipation significantly disordered the functions and the compositions of gut microbiota of rats, and decreased the ratio of Firmicutes to Bacteroidetes. The current findings provide multiscale and multifactorial perspectives for understanding the correlations between depression and constipation, and demonstrate new mechanisms of comorbidity of depression and constipation.

Parkinson's disease constipation effect of electroacupuncture at ST25 through colonic motility and enteric neuropathology.

The enteric nervous system (ENS) plays a central role in developing Parkinson's disease (PD) constipation, and the regulation of the ENS may be a key component in treating PD constipation. Electroacupuncture (EA) can effectively treat constipation symptoms in PD, but research on its specific mechanisms, especially in terms of ENS, is relatively lacking. Therefore, we investigated whether EA at ST25 promotes the restoration of ENS structure and colonic motor function in the rotenone-induced PD constipation rat model. In this study, we evaluated constipation symptoms by stool characteristics, excretion and water volume, and whole gut transit time and observed colonic motility regulation through colonic motion detection and pathological changes in the colonic myenteric nervous plexus by transmission electron microscopy and immunofluorescence staining. EA significantly improved the constipation symptoms and positively adjusted the colonic motility in rotenone-induced PD constipation rats. At the same time, EA reversed the rotenone-induced colonic myenteric nervous plexus injury and regulated the ratio of inhibitory and excitatory neurotransmitters. Our results indicate that EA treatment of PD constipation may be mediated through the adjustment of ENS.

Apple juice relieves loperamide-induced constipation in rats by downregulating the intestinal apical sodium-dependent bile acid transporter ASBT.

Apples are known to exhibit various beneficial effects on human health. In the present study, we investigated the effect of continuous intake of apple juice (AJ) on constipation status. A single dose of loperamide in rats as the constipation model markedly decreased the weight and number of fecal pellets compared to saline-administered rats as a control. After the administration of AJ twice a day for seven days, recovery of defecation close to that of the control was observed in loperamide-treated rats. In addition, the total bile acid content in the feces increased from day 4 after the administration of AJ. Among hepatic and intestinal transporters and enzymes that regulate bile acids, the mRNA expression of the apical sodium-dependent bile acid transporter (Asbt, slc10a2) was decreased by AJ in rats. Furthermore, the Asbt-mediated bile acid transport activity in the rat ileum decreased after AJ administration. Moreover, in human colonic cancer-derived Caco-2 cells, AJ exposure for 24 and 48 h decreased the expressions of ASBT mRNA and protein, and the uptake activity of taurocholic acid in both 7- and 21-d cultures. Several components of AJ, such as procyanidins, decreased the expression of ASBT in Caco-2 cells. In conclusion, ASBT downregulation is a possible mechanism responsible for the constipation-relieving effect of apples, and procyanidins may play a role in downregulating ASBT, which leads to the beneficial effects of apples against constipation. Although it is generally agreed that the common dietary compositions play a role in constipation relief, the novel specific mechanism of apples found in this study would facilitate understanding food functions.

BIOVITA 3, a Mixture of Three Probiotics, Ameliorates the Loperamide-Induced Constipation in Rats

BIOVITA 3, a Mixture of Three Probiotics, Ameliorates the Loperamide-Induced Constipation in Rats

Effects of electroacupuncture at "Zhongliao" and "Xialiao" on serotonin signaling system and short-chain fatty acids in slow transit constipation rats

To observe the effect of electroacupuncture (EA) at "Zhongliao" (BL33) and "Xialiao" (BL34) on the 5-hydroxytryptamine (5-HT) signaling system in colon tissue and short-chain fatty acids in feces of rats with slow transit constipation (STC), so as to explore the underlying mechanisms of EA in the treatment of STC. A total of 32 SD rats were randomly divided into normal, model, drug control and EA groups, with 8 rats in each group. The STC model was established by intragastric administration of loperamide for 14 days. The EA stimulation (2 Hz/15 Hz) was performed at bilateral BL33 and BL34 for 30 min, once a day for 14 days. The first black stool de-fecation time and fecal water content were detected after treatment. The expressions of 5-hydroxytryptamine 4 receptor (5-HT4R), tryptophan hydroxylase 1 (TPH1) and 5-HT transporter (SERT) in colon tissues were detected by Western blot. The contents of substance P (SP) and vasoactive intestinal peptide (VIP) in serum were detected by ELISA. The contents of 5-HT in colon tissue and short chain fatty acid (SCFA) in feces were detected by mass spectrometry. Compared with the normal group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissue, the content of serum SP were significantly decreased (P<0.05), the first black stool de-fecation time, and the content of serum VIP was significantly increased (P<0.05), the contents of SCFA in feces were significantly decreased except isobutyric acid (P<0.05) in the model group. Compared with the model group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissues, the contents of acetic acid and butyrate in feces were significantly increased (P<0.05) in the EA and drug control groups, the first black stool defecation time was decreased (P<0.05) in the EA and drug control groups, and the content of serum SP was increased and the content of serum VIP was decreased (P<0.05) in the EA group. Compared with the drug control group, the content of serum VIP was significantly decreased (P<0.05), and the expressions of TPH1 and SERT in colon tissue were significantly increased (P<0.05) in the EA group. EA at BL33 and BL34 can promote intestinal motility by intervening multiple links of 5-HT signaling system in treating STC.

P2Y1 receptor in the colonic submucosa of rats and its association with opioid‑induced constipation.

The aim of the present study was to explore the expression changes of P2Y purinergic receptor 1 (P2Y1) in the distal colonic submucosa of opioid-induced constipation (OIC) rats and its association with the occurrence of OIC, an OIC rat model was generated by intraperitoneal injection of loperamide hydrochloride, a selective agonist of µ-opioid receptors (MORs). At 7 days post-treatment, the model was assessed by analyzing stool scores and calculating the gastrointestinal (GI) transit ratio of rats. The distribution of P2Y1-expressing neurons in the colonic submucosal plexus was demonstrated by immunofluorescence (IF). Western blotting was performed to evaluate the expression changes of MOR, P2Y1 and ATP synthase subunit β (ATPB) proteins in the colonic submucosa, while reverse transcription-quantitative PCR (RT-qPCR) analysis was performed to determine the relative mRNA expression of MOR and P2Y1. After 7 days, the feces of OIC rats exhibited an appearance of sausage-shaped pieces and both the stool weight and GI transit ratio of OIC rats were significantly decreased. IF revealed co-expression of P2Y1 and calbindin and MOR and ATPB in the nerve cells of the distal colonic submucosal plexus. Moreover, RT-qPCR analysis showed that the MOR mRNA levels were significantly increased in the distal colonic submucosa of OIC rats, while mRNA levels of P2Y1 were decreased. WB showed that in the distal colonic submucosa of OIC rats, MOR protein expression was increased, whereas that of P2Y1 was significantly decreased. GI transit ratio analysis suggested that the P2Y agonist ATP significantly relieved constipation symptoms in rats, while the P2Y inhibitor MRS2179 aggravated these symptoms. Finally, P2Y1 expression change was shown to be associated with the occurrence of OIC, while expression of MOR and P2Y1 was associated with OIC development in rats.

A Combination of Xyloglucan, Pea Protein and Chia Seed Ameliorates Intestinal Barrier Integrity and Mucosa Functionality in a Rat Model of Constipation-Predominant Irritable Bowel Syndrome

Irritable Bowel Syndrome is a gastrointestinal disorder that affects the large intestine, which encompasses several symptoms including, but not limited to, abdominal pain, bloating and dysmotility. In particular, IBS associated with constipation (IBS-C) is characterized by hard and dry stools and inadequate evacuation and difficulty in defecation. Although several drugs ameliorate intestinal modifications and constipation-associated features, management of IBS is still a challenge. Natural compounds including Xyloglucan and pea protein (XP) and Chia seed powder (CS) are widely known to possess beneficial effects in counteracting several gastrointestinal disorders. Here, we aimed to assess the combined effects of XP and CS to treat constipation-related alterations in an IBS-C rat model. IBS-C was induced by gastric instillation of 2 mL of cold water (0-4 °C) for 14 days and Xiloglucan, Pea protein and Chia seeds (XP + CS) treatment was orally administered for 7 days. On day 22, colon tissues were collected for histological analysis. Our results showed that XP + CS administration attenuated constipation-related parameters by increasing body weight and food and water intake. Upon XP + CS treatment, from day 14 to 22, stool moisture content was restored to physiological level. Colonic tissues from IBS-C rats depicted a disruption of the organ architecture accompanied by edema. Loss of colonic structure was reflected by the marked reduction of tight junction protein expression, Occludin and zona occludens-1 (ZO-1). Administration of XP + CS treatment in IBS-C rats significantly ameliorated the colonic histological parameters and exerted a positive effect on barrier integrity by restoring the expression of Occludin and zona occludens-1 (ZO-1). Our findings demonstrated that the efficacy of XP and CS in managing constipation in rats is due to the ability of these compounds to form a protective barrier fortifying intestinal integrity and gut functionality.

Effects of Mijiandao suppository on intestinal laxation in rats and its mechanisms

Objective: To investigate the effects of Mijian Daotong Bowel Suppository (MJDs) on the compound diphenoxylate induced constipation model of male rats and its mechanisms. Methods: Sixty SD male rats were randomly divided into blank group, model group, positive group and MJDs group. The constipation model was established by using compound diphenoxylate gavage. The rats in blank group and model group were treated with saline by enema, the rats in positive group and MJDs group were given Kaisailu and honey decoction laxative suppository by enema, respectively, once a day for 10 days. The body weight, fecal water content, gastric emptying rate (GER) and carbon ink propulsion rate (CIPR) of rats were observed during modeling and administration. The effects of MJDs on the pathological changes of colon tissue in constipation rats were investigated by hematoxylin-eosin (HE) staining. The effect of MJDs on 5-hydroxytryptamine (5-HT) in the colon of constipation rats was investigated by ELISA kit. The effects of MJDs on the expressions of aquaporins 3 (AQP3) and aquaporins 4 (AQP4) in the colon of constipation rats were detected by immunohistochemistry. Results: After 10 days of administration, compared with the blank group, the body weight, fecal water content, carbon ink propulsion rate and colon 5-HT content in the model group were decreased significantly, while the expression levels of AQP3 and AQP4 in the colon were increased significantly (P＜0.05, P＜0.01). Compared with the model group, the fecal water content and colon 5-HT content in the positive group were increased significantly, and the expressions of AQP3 and AQP4 in the colon were decreased significantly. The body weight, fecal water content and colon 5-HT content in the MJDs group were increased significantly, and the expressions of AQP3 and AQP4 was decreased significantly (P＜0.05, P＜0.01). Compared with the positive group, the fecal water content of the MJDs group was decreased significantly, and the expressions of AQP3 and AQP4 in the colon of the MJDs group was decreased significantly (P＜0.05, P＜0.01). Gastric emptying rate was not statistically significant difference between the groups. Conclusion: MJDs has good therapeutic effects on constipation, and its mechanisms may be related to up-regulating the content of 5-HT in the colon and down-regulating the expressions of AQP3 and AQP4 in the colon.

Integrated metagenomics and targeted-metabolomics analysis of the effects of phenylalanine on loperamide-induced constipation in rats.

Functional constipation is a common functional gastrointestinal disease. In our previous study, we found that the gut microbiota structure was disordered and the level of phenylalanine (Phe) in serum was decreased in constipated women. We conducted the present study to elucidate the role of Phe in remodeling the composition of gut microbiota and the relationship between gut microbiota and serum metabolites. Here, we demonstrated that Phe treatment significantly enhanced intestinal motility, suppressed inflammatory responses, and prevented intestinal barrier damage in rats with loperamide (Lop)-induced constipation. By metagenomic sequencing, the disbalanced gut microbial profile was analyzed in constipated rats. Phe treatment reversed changes in the abundance of several gut bacteria at the phylum, genus, and species levels. Further, we observed distinct metabolic patterns in constipated rats through targeted metabolomics and identified constipation-related gut microbial species linked to changes in circulating neurotransmitter metabolites. The abundances of species s_Lactobacillus murinus, s_Enterococcus italicus, s_Lactobacillus animalis, s_Lactobacillus apodemi, s_Enterococcus faecalis, and s_Lactobacillus backii were positively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. The abundances of s_Lactobacillus johnsonii and s_Butyricimonas virosa were negatively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. Taken together, our findings suggest that Phe can ameliorate the development of Lop-induced constipation in rats by remodeling the gut microbial community structure and changing metabolite levels.

In vivo functional effects of Weissella confusa VP30 exopolysaccharides on loperamide-induced constipation in rats.

In this work, the in vivo functionalities of milk fermented with Weissella confusa VP30 (VP30-EPS) and purified exopolysaccharide (pEPS) from the milk fermented with Weissella confusa VP30 were evaluated for their effect on constipation using an experimental constipated rat model. Rats were randomly divided into four groups: (i) control group (PBS administered normal group), (ii) loperamide treated group (constipation group), (iii) constipation with loperamide plus VP30-EPS (1g/kg), and (iv) constipation with loperamide plus pEPS (0.6g/kg) groups. Loperamide treatment induced animal constipation and significantly reduced the frequency of defecation, intestinal transit ratio, and water content of feces. However, all four fecal parameters were improved in both the loperamide plus VP30-EPS and pEPS administered groups as compared to the loperamide group. These results suggest that the addition of VP30-EPS potentially improves the functional laxative effects of commercial products. This study suggests the possibility that VP30-EPS can be applied to fermented and/or functional foods to relieve constipation.

Short-term stress significantly decreases morphine analgesia in trigeminal but not in spinal innervated areas in rats

Plenty information exists regarding the effects of chronic stress, although few data exist on the effects of short-lasting stressors, which would mimic daily challenges. Differences in craniofacial and spinal nociception have been observed, thus those observations obtained in spinally innervated areas cannot be directly applied to the orofacial region. Although, opioids are considered amongst the most effective analgesics, their use is sometimes hampered by the constipation they induce. Thus, our aims were to study if a short-lasting stressor, forced swim stress (FSS), modifies nociception, morphine antinociception and constipation in rats. Animals were submitted to 10–20 min of FSS for three days, nociception and gastrointestinal transit were studied 24 h after the last swimming session. Nociception and morphine (0.6–5 mg/kg) antinociception were evaluated in the formalin and hypertonic saline tests in the orofacial area and limbs. Morphine-induced modifications in the GI transit were studied through radiographic techniques. Naloxone was administered, before each swimming session, to analyse the involvement of the endogenous opioid system on the effect of stress. Overall, stress did not alter nociception, although interestingly it reduced the effect of morphine in the orofacial tests and in the inflammatory phase of the formalin tests. Naloxone antagonized the effect of stress and normalized the effect of morphine. Stress did not modify the constipation induced by morphine. Opioid treatment may be less effective under a stressful situation, whilst adverse effects, such as constipation, are maintained. The prevention of stress may improve the level of opioid analgesia.

Chinese patent medicine shouhui tongbian capsule attenuated loperamide-induced constipation through modulating the gut microbiota in rat

Ethnopharmacological relevanceShouhui tongbian capsule (SHTC) is a commercial Chinese patent medicine used in the treatment of constipation. However, its mechanism of action remains unclear.Aim of the study: The present study was undertaken to assess SHTC relieved effects on the clinical symptoms of loperamide (LOP) induced constipation in Sprague Dawley (SD) rat model and to clarify the relationship between the protective effect of SHTC on constipation and the gut microbiota. Materials and methodsConstipation male SD rats models were induced with solution of LOP (1.5 mg/kg bw), and rats were treated with an oral dose of SHTC (35, 70 mg/kg bw) three times a day after successful modeling. All rats were assessed weekly by change in body weight, gastric emptying rate, fecal moisture content and wet/dry weight. Hematoxylin and eosin (H&E) were used to observe parts of the rats small intestine. The gut microbiota in colonic contents was analyzed using 16SrRNA gene sequencing. Contents of short-chain fatty acids (SCFAs) were analyzed by gas chromatography-mass spectrometer (GCMS). ResultsThe results confirmed the therapeutic effects of SHTC on constipation. Specifically, SHTC could alleviate the decrease in body weight, gastric emptying rate and fecal moisture content caused by LOP-induced constipation. The pathological damage of small intestine was significantly improved by H&E staining. Notably, SHTC increased the relative abundances of Lactobacillus and the ratio of Firmicutes to Bacteroides (F/B). In addition, the content of acetic acid and propionic acid was significantly increased in constipated rats fed with SHTC. ConclusionSHTC could ameliorate the development of LOP-induced constipation in rats by remodeling the structure of gut microbial community and regulating production of intestinal metabolites.

Short-term acute constipation and not short-term acute diarrhea altered cardiovascular variables in male Wistar rats.

Gastrointestinal dysmotility is a substantial public health challenge globally. Based on previous findings in developed countries, it has been observed that there is an association between diarrhea, constipation, and some cardiovascular variables. This study investigated the effects of experimentally-induced short-term acute constipation and short-term acute diarrhea on certain cardiovascular variables in rats. Thirty (30) male Wistar rats (150 -180 g) were divided into three groups; Control, Diarrhoea, and Constipation. The experiment was carried out in 2 phases, the period after induction and the recovery period, and 5 animals per group were used for each phase. The control group received an equivalent amount of distilled water while Diarrhoea and the Constipation group were induced by oral administration of 2ml Castor oil and administration of Loperamide (3mg/kg, b.d, orally x 3 days), respectively. Cardiovascular variables were assessed using the Edan Scientific®Electrocardiography and Heart Rate Variability machine. Recovery was allowed for 4 days after the onset of the procedure and cardiovascular parameters were reassessed. Post-induction Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) and Heart Rate (HR) significantly increased in constipated rats (153.2 ± 2.9 mmHg; 109.0 ± 3.7 mmHg; 123.7 ± 3.2 mmHg; 123.4±5.6 bpm) when compared with the control values (95.5±4.8 mmHg; 61.2 ± 3.5 mmHg; 72.6 ± 3.6 mmHg; 72.3 ± 5.2 bpm), respectively. The recovery SBP, DBP, MAP, and Heart Rate in the constipated group remained significantly higher compared to the control. Diarrhea had no significant effect on the parameters determined in both post-induction and recovery phases. The electrical activities did not change in both experimental groups compared to the control.This study revealed increased SBP, DBP, MAP, and HR in short-term acute constipated rats but not so with short-term acute experimental diarrhea.