Functional Dyspepsia Rat Research Articles

Weichang' an pill alleviates functional dyspepsia through modulating brain-gut peptides and gut microbiota.

To evaluate the effect of Weichang'an pill (, WCAP) on functional dyspepsia (FD) and explore its regulation of brain-gut peptides (BGPs) and gut microbiota balance as a potential treatment mechanism. The "0 ℃ saline gavage + irregular feeding and tail clamp" method was used to establish the FD rat model, excluding the normal group. The successfully established FD rat models were randomly divided into the model group and the WCAP1 (WC1), WCAP2 (WC2), WCAP3 (WC3), WCAP4 (WC4), WCAP5 (WC5), and Domperidone (Dom) groups (n = 10 per group). The unhandled rats were designated as the control group. The gastrointestinal motility of the rats was evaluated using the charcoal propulsion test. Histopathology was assessed by hematoxylin and eosin (HE) staining. The enzyme-linked immunosorbnent assay method was used to detect the levels of motilin (MTL), gastrin (GAS), vasoactive intestinal peptide (VIP), and somatostatin (SS) in the serum from each group. In addition, the gut microbiota composition of fecal samples was analyzed using 16S rRNA sequencing. Rat models were successfully established according to data from rat state, gastrointestinal motility assessments, and HE staining. WCAP improved FD symptoms by accelerating the gastric emptying and small intestinal transit of FD rats. Mechanistically, WCAP increased the levels of GAS and MTL and reduced the levels of VIP and SS. Moreover, WCAP treatment restored the total relative abundance of Firmicutes and Bacteroidetes, increased the species richness of the gut flora, and modulated the changes in the composition and function of the gut microbiota. WCAP can effectively promote the recovery of gastrointestinal motility disorders in FD rats. The mechanism may be related to regulating the secretion of BGPs and the composition of the gut microbiota.

Comparison of the effects of Amomum tsaoko and its adulterants on functional dyspepsia rats based on metabolomics analysis

Amomum tsaoko (AT) is commonly used in clinical practice to treat abdominal distension and pain. It is also a seasoning for cooking, with the functions of appetizing, invigorating the spleen, and being digestive-promoting. Amomum tsaoko (AT) has three adulterants, Amomum paratsaoko (AP), Amomum koenigii (AK), and Alpinia katsumadai Hayata, because of the confusion in historical classics regarding recorded sources as well as the near geographic distribution and fruit morphological similarities. In this study, we established a functional dyspepsia (FD) rat model and then treated it with the corresponding medicinal solutions AT, AP, AK, and AKH. The gastric emptying rate, intestinal propulsion rate, serum biochemical indicators, histopathological changes, and fecal metabolism were measured. The efficacy and mechanism of AT, AP, AK, and AKH in the treatment of FD were compared. Fecal metabolomics revealed that 20 potential biomarkers were involved in seven significant metabolic pathways in FD rats. These pathways include ubiquinone and other terpenoid-quinone biosynthesis, glycerophospholipid metabolism, tyrosine metabolism, primary bile acid biosynthesis, purine metabolism, folate biosynthesis, and amino sugar and nucleotide sugar metabolism. AP regulates 6 metabolic pathways, 5 metabolic pathways affected by AT, 4 metabolic pathways affected by AK, and 2 metabolic pathways affected by AKH.The above results suggest that the different effects of AT, AP, AK, and AKH on FD rats may be due to their different regulatory effects on the metabolome.

Electroacupuncture improves low-grade duodenal inflammation in FD rats by reshaping intestinal flora through the NF-κB p65/NLRP3 pyroptosis pathway

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11–7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats.

Comparative analysis of efficacy of different forms of Galli Gigerii Endothelium Corneum on functional dyspepsia in rats based on composition-pharmacodynamics

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model, which clarifies the material basis of the digestive efficacy of GGEC. Proteins, enzymes, polysaccharides, amino acids, and flavonoids in GGEC powder and decoction were determined respectively. The total protein of the powder and decoction was 0.06% and 0.65%, respectively, and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively. The polysaccharide of the decoction was 0.03%, and there was no polysaccharide detected in the powder. The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively, and the total flavonoid content was 59.51 μg·g~(-1). Enzymes and flavonoids were not detected in the decoction. The powder significantly reduced nutrient paste viscosity, while the decoction and control group showed no significant reduction in nutrient paste viscosity. FD rat models were prepared by iodoacetamide gavage and irregular diet. The results showed that both powder and decoction significantly increased the gastric emptying effect, small intestinal propulsion rate, digestive enzymes activity, gastrin(GAS), motilin(MTL), ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP), 3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT), and somatostatin(SST) content in rats(P<0.05, P<0.01). Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS, GHRL, VIP, and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion, as well as serum levels of MTL, GAS, and GHRL were slightly higher than those of the decoction with two times its raw dose, and the serum levels of SST, 5-HT, and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose. In conclusion, both decoction and powder have therapeutic effects on FD, but there is a significant difference between the two effects. Under the same dosage, the digestive efficacy of the powder is significantly better than that of the decoction, and the decoction needs to increase the dosage to compensate for the efficacy. It is hypothesized that the digestive efficacy of the GGEC has a duality, and the digestive active ingredients of the powder may include enzymes and L-type amino acids, while the decoction mainly relies on L-type amino acids to exert its efficacy. This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.

Chaihu Shugan Powder inhibits interstitial cells of cajal mitophagy through USP30 in the treatment of functional dyspepsia

Ethnopharmacological relevanceChaihu Shugan Powder (CHSGP) has significant clinical efficacy in the treatment of functional dyspepsia (FD), but the specific mechanism requires further study. Aim of studyThe aim of this study was to investigate the therapeutic effect of CHSGP on FD rats and the underlying mechanism of the effect on interstitial cells of cajal (ICC) mitophagy. Materials and methodsThe tail-clamping stimulation method was utilized to establish an FD rat model in vivo. Gastric emptying rate and small intestinal propulsion rate test, H&E staining, and Immunohistochemistry were conducted to evaluate the therapeutic effects of CHSGP on FD rats. In vitro, the regulatory effect of CHSGP on CCCP-mediated ICC mitophagy was further investigated by CCK8, Transmission electron microscope, immunofluorescence co-staining, Quantitative polymerase chain reaction and Western blot to reveal the potential mechanisms of CHSGP inhibited ICC mitophagy. ResultsAnimal experiments provided evidence that CHSGP promoted gastric motility, increased ICC numbers, reduced Parkin expression, and elevated USP30 expression in FD rats. In vitro, further mechanism research demonstrated that CHSGP decreased LC3Ⅱ/LC3Ⅰ、PINK1、Parkin、PHB2 protein expression and increased USP30 protein expression. Furthermore, CHSGP increased Mfn2 protein expression by suppressing activation of the PINK1/Parkin pathway when USP30 is knocked down, consequently reducing CCCP-induced ICC mitophagy. ConclusionsThese results suggest that CHSGP may treat FD against CCCP-induced ICC mitophagy by the up-regulation of via PINK1/Parkin pathway.

Rhizoma Atractylodis Macrocephalae-Assessing the influence of herbal processing methods and improved effects on functional dyspepsia.

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.

Oral suspension of thaliporphine alter the functional dyspepsia in gastroduodenal lesions rats via gastrointestinal hormones and brain-gut peptides

Functional dyspepsia (FD), also known as nonulcer dyspepsia, is distinguished by epigastric burning or pain, nausea, a feeling of being overly full, and bloating. Thaliporphine an alkaloid exhibited the protective effect against the inflammatory reaction and oxidative stress. Our aim to scrutinized the therapeutic potential of thaliporphine against FD in rats. Sprague-Dawley (SD) rats were randomised into six groups at random, and the FD model was created using irregular tail clamp stimulation over 14 days (except from rats in the control group). The normal and model group rats got menstruum and thaliporphine oral administration for 14 days after the FD rat models were effectively established. The body weight, food and water intake were estimated. The level of plasma gastrin (GAS), motilin (MTL), vasoactive intestinal peptide (VIP), somatostatin (SS), calcitonin gene-related peptide (CGRP), acetylcholine (AChE), antioxidant, cytokines and inflammatory parameters were estimated. Thaliporphine treated group rats exhibited the increased body weight and food intake, which was suppressed during the FD. Thaliporphine significantly increased the rate of intestinal propulsion and gastric emptying in addition to changing the levels of leptin, CGRP, MLT, SS, and VIP. Thaliporphine significantly (P <0.001) reduced the level of AChE in serum and boosted the level in stomach and hypothalamus. Thaliporphine significantly changed the cytokine and inflammatory parameter levels. Treatment with thaliporphine improves gut peptide levels, controls the peripheral and central nervous systems, and restores levels of gastrointestinal hormones, all of which point to the drug’s potential for protecting against FD.

Deciphering the function of Xiangsha-Liujunzi-Tang in enhancing duodenal mucosal barrier by inhibiting MC/Tryptase/PAR-2 signaling pathway in functional dyspepsia rats

Ethnopharmacological relevanceXiangsha-Liujunzi-Tang (XSLJZT) is a classical formula for treating the diseases of digestive system, which can effectively and significantly improve the symptoms of functional dyspepsia (FD) patients. The main function of XSLJZT is to benefit Qi and spleen, and harmonize stomach. Aim of the studyThe purpose of this study was to investigate the intervention effect of XSLJZT on duodenal mucosal injury in FD rats and the response mechanism of MC/Tryptase/PAR-2 signal pathway. Materials and methodsUltra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively identify the chemical component of XSLJZT. A comprehensive modeling method (iodoacetamide infusion + irregular diet + swimming exhaustion) was used to construct the FD rat model. XSLJZT decoction was given to intervene FD rats for 2 weeks. The indicators of digestive function including body mass, 3-h food intake, visceral sensitivity, gastric emptying rate and intestinal propulsion rate were routinely measured for FD rats. The pathological changes of duodenum and microstructure of intestinal epithelial cells were observed by HE staining and transmission electron microscopy respectively. The inflammatory factors (VCAM-1, IL-6, TNF-α, and ICAM-1) and histamine content were evaluated by enzyme-linked immunosorbent assay (ELISA). The expression levels of Tryptase, PAR-2, ZO-1, β-catenin, p–NF–κBp65 and p-ERK1/2 in duodenal tissues were measured by Western blot (WB) and immunofluorescence colony-staining (IFC). ResultsXSLJZT administration significantly improved the survival of FD rats, increased body mass and 3-h food intake, improved visceral sensitivity, and restored gastric emptying rate and intestinal propulsion rate. HE staining showed that XSLJZT recovered the structure of duodenal mucosal and reduced inflammatory infiltration. ELISA revealed that XSLJZT reduced the content of inflammatory factors (VCAM-1, IL-6, TNF-α, and ICAM-1) and histamine. In addition, WB and IFC uncovered that the protein levels of ZO-1 and β-catenin were up-regulated and MC/Tryptase/PAR-2 signaling pathway was inhibited by XSLJZT. ConclusionXSLJZT significantly improved the integrity of duodenal mucosa and decreased the inflammation in FD rats through the inhibition of MC/Tryptase/PAR-2 signaling pathway response.

Pitongshu Alleviates the Adverse Symptoms in Rats with Functional Dyspepsia Through Regulating Visceral Hypersensitivity Caused by 5-HT Overexpression.

The aim of the study was to explore the efficacy as well as the mechanism of action of Pitongshu (PTS) on rats with functional dyspepsia (FD) induced by iodoacetamide gavage and tail clamping. The bioactive components of PTS were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), whereas the potential targets of PTS were obtained from the Similarity Ensemble Approach (SEA), TCMSP, and Swiss Target Prediction Database. The disease targets were obtained from the DisGeNET database, whereas Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the R Software. The method of iodoacetamide gavage combined with tail clamping was used to establish the FD rat model in this study. Body weight, food intake, gastrointestinal motility, gastric acidity and secretion, and the mechanical pain threshold of rats were measured. The open-field test was also performed. The stomach and duodenum were histologically observed. The levels of serotonin (5-HT), Calcitonin Gene-Related Peptide (CGRP), Motilin (MTL), and Gastrin (GAS) in gastric tissues were detected by ELISA. A total of 139 bioactive components and 17 potential targets of PTS were identified through a network pharmacology approach. The results of GO and KEGG enrichment analyses indicated that PTS could reduce the 5-HT secretion of gastric tissues through the serotonergic synaptic pathway and alleviate the symptoms of FD, indicating that PTS plays a therapeutic role. The results of animal experiments showed that PTS could increase body weight and food intake, improve autonomous activity, and decrease gastric acidity and secretion in FD rats. Furthermore, gastric sensitivity increased in FD rats, and PTS treatment could significantly decrease it. The results of ELISA showed that the overexpression of 5-HT and CGRP was decreased after PTS treatment in FD rats. Lastly, PTS could significantly improve gastrointestinal motility, as well as the levels of GAS and MTL in FD rats. PTS may reduce 5-HT secretion by regulating the serotonergic synaptic pathway, thereby reducing visceral sensitivity and alleviating the symptoms of FD.

Fructus Aurantii Extracts Ameliorate Intestinal Inflammation and Regulate the Intestinal Barrier through Fc Epsilon RI Signaling Pathway

Fructus Aurantii (FA) is the dry and immature fruit of Citrus aurantium L. and its rutaceous cultivars. FA has been widely used to treat digestive system diseases since ancient China, and it promotes gastrointestinal (GI) motility in functional dyspepsia (FD), but its potential therapeutic mechanisms remain unclear. We examined the effects of FA ethanol extracts in an iodoacetamide (IA)-induced FD rat model. Firstly, key FA therapy targets for FD were gathered using systematic pharmacology. Combined with systemic pharmacological analyses, plasma metabolomics based on UPLC-QTOF-MS were conducted. Then, MetaboAnalyst was used to jointly analyze systemic pharmacology targets and metabolomic metabolites to select key metabolic pathways. Finally, the key path is verified by experiments. FA exerted distinct therapeutic effects in anti-inflammation and promoting gastrointestinal motility in our IA-induced FD rat model. When compared with the model group, FA down-regulated the inflammatory factors interleukin 1β and tumor necrosis factor-α. At the same time, FA up-regulated tight junction proteins in the intestinal epithelial barrier. Through the integrated analysis of metabolomics and systemic pharmacology, we conducted experimental verification on Fc epsilon RI signaling pathway. When compared with the model group, FA down-regulatedphospho-mitogen activated protein kinase, phospho-extracellular signal regulated kinase1/2, myosin light chain kinase, and phospho-myosin regulatory light chain protein levels. Thus, FA ameliorated FD by regulating the Fc epsilon RI signaling pathway. Our integrated strategy identified underlying FA mechanisms toward FD treatment and provided a foundation for FA development as a clinical agent for FD.

Investigation of the improving effect of raw and charred hawthorn on functional dyspepsia based on interstitial cells of Cajal

BackgroundRaw hawthorn (RH) is a traditional Chinese medicine commonly used to treat indigestion. Charred hawthorn (CH) is obtained from RH by charring. It is reported that the effect of CH treatment on dyspepsia is stronger than RH. However, this has not been fully proven. The purpose of this study was to compare the effects of RH and CH on functional dyspepsia (FD) model rats. And contribute to the development of dietary therapy for dyspepsia.MethodsSPF-grade male SD rats were divided into 5 groups: the control group, the model group, the Mos group, the RH group, and the CH group. The FD rat model was established by using the methods of water restriction, fasting, tilting cage restraint, day and night upside down, swimming, and tail damping. The body weight of rats in each group was recorded. And the gastric emptying rate, intestinal propulsive rate, and the levels of motilin (MTL), gastrin (GAS), and 5-HT in serum were compared in each group. The expression of C-kit in the stomach and small intestine of each group was compared by immunofluorescence and PCR.ResultsRH and CH could increase weight, improve the gastric emptying rate and intestinal propulsive rate, and promote the secretion of motilin (MTL), gastrin (GAS), and 5-HT in the serum of FD rats. RH and CH can upregulate the expression of the characteristic protein c-kit of ICC in the stomach and small intestine of FD model rats, and the effect of CH is stronger than RH.ConclusionRH and CH may increase the number of interstitial cells of Cajal (ICC) in the gastrointestinal tract by upregulating c-kit expression, thus improving gastrointestinal motility in FD model rats. And compared with RH, CH has certain advantages.

Multi-omics analysis reveals the metabolic regulators of duodenal low-grade inflammation in a functional dyspepsia model.

Several gastrointestinal phenotypes and impairment of duodenal mucosal barrier have been reported in clinical studies in patients with functional dyspepsia (FD). Due to the preferential colonization of the mucosa, intestinal microbes and their metabolites are commonly involved in host metabolism and immune responses. However, there are no studies on the intertwined correlation among multi-level data. For more comprehensive illustrating, a multi-omics analysis focusing on the duodenum was performed in the FD rat model. We found that differential microbiomes in the duodenum were significantly correlated with the biosynthesis of lipopolysaccharide and peptidoglycan. The innate immune response-related genes, which were upregulated in the duodenum, were associated with the TLR2/TLR4-NFκB signaling pathway. More importantly, arachidonyl ethanolamide (anandamide, AEA) and endocannabinoid analogues showed linear relationships with the FD phenotypes. Taken together, multi-level data from microbiome, transcriptome and metabolome reveal that AEA may regulate duodenal low-grade inflammation in FD. These results suggest an important cue of gut microbiome–endocannabinoid system axis in the pathogenesis of FD.

Electroacupuncture Regulates TRPV1 through PAR2/PKC Pathway to Alleviate Visceral Hypersensitivity in FD Rats.

Visceral hypersensitivity (VH) is the predominant pathogenesis of functional dyspepsia (FD). Duodenal hypersensitivity along with nausea further reduces the comfort level in gastric balloon dilatation and inhibits gastric receptive relaxation. The potential mechanism behind electroacupuncture- (EA-) mediated alleviation of VH has not been elucidated. In an FD rat model with tail clamping stress, iodine acetamide (IA) induced VH. The rats were treated with EA with or without PAR2 antagonist FSLLRY-NH2, and the body weight, gastric sensitivity, compliance, and gastrointestinal motility were determined. Mast cells and activated degranulation were stained with toluidine blue (TB) staining and visualized under a transmission electron microscope (TEM). Immunofluorescence was used to detect the expression of PAR2, PKC, and TRPV1 in the duodenum and dorsal root ganglion (DRG) and that of CGRP, SP in DRG, and c-fos in the spinal cord. EA alone and EA + antagonist enhanced the gastrointestinal motility but diminished the expression of TRPV1, CGRP, SP, and c-fos-downstream of PAR2/PKC pathway and alleviated VH in FD rats. However, there was no obvious superposition effect between the antagonists and EA + antagonists. The effect of EA alone was better than that of antagonists and EA + antagonists 2 alone. EA-induced amelioration of VH in FD rats was mediated by TRPV1 regulation through PAR2/PKC pathway. This protective mechanism involved several pathways and included several targets.

Ameliorative Effect of Poria cocos -Yam Riched Rice Paste and Hericium erinaceus Biscuit on Rats with Functional Dyspepsia

Effect of rice paste based on Poria cocos-yam extract and biscuit riched in Hericium erinaceus extract on functional dyspepsia in rats were investigated. Functional dyspepsia rat mblished, and rats were randomly divided into model-, positive-, Poria cocos-yam extracts-(low, medium and high dose), rice paste-(low, medium and high dose), Hericium erainaceus extract-(low, medium and high dose), and biscuit-(low, medium and high dose) treated groups. The corresponding materials were orally administered for 14 days. The results showed that giving the four materials significantly(P<0.05) increased the body weight, feed intake, gastric emptying rate, small intestinal propulsion rate, serum motilin and gastrin levels, and significantly(P<0.05) reduced serum cholecystokinin level in rats with functional dyspepsia, with the colonic levels of acetic-, propionic-, butyric- and total short-chain fatty acids also increased. In summary, the four materials could effectively ameliorate the symptoms of functional dyspepsia in rats, while Poria cocos-yam extract and rice paste functioned better than Hericium erinaceus extract and biscuit, the extract exerted similar effect with the corresponding product, and the medium dose showed the best effect. The results of this study could provide data to support the development of products which improved gastrointestinal function and health.

The Influence of Stomach Back-Shu and Front-Mu Points on Insular Functional Connectivity in Functional Dyspepsia Rat Models.

Functional Dyspepsia (FD) is a common functional gastrointestinal disease, which can reduce the quality of life in patients. Prior research has indicated that insula is closely related to FD and that acupuncture can regulate the functional connectivity (FC) of FD. Therefore, we hypothesized that acupuncture on FD was effected through the insular pathway. To test our hypothesis, we performed electroacupuncture (EA) on FD rat models and then examined the FC between insula and other brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). Seven-day-old male infant Sprague-Dawley (SD) rats were randomly divided into control group, FD model group, and FD acupuncture group, with twelve rats per group (n = 36). Upon establishing successful models, the FD acupuncture group was subjected to EA intervention using Stomach back-shu (BL-21) and front-mu (RN-12) points for ten consecutive days for durations of 20 minutes each day. After intervention, each group was subject to rs-fMRI. The digital image data obtained were analyzed using FC analysis methods. Subsequently, gastric ligation was performed to measure gastric emptying rates. Before EA intervention, the FD model group exhibited decreased functional connections between the insula and a number of brain regions. After EA intervention, FD acupuncture group exhibited increasing FC between insula and regions when compared to the FD model group, such as the primary somatosensory cortex (S1), hippocampal CA3 (CA3), polymorphic layer of dentate gyrus (PoDG), caudate putamen (CPu), and oral pontine reticular nuclei (PnO) (P < 0.05); decreasing FC was also exhibited between insula and regions such as the bilateral primary and secondary motor cortexes (M1/2), paraventricular hypothalamic nucleus (PVA), and limbic cortex (LC). These findings indicate that the effective treatment of FD using EA may be through regulating the abnormal FC between insula and several brain regions, in particular CA3, PoDG, and PVA.

D-galacturonic acid ameliorates the intestinal mucosal permeability and inflammation of functional dyspepsia in rats.

Functional dyspepsia (FD) is a gastrointestinal disease caused by imbalanced gastrointestinal function. Traditional treatments are deemed to be limited, and new therapeutic drugs are required. New study suggested that duodenal low-grade inflammation and increased intestinal permeability play an important role in the pathogenesis of FD. Previous studies have shown that polysaccharides containing D-galacturonic acid (GA) could modulate intestinal immune activity in vitro and in animal models. However, the ability of GA monomer to improve intestinal mucosal permeability and inflammation in FD has not been clearly elucidated. A FD rat model was established using iodoacetamide (IA). FD Rats were administrated different doses of GA. Subsequently, the body weight and behavioral sensitivity of the rats were measured and evaluated; the permeability of the intestinal barrier was measured by determining D-lactose, lactulose/mannitol ratio (LMR), and permeability-related genes [desmocollin-2 (DSC2), TJP1, and OCLN] in FD rats. Also, inflammatory cells [cluster of differentiation (CD)3+ cells and mast cells] were assessed by immunohistochemistry, and the levels of immune-related factors, such as the Toll-like receptor-nuclear factor kappa B (TLR/NF-κB) pathway, were monitored by reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blot assays. Our results suggested that GA could markedly increase the body weight and attenuate the behavioral sensitivity of FD rats. Moreover, GA also has an obvious ameliorating effect on the intestinal mucosal permeability and inflammatory response of FD rats. Furthermore, we found that GA could markedly downregulate TLR2, TLR4, and NF-κB in FD rats. These findings indicate that GA could significantly attenuate the intestinal mucosal permeability and inflammation FD rats. The effect of GA was partially mediated by the TLR/NF-κB signaling pathway.

Paeoniflorin Alleviates Abnormalities in Rats with Functional Dyspepsia by Stimulating the Release of Acetylcholine

IntroductionPaeoniflorin is a main active component in traditional Chinese medicine. Paeoniae alba radix is widely used as a spasmolytic and pain-relieving agent for abdominal spasmodic pain. Functional dyspepsia (FD) is characterized by pain or burning in the epigastrium, fullness, bloating and nausea. However, limited information is available about the effect of paeoniflorin on FD.Materials and MethodsIn this study, iodoacetamide or clonidine-induced FD rat models were established to investigate the impacts of paeoniflorin on FD induced by different pathophysiologic disturbances.ResultsWe found the therapeutic effect of paeoniflorin through assessing the gastric emptying, gastric accommodation and visceral hypersensitivity. This function of paeoniflorin was related to the release of acetylcholine (ACh), which was accompanied by reduced acetylcholinesterase (AchE) activity in stomach and hypothalamus. Paeoniflorin administration inhibited the cyclo-oxygenase-2 (COX-2) expression and increased the level of ghrelin in the stomach. Besides, the levels of occludin and ZO-1 were elevated in the duodenum from paeoniflorin-treated rats, suggesting the impaired duodenal barrier was ameliorated.DiscussionThese results indicate that paeoniflorin possesses the ability to alleviate functional dyspepsia.

The Effects of Low-Dose and High-Dose Decoctions of Fructus aurantii in a Rat Model of Functional Dyspepsia.

BackgroundFructus aurantii is a flavonoid derived from Citrus aurantium (bitter orange) that is used in traditional Chinese medicine (TCM) to treat gastric motility disorders. This study aimed to investigate the effects of low-dose and high-dose decoctions of Fructus aurantii in a rat model of functional dyspepsia (FD).Material/MethodsSprague-Dawley rats (n=90) were divided into nine study groups: the control group, the FD model group, the domperidone-treated (Domp) group, the low-dose raw Fructus aurantii (FA-L) group, the high-dose raw Fructus aurantii (FA-H) group, the low-dose Fructus aurantii with stir-fried wheat bran (Bran-L) group, the high-dose Fructus aurantii with stir-fried wheat bran (Bran-H) group, the low-dose Fructus aurantii with stir-fried wheat bran and honey (Honey-L) group, and the high-dose Fructus aurantii with stir-fried wheat bran and honey (Honey-H) group. The FD rat model was established by semi-starvation, followed by tail damping, stimulation, and forced exercise with fatigue. Change in weight, rate of gastric emptying and intestinal propulsion, and serum levels of leptin, motilin, vasoactive intestinal peptide (VIP), gastrin, calcitonin gene-related peptide (CGRP), ghrelin, and cholecystokinin were compared between the groups.ResultsIn the FD model group, weight, rate of gastric emptying and intestinal propulsion significantly decreased, the expression of leptin, VIP and CGRP increased, and expression of motilin, gastrin, ghrelin, and cholecystokinin significantly decreased. Treatment with low-dose Fructus aurantii with stir-fried wheat bran significantly reversed these effects.ConclusionsIn the rat model of FD, low-dose Fructus aurantii with stir-fried wheat bran increased gastrointestinal motility and gastrointestinal hormone levels.

Shenling Baizhu San improves functional dyspepsia in rats as revealed by 1H-NMR based metabolomics.

Functional dyspepsia (FD), a common gastrointestinal disorder around the world, is driven by multiple factors, making prevention and treatment a major challenge. Shenling Baizhu San (SBS), a classical prescription of traditional Chinese medicine, has been proven to be effective in gastrointestinal disorders. However, studies on SBS improving FD are few. Thus, our study aimed to evaluate the effect of SBS on FD and further to explore the mechanism underlying the interactions between FD and SBS by the metabolomics approach. A FD rat model was induced by multiple forms of mild stimulation, and proton nuclear magnetic resonance (1H-NMR) spectroscopy and multivariate data analysis were used to profile the fecal and urinary metabolome in the FD rats during SBS intervention. Significant dyspeptic symptoms such as weight loss, poor appetite, reduced gastrointestinal motility and decreased absorptive capacity were observed in the FD rats, which were subsequently improved by SBS. Additionally, the levels of citrate, branched chain acids and pyruvate decreased, and the levels of choline, trimethylamine and taurine increased in the FD rats. Furthermore, the metabolic disorders were amended with SBS intervention mainly by modulating the metabolic pathways involved in energy metabolism, amino acid metabolism, and gut microbiota and host co-metabolism. Overall, our study highlighted the effect of SBS on the disturbed metabolic pathways in the FD rats, providing new insight into the mechanism of SBS treatment for FD from the perspective of metabolomics.

Effect of Artemisia rupestris L. Extract on Gastrointestinal Hormones and Brain-Gut Peptides in Functional Dyspepsia Rats.

Artemisia rupestris L. is the perennial herb of rupestris belonging to Artemisia (Compositae), which is wildly distributed in Xinjiang (China), middle Asia, and Europe. It is known to have anti-inflammatory, hepatoprotective, immune function regulation, and gastrointestinal function regulation effects. AR is used to treat digestive diseases, but the effects of AR on antifunctional dyspepsia (FD) activity have not yet been reported. In this study, we aimed to investigate the therapeutic effects of Artemisia rupestris L. extract (ARE) on gastrointestinal hormones and brain-gut peptide in functional dyspepsia (FD) rats. Sixty Sprague-Dawley rats were randomly divided into 6 groups. An FD rat model was established by irregular tail clamp stimulation for 14 days except the blank group. After FD rat models, the blank group and model group were given menstruum, and the medicated rats were given corresponding medicine for 14 days. The general observations, bodyweight, and food intake were observed, and the content of serum gastrin (GAS), plasma motilin (MTL), plasma vasoactive intestinal peptide (VIP), and plasma somatostatin (SS) by the enzyme-linked immunosorbent assay was observed. The content of plasma VIP and plasma SS in the ARE group was significantly lower than in the model group, and the content of serum GAS and plasma MTL was increased in the ARE group; the GAS expression of antrum and hypothalamus was increased in the ARE group, and SS expression of antrum and hypothalamus was decreased in the ARE group by immunohistochemical detection; the results of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) indicate that ARE inhibits the mRNA expression of VIP. Our results suggest that ARE can recover gastrointestinal hormone levels and regulation of the peripheral and central nervous system and alter gut peptide levels, which confirm the therapeutic effect of ARE on functional dyspepsia.