-
Nutrients Aug 2023Slow transit constipation (STC) is a prevalent gastrointestinal condition with slow transit, and some probiotics can effectively relieve constipation, but the exact...
Slow transit constipation (STC) is a prevalent gastrointestinal condition with slow transit, and some probiotics can effectively relieve constipation, but the exact mechanisms have not been fully understood. In this study, we evaluate the impact of GUANKE (GUANKE) on diphenoxylate-induced slow transit constipation and speculate on the underlying mechanisms in a mouse model. Administration of GUANKE alleviated constipation indexes, including defecation time, fecal output and water content, and gastrointestinal transit ratio. In addition, GUANKE restored the protein expression of constipation-related intestinal factors (aquaporins (AQPs) and interstitial Cajal cells (ICCs)) in colon tissues measured using immunofluorescence staining; regulated the neurotransmitters and hormones, such as increased levels of 5-hydroxytryptamine, substance P, and motilin; and decreased levels of vasoactive intestinal peptide and nitric oxide in serum, as measured by an ELISA. 16S rRNA and correlation analysis of feces indicated that GUANKE administration effectively reduced constipation-induced enrichment and suggested a potential contribution of to diphenoxylate-induced STC in mice. GUANKE had no effect on short-chain fatty acids (SCFAs) in cecum content. This study revealed that GUANKE may alleviate constipation in mice through regulating intestinal neurotransmitter and hormone release and altering specific bacterial taxa, rather than by affecting SCFAs and the diversity of microbiota in the gut. Further research is needed to confirm if the findings observed in this study will be consistent in other animal studies or clinical trials.
Topics: Animals; Mice; Gastrointestinal Microbiome; Diphenoxylate; RNA, Ribosomal, 16S; Constipation
PubMed: 37686774
DOI: 10.3390/nu15173741 -
Journal of Integrative Medicine Jul 2023Abnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC)....
OBJECTIVE
Abnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC). Electro-acupuncture (EA) has been shown to improve constipation-related symptoms and rebalance the gut microbiota. However, it is currently unknown whether the gut microbiota is a key mechanistic target for EA or how EA promotes gut motility by regulating the gut microbiota and SCFAs. Therefore, we assessed the effects of EA in FC mice and pseudo-germfree (PGF) mice to address these questions.
METHODS
Forty female Kunming mice were randomly separated into a normal control group (n = 8), an FC group (n = 8), an FC + EA group (n = 8), a PGF group (n = 8) and a PGF + EA group (n = 8). The FC group and FC + EA group were treated with diphenoxylate to establish the FC model; the PGF group and PGF + EA group were given an antibiotic cocktail to initiate the PGF model. After maintaining the model for 14 d, mice in the FC + EA and PGF + EA groups received EA stimulation at the ST25 and ST37 acupoints, once a day, 5 times per week, for 2 weeks. Fecal parameters and intestinal transit rate were calculated to assess the efficacy of EA on constipation and gastrointestinal motility. Colonic contents were used to quantify gut microbial diversity using 16S rRNA sequencing, and measure SCFA concentrations using gas chromatography-mass spectrometry.
RESULTS
EA significantly shortened the first black stool defecation time (P < 0.05) and increased the intestinal transit rate (P < 0.01), and fecal pellet number (P < 0.05), wet weight (P < 0.05) and water content (P < 0.01) over 8 h, compared with the FC group, showing that EA promoted gut motility and alleviated constipation. However, EA treatment did not reverse slow-transit colonic motility in PGF mice (P > 0.05), demonstrating that the gut microbiota may play a mechanistic role in the EA treatment of constipation. In addition, EA treatment restored the Firmicutes to Bacteroidetes ratio and significantly increased butyric acid generation in FC mice (P < 0.05), most likely due to the upregulation of Staphylococcaceae microorganisms (P < 0.01).
CONCLUSION
EA-mediated resolution of constipation occurs through rebalancing the gut microbiota and promoting butyric acid generation. Please cite this article as: Xu MM, Guo Y, Chen Y, Zhang W, Wang L, Li Y. Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice. J Integr Med. 2023; Epub ahead of print.
Topics: Mice; Female; Animals; Gastrointestinal Microbiome; Butyric Acid; RNA, Ribosomal, 16S; Constipation; Acupuncture Therapy; Electroacupuncture
PubMed: 37331860
DOI: 10.1016/j.joim.2023.05.003 -
Luminescence : the Journal of... Jun 2024In this study, a chemiluminescence (CL) method was developed to determine diphenoxylate in tablets and human plasma. This is the first CL method proposed to determine...
In this study, a chemiluminescence (CL) method was developed to determine diphenoxylate in tablets and human plasma. This is the first CL method proposed to determine diphenoxylate. Creating three-dimensional data caused the parallel factor analysis algorithm (PARAFAC) to be used for the first time in CL methods. The method is based on the fact that diphenoxylate enhances the weak CL produced in the reaction of Ru(phen) and acidic Ce(IV), and the concentration of Ce(IV) solution has a different effect on the CL response of diphenoxylate and the blank plasma. The calibration curve was linear from 4.0 × 10 to 1.6 × 10 mol L (R = 0.9954), and the detection limit was 1.3 × 10 mol L (S/N = 3). The sampling rate was about 30 samples per hour, and the % RSD for 10 repeated measurements of 4 × 10 mol L diphenoxylate was 5.4%. The interference effects of some ions, amino acids, and common additives were also investigated. The CL method was successfully used to determine diphenoxylate in tablets, and the results were statistically confirmed by the reference method. The proposed CL method and the PARAFAC algorithm were successfully used to determine the concentration of diphenoxylate in human blood plasma samples.
Topics: Humans; Tablets; Luminescent Measurements; Luminescence; Limit of Detection; Algorithms; Oxalates; Factor Analysis, Statistical
PubMed: 38859619
DOI: 10.1002/bio.4805 -
International Journal of Biological... Feb 2024Chronic constipation has been associated with depression-like behavior. Previous study identified the crucial role of gut microbiota in the development of constipation...
Chronic constipation has been associated with depression-like behavior. Previous study identified the crucial role of gut microbiota in the development of constipation and depression. Dietary inulin (INU) could regulate gut microbiota. Whether INU treatment could ameliorate constipation induced depression was not clear. For this purpose, male CD-1 mice were administered diphenoxylate (20 mg/kg body weight/day) to induce constipation. We found that INU (10 % in standard diet) alleviated the diphenoxylate-induced constipation, manifested as the increase weight and moisture content of feces. Furthermore, the associated depression and anxiety-like behavior disorders were improved by inhibiting neuro-inflammation and preventing synaptic ultrastructure damage under INU treatment. Moreover, INU pretreatment improved the diphenoxylate-induced gut barrier damage by upregulating tight junction protein expression. INU also reshaped gut microbiota in constipation mice by increasing the relative abundance of Bacteroides and Proteobacteria and downregulating the abundance of Muribacalum and Melaminabacteria. The effects of INU on diphenoxylate-induced depression were abolished by gut microbiota depletion via antibiotic treatment. In addition, INU increased the concentration of short chain fatty acids (SCFAs) in feces contents. Meanwhile, supplementation of SCFAs could also partly improve diphenoxylate-induced depression. In conclusion, INU intake was a potential nutritional intervention strategy to prevent constipation induced depression via microbiota-gut-SCFAs axis.
Topics: Male; Mice; Animals; Inulin; Gastrointestinal Microbiome; Depression; Diphenoxylate; Fatty Acids, Volatile; Constipation; Diet; Anxiety
PubMed: 38219945
DOI: 10.1016/j.ijbiomac.2024.129420 -
Current Opinion in Gastroenterology May 2024Chronic diarrhea is a common disorder that interferes with normal daily activities and results in poor quality of life. Fecal urgency and incontinence often necessitate... (Review)
Review
PURPOSE OF REVIEW
Chronic diarrhea is a common disorder that interferes with normal daily activities and results in poor quality of life. Fecal urgency and incontinence often necessitate clinical consultation, but the pathophysiological mechanisms are difficult to differentiate in a clinical setting. Therefore, drugs targeting the opioid receptors, such as diphenoxylate and loperamide, are typically used, as they reduce both gut motility and secretion.
RECENT FINDINGS
For severe diarrhea, morphine-containing extemporaneous opium tincture drops have recently been reprofiled to a pharmaceutical. The drug is indicated for severe diarrhea in adults when other antidiarrheals do not give sufficient fecal emptying control. The pronounced effect is due to the liquid formulation with rapid onset as a drug dissolution step is avoided. A recent prospective, noninterventional study (CLARIFY) of patients treated with opioid drops demonstrates a rapid and sustained therapeutic effect. Tolerance does not develop for the antidiarrheal effect and no dependence was observed after discontinuation.
SUMMARY
This mini-review discusses the use of opium derivates for treatment of diarrhea, with an emphasis on opium drops as a new medicinal grade opium for the use as additional treatment of severe diarrhea, emphasizing its mechanism of action and evaluation of the risk-benefit ratio in the clinical setting.
Topics: Adult; Humans; Opium; Quality of Life; Diarrhea; Antidiarrheals; Loperamide; Observational Studies as Topic
PubMed: 37903075
DOI: 10.1097/MOG.0000000000000985 -
Journal of Ethnopharmacology Feb 2024Functional constipation (FC), characterized by chronic constipation, significantly impacts physiological function and induces psychological stress in patients. However,...
HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE
Functional constipation (FC), characterized by chronic constipation, significantly impacts physiological function and induces psychological stress in patients. However, current clinical treatment options for FC are currently limited. Cistanche deserticola, a traditional Chinese medicine that promotes intestinal moisture and bowel relaxation, contains cistanche total alditol extract (CTAE) as its primary active extract. However, the production of CTAE, its overall efficacy, and potential mechanisms for treating FC have yet to been investigated.
AIM OF THE STUDY
This study aimed to reveal the overall efficacy and potential mechanism of action of CTAE in rats with FC using a combination of stable preparation, pharmacodynamics, non-targeted metabolomics, bile acid metabolomics, and western blotting.
MATERIALS AND METHODS
Fourteen batches of CTAE underwent quality testing. A rat model of FC was developed using diphenoxylate tablets. The comprehensive pharmacodynamic effects of CTAE on FC were evaluated using fecal characteristics (wet weight, dry weight, and water content), intestinal transmission (colonic EMG amplitude, colonic EMG frequency, propulsion length, and propulsion rate), serum and colon biochemical indicators, distribution of interstitial cells of Cajal (ICC), and pathological examination. Non-targeted metabolomics was performed to assess the changes in endogenous metabolite profiles induced by CTAE. Bile acid metabolomics and western blotting analyses were employed to validate the potential mechanisms of action of CTAE.
RESULTS
CTAE, with a total content of betaine, mannitol, D-fructose, glucose, and sucrose of (75.67 ± 3.73) %, significantly enhanced intestinal transit, regulated neurotransmitters, increased the expression of c-kit in ICC, and alleviated intestinal inflammation in rats with FC. Non-targeted metabolomics revealed that CTAE significantly alleviated FC-induced metabolic disorders, mainly the biosynthesis of primary bile acids. Targeted metabolomic analysis confirmed that CTAE regulated FC-induced bile acid disorders. Western-blotting results confirmed that CTAE increased the expression of CYP8B1, FGF15, TGR5, and FXR, thereby modulating bile acid synthesis and enterohepatic circulation.
CONCLUSION
CTAE demonstrates significant therapeutic effects on FC, primarily through the regulation of bile acid synthesis and enterohepatic circulation. These findings provide a promising foundation for the development and clinical application of novel CATE-based drugs.
Topics: Humans; Rats; Animals; Cistanche; Sugar Alcohols; Constipation; Intestines; Bile Acids and Salts
PubMed: 37967778
DOI: 10.1016/j.jep.2023.117420 -
Medeniyet Medical Journal Dec 2023Potentially inappropriate medications (PIM) is a crucial problem in the geriatric population. The amount of prescription and unadherence increase because of the...
OBJECTIVE
Potentially inappropriate medications (PIM) is a crucial problem in the geriatric population. The amount of prescription and unadherence increase because of the different problems encountered in cancer patients. Our aim was to evaluate the effects of PIM in patients with gastrointestinal system cancer and to investigate its relationship with chemotherapy side effects, mortality, and progression.
METHODS
This retrospective cohort study assessed 154 patients with gastrointestinal system cancer. Demographics and disease features, the presence of PIM according to the "TIME-to-STOP" criteria and baseline laboratory parameters were recorded. The effects of PIM on survival and adverse treatment events were evaluated.
RESULTS
66.9% of the cases were male and 33.1% were female. The mean age was 71.9±6.4 years. The most common side effects of chemotherapy are nausea, vomiting, kidney injury, and pain. The most frequently used prescriptions among the 98 PIMs were gliclazide, hyoscine N-butylbromide, simethicone, diphenoxylate atropine, and thiocolchicoside. PIM was detected in 68.1% of the participants. Chemotherapy side effects were more common in PIM group (p<0.001, odds ratio =5.6). PIM had no effect on mortality. Factors associated with mortality were age, stage, albumin, creatinine, operation history, and progression. A significant relationship was found between age, cancer stage, albumin, creatinine, operation history, and PIM in the regression model. There was no relationship between PIM and progression-free survival.
CONCLUSION
Chemotherapy toxicity may increase with PIM detected on diagnosis. We suggest that PIM is an important factor in predicting the side effects of chemotherapy and minimizing the adverse effects.
PubMed: 38148726
DOI: 10.4274/MMJ.galenos.2023.03063 -
Zhen Ci Yan Jiu = Acupuncture Research Jul 2023To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial...
OBJECTIVE
To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial cells of Cajal (ICC) in rats with slow transit constipation (STC), so as to explore its mechanisms underlying improvement of STC..
METHODS
Fifty male Wistar rats were selected and randomly divided into control,STC model,conventional acupuncture,deep needling group 1 and deep needling group 2 groups,with 10 rats in each group.The STC model was established by gavage of 1 mg/mL compound diphenoxylate suspension (10 mg/kg), once every other day for 21 days, and rats of the control group were given the same dose of distilled water by gavage.EA (2 Hz, 2 mA) was applied to "Tianshu"(ST25), with the acupuncture needle inserted to a depth of 3 mm for rats of the conventional acupuncture group, 4.5 mm for those of deep needling group 1, and 10 mm for those of the deep needling group 2. The acupuncture needle was twirled for 1 min, then retained for 15 min each time, once a day for 15 consecutive days.Following modeling, rats of the 4 groups and the control group received gavage of active carbon 2 mL (100 g/L) for observing the excretion time of the first black stool grain to assess the intestinal transit function. The colonic myoelectric activities (frequency and amplitude) were recorded by using BIOPAC multichannel physiograph. The immunoactivity of SP and c-kit (a transmembrane protein kinase for identification of ICC) of colonic musculature was detected by immunohistochemistry.
RESULTS
Compared with the control group,the time of excretion of the first black stool grain, and the amplitude of colonic electromyogram (EMG) were significantly increased (<0.01), while the frequency of EMG, expressions of SP and c-kit (ICC) were significantly decreased in the model group (<0.01). In contrast to the model group, both deep needling group 1 and 2 had a decrease in the time of excretion of the first black stool grain, and amplitude of intestinal EMG, and an increase of frequency of intestinal EMG, and immunoactivity of SP and c-kit (<0.01). The effect of deep needling 2 is superior to that of deep needling 1 in reducing the time of excretion of the first black stool grain (<0.05), lowering the amplitude of EMG of the gut smooth muscle (<0.05) and in increasing the frequency of EMG (<0.05) and the expressions of SP and c-kit (<0.05). No significant changes were found in the levels of frequency and amplitude of EMG, and expressions of SP and c-kit after routine needling in comparison with the model group (>0.05), except the excretion time of the first black stool grain (<0.05).
CONCLUSION
Deep needling at ST25 at depth of 4.5 mm and 10 mm,especially at depth of 10 mm,has a significant effect in promoting gut motility to ameliorate constipation in rats with STC, which may be related to its function in up-regulating the expressions of SP and ICC activity.
Topics: Animals; Male; Rats; Acupuncture Points; Colon; Constipation; Defecation; Proto-Oncogene Proteins c-kit; Rats, Wistar; Substance P
PubMed: 37518957
DOI: 10.13702/j.1000-0607.20220588