{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:03:04Z","timestamp":1791388984496,"version":"4.3.3"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available.<\/jats:p><jats:p><jats:bold>Aim of the study:<\/jats:bold> To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model.<\/jats:p><jats:p><jats:bold>Materials and methods:<\/jats:bold> BALB\/C mice were pretreated with Yeokwisan (100, 200, and 400\u00a0mg\/kg, po) or mosapride (3\u00a0mg\/kg, po) for 5\u00a0days and then treated with loperamide (10\u00a0mg\/kg, ip) after 20\u00a0h of fasting. A solution of 0.05% phenol red (500\u00a0\u03bcL) or diet of 5% charcoal (200\u00a0\u03bcL) was orally administered, followed by assessment of gastric emptying or intestinal transit. Plasma acyl-ghrelin (ELISA), C-kit (immunofluorescence and western blotting), nNOS (western blotting) and gastric contraction- and ghrelin-related gene\/protein expression levels were examined in stomach and small intestine tissues.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Loperamide injection substantially delayed gastric emptying, while Yeokwisan pretreatment (especially 200 and 400\u00a0mg\/kg Yeokwisan) significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of phenol red retained in the stomach (<jats:italic>p<\/jats:italic> &amp;lt; 0.05 or 0.01) and stomach weight (<jats:italic>p<\/jats:italic> &amp;lt; 0.05 or 0.01). The levels of plasma acyl-ghrelin and expression of gastric ghrelin-related genes, such as growth hormone secretagogue receptor (GHSR), ghrelin-O-acyltransferase (GOAT), adrenergic receptor \u03b21 (ADRB1) and somatostatin receptor (SSTR), were significantly normalized (<jats:italic>p<\/jats:italic> &amp;lt; 0.05 or 0.01) by Yeokwisan (400\u00a0mg\/kg). Yeokwisan (400\u00a0mg\/kg) significantly tempered the loperamide-induced alterations in the c-kit and nNOS levels (<jats:italic>p<\/jats:italic> &amp;lt; 0.01) as well as the expression of contraction- and ghrelin-related genes, such as 5-HT4 receptor (5-HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK), in the stomach, but not in the small intestine.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present results showed the clinical relevance of Yeokwisan, in treating FD, especially in promoting gastric emptying but not small intestinal transit. The main mechanisms corresponding to these effects may involve the modulation of the ghrelin pathway and activation of interstitial cells of Cajal in stomach tissue.<\/jats:p>","DOI":"10.3389\/fphar.2021.753153","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T06:17:27Z","timestamp":1632291447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Yeokwisan, a Standardized Herbal Formula, Enhances Gastric Emptying via Modulation of the Ghrelin Pathway in a Loperamide-induced Functional Dyspepsia Mouse Model"],"prefix":"10.3389","volume":"12","author":[{"given":"Seung-Ju","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Seok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwa-Dong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Joon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Hyung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Gue","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.bbrc.2016.02.078","article-title":"Anethole Restores Delayed Gastric Emptying and Impaired Gastric Accommodation in Rodents","volume":"472","author":"Asano","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1016\/j.peptides.2005.12.008","article-title":"Ghrelin Gastrokinetic Action in Patients with Neurogenic Gastroparesis","volume":"27","author":"Binn","year":"2006","journal-title":"Peptides"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.3748\/wjg.v18.i12.1391","article-title":"Opiate-induced Constipation Related to Activation of Small Intestine Opioid \u03bc2-receptors","volume":"18","author":"Chen","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1111\/jgh.13756","article-title":"Overlap between Irritable Bowel Syndrome and Functional Dyspepsia Including Subtype Analyses","volume":"32","author":"Choi","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/j.1365-2982.2007.01059.x","article-title":"5-HT4 Receptor Agonists: Similar but Not the Same","volume":"20","author":"De Maeyer","year":"2008","journal-title":"Neurogastroenterol Motil."},{"key":"B6","article-title":"Protective Effects of Naringin in Indomethacin-Induced Gastric Ulcer in Rats","volume":"8","author":"Emin","year":"2019","journal-title":"GSC Biol. Pharm. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2017.81","article-title":"Functional Dyspepsia","volume":"3","author":"Enck","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B8","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.molmet.2013.08.006","article-title":"Seven Transmembrane G Protein-Coupled Receptor Repertoire of Gastric Ghrelin Cells","volume":"2","author":"Engelstoft","year":"2013","journal-title":"Mol. Metab."},{"key":"B9","article-title":"Association of Functional Dyspepsia with Depression and Anxiety: A Systematic Review","volume":"30","author":"Esterita","year":"2021","journal-title":"Journal of Gastrointestinal and Liver Diseases"},{"key":"B10","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/j.1365-2982.2008.01109.x","article-title":"Interstitial Cells of Cajal in Health and Disease","volume":"20","author":"Farrugia","year":"2008","journal-title":"Neurogastroenterology Motil."},{"key":"B11","article-title":"Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers","volume":"7","year":"2005","journal-title":"Cent. Drug Eval. Res. (Cder)"},{"key":"B12","article-title":"The Korean Herbal Pharmacopoeia","year":"2012","journal-title":"The KFDA Notification"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1136\/gutjnl-2014-307843","article-title":"Global Prevalence of, and Risk Factors for, Uninvestigated Dyspepsia: a Meta-Analysis","volume":"64","author":"Ford","year":"2015","journal-title":"Gut"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30469-4","article-title":"Functional Dyspepsia","author":"Ford","year":"2020","journal-title":"The Lancet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.gassur.2004.10.001","article-title":"Absence of the Interstitial Cells of Cajal in Patients with Gastroparesis and Correlation with Clinical Findings","volume":"9","author":"Forster","year":"2005","journal-title":"J. Gastrointest. Surg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1165\/ajrcmb.16.5.9160829","article-title":"Myosin Light Chain Kinase in Endothelium: Molecular Cloning and Regulation","volume":"16","author":"Garcia","year":"1997","journal-title":"Am. J. Respir. Cel Mol Biol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.jad.2017.09.049","article-title":"Autonomic Dysfunction of Gastric Motility in Major Depression","volume":"226","author":"Haj Kheder","year":"2018","journal-title":"J. Affect Disord."},{"key":"B18","first-page":"15","article-title":"The Role of Loperamide in Gastrointestinal Disorders","volume":"8","author":"Hanauer","year":"2008","journal-title":"Rev. Gastroenterol. Disord."},{"key":"B19","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1159\/000354579","article-title":"Naringin Exhibits In Vivo Prokinetic Activity via Activation of Ghrelin Receptor in Gastrointestinal Motility Dysfunction Rats","volume":"92","author":"Jang","year":"2013","journal-title":"Pharmacology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"111834","DOI":"10.1016\/j.jep.2019.111834","article-title":"Banha-sasim-tang Improves Gastrointestinal Function in Loperamide-Induced Functional Dyspepsia Mouse Model","volume":"238","author":"Jeon","year":"2019","journal-title":"J. Ethnopharmacol"},{"key":"B21","volume-title":"Basic & Clinical Pharmacology","author":"Katzung","year":"2004"},{"key":"B22","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.jep.2013.10.033","article-title":"A Traditional Herbal Formula, Hyangsa-Pyeongwi San (HPS), Improves Quality of Life (QoL) of the Patient with Functional Dyspepsia (FD): Randomized Double-Blinded Controlled Trial","volume":"151","author":"Kim","year":"2014","journal-title":"J. Ethnopharmacol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"470","DOI":"10.14348\/molcells.2019.0028","article-title":"The Mechanism of Action of Ghrelin and Motilin in the Pacemaker Potentials of Interstitial Cells of Cajal from the Murine Small Intestine","volume":"42","author":"Kim","year":"2019","journal-title":"Mol. Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"636752","DOI":"10.3389\/fphar.2021.636752","article-title":"Beneficial Potential of Banha-Sasim-Tang for Stress-Sensitive Functional Dyspepsia via Modulation of Ghrelin: A Randomized Controlled Trial","volume":"12","author":"Kim","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1111\/apt.12355","article-title":"Functional Dyspepsia: the Economic Impact to Patients","volume":"38","author":"Lacy","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1177\/2050640613499567","article-title":"A Survey of Pharmacological and Nonpharmacological Treatment of Functional Gastrointestinal Disorders","volume":"1","author":"Lahner","year":"2013","journal-title":"United Eur. Gastroenterol J"},{"key":"B27","doi-asserted-by":"publisher","first-page":"393","DOI":"10.4196\/kjpp.2013.17.5.393","article-title":"Chronic Administration of Baicalein Decreases Depression-like Behavior Induced by Repeated Restraint Stress in Rats","volume":"17","author":"Lee","year":"2013","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.jep.2005.08.015","article-title":"Effect of an Aqueous Extract of Dried Immature Fruit of Poncirus Trifoliata (L.) Raf. On Intestinal Transit in Rodents with Experimental Gastrointestinal Motility Dysfunctions","volume":"102","author":"Lee","year":"2005","journal-title":"J. Ethnopharmacol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1002\/ptr.2840","article-title":"Protective Effects of Neohesperidin and Poncirin Isolated from the Fruits of Poncirus Trifoliata on Potential Gastric Disease","volume":"23","author":"Lee","year":"","journal-title":"Phytother Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1159\/000215389","article-title":"Plasma Ghrelin Levels and Their Relationship with Gastric Emptying in Patients with Dysmotility-like Functional Dyspepsia","volume":"80","author":"Lee","year":"","journal-title":"Digestion"},{"key":"B31","doi-asserted-by":"publisher","first-page":"7778","DOI":"10.3748\/wjg.v22.i34.7778","article-title":"Effects of Lizhong Tang on Gastrointestinal Motility in Mice","volume":"22","author":"Lee","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"239","DOI":"10.5056\/jnm.2012.18.3.239","article-title":"Investigating Functional Dyspepsia in Asia","volume":"18","author":"Lee","year":"2012","journal-title":"J. Neurogastroenterol Motil."},{"key":"B33","doi-asserted-by":"publisher","first-page":"113411","DOI":"10.1016\/j.jep.2020.113411","article-title":"Laxative Effect and Mechanism of Tiantian Capsule on Loperamide-Induced Constipation in Rats","volume":"266","author":"Li","year":"2021","journal-title":"J. Ethnopharmacol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/s0254-6272(13)60168-5","article-title":"Effect of Herbal Formula Xiao Pi-II on Functional Dyspepsia","volume":"33","author":"Liu","year":"2013","journal-title":"J. Tradit Chin. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"326","DOI":"10.3390\/molecules24020326","article-title":"Anti-depressive Effectiveness of Baicalin In Vitro and In Vivo","volume":"24","author":"Liu","year":"2019","journal-title":"Molecules"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.3748\/wjg.v12.i17.2661","article-title":"Epidemiology of Functional Dyspepsia: a Global Perspective","volume":"12","author":"Mahadeva","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1258\/002367704323133637","article-title":"Protocol to Refine Intestinal Motility Test in Mice","volume":"38","author":"Marona","year":"2004","journal-title":"Lab. Anim."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1211\/jpp.59.11.0015","article-title":"Scutellaria Baicalensis and a Constituent Flavonoid, Baicalein, Attenuate Ritonavir-Induced Gastrointestinal Side-Effects","volume":"59","author":"Mehendale","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1053\/j.gastro.2005.08.055","article-title":"Neural Stem Cell Transplantation in the Stomach Rescues Gastric Function in Neuronal Nitric Oxide Synthase-Deficient Mice","volume":"129","author":"Micci","year":"2005","journal-title":"Gastroenterology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.vascn.2005.04.017","article-title":"Effects of Fasting on Evaluation of Gastrointestinal Transit with Charcoal Meal","volume":"52","author":"Mittelstadt","year":"2005","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1136\/gut.2005.069088","article-title":"Ghrelin Enhances Gastric Emptying in Diabetic Gastroparesis: a Double Blind, Placebo Controlled, Crossover Study","volume":"54","author":"Murray","year":"2005","journal-title":"Gut"},{"key":"B42","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"B43","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1023\/b:ddas.0000020490.34220.6d","article-title":"Preventive Effect of the Flavonoid, Wogonin, against Ethanol-Induced Gastric Mucosal Damage in Rats","volume":"49","author":"Park","year":"2004","journal-title":"Dig. Dis. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/0014-2999(94)90236-4","article-title":"Delayed Gastric Emptying Induced by Inhibitors of Nitric Oxide Synthase in Rats","volume":"256","author":"Plourde","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.3748\/wjg.14.1419","article-title":"Gastric Motor Effects of Ghrelin and Growth Hormone Releasing Peptide 6 in Diabetic Mice with Gastroparesis","volume":"14","author":"Qiu","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"330","DOI":"10.5056\/jnm15094","article-title":"Prokinetics in the Management of Functional Gastrointestinal Disorders","volume":"21","author":"Quigley","year":"2015","journal-title":"J. Neurogastroenterol Motil."},{"key":"B47","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/216970","article-title":"An Extract of Glycyrrhiza Glabra (GutGard) Alleviates Symptoms of Functional Dyspepsia: a Randomized, Double-Blind, Placebo-Controlled Study","volume":"2012","author":"Raveendra","year":"2012","journal-title":"Evidence-Based Complement. Altern. Med."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/945056","article-title":"Ghrelin Cells in the Gastrointestinal Tract","volume":"2010","author":"Sakata","year":"2010","journal-title":"Int. J. peptides"},{"key":"B49","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev.physiol.68.040504.094718","article-title":"Interstitial Cells of Cajal as Pacemakers in the Gastrointestinal Tract","volume":"68","author":"Sanders","year":"2006","journal-title":"Annu. Rev. Physiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1113\/expphysiol.2011.058248","article-title":"Anoctamins and Gastrointestinal Smooth Muscle Excitability","volume":"97","author":"Sanders","year":"2012","journal-title":"Exp. Physiol."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2013","article-title":"Interstitial Cells: Regulators of Smooth Muscle Function","author":"Sanders","year":"2014","journal-title":"Physiol. Rev."},{"key":"B52","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1111\/j.1572-0241.2003.07389.x","article-title":"Symptoms Associated with Impaired Gastric Emptying of Solids and Liquids in Functional Dyspepsia","volume":"98","author":"Sarnelli","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e0124653","DOI":"10.1371\/journal.pone.0124653","article-title":"Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population","volume":"10","author":"Shah","year":"2015","journal-title":"PloS one"},{"key":"B54","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1159\/000500134","article-title":"Timing and Predictors of Recurrence of Dyspepsia Symptoms after Cessation of Acotiamide Therapy for Functional Dyspepsia: a Long-Term Observational Study","volume":"101","author":"Shinozaki","year":"2020","journal-title":"Digestion"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1053\/j.gastro.2016.02.011","article-title":"Gastroduodenal Disorders","volume":"150","author":"Stanghellini","year":"2016","journal-title":"Gastroenterology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"360","DOI":"10.5056\/jnm.2011.17.4.360","article-title":"Overlap Syndrome of Functional Dyspepsia and Irritable Bowel Syndrome - Are Both Diseases Mutually Exclusive?","volume":"17","author":"Suzuki","year":"2011","journal-title":"J. Neurogastroenterol Motil."},{"key":"B57","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1136\/gut.51.2.219","article-title":"Role of Nitric Oxide in the Gastric Accommodation Reflex and in Meal Induced Satiety in Humans","volume":"51","author":"Tack","year":"2002","journal-title":"Gut"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1016\/s0016-5085(98)70012-5","article-title":"Role of Impaired Gastric Accommodation to a Meal in Functional Dyspepsia","volume":"115","author":"Tack","year":"1998","journal-title":"Gastroenterology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"204","DOI":"10.14309\/ajg.0000000000000072","article-title":"The Unfulfilled Promise of Prokinetics for Functional Dyspepsia\/postprandial Distress Syndrome","volume":"114","author":"Tack","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1097\/01.mcg.0000225614.94470.47","article-title":"Relation Among Plasma Ghrelin Level, Gastric Emptying, and Psychologic Condition in Patients with Functional Dyspepsia","volume":"41","author":"Takamori","year":"2007","journal-title":"J. Clin. Gastroenterol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1111\/j.1572-0241.2001.03683.x","article-title":"Can Symptoms Discriminate Among Those with Delayed or normal Gastric Emptying in Dysmotility-like Dyspepsia?","volume":"96","author":"Talley","year":"2001","journal-title":"Am. J. Gastroenterol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/jgh.14905","article-title":"Herbal Medicine in the Treatment of Functional Gastrointestinal Disorders: A Systematic Review with Meta-Analysis","volume":"35","author":"Tan","year":"2020","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"G291","DOI":"10.1152\/ajpgi.00005.2005","article-title":"Distinct Roles of Nitric Oxide Synthases and Interstitial Cells of Cajal in Rectoanal Relaxation","volume":"289","author":"Terauchi","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"G948","DOI":"10.1152\/ajpgi.00339.2001","article-title":"Ghrelin\/motilin-related Peptide Is a Potent Prokinetic to Reverse Gastric Postoperative Ileus in Rat","volume":"282","author":"Trudel","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3892\/ijmm.2013.1418","article-title":"The Role of Ghrelin in Patients with Functional Dyspepsia and its Potential Clinical Relevance (Review)","volume":"32","author":"Yagi","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.3892\/mmr.2014.2571","article-title":"Function of Ghrelin and Ghrelin Receptors in the Network Regulation of Gastric Motility","volume":"10","author":"Yang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12876-017-0639-0","article-title":"Prokinetics for the Treatment of Functional Dyspepsia: Bayesian Network Meta-Analysis","volume":"17","author":"Yang","year":"2017","journal-title":"BMC Gastroenterol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.753153\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T06:17:35Z","timestamp":1632291455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.753153\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,22]]},"references-count":67,"alternative-id":["10.3389\/fphar.2021.753153"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.753153","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,22]]},"article-number":"753153"}}