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Journal of Ethnopharmacology Feb 2024Rhubarb, a prominent traditional Chinese medicine, has been employed as a potent laxative for centuries and garnered particular popularity among the youth owing to its...
ETHNOPHARMACOLOGICAL RELEVANCE
Rhubarb, a prominent traditional Chinese medicine, has been employed as a potent laxative for centuries and garnered particular popularity among the youth owing to its notable efficacy in weight management. Historical records indicated that rhubarb initially exhibited robust laxative properties, but extended and consistent usage may lead to an astringent response in the later stage of long-term use. In contrast, steamed pieces of rhubarb (SR), preparing through the process of steaming with wine, have demonstrated a gentle laxative effect with no reported adverse effects.
AIM OF THE STUDY
Our study was designed to explore the intricate mechanisms underlying laxative and astringent properties of rhubarb through metabolomics research.
MATERIALS AND METHODS
In this investigation, we employed a serum metabolomics approach utilizing the UPLC-Q-Extractive-Orbitrap-MS method to delve into the contrasting laxative and astringent effects of rhubarb, as well as to unravel the mechanisms of underpinning its bidirectional regulatory influence. To commence, we assessed alterations in Evacuation Index (EI) values, intestinal hormone levels, and colon histopathology in mice to gauge rhubarb's laxative and astringent effects. Subsequently, metabolomics methodology was employed for cluster analysis through Principal Component Analysis (PCA) and biomarker identification via Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA). Then, we delved into the distinctions in characteristic biomarkers, metabolic pathways, their association with pathological changes, and correlation heatmap for biomarkers between raw pieces of rhubarb (RR) and SR to gain insights into the potential mechanisms behind rhubarb's bidirectional regulatory effects.
RESULTS
Our findings revealed that RR exhibited a laxative effect in the early stage and transitioned to an astringent effect in the later stage, as indicated by the EI values. In contrast, SR consistently demonstrated a mild laxative effect. Biochemical indexes and histopathological assessments unveiled that RR triggered its astringent effect by inhibiting secretion of motilin (MTL), promoting secretion of vasoactive intestinal peptide (VIP) and epinephrine (EPI), and inducing onset of inflammation. Furthermore, serum metabolomics analysis identified 59 discriminative biomarkers modulated by RR and SR. Through comprehensive analysis, we elucidated the in vivo transformation relationships among multiple endogenous metabolites. Notably, our results underscored the down-regulation of certain phosphatidylcholines (PCs), amino acids, acylcarnitines, and up-regulation of lysophosphatidylcholines (LysoPCs) played pivotal roles in the onset of gut dysfunction, intestinal inflammation, gut barrier damage, and gastrointestinal motility disorder upon prolonging RR administration, ultimately contributing to its astringent effect. Additionally, our correlation analysis elucidated that anthraquinones, stilbenes, and phenylbutanones were the pharmacodynamic material basis responsible for inducing the astringent effect of RR.
CONCLUSION
This study provides valuable insights into the bidirectional regulatory effects of rhubarb and sheds light on its underlying mechanisms through a comprehensive metabolomics approach.
Topics: Mice; Animals; Laxatives; Astringents; Rheum; Metabolomics; Inflammation; Biomarkers
PubMed: 37944871
DOI: 10.1016/j.jep.2023.117348 -
Journal of Dairy Science Apr 2024Constipation is directly related to the intestinal microenvironment, in which the promotion of gastrointestinal (GI) motility and improvement of gut microbiota...
The probiotic fermented milk of Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 alleviates constipation via improving gastrointestinal motility and gut microbiota.
Constipation is directly related to the intestinal microenvironment, in which the promotion of gastrointestinal (GI) motility and improvement of gut microbiota distribution are important for alleviating symptoms. Herein, after the intervention of probiotic fermented milk (FMMIX) containing Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 for 14 d in Kunming mice with loperamide-induced constipation, the results indicated that FMMIX significantly increased the secretion of serum motilin, gastrin and 5-hydroxytryptamine, as well as decreased the secretion of peptide YY, vasoactive intestinal peptide, and nitric oxide in mice. As determined by immunohistochemical analysis, FMMIX promoted an augmentation in the quantity of Cajal interstitial cells. In addition, the mRNA and protein expression of c-kit and stem cell factor (SCF) were upregulated to facilitate intestinal motility. High-throughput sequencing and gas chromatography techniques revealed that FMMIX led to an increase in the relative abundance of beneficial bacteria (Lactobacillus, Oscillospira, Ruminococcus, Coprococcus, and Akkermansia), reduced the presence of harmful bacteria (Prevotella), and resulted in elevated levels of short-chain fatty acids (SCFA) with a superior improvement compared with unfermented milk. Untargeted metabolomics revealed significant upregulation of functional metabolites such as l-pipecolinic acid, dl-phenylalanine, and naringenin in FMMIX, presumably playing a potential role in constipation relief. Overall, our results showed that FMMIX had the potential to alleviate constipation symptoms in mice by improving the secretion of serum GI regulatory peptides and neurotransmitters, increasing the expression of c-kit and SCF proteins, and modulating the gut microbiota structure and SCFA levels, and may be associated with an increase in these functional metabolites. This suggested that FMMIX could be a promising adjunctive strategy for managing constipation symptoms and could contribute to the development of functional foods aimed at improving gut health.
Topics: Mice; Animals; Gastrointestinal Microbiome; Milk; Lacticaseibacillus paracasei; Lactobacillus gasseri; Constipation; Gastrointestinal Motility; Probiotics
PubMed: 37923200
DOI: 10.3168/jds.2023-24154 -
Food & Nutrition Research 2023To explore the risk factors of duodenogastric reflux (DGR) in relation to different dietary habits.
OBJECTIVE
To explore the risk factors of duodenogastric reflux (DGR) in relation to different dietary habits.
METHODS
A total of 106 patients with symptoms of DGR who underwent electronic gastroscopy from June 2019 to June 2020 were selected and divided into the DGR group ( = 33) and the non-DGR group ( = 73) according to the diagnosis of bile reflux. Questionnaires were used to collect the basic information and dietary habits of the patients, including age, gender, body mass index, place of residence, comorbidities, dietary composition, salt intake, smoking and drinking consumption. The total bile acid (TBA) and cholesterol (CHO) of the gastric juice were measured using a fully automated biochemical analyser, with an enzyme-linked immunosorbent assay used for the serum cholecystokinin, gastrin and gastrin levels. Univariate analysis and multivariate logistic regression analysis were used to predict the attendant DGR risk factors.
RESULTS
There was no significant difference in age or gender between the DGR and the non-DGR groups ( > 0.05). The proportion of patients living in the Bashang region was significantly higher in the DGR group (78.79%) than in the non-DGR group (38.36%) ( < 0.05). The levels of TBA and CHO in the gastric juice and the cholecystokinin and gastrin levels in the serum of the DGR group were higher than those in the non-DGR group, while the serum motilin levels were significantly lower in the DGR group than in the non-DGR group ( < 0.05). The univariate analysis indicated that the proportion of patients with daily consumption of dairy products and fried foods, a high salt intake and smoking and drinking consumption were significantly higher in the DGR than in the non-DGR group ( < 0.05).
CONCLUSION
The daily consumption of dairy products and a preference for fried food are independent risk factors for the occurrence of DGR (odds ratio ≥ 1, < 0.05).
PubMed: 37920676
DOI: 10.29219/fnr.v67.9385 -
Journal of Ethnopharmacology Jan 2024In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that...
ETHNOPHARMACOLOGICAL RELEVANCE
In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined.
AIM OF THE STUDY
The current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats.
MATERIALS AND METHODS
A rat model of water deficit-induced constipation was established to induce constipation, and these rats were treated with RhA and its monomers. ELISA, histopathology, immunohistochemistry, qPCR and Western blotting based on network pharmacology and molecular docking were conducted to explore the possible mechanism of action of RhA and its monomers.
RESULTS
RhA, aloe-emodin, rhein, and chrysophanol showed stool-softening activity, and the combination of aloe-emodin and rhein had the strongest softening effect on faecal pellets. Aloe-emodin, rhein, and chrysophanol significantly increased the serum levels of vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP), upregulated the expression of VIP, cyclase-associated protein 1 (CAP1), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3), aquaporin 4 (AQP4), and aquaporin 8 (AQP8), decreased the expression of epithelial sodium channel (ENaC) and Na/H exchanger 3 (NHE3), and reduced the colonic tissue concentration of Na-K-ATPase in the constipated rats. Osmolality of colonic fluid in model rats treated by RhA, aloe-emodin, rhein, and chrysophanol was increased.
CONCLUSION
Aloe-emodin, rhein, and chrysophanol were the stool-softening components of the RhA extract, and there were certain drug-interactions between the components. RhA upregulated VIP expression, activated the cyclic adenosine monophosphate protein kinase A (cAMP/PKA) pathway, and further stimulated CFTR expression while inhibiting NHE3 and ENaC expression, resulting in a hypertonic state in the colonic lumen. Water transport could then be driven by an osmotic gradient, which in turn led to the upregulation of AQP3, AQP4, and AQP8 expression. In addition, RhA likely improved gastrointestinal motility by increasing serum VIP, SP, and MTL concentrations, thus promoting faecal excretion.
Topics: Animals; Rats; Rheum; Cystic Fibrosis Transmembrane Conductance Regulator; Emodin; Molecular Docking Simulation; Sodium-Hydrogen Exchanger 3; Constipation; Anthraquinones; Aquaporin 3; Cyclic AMP-Dependent Protein Kinases; Plant Extracts
PubMed: 37907143
DOI: 10.1016/j.jep.2023.117336 -
Zhongguo Dang Dai Er Ke Za Zhi =... Oct 2023To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
[Effect of somatostatin on gastrointestinal hormone levels and clinical outcomes in critically ill infants after gastrointestinal surgery: a prospective randomized controlled study].
OBJECTIVES
To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery.
METHODS
Using a random number table method, critically ill infants after gastrointestinal surgery who were admitted to the Intensive Care Unit of Xuzhou Children's Hospital from June 2019 to June 2021 were randomly divided into an observation group (29 cases) and a control group (30 cases). The control group received routine treatment such as anti-infection and hemostasis after surgery, while the observation group received somatostatin in addition to the routine treatment [3.5 μg/(kg·h) infusion for 7 days]. The levels of serum gastrin (GAS), motilin (MTL), insulin, and glucagon-like peptide-1 (GLP-1) before surgery, on the 3rd day after surgery, and on the 7th day after surgery were compared between the two groups. The recovery progress and incidence of complications after surgery were also compared between the two groups.
RESULTS
There was no significant difference in the levels of serum GAS, MTL, insulin, and GLP-1 between the two groups before surgery (>0.05). On the 3rd and 7th day after surgery, the levels of serum GAS, MTL, insulin, and GLP-1 in the observation group were higher than those in the control group (<0.05). In the observation group, the levels of GAS, MTL, insulin, and GLP-1 on the 7th day after surgery were higher than those before surgery and on the 3rd day after surgery (<0.05), and the levels on the 3rd day after surgery were higher than those before surgery (<0.05). There was no significant difference in the levels of serum GAS, MTL, and insulin before surgery, on the 3rd day after surgery, and on the 7th day after surgery in the control group (>0.05). The level of GLP-1 on the 7th day after surgery was higher than that before surgery and on the 3rd day after surgery (<0.05), and the level on the 3rd day after surgery was higher than that before surgery (<0.05) in the control group. The observation group had shorter first time of anal exhaust, recovery time of bowel sounds, and first time of defecation after surgery compared to the control group (<0.05). The incidence of complications after surgery in the observation group was lower than that in the control group (10% vs 33%, <0.05).
CONCLUSIONS
Somatostatin can increase the levels of serum GAS, MTL, insulin, and GLP-1 in critically ill infants after gastrointestinal surgery, promote the recovery of gastrointestinal function, and reduce the incidence of postoperative complications.
Topics: Humans; Infant; Critical Illness; Digestive System Surgical Procedures; Glucagon-Like Peptide 1; Insulin; Prospective Studies; Somatostatin
PubMed: 37905754
DOI: 10.7499/j.issn.1008-8830.2305022 -
Nutrients Oct 2023To investigate the role of gastrointestinal (GI) polysaccharide fermentation in alleviating constipation, two polysaccharide fractions were isolated from a soluble fiber...
To investigate the role of gastrointestinal (GI) polysaccharide fermentation in alleviating constipation, two polysaccharide fractions were isolated from a soluble fiber extract with determined anti-constipation activity: a 2.04 kDa neutral fraction (SSP-1) contained 99.29% glucose, and a 41.66 kDa acidic fraction (SSP-2) contained 63.85% uronic acid. After mice were given loperamide for 14 d to induce constipation, the GI transit rate increased significantly in the SSP-1 group ( < 0.05) but not in the SSP-2 group. The stool weight in the SSP-2 group was significantly higher than that in SSP-1 (383.60 mg vs. 226.23 mg) ( < 0.05). Both SSP-1 and SSP-2 groups had significantly increased serum gastrin and motilin levels ( < 0.05) and changes in their fecal short-chain fatty acid (SCFA) profiles, while SSP-1 showed better fermentation properties than SSP-2 in terms of statistically higher fecal contents of acetic acid and total SCFAs ( < 0.05). Bioinformatic analysis indicated that SSP-1 upregulated bacteria such as to improve SCFA metabolism and stimulate GI hormone secretion, while SSP-2 had less influence on the gut microbiota. These results suggest that the neutral polysaccharide with superior GI fermentation properties exerted beneficial effects on constipation, while the less fermentable pectic fraction might act as a stool-bulking agent.
Topics: Mice; Animals; Loperamide; Constipation; Polysaccharides; Fatty Acids, Volatile; Feces
PubMed: 37892439
DOI: 10.3390/nu15204364 -
American Journal of Translational... 2023This study was designed to explore the effects of ulinastatin combined with somatostatin on disease control and serum inflammatory factors in patients with severe...
OBJECTIVE
This study was designed to explore the effects of ulinastatin combined with somatostatin on disease control and serum inflammatory factors in patients with severe pancreatitis.
METHODS
The data of 80 patients with severe pancreatitis treated in the First Affiliated Hospital of Jiangxi Medical College from May 2020 to April 2022 were analyzed retrospectively. Among them, 36 patients treated with somatostatin alone (3 mg somatostatin added in 50 mL normal saline) on the basis of standard treatment were assigned to a control group, and the other 44 patients treated with both ulinastatin (100,000 U of ulinastatin injection added in 250 mL 5% glucose solution) and somatostatin (3 mg somatostatin added in 50 mL normal saline) were enrolled into a study group. The levels of serum inflammatory factors (interleukin-1β (IL-1β), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1)), biochemical indexes (C-reactive protein, white blood cell count, and serum amylase) and gastrointestinal function indexes (motilin and gastrin) in the two groups were analyzed and compared before and after treatment. Additionally, the alleviation of clinical symptoms, treatment response and occurrence of adverse reactions were compared between the two groups. The mortality rate of patients within 1 month after the treatment was evaluated, and the risk factors affecting the prognosis were analyzed through logistics regression.
RESULTS
Before treatment, there was no significant difference between the two groups in the levels of IL-1β, IL-6 and sICAM-1 (P>0.05), while after treatment, the levels of all three factors decreased significantly in both groups (P<0.0001), with more notable decreases in the study group than those in the control group (P<0.0001). Before treatment, the two groups were not significantly different in the levels of C-reactive protein, white blood cell count, and serum amylase (P>0.05), while after treatment, all the three levels decreased notably in both groups (P<0.0001), with notably lower levels in the study group than those in the control group (P<0.0001). Before treatment, the levels of motilin and gastrin in the two groups were not significantly different (P>0.05), while after treatment, motilin increased significantly and gastrin decreased significantly in both groups (P<0.0001), and the study group showed a notably higher motilin level and a notably lower gastrin level than the control group (P<0.0001). The study group experienced a significantly earlier disappearance time of abdominal distension and abdominal pain and a significantly shorter hospitalization time than the control group (P<0.0001). Moreover, the study group showed a notably higher overall response rate than the control group (P=0.029), and presented a notably lower incidence of adverse reactions than the control group (P=0.036). According to univariate analysis, age, onset time, Acute Physiology and Chronic Health Evaluation II score and therapeutic regimen were the factors impacting the patients' prognosis. According to logistics regression analysis, therapeutic regimen was an independent risk factor affecting the prognosis.
CONCLUSION
Compared with somatostatin alone, ulinastatin combined with somatostatin is more effective in the treatment of severe pancreatitis. The combination can substantially alleviate the inflammatory response and improve the gastrointestinal function and clinical symptoms of patients, without increasing adverse reactions. Therefore, ulinastatin combined with somatostatin is worthy of clinical promotion.
PubMed: 37854214
DOI: No ID Found -
Nutrients Oct 2023The direct infusion of bitter solutions in the gastrointestinal tract can reduce the secretion of orexigenic hormones and influence appetite and food intake. We aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
The direct infusion of bitter solutions in the gastrointestinal tract can reduce the secretion of orexigenic hormones and influence appetite and food intake. We aimed to explore whether oral ingestion of the bitter tastant hydroxychloroquine sulfate can exert similar effects. Ten lean adult women were included in this double-blind, randomized, two-visit, crossover study. After an overnight fast, each volunteer received film-coated tablets containing 400 mg of hydroxychloroquine sulfate (Plaquenil) or placebo. Plasma-ghrelin, -motilin, -insulin and blood-glucose concentrations were determined every 10 min before and 30 min after feeding; appetite was scored every 10 min. Hunger scores were investigated with a special interest 50-60 min after the ingestion of hydroxychloroquine sulfate, right before a rewarding chocolate milkshake was offered to drink ad libitum. Compared with the placebo, hydroxychloroquine sulfate tended to reduce hunger at the time of interest ( = 0.10). No effect was found upon subsequent milkshake intake. Motilin plasma concentrations were unaltered, but acyl-ghrelin plasma concentrations decreased after the ingestion of hydroxychloroquine sulfate (t = 40-50; < 0.05). These data suggest that the oral intake of hydroxychloroquine sulfate tablets reduces subjective hunger via a ghrelin-dependent mechanism but does not affect motilin release, hedonic food intake or insulin levels in healthy women.
Topics: Adult; Female; Humans; Appetite; Cross-Over Studies; Eating; Energy Intake; Ghrelin; Hunger; Hydroxychloroquine; Insulins; Motilin; Pilot Projects; Double-Blind Method
PubMed: 37836548
DOI: 10.3390/nu15194264 -
Nutrients Sep 2023Constipation is currently one of the most common gastrointestinal disorders, and its causes are diverse. Multi-strain probiotics are often considered a more effective...
Constipation is currently one of the most common gastrointestinal disorders, and its causes are diverse. Multi-strain probiotics are often considered a more effective treatment than single-strain probiotics. In this study, a constipation model was constructed using loperamide hydrochloride to evaluate the ability of a multi-strain probiotic combination of four different ratios of and to regulate intestinal flora, relieve constipation, and explore the initial mechanism in mice. After four weeks of probiotic intervention, BM1, BM2, and PB2 effectively relieved constipation; however, the pathways involved were different. The -dominated formulations BM1 and BM2 mainly changed the composition and structure of the intestinal flora and significantly decreased the relative abundance of , , , , and in stool; increased the relative abundance of and the content of short-chain fatty acids (SCFAs) in stool; restored motilin (MTL) and vasoactive intestinal peptide (VIP) levels; and downregulated interleukin 6 (IL-6) and IL-8 levels in serum. This repaired the inflammatory response caused by constipation. Finally, it promoted peristalsis of the gastrointestinal tract, increasing stool water content, and relieving constipation. While -dominated formula PB2 mainly restored the levels of serum neurotransmitters (MTL, SP (substance P), VIP and PYY (Peptide YY)) and inflammatory factors (IL-1, IL-6 and IL-8), it significantly decreased the relative abundance of , , , and in stool; it then increased acetic acid content, thereby reducing the level of inflammation and changing stool properties and gastrointestinal motility.
Topics: Animals; Mice; Loperamide; Lactobacillus; Bifidobacterium; Interleukin-6; Interleukin-8; Constipation; Gastrointestinal Diseases; Probiotics
PubMed: 37836514
DOI: 10.3390/nu15194230 -
Journal of Pediatric Gastroenterology... Dec 2023Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy....
OBJECTIVES
Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy. Numerous case series suggest that intrapyloric botulinum toxin injection (IPBI) may be beneficial in treating gastroparesis and dyspepsia in children. We hypothesized that nausea, vomiting, and other symptoms, independent of gastroparesis, may improve with IPBI. We sought to identify gastric emptying (GE) and manometric patterns in IPBI responders versus nonresponders.
METHODS
Electronic records of 25 pediatric patients who received IPBI for refractory nausea, vomiting, or both were retrospectively reviewed. We assessed symptom improvement post-IPBI and compared symptoms, GE, and antroduodenal manometry (ADM) findings between IPBI responders and nonresponders.
RESULTS
At least one major symptom improved in 19 patients (76%) after IPBI. Of 22 patients completing a GE study, 14 had delayed GE with no significant difference between IPBI responders and nonresponders. Of 22 patients who underwent ADM, 18 had normal fasting peristalsis, 5 had postprandial antral hypomotility, 4 had neuropathic findings, and 19 had pylorospasm. IPBI responders, compared to nonresponders, demonstrated higher antral pressures with feeding ( P < 0.0001) and shorter duration of pylorospasm ( P = 0.0036). Antral pressures did not differ significantly with fasting or following motilin agonists.
CONCLUSIONS
Our findings suggest that IPBI may have therapeutic benefit in pediatric patients with chronic nausea and/or vomiting, independent of gastroparesis. ADM findings of intact antral peristalsis and elevated antral pressures, in conjunction with efficacy of IPBI, support pyloric non-relaxation as a potential contributor to nausea and/or vomiting in pediatric patients.
Topics: Humans; Child; Gastroparesis; Retrospective Studies; Gastric Emptying; Vomiting; Nausea; Botulinum Toxins
PubMed: 37794574
DOI: 10.1097/MPG.0000000000003954