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Journal of Chromatography. B,... Jul 2023Functional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 20-25 %. It seriously affects the quality life of patients. Xiaopi Hewei...
Functional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 20-25 %. It seriously affects the quality life of patients. Xiaopi Hewei Capsule (XPHC) is a classic formula originated from the Chinese Miao minority. Clinical studies have demonstrated that XPHC can effectively alleviate the symptoms of FD, but the molecular mechanism has not been elucidated. The purpose of this work is to investigate the mechanism of XPHC on FD by integrating metabolomics and network pharmacology. The mice models of FD were established, and gastric emptying rate, small intestine propulsion rate, serum level of motilin and gastrin were evaluate to study the interventional effect of XPHC on FD. Next, a metabolomics strategy has been developed to screen differential metabolites and related metabolic pathways induced by XPHC. Then, prediction of active compounds, targets and pathways of XPHC in treating FD were carried out by commonly used network pharmacological method. Finally, two parts of the results were integrated to investigate therapeutic mechanism of XPHC on FD, which were preliminary validated based on molecular docking. Thus, twenty representative different metabolites and thirteen related pathways of XPHC in treating FD were identified. Most of these metabolites were restored using modulation after XPHC treatment. The results of the network pharmacology analysis showed ten crucial compounds and nine hub genes related to the treatment of FD with XPHC. The further integrated analysis focused on four key targets, such as albumin (ALB), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF) and roto-oncogene tyrosine-protein kinase Src (SRC), and three representative biomarkers such as citric acid, L-leucine and eicosapentaenoic acid. Furthermore, molecular docking results showed that ten bioactive compounds from XPHC have good binding interactions with the four key genes. The functional enrichment analysis indicated that the potential mechanism of XPHC in treating FD was mainly associated with energy metabolism, amino acid metabolism, lipid metabolism, inflammatory reactions and mucosal repair. Our work confirms that network pharmacology-integrated metabolomics strategyis a powerful means to reveal the therapeutic mechanisms of XPHC improves FD, which contribute its further scientific research.
Topics: Animals; Mice; Dyspepsia; Network Pharmacology; Systems Biology; Molecular Docking Simulation; Metabolomics; Drugs, Chinese Herbal
PubMed: 37329776
DOI: 10.1016/j.jchromb.2023.123676 -
Microbiome Jun 2023Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota.
RESULTS
Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage.
CONCLUSIONS
Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract.
Topics: Humans; Infant; Anti-Bacterial Agents; Azithromycin; Bile Acids and Salts; Bronchoalveolar Lavage Fluid; Cystic Fibrosis; Inflammation; Motilin; Penicillins
PubMed: 37312128
DOI: 10.1186/s40168-023-01543-9 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Apr 2023On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper...
On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed_otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae_NK4A136_group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed_otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae_NK4A136_group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.
Topics: Rats; Animals; AMP-Activated Protein Kinases; Rats, Sprague-Dawley; Cholesterol, LDL; Fermentation; Aquaporin 2; Lipid Metabolism; Liver; Lipids; Hyperlipidemias; Adenosine Triphosphate; Diet, High-Fat
PubMed: 37282903
DOI: 10.19540/j.cnki.cjcmm.20230112.301 -
Food & Function Jun 2023Refractory constipation is the most severe form of constipation, and its etiology remains unknown. The symptoms of constipation occur repeatedly, which brings great pain...
Refractory constipation is the most severe form of constipation, and its etiology remains unknown. The symptoms of constipation occur repeatedly, which brings great pain to the patient's body and psychology. Accumulating studies suggest that constipation patients present a significant dysbiosis of the gut microbiota compared with healthy individuals. In this study, we analyzed the gut microbiota composition of fresh feces and accumulated feces (old feces) of patients with refractory constipation and found that there was a significant difference between them. Through a mouse model of loperamide-induced constipation, it was proved that the old feces of patients with refractory constipation could aggravate the constipation symptoms in mice, while the fresh feces could alleviate the symptoms, which is consistent with the effect of feces from healthy volunteers in a mouse model of loperamide-induced constipation. We identified an indigenous strain (), which is highly enriched in the fresh feces of patients with refractory constipation, and found that oral administration of could effectively improve the constipation symptoms in mice with constipation induced by loperamide and fecal bacteria transplanted from patients with constipation and significantly improve the stress-related behaviors of mice. This result may be related to the regulation of intestinal , , and other gene expression by and the control of somatostatin (SS) and motilin (MTL) production. Our results suggest that gut microbe intervention with indigenous strains such as is a potential and promising alternative for the treatment of constipation, especially for refractory constipation.
Topics: Mice; Animals; Loperamide; Ruminococcus; Constipation; Clostridiales; Feces
PubMed: 37278206
DOI: 10.1039/d2fo03574j -
Frontiers in Pharmacology 2023The demand for complementary and alternative medicine for the management of functional dyspepsia (FD) is increasing due to the insufficient efficacy of conventional...
The demand for complementary and alternative medicine for the management of functional dyspepsia (FD) is increasing due to the insufficient efficacy of conventional treatment options. In Asia, the Chinese herbal medicine formula (BXT) has been used to treat FD. We searched 11 digital medical databases on 1 September 2021. Randomized controlled trials (RCTs) that investigated the efficacy of BXT or combination therapy (BXT plus Western medicines) for FD were selected. The outcome parameters were total clinical efficacy rate (TCE), motilin level, symptom checklist-90-revised (SCL-90-R), and visual analog scale (VAS) for dyspepsia and adverse events. Cochrane risk of bias tool 2.0 (RoB 2) was used for the quality assessment of included studies. The meta-analysis comprised 57 RCTs with 5,525 participants. BXT was more efficacious, with a higher TCE than Western medicine. Combination therapy (BXT plus Western medicine) also resulted in a higher TCE than Western medicine. Combination therapy improved motilin levels and psychological symptoms to a greater extent than Western medicine, evidenced by a higher SCL-90-R score. However, no significant difference in VAS scores was observed between the BXT and placebo groups. BXT and combination therapy were associated with fewer adverse events than Western medicine or placebo. Our findings suggest that BXT and its combination therapy may be an effective and safe alternative treatment for FD. More RCTs with better methodologies are required to strengthen this evidence. [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019123285], identifier [CRD42019123285].
PubMed: 37274096
DOI: 10.3389/fphar.2023.1130257 -
International Journal of Physiology,... 2023To explore the effect of Shenqi millet porridge on treating gastrointestinal function decline.
OBJECTIVE
To explore the effect of Shenqi millet porridge on treating gastrointestinal function decline.
METHODS
Clinical data of 72 patients with gastrointestinal function decline were retrospectively analyzed. Patients were divided into an observation group (n=36, treated with Shenqi millet porridge) and a control group (n=36, treated with Changweikang granule) according to the treatment methods. The therapeutic effect, quality of life, nutritional status, and levels of motilin and gastrin were analyzed.
RESULTS
The total response rate of the observation group was significantly higher than that of the control group (97.22% vs. 72.22%; P<0.05). Compared with the control group, the quality of life in the observation group was increased after treatment (all P<0.05), and the total protein and body mass index in the observation group were higher than those in the control group (all P<0.05), while the levels of motilin and gastrin in the observation group were lower than those in the control group (all P<0.05).
CONCLUSION
For patients with gastrointestinal function decline, the therapeutic regimen Shenqi millet porridge ameliorates the nutritional status of patients, as well as the quality of life and total therapeutic efficacy, also reduces the levels of motilin and gastrin. This regimen has high safety and clinical application value.
PubMed: 37216173
DOI: No ID Found -
Food & Function Jun 2023Fermented dairy food, such as yogurt, exhibits some beneficial effects on consumers, including alleviating constipation. In this study, subsp. DPUL-36, DPUL-40 and...
Fermented dairy food, such as yogurt, exhibits some beneficial effects on consumers, including alleviating constipation. In this study, subsp. DPUL-36, DPUL-40 and DPUL-44 were used as combined starter cultures at a bacterial cell ratio of 1 : 1 : 1 for reconstituted skim milk fermentation. The milk fermented with the combined starter culture showed good sensory properties. During the storage period, the yogurt showed high lactic acid bacteria vitality and quality stability. Constipated BALB/c mice induced by loperamide (Lop) were orally administered with the combined starter culture fermented milk for 14 days. The results clearly showed that oral administration of the fermented milk relieved Lop-induced constipation in the mice, as evidenced by the significantly increased fecal water content, reduced first black stool time, improved gastrointestinal transmission rate, recovered colon tissue damage, increased level of excitatory neurotransmitters (motilin, gastrin, and substance P) and reduced level of inhibitory neurotransmitters (vasoactive intestinal peptide, somatostatin and endothelin-1) of the mice. Compared with the mice in the Lop group, oral administration of the fermented milk significantly increased the concentrations of acetic acid, propionic acid, butyric acid, isovaleric acid and valeric acid in the feces of the mice, and furthermore, exerted a regulatory effect on the gut microbiota of the mice by up-regulating the abundance of and , and decreasing the abundance of , and . Our results indicated that the combined starter culture fermented milk can effectively alleviate Lop-induced-constipation in BALB/c mice. The relationship between the nutrient profiles and the health promoting function of the yogurt should be further illustrated.
Topics: Animals; Mice; Male; Mice, Inbred BALB C; Fermentation; Lactobacillus; Constipation; Loperamide; Yogurt; Gastrointestinal Microbiome
PubMed: 37194317
DOI: 10.1039/d3fo00222e -
Frontiers in Pediatrics 2023Children with intractable functional constipation (IFC) who are refractory to traditional pharmacological intervention develop severe symptoms that can persist even in...
BACKGROUND
Children with intractable functional constipation (IFC) who are refractory to traditional pharmacological intervention develop severe symptoms that can persist even in adulthood, resulting in a substantial deterioration in their quality of life. In order to better manage IFC patients, efficient subtyping of IFC into its three subtypes, normal transit constipation (NTC), outlet obstruction constipation (OOC), and slow transit constipation (STC), at early stages is crucial. With advancements in technology, machine learning can classify IFC early through the use of validated questionnaires and the different serum concentrations of gastrointestinal motility-related hormones.
METHOD
A hundred and one children with IFC and 50 controls were enrolled in this study. Three supervised machine-learning methods, support vector machine, random forest, and light gradient boosting machine (LGBM), were used to classify children with IFC into the three subtypes based on their symptom severity, self-efficacy, and quality of life which were quantified using certified questionnaires and their serum concentrations of the gastrointestinal hormones evaluated with enzyme-linked immunosorbent assay. The accuracy of machine learning subtyping was evaluated with respect to radiopaque markers.
RESULTS
Of 101 IFC patients, 37 had NTC, 49 had OOC, and 15 had STC. The variables significant for IFC subtype classification, according to SelectKBest, were stool frequency, the satisfaction domain of the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL), the emotional self-efficacy for Functional Constipation questionnaire (SEFCQ), motilin serum concentration, and vasoactive intestinal peptide serum concentration. Among the three models, the LGBM model demonstrated an accuracy of 83.8%, a precision of 84.5%, a recall of 83.6%, a f1-score of 83.4%, and an area under the receiver operating characteristic curve (AUROC) of 0.89 in discriminating IFC subtypes.
CONCLUSION
Using clinical characteristics measured by certified questionnaires and serum concentrations of the gastrointestinal hormones, machine learning can efficiently classify pediatric IFC into its three subtypes. Of the three models tested, the LGBM model is the most accurate model for the classification of IFC, with an accuracy of 83.8%, demonstrating that machine learning is an efficient tool for the management of IFC in children.
PubMed: 37168808
DOI: 10.3389/fped.2023.1148753 -
Journal of Traditional Chinese Medicine... Jun 2023To observe and explore the effect of Fuling () in alleviating the spleen deficiency symptom pattern (SDSP).
OBJECTIVE
To observe and explore the effect of Fuling () in alleviating the spleen deficiency symptom pattern (SDSP).
METHODS
We established an animal model of SDS in Sprague-Dawley () rats by treating them with deficiency-inducing factors, including irregular feeding and tail clamping. Mice were administered Fuling () and its extracts (raw/cooked powder, aqueous/alcohol extract) by gavage once a day for 21 d. The body weight, rectal temperature, and spleen and thymus organ coefficients were calculated. The levels of motilin (MTL), gastrin (GAS), aquaporin 2 (AQP2), interleukin 2 (IL-2), IL-4, and 5-hydroxytryptamine (5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay.
RESULTS
Fuling () and its extracts did not change the body weight, rectal temperature, and organ coefficients of the spleen and thymus. However, it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2. In addition, the levels of IL-4 and 5-HT showed no significant alteration.
CONCLUSIONS
These results suggested the crucial function of () in SDSP, especially promoting digestive function and water metabolism.
Topics: Rats; Mice; Animals; Rats, Sprague-Dawley; Spleen; Interleukin-2; Wolfiporia; Interleukin-4; Serotonin; Aquaporin 2; Body Weight; Gastrins
PubMed: 37147751
DOI: 10.19852/j.cnki.jtcm.2023.03.002 -
Journal of Ethnopharmacology Sep 2023Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since... (Meta-Analysis)
Meta-Analysis Review
ETHNOPHARMACOLOGICAL RELEVANCE
Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since the pathological mechanisms of FD have not been fully elucidated, conventional therapies such as prokinetics, proton pump inhibitors, and antidepressants have some limitations. Siho-sogan-san (SHS) is commonly used as a therapeutic alternative in traditional medicine; however, scientific and clinical evidence supporting its application in FD remains insufficient.
AIM OF THE STUDY
This review aimed to assess the safety and effectiveness of SHS and in combined with Western medicine (WM) for the treatment of FD.
METHODS
Eleven databases, including EMBASE, Medline, and Cochrane Library, were searched for randomized controlled trials (RCTs) on FD published before December 31, 2022. After two independent reveiwers sceened and selected studies according to the inclusion and exclusion criteria, clinical data was pooled and synthesized via Review Manager software. The outcome parameters included total clinical effectiveness rate (TCE), time for symptom improvement, levels of motilin and corticotropin-releasing hormone (CRH), and adverse events. Cochrane's risk of bias tool was used for quality assessment.
RESULTS
A total of 12 studies that included 867 participants comparing WM with SHS or combination therapy (SHS plus WM) were identified. Through a meta-analysis of five studies including 363 patients, SHS compared with WM showed a positive result in safely increasing TCE [risk ratio = 1.36, 95% confidence interval (CI) 1.22 to 1.51, P < 0.00001]. The time for symptom improvement, including abdominal pain, belching, nausea, vomiting, and abdominal distension, was significantly more shortened in the combination therapy than WM group. Furthermore, combination therapy resulted in greater secretion of motilin than WM alone [mean difference = 67.95, 95% CI 39.52 to 96.39, P < 0.00001]. No remarkable difference was observed in CRH levels between the combination therapy and WM groups. For a subgroup analysis, the administration of SHS based on the type of pattern identification (PI) showed larger effect size than in the group that do not consider PI.
CONCLUSIONS
These results suggest that SHS and combination therapy can be considered effective and safe options for the treatment of FD. However, owing to the low quality of the included studies, more well-designed investigational studies and RCTs with longer treatment and follow-up period are needed.
Topics: Humans; Dyspepsia; Motilin; Drugs, Chinese Herbal; Phytotherapy; Plants, Medicinal; Medicine, Traditional
PubMed: 37127143
DOI: 10.1016/j.jep.2023.116518