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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 -
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 -
Pharmaceutical Biology Dec 2023L (Rutaceae) (Au) and Blanco (Rutaceae) (Ci) are commonly used as couplet prokinetics and DC. (Umbelliferae) (Bup) is an herbal antidepressant in traditional Chinese...
CONTEXT
L (Rutaceae) (Au) and Blanco (Rutaceae) (Ci) are commonly used as couplet prokinetics and DC. (Umbelliferae) (Bup) is an herbal antidepressant in traditional Chinese medicine.
OBJECTIVE
This study evaluates the synergistic prokinetic effects of Bup with Au and Ci in mice suffering from multistress-induced delayed gastric emptying (DGE).
MATERIALS AND METHODS
Kunming mice were divided into four groups: control, DGE, AuCi and AuCiBup. Mice were gavaged with AuCi (14.25 g/kg) or AuCiBup (22.13 g/kg) extract for 12 days. Gastric reminder rate, intestinal driving ratio, sucrose preference and open field test were examined, and serotonin (5-HT), motilin (MTL), substance P (SP), 5-HTR and c-kit were assayed. Intracellular Ca levels in primary cultured gastric smooth muscle cells (GSMCs) were determined.
RESULTS
Both AuCi and AuCiBup treatment significantly reduced gastric residual rate (39.5% and 67.7%, < 0.01). Higher serum levels of 5-HT, MTL and SP were observed in treatment groups (AuCi: 0.060 mg/L, AuCiBup: 0.089 mg/L, DGE: 0.025 mg/L, < 0.01). The expression of 5-HTR and c-kit in the antrum and duodenum was upregulated after treatment (AuCi and AuCiBup, 4.3-times, 2.8-times to DGE, < 0.01). Medicated serums of AuCi and AuCiBup effectively increased the influx of Ca into GSMCs (1.8-times, < 0.01). In terms of 5-HTR expression, circulatory contents of 5-HT and SP and Ca influx, AuCiBup demonstrated better prokinetic effects than AuCi.
CONCLUSIONS
These findings indicate the potential for developing combination therapy with antidepressants and prokinetics in gastrointestinal dysmotility management.
Topics: Mice; Animals; Serotonin; Citrus; Gastroparesis; Drugs, Chinese Herbal; Antidepressive Agents; Gastric Emptying
PubMed: 36728913
DOI: 10.1080/13880209.2023.2173249 -
Pharmaceutical Biology Dec 2023Linnaeus (Bombacaceae) is known as silk cotton tree, the flowers of which are used in many medicinal applications.
CONTEXT
Linnaeus (Bombacaceae) is known as silk cotton tree, the flowers of which are used in many medicinal applications.
OBJECTIVE
To investigate the therapeutic effect of flower aqueous extracts (BCE) against loperamide-induced constipation and characterize the chemical composition of BCE.
MATERIALS AND METHODS
Sixty male Kunming mice were divided into control (saline), model (10 mg/kg loperamide + saline), phenolphthalein (10 mg/kg loperamide + 10 mg/kg phenolphthalein) and different dosage of BCE (10 mg/kg loperamide + 40, 80 and 160 mg/kg BCE, respectively) groups, and received intragastric administrations for eight days. Faecal water content, number of faeces, first black-stool defecation time and gastrointestinal transit rates were evaluated. Various biochemical and molecular biomarkers were assessed in blood and colon. UPLC-ESI-QTOF-MS/MS was used to tentatively identify the composition of the BCE.
RESULTS
BCE treatment (160 mg/kg) could increase faecal water (15.75%), faeces number (11.65%), gastrointestinal transit rate (25.37%) and decrease first black-stool defecation time (24.04%). The BCE (80 mg/kg) increased the serum level of motilin (30.62%), gastrin (54.46%) and substance P (18.99%), and decreased somatostatin (19.47%). Additionally, the BCE (160 mg/kg) reduced the mucosal damage, restored colonic goblet cell function, down-regulated the protein expression of AQP (33.60%) and increased c-kit protein expression (11.63%). Twelve known compounds, including protocatechuic acid, chlorogenic acid and rutin, previously reported in were identified in the BCE.
DISCUSSION AND CONCLUSIONS
This study suggested that BCE is a promising agent for the treatment of constipation.
Topics: Mice; Animals; Loperamide; Bombax; Tandem Mass Spectrometry; Constipation; Flowers; Water; Phenolphthaleins
PubMed: 36582187
DOI: 10.1080/13880209.2022.2157841 -
Probiotics and Antimicrobial Proteins Oct 2023Functional constipation is one of the most common gastrointestinal disorders. Oxidative stress can aggravate organ dysfunction. Enteric neurotransmitters have...
Functional constipation is one of the most common gastrointestinal disorders. Oxidative stress can aggravate organ dysfunction. Enteric neurotransmitters have significant effects on the regulation of the enteric nervous system and intestinal muscle contraction. Oxidative stress and reduced gastrointestinal motility are considered to be one of the main causes of constipation. This study aimed to investigate whether LimosiLactobacillus pentosus CQZC02 alleviated loperamide hydrochloride (Lop)-induced constipation in mice under high-fat diet (HFD) conditions and to elucidate the underlying mechanism, focusing on enteric neurotransmitters. Four-week-old female BALB/c mice were randomly divided into five groups: normal group (Nor), constipation model group (H-Lop), L. pentosus CQZC02 low-dose group (H-Lop + ZC02L), L. pentosus CQZC02 high-dose group (H-Lop + ZC02H), and LimosiLactobacillus bulgaricus control group (H-Lop + LB). The fecal weight, water content, and total gastrointestinal transit time were measured to determine whether the mice were constipated. Small bowel and colon tissue damage was assessed by hematoxylin and eosin staining, while the degree of damage was determined by double-blind scoring. The levels of serum oxidative stress markers malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase and neurotransmitters motilin, gastrin, substance P, endothelin, somatostatin, and vasoactive intestinal peptide were measured. The gene expression levels of endothelial nitric oxide synthase, inducible nitric oxide synthase, neuronal nitric oxide synthase, nuclear factor kappa-B, and cyclooxygenase-2 in small intestine tissue were calculated. The constipation symptoms of mice in H-Lop group were manifested by a variety of physiological indicators. In addition, compared with the H-Lop group, H-Lop + ZC02H could effectively relieve the symptoms of constipation in mice. In symptom characterization, the mice in the H-Lop + ZC02H group lost weight and increased feces and water content. In functional experiments, gastrointestinal motility was enhanced; the inflammation score of intestinal tissue was decreased, and gene expression levels were modulated; serum oxidative factor levels were modulated, and oxidative stress levels were decreased.
Topics: Mice; Female; Animals; Mustard Plant; Diet, High-Fat; Constipation; Intestine, Small; Neurotransmitter Agents
PubMed: 36083465
DOI: 10.1007/s12602-022-09991-9 -
Chinese Journal of Integrative Medicine Aug 2023To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI)... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI).
METHODS
This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia.
RESULTS
The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group.
CONCLUSION
Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).
Topics: Humans; Electroacupuncture; Lipopolysaccharides; Single-Blind Method; Acupuncture Therapy; Brain Injuries, Traumatic
PubMed: 35508860
DOI: 10.1007/s11655-022-3670-0