Huanglian-banxia promotes gastric motility of diabetic rats by modulating brain-gut neurotransmitters through MAPK signaling pathway.

BACKGROUND: Gastric motility disorder is an increasingly common problem among people with diabetes. Neurotransmitters have been recognized as critical regulators in the process of gastric motility. Previous study has shown that herb pair huanglian-banxia (HL-BX) can improve gastric motility, but the underlying mechanism is still unclear. The aim of this study was to further investigate the role of HL-BX in modulating brain-gut neurotransmission to promote gastric motility in diabetic rats, and to explore its possible mechanism. METHODS: The diabetic rats were divided into five groups. Gastric emptying rate, intestinal propulsion rate, body weight, and average food intake were determined. Substance P (SP), 5- hydroxytryptamine (5-HT), and glucagon-like peptide -1 (GLP-1) in the serum were measured by enzyme-linked immunosorbent assay. Dopamine (DA) and norepinephrine (NE) in the brain were analyzed by high-pressure liquid chromatography with a fluorescence detector. Protein expression of the tissues in the stomach and brain was determined by Western blot. KEY RESULTS: HL-BX reduced average food intake significantly, increased body weight, and improved gastric emptying rate and intestinal propulsion rate. HL-BX administration caused a significant increase in SP, GLP-1, and 5-HT, but a significant decrease in DA and NE. Interestingly, HL-BX regulated simultaneously the different expressions of MAPK and its downstream p70S6K/S6 signaling pathway in the stomach and brain. Moreover, berberine exhibited a similar effect to HL-BX. CONCLUSIONS: These results indicated that HL-BX promoted gastric motility by regulating brain-gut neurotransmitters through the MAPK signaling pathway. HL-BX and MAPK provide a potential therapeutic option for the treatment of gastroparesis.

Mind shift I: Fructus Aurantii - Rhizoma Chuanxiong synergistically anchors stress-induced depression-like behaviours and gastrointestinal dysmotility cluster by regulating psycho-immune-neuroendocrine network.

BACKGROUND: Researchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PURPOSE: MDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. STUDY DESIGN: Acute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. METHODS/RESULTS: Here, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. CONCLUSION: Brain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.

Research progress on mechanism of acupuncture in treating functional constipation. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§ä¾¿ç§˜çš„æœºåˆ¶ç ”ç©¶è¿›å±•.

Acupuncture treatment for functional constipation (FC) is characterized by precise efficacy, rapid onset of action in the early stages, long-term stable effects, and overall regulation. This paper reviews recent literatures on acupuncture treatment for FC, indicating that acupuncture acts from multiple perspectives and pathways, including promoting intestinal motility, regulating intestinal microbiota, modulating the brain-gut axis, alleviating intestinal inflammation, and improving rectal hyposensitivity. Future research could delve into the mechanical sensation conduction mechanisms of acupuncture in improving rectal hyposensitivity, identify key intestinal microbiota genera and metabolic characteristics regulated by acupuncture, explore the network relationships among different mechanisms, and clarify the differential mechanisms of various acupuncture treatment protocols to optimize clinical therapy and enhance the clinical efficacy of acupuncture for FC.

Chronic Electroacupuncture With High-Frequency at ST-36 Promotes Gastrointestinal Motility by Regulating Bone Morphogenetic Protein 2 Secretion of Muscularis Macrophages.

BACKGROUND: Electroacupuncture (EA) at Zusanli (ST36) is an alternative treatment for several gastrointestinal motility disorders; however, the exact mechanism is unconfirmed. We aimed to show the potential effects of EA on muscularis macrophages (MMφ), the bone morphogenetic protein (BMP)/BMP receptor (BMPR)-Smad signal pathway, and enteric neurons in diabetic mice. This may provide fresh insight into ways EA affects gastrointestinal motility. MATERIALS AND METHODS: C57BL/6J healthy adult male mice were randomly divided into five groups: regular control group, diabetes group, diabetes with sham EA group (acupuncture only), diabetes with low-frequency EA group (10 Hz), diabetes with high-frequency EA group (HEA) (100 Hz). The stimulation lasted eight weeks. Gastrointestinal motility was assessed. We identified M2-like MMφ in the layer of colonic muscle by flow cytometry. Western Blot, real-time polymerase chain reaction, and immunofluorescent staining were also used to determine the MMφ, molecules in the BMP2/BMPR-Smad pathway, and PGP9.5, neuronal nitric oxide synthase (nNOS) expression of enteric neurons in the colon of each group. RESULTS: 1) HEA improved the gastrointestinal motility (gastrointestinal transit time, defecation frequency) of diabetic mice. 2) HEA reversed the decreased proportion of M2-like MMφ and expression of the CD206 in the colon of diabetic mice. 3) HEA restored the downregulations of BMP2, BMPR1b, and Smad1 in the BMP2/BMPR-Smad pathway and increased downstream enteric neurons marked by PGP9.5, nNOS in the colon of diabetes mice. CONCLUSIONS: HEA might promote gut dynamics by upregulating M2-like MMφ in the colon of diabetic mice, which in turn leads to the accumulation of molecules in the BMP2/BMPR-Smad signaling pathway and downstream enteric neurons.

Effects of electroacupuncture combined with acupoint catgut embedding on gastrointestinal motility and gastrointestinal hormones in rats with functional dyspepsia.

Electroacupuncture (EA) or acupoint catgut embedding (ACE) plays a therapeutic role in functional dyspepsia (FD). Herein, we aimed to elucidate the influences of EA combined with ACE on gastrointestinal motility and gastrointestinal hormones in rats with FD. Sprague-Dawley rats were randomized into the control group, model group, EA group, ACE group, and EA + ACE group (n = 10). Except for the control group, the rats in all groups were modeled by combining neonatal iodoacetamide gastrogavage and modified tail-clamping stimulation. The rats were treated with different treatments according to their groups. The rats were observed for changes in general behavior, body weight, food intake, and paw mechanical pain threshold. Gastric emptying rate (GER) and intestinal propulsive ratio (IPR) were measured in each group, and serum gastrointestinal hormone (motilin [MTL], leptin, gastrin [GAS], vasoactive intestinal peptide [VIP], calcitonin gene-related peptide [CGRP], and somatostatin [SS]) levels, oxidative stress factors (superoxide dismutase [SOD] and malondialdehyde [MDA]) and 5-hydroxytryptamine (5-HT) levels were also measured. Decreased mean body weight, paw mechanical pain thresholds, food intake, and GER and IPR were found in rats of the model group in comparison to the control group. Serum MTL, GAS, SS, and SOD levels were reduced, and serum leptin, VIP, CGRP, MDA, and 5-HT levels were increased in rats of the model group in comparison to the control group. Elevated mean body weight, paw mechanical pain threshold, food intake, GER and IPR, and serum MTL, GAS, SS, and SOD levels, and reduced serum leptin, VIP, CGRP, MDA, and 5-HT levels were observed in rats of the EA, ACE, and EA + ACE groups relative to the model group. EA combined with ACE treatment was more effective than the EA or ACE treatment alone. EA combined with ACE treatment improves gastrointestinal motility and gastrointestinal hormone levels, promotes food intake, and reduces visceral hypersensitivity in FD rats.

Noninvasive electrical neuromodulation for gastrointestinal motility disorders.

INTRODUCTION: Gastrointestinal motility disorders are highly prevalent without satisfactory treatment. noninvasive electrical neuromodulation is an emerging therapy for treating various gastrointestinal motility disorders. AREAS COVERED: In this review, several emerging noninvasive neuromodulation methods are introduced, including transcutaneous auricular vagal nerve stimulation, percutaneous auricular vagal nerve stimulation, transcutaneous cervical vagal nerve stimulation, transcutaneous electrical acustimulation, transabdominal interference stimulation, tibial nerve stimulation, and translumbosacral neuromodulation therapy. Their clinical applications in the most common gastrointestinal motility are discussed, including gastroesophageal reflux disease, functional dyspepsia, gastroparesis, functional constipation, irritable bowel syndrome, and fecal incontinence. PubMed database was searched from 1995 to June 2023 for relevant articles in English. EXPERT OPINION: Noninvasive neuromodulation is effective and safe in improving both gastrointestinal symptoms and dysmotility; it can be used when pharmacotherapy is ineffective. Future directions include refining the methodology, improving device development and understanding mechanisms of action.

Transcutaneous electrical stimulation for gastrointestinal motility disorders.

BACKGROUND/PURPOSE: Gastrointestinal (GI) dysmotility is categorized by muscle or nerve dysfunctions in any portion of the GI tract, which leads to abnormalities in GI motor and sensory function. Symptoms may vary depending on the organ affected and can be debilitating. Treatment usually involves diet and lifestyle changes. Pharmacotherapy is limited in effectiveness with various side effects. Transcutaneous electrical stimulation (TES), a noninvasive, needleless technique that provides electrical stimulation using cutaneous non-needle electrodes, has become increasingly popular. It has been shown to be beneficial in treating GI motility disorders. METHODS: This review paper navigates through the different TES techniques, including transcutaneous peripheral nerve (vagal/sacral/tibial nerves) electrical stimulation, transcutaneous electrical acustimulation (stimulation via acupuncture point), transcutaneous interferential current therapy, and transcutaneous electrical nerve stimulation. KEY RESULTS: As we delve deeper, we explore the promising effects of TES on dysphagia, gastroesophageal reflux disease, functional dyspepsia, gastroparesis, postoperative ileus, constipation, and irritable bowel syndrome. The literature at hand speaks volumes about the therapeutic prowess of this noninvasive technique. CONCLUSION & INFERENCES: The time is ripe to evaluate further the full therapeutic potential of TES, a noninvasive, nonpharmaceutical, nonsurgical, and home-based self-administrative technique in managing GI motility disorders.

Gum Chewing and Coffee Consumption but not Caffeine Intake Improve Bowel Function after Gastrointestinal Surgery: a Systematic Review and Network Meta-analysis.

BACKGROUND: Postoperative ileus is common after gastrointestinal surgery. This network meta-analysis aimed to compare the effectiveness of gum chewing and coffee and caffeine intake on ileus-related outcomes. METHODS: A systematic literature review was performed to identify randomized controlled trials (RCTs) comparing noninvasive treatments for ileus after gastrointestinal surgery. The main analyses included random effects network meta-analyses using frequentist methods with simultaneous direct and indirect comparisons of time to first flatus, time to first defecation, and length of stay. Bayesian network meta-analysis using Markov chains was also used. RESULTS: A total of 32 RCTs comparing 4999 patients were included in this network meta-analysis. Time to flatus was reduced by gum chewing (mean difference compared to control (MD): -11 h, 95% confidence interval (95% CI) - 16 to - 5 h, P < 0.001). Time to defecation was reduced by gum chewing and coffee, with MDs of -18 h (95% CI - 23 to - 13 h, P < 0.001) and -13 h (95% CI - 24 to - 1 h, P < 0.001), respectively. Length of stay was reduced by coffee and gum chewing with MDs of - 1.5 days (95% CI: - 2.5 to - 0.6 days, P < 0.001) and - 0.9 days (95% CI: - 1.3 to - 0.4 days, P < 0.001), respectively. CONCLUSION: Coffee and gum chewing were proven to be effective noninvasive approaches for shortening the postoperative length of hospital stay and time to first defecation, especially in open gastrointestinal surgery; thus these actions should be recommended after gastrointestinal surgery.

Effect of Acupoint Stimulation on Improving Gastrointestinal Motility in Patients After Gastrectomy: A Systematic Review and Meta-Analysis.

Introduction: Gastrointestinal immobility is experienced by many patients who undergo gastric surgery. This complication delays enteral nutrition, prolongs hospitalization, and causes discomfort. Acupoint stimulation is a popular alternative nonpharmacological treatment for gastrointestinal immobility. This study aimed to explore the effects of acupoint stimulation on gastrointestinal immobility after gastrectomy. Design: Systematic review and meta-analysis. Methods: Databases (PubMed, Cochrane, Joanna Briggs Institute EBP Database, Medline, CINAHL Complete, and Airiti library) were searched from their inception to April 2022 for relevant articles. Articles in Chinese and English were included, without limitations on year, region, or country. The inclusion criteria were studies with participants >18 years of age, postgastric surgery, and hospitalization. In addition, randomized controlled trials (RCTs) were included. Data were analyzed using random effects models, and data heterogeneity was investigated using subgroup analysis. Meta-analysis was performed using Review Manager 5.4 software. Results: We included 785 participants from six studies. Invasive and noninvasive acupoint stimulation reduced the time of gastrointestinal mobility better than usual care. In the control group, the time of first flatus was 43.56 ± 9.57 h to 108 ± 19.2 h, and the time of first defecation was 77.27 ± 22.67 h to 139.2 ± 24 h. In the experimental group, the time of first flatus and defecation was 36.58 ± 10.75 h to 79.97 ± 37.31 h and 70.56 ± 15.36 h to 108.55 ± 10.75 h, respectively. Subgroup analysis showed that invasive acupoint stimulation with acupuncture reduced the time of first flatus and defecation to 15.03 h (95% confidence interval [CI] = -31.06 to 1.01) and 14.12 h (95% CI = -32.78 to 4.54), respectively. Noninvasive acupoint stimulation, including acupressure and transcutaneous electrical acupoint stimulation (TEAS), reduced the time of first flatus and defecation to 12.33 h and (95% CI = -20.59 to -4.06) and 12.20 h (95% CI = -24.92 to 0.52), respectively. Conclusions: Acupoint stimulation improved the gastrointestinal immobility of postgastrectomy. In the included RCT articles, invasive and noninvasive stimulations were effective. However, noninvasive acupoint stimulation, such as with TEAS and acupressure, was more efficient and convenient than invasive stimulation. Overall, health care professionals with adequate training or under the supervision of an acupuncturist can effectively perform acupoint stimulation to improve the quality of postgastrectomy care. They can select commonly used and effective acupoints to enhance gastrointestinal motility. Clinical relevance: Acupoint stimulation, such as acupressure, electrical acupoint stimulation, or acupuncture, can be included in postgastrectomy routine care to improve gastrointestinal motility and reduce abdominal discomfort.

Prokinetic Activity of Mulberry Fruit, Morus alba L.

The fruit of Morus alba L. (MAF) has been consumed as a food worldwide. MAF has also been widely used in traditional medicine for thousands of years in East Asia, and its diverse bioactivities have been reported in numerous publications. However, no prokinetic activity has been reported for MAF or its components. In the present study, therefore, we investigated the effects of MAF on gastrointestinal motor function by measuring the intestinal transit rate (ITR) of Evans blue in mice in vivo. The ITR values accelerated by MAF were significantly higher than those accelerated by cisapride or metoclopramide, suggesting that MAF has potential as a new prokinetic agent to replace cisapride and metoclopramide. We also investigated the effects of MAF on myogenic and neurogenic contractions in human intestinal smooth muscles by measuring spontaneous contractions of smooth muscle strips, smooth muscle contractions induced by neural stimulation, and migrating motor complexes from intestinal segments in the human ileum and sigmoid colon in situ. MAF increased both myogenic and neurogenic contractions to enhance ileal and colonic motility in the human intestine. Taken together, these results indicate that MAF enhanced intestinal motility by increasing both myogenic and neurogenic contractions, thereby accelerating the ITR.

Effects of opium tincture on the enteric and central nervous systems: A randomized controlled trial.

Opioids change gut motility, and opium tincture has been used for treatment of chronic diarrhoea for centuries. However, the effects have never been documented in controlled trials. We aimed to investigate the effects of opium tincture on gastrointestinal transit and motility, frequency of bowel movements, stool consistency, gastrointestinal symptoms and sedation. Twenty healthy subjects were included in this randomized controlled trial. Opium tincture or placebo was each applied for 9 days. Gastrointestinal transit and motility were investigated with the 3D-transit system. Bowel movements and gastrointestinal symptoms were recorded daily. General cognition, reaction time, memory and electroencephalography were used to assess effects on the central nervous system. Opium tincture doubled colonic transit (49 vs. 23 h, p < 0.001), decreased antegrade colonic movements (p < 0.05), reduced daily bowel movements (0.7 vs. 1.2, p < 0.001) and increased stool consistency (Type 3 vs. Type 4, p < 0.001). No changes in general cognition, reaction time or memory were observed, and minor changes of power observed by electroencephalography did not indicate sedation. This study is the first to show that opium tincture has anti-propulsive properties in the healthy gut, while no sedative effects were seen. This indicates that opium tincture is a relevant and safe treatment option in chronic diarrhoea.

Laparoscopic Electromyography and Electrostimulation of the Gastrointestinal Tract Before Placement of Theranostic Devices.

NEED: Electrical stimulation (ES) is a promising therapy for multisegmental gastrointestinal (GI) motility disorders such as gastroparesis with slow-transit constipation or chronic intestinal pseudo-obstruction. Wireless communicating GI devices for smart sensing and ES-based motility modulation will soon be available. Before placement, a potential benefit for each GI segment must be intraoperatively assessed. TECHNICAL SOLUTION: A minimally invasive multisegmental electromyography (EMG) analysis with ES of the GI tract is required. PROOF OF CONCEPT: Two porcine experiments were performed with a laparoscopic setup. Multiple hook-needle electrodes were subserosally applied in the stomach, duodenum, jejunum, ileum, and colon. EMG signals were acquired for computer-assisted motility analysis. Gastric ES, duodenal ES, jejunal ES, ileal ES, and colonic ES were applied. NEXT STEPS: Further technological and rapid regulatory solutions are desired to initialize a clinical trial of the next generation devices in the near future. CONCLUSION: We demonstrate a laparoscopic strategy with EMG analysis and ES of multiple GI segments. Thus, GI function may be evaluated before theranostic devices are placed. Extended GI resection or organ transplantation may be delayed or even avoided in affected patients.

Effects of Citrus aurantium L. on Gastrointestinal Motility and Gastric Cancer Cell Proliferation.

Background: To research the impact of a Chinese traditional medicine (Citrus aurantium L.) on gastric cancer proliferation and mice gastrointestinal motility. Materials and Methods: The intestinal transit rates (ITRs) and gastric emptying (GE) values in mice with experimentally induced gastrointestinal motility dysfunction (GMD) and in normal mice were calculated to research the in vivo influences of C. aurantium L. on gastrointestinal motility. CCK-8 was used to examined the effect of C. aurantium L. on gastric cancer proliferation. Results: The GE and ITR values were dose-dependently and notably added by C. aurantium L. in normal ICR mice (with 1 g/kg C. aurantium L., ITR values: 53.3% ± 0.8% versus 64.3% ± 0.9% and 53.3% ± 0.8% versus 79.8% ± 2.0%, p < 0.01; GE values: 59.3% ± 0.8% versus 70.1% ± 1.9% and 59.9% ± 0.8% versus 69.9% ± 2.1%, p < 0.01). Compared with the normal mice, the GMD mice's ITRs were notably declined; however, C. aurantium L. could dose-dependently and significantly reverse it. In addition, in the model of delayed GE induced by loperamide and cisplatin, C. aurantium L. administration reversed the GE deficit. Furthermore, C. aurantium L. significantly reduced gastric cancer proliferation. Conclusion: The results indicate that C. aurantium L. could become a new drug for gastrointestinal prokinetic and gastric cancer therapy.

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

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: PTS may reduce 5-HT secretion by regulating the serotonergic synaptic pathway, thereby reducing visceral sensitivity and alleviating the symptoms of FD.

[Electroacupuncture promotes gastrointestinal motility by activating autophagy of Cajal interstitial cells via downregulating PI3K/Akt/mTOR signaling pathway in stomach of diabetic gastro-paresis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36), "Sanyinjiao" (SP6) and "Liangmen" (ST21) on gastrointestinal motility, blood glucose content and expression of autophagy-related proteins 1 light chain 3 (LC3), p62, phosphatidyli-nositol-3 kinase (PI3K), protein kinase B (Akt), p-Akt and mammalian target protein of rapamycin (mTOR) of interstitial cells of Cajal (ICCs) in the cultured gastric antrum cells in diabetic gastroparesis (DGP) rats, so as to reveal its mechanisms underlying improvement of DGP. METHODS: A total of 45 Sprague Dawley (SD) rats were randomly divided into blank control, model, EA, medication (3-methyladenine, 3-MA) and EA+3-MA groups, with 9 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ) combined with high-fat and high sugar diet for 8 weeks. The gastric emptying rate was measured by using gavage of phenol red (to measure the propelling length of the phenol red/total length of small intestine ×100%). The symptom score (mental state, coat color and luster, behavior and activity, stool traits) of rats was observed every week and the blood glucose content was measured by using a glucometer. EA (20 Hz/100 Hz, 2 mA) was applied to unilateral ST36, SP6 and ST21 alternatively for 15 min, once daily, 5 days a week for 3 weeks. Rats of the 3-MA and 3-MA+EA groups received intraperitoneal injection of 3-MA (30 mg·kg-1·d-1, 10 mg/mL), once daily, 5 days a week for 3 weeks. After 15 days' intervention, the rats were operated for gastric emptying rate test, specimen collection, isolation, and culture of primary ICCs. The expression levels of microtubule associated protein LC3, p62, PI3K, Akt, p-Akt and mTOR of ICCs of cultured gastric antrum cells were detected using Western blot, and the number of autophagosomes in ICC of gastric antrum was observed under transmission electron microscope. RESULTS: Compared with the blank control group, the symptom score, blood glucose, and the expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins were increased significantly (P<0.01), while the gastric emptying rate and ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein were significantly decreased (P<0.05, P<0.01) in the model group. In comparison with the model group, the increase of symptom score, blood glucose, and expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins and the decrease of gastric empty rate and LC3Ⅱ/LC3Ⅰ ratio and the expression level of class Ⅲ PI3K protein were all reversed in both EA and EA+3-MA groups (P<0.05, P<0.01), rather than in the 3-MA group. In addition, 3-MA also reversed modeling-induced increase of class Ⅰ PI3K, Akt, p-Akt and mTOR proteins expression (P<0.01). No significant differences were found between the EA and EA+3-MA in downregulating the levels of symptom score and blood glucose content, and in upregulating gastric empty rate(P>0.05). The effect of EA was notably superior to that of EA+3-MA in upregulating the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein, and in downregulating the expression of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins (P<0.05, P<0.01). The findings of transmission electron microscopy showed obvious swelling, breakage of some mitochondrial cristae in the ICC cells of antrum and no autophagosomes in the model group and 3-MA group, which was milder in the damage of mitochondrial cristae and marked increase in the autophagosomes in both EA and EA+3-MA groups. CONCLUSION: EA can improve the gastrointestinal motility and symptoms in DGP rats, which may be related to its functions in downregulating PI3K/Akt/mTOR signaling to promote autophagy level of ICC.

[Analysis on the gastrointestinal motility disorder of gastroesophageal reflux disease and the mechanism of acupuncture-moxibustion from the perspective of autonomic nervous system].

From the perspective of autonomic nervous system, this paper analyzes the mechanism, current western medicine treatment methods and acupuncture-moxibustion treatment mechanism of gastroesophageal reflux disease (GERD). It is believed that the main cause of GERD is that the gastric acid goes to the wrong place due to gastrointestinal motility disorder, which belongs to "acid dislocation". At present, western medical treatment cannot effectively target the pathogenesis of the disease, and its effect is limited. Acupuncture-moxibustion could regulate the neuroendocrine immune network to regulate the function of autonomic nerve, restore the power of digestive tract to treat GERD, which is worthy of further research.

Acupuncture Enhances Gastrointestinal Motility and Improves Autonomic Nervous Function in Patients with Septic Gastrointestinal Dysfunction.

Gastrointestinal dysfunction (GD) is a common complication after endotoxemia, which can further aggravate the progress of infection. Acupuncture uses metal needles of different shapes and techniques to stimulate specific points on the human body, which are effective in treating various diseases, including gastrointestinal diseases. We aimed at exploring the clinical effect of acupuncture on the recovery of visceral sensation, proximal gastric compliance, and autonomic nervous function in patients with septic GD. A total of 73 sepsis with GD patients were selected using modified single section ultrasonography combined with clinical symptoms in the First People's Hospital of Lanzhou City during 2019. The participants were randomly allocated to routine-treatment (control group) and study group receiving acupuncture. The indexes before and after treatment included gastric residue, gastric dilatation, pressure and volume, gastric compliance, autonomic nerve function, APACHE II score, and infection index were measured and compared. Before treatment, there was no significant difference in the basic information of the two groups, including gastric volume and pressure, gastric residue, gastric compliance, autonomic nerve function, and APACHE II score. After treatment, the maximum gastric volume and pressure, gastric residue, and APACHE II score of the two groups were significantly improved (P < 0.05). In addition, the maximum gastric volume and pressure of the study group were significantly higher, while gastric residual, autonomic nerve function, and APACHE II were significantly lower than those of the control group (P < 0.05). However, our results showed that acupuncture did not further reduce inflammatory markers, including white blood cells, C-reactive protein, and procalcitonin. To sum up, on the basis of basic treatment, the application of acupuncture can further improve the clinical symptoms of GD in patients with sepsis, enhance gastrointestinal motility, and improve autonomic nervous function, which is worthy of clinical application and promotion.

Xiangsha Liujunzi Decoction improves gastrointestinal motility in functional dyspepsia with spleen deficiency syndrome by restoring mitochondrial quality control homeostasis.

BACKGROUND: Xiang Sha Liu Junzi decoction (XSLJZD) is a famous traditional Chinese medicinal prescription for the treatment of functional dyspepsia (FD) in spleen deficiency. However, its therapeutic mechanism has not been fully clarified. PURPOSE: The present study aimed to determine the role of mitochondrial quality control (MQC)-mediated gastrointestinal motility disorder in FD treated with XSLJZD by using spleen-deficient FD rats and gastrointestinal smooth muscle cells (GSMCs). METHODS: In vivo, an FD with spleen deficiency syndrome model was established by gastric perfusion with iodoacetamide solution combined with the modified multiple platform method (MMPM), followed by intragastric gavage with XSLJZD for 4 weeks. Improvement of pathological symptoms was evaluated based on food intake, water intake, grip strength, gastric histopathological changes, gastric emptying rate, small intestinal propulsion rate, and average amplitude and frequency of smooth muscle strips. The mitochondrial ultrastructure was observed by transmission electron microscopy. The colocalization of LC3 and Parkin with mitochondria was detected by immunofluorescence. The expression and localization of Drp1 proteins were detected by immunohistochemistry. In vitro, GSMCs were treated with different concentrations of XSLJZD-CS for 24 h, followed by treatment with 20 µM carbon cyanide 3-chlorophenylhydrazone (CCCP) for 4 h. Cell viability, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS), cellular ATP generation and mitochondrial Keima (mtKeima) expression were examined. Both in vivo and in vitro, gene expression was assessed by Western blotting. All experiments were performed in duplicate. RESULTS: Disorders of the mitochondrial quality control system existed in gastric smooth muscle in FD spleen deficiency syndrome. XSLJZD administration promoted the contraction of gastric smooth muscle and restored mitochondrial function by downregulating the colocalization of LC3 or Parkin with mitochondria, reducing the ratio of LC3II/LC3I, decreasing the expression of PINK1, Parkin and Drp1 and increasing the expression of p62 to restore mitochondrial morphology and function. In vitro studies showed that the improvement in mitochondrial function by XSLJZD was related to PINK1-parkin-mediated mitochondrial quality control. CONCLUSION: We demonstrated that XSLJZD can improve gastrointestinal motility disorder in functional dyspepsia with spleen deficiency syndrome, which was related to reconstruction of the mitochondrial quality control system by restraining PINK1/Parkin-mediated mitophagy and division. This study illustrates a novel clinical significance of herbal medicine in the treatment of FD and clarifies the important role of MQC in treating gastrointestinal motility disorder.

[Application of acupuncture in inhibiting intestinal peristalsis in colonoscopy].

Acupuncture regulating gastrointestinal motility has the characteristics of bidirectional benign regulation, acupoint specificity and immediacy. And its regulation is mainly achieved through the "neuro-endocrine-immune" network system. Acupuncture at Neiguan (PC 6) and Hegu (LI 4) to inhibit intestinal peristalsis may have good application value in colonoscopy.