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Zhongguo Zhen Jiu = Chinese Acupuncture... Oct 2023To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower -sea and front- points of large intestine based on...
OBJECTIVES
To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower -sea and front- points of large intestine based on enteric neuronal autophagy.
METHODS
A total of 40 SPF Kunming mice were randomly divided into 5 groups ( = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry.
RESULTS
Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (<0.01, <0.05), and numbers (<0.01), wet weight (<0.01, <0.05) and water content (<0.05, <0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (<0.05), and numbers (<0.01), wet weight (<0.01) and water content (<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (<0.01), and numbers (<0.01), wet weight (<0.01) and water content (<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (<0.01), and numbers (<0.01), wet weight (<0.01) and water content (<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (<0.01,<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (<0.05,<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group.
CONCLUSIONS
Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.
Topics: Mice; Animals; Electroacupuncture; Beclin-1; Acupuncture Points; Constipation; Intestine, Small; Autophagy; Water
PubMed: 37984922
DOI: 10.13703/j.0255-2930.20230418-k0002 -
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 -
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 -
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 Agricultural and Food... Aug 2023Veterinary drug residues present in foods can pose severe health threats to the population. The present study aims to develop a high-resolution mass spectral library of...
Veterinary drug residues present in foods can pose severe health threats to the population. The present study aims to develop a high-resolution mass spectral library of 158 veterinary drugs of 16 different classes for their rapid identification in food samples through liquid chromatography-high-resolution electrospray ionization-tandem mass spectrometry (LC-HR-ESI-MS/MS). Standard drugs were pooled according to their log values and exact masses before analysis. Spectra were collected at system automated collision energy, i.e., of 25-60 eV and four predetermined collision energies (10, 20, 30, and 40 eV) for each compound using a schedule precursor list of [M + H], [M + Na], and [M + NH] ions. The utility of the developed database was checked by analyzing food samples. A total of 17 veterinary drugs based on the reference standard retention times (RTs), HR-MS spectra, and MS/MS spectra were identified in the analyzed samples. Moreover, five veterinary drugs were selected for quantitative analysis, including doxycycline hyclate, lincomycin, sulfasalazine, moxifloxacin, and diphenoxylate, using liquid chromatography-ion trap mass-spectrometry (LC-IT-MS). Concentrations of the drug were obtained to vary from 0.0805 to 0.9731 mg/kg in food samples and were found to be exceeded in most of the cases as per the maximum residue levels described by Food and Agriculture Organization (FAO)/World Health Organization (WHO). The MS data were submitted to the MetaboLights online database (MTBLS2914). This study will help in the high-throughput screening of multiclass veterinary drugs in foodstuffs.
Topics: Tandem Mass Spectrometry; Spectrometry, Mass, Electrospray Ionization; Veterinary Drugs; Gas Chromatography-Mass Spectrometry; Chromatography, Liquid; Ions; Chromatography, High Pressure Liquid
PubMed: 37528805
DOI: 10.1021/acs.jafc.3c03715 -
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 -
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