{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:33:21Z","timestamp":1792262001150,"version":"4.4.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800463 81720108006"],"award-info":[{"award-number":["81800463 81720108006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Ethnopharmacological relevance:<\/jats:bold> Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in \u201cSynopsis of Golden Chamber\u201d (Han Dynasty in the 3<jats:sup>rd<\/jats:sup> century) and the Zhizhu pill in \u201cDifferentiation on Endogenous\u201d in Jin Dynasty (1,115\u20131,234). ZZKZ contains four botanical drugs, including <jats:italic>Citrus \u00d7 Aurantium<\/jats:italic> L [Rutaceae; <jats:italic>Aurantii Fructus Immaturus<\/jats:italic>], <jats:italic>Atractylodes Macrocephala<\/jats:italic> Koidz. [Compositae; <jats:italic>Rhizoma Atractylodis Macrocephalae<\/jats:italic>], <jats:italic>Bupleurum Chinense<\/jats:italic> DC [Apiaceae; <jats:italic>Radix Bupleuri Chinensis<\/jats:italic>], and <jats:italic>Crataegus Pinnatifida<\/jats:italic> Bunge [Rosaceae; <jats:italic>Fructus Crataegi Pinnatifidae<\/jats:italic>], which have been widely used in clinical therapy for functional dyspepsia (FD).<\/jats:p><jats:p><jats:bold>Aim of the study:<\/jats:bold> This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD.<\/jats:p><jats:p><jats:bold>Materials and methods:<\/jats:bold> FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5\u00a0g\/kg, 1.0\u00a0g\/kg, or 1.5\u00a0g\/kg respectively) by gavage for 7\u00a0days, while domperidone (3\u00a0mg\/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. <jats:italic>Ex vivo<\/jats:italic> gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT<jats:sub>3<\/jats:sub> receptor and increased 5-HT<jats:sub>4<\/jats:sub> receptor mRNA expression in the guts of FD rats.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT<jats:sub>3<\/jats:sub> activity and increased 5-HT<jats:sub>4<\/jats:sub> distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.<\/jats:p>","DOI":"10.3389\/fphar.2022.1026660","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T05:19:54Z","timestamp":1668662394000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhuanglong","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1365-2982.2006.00871.x","article-title":"Sensory transmission in the gastrointestinal tract","volume":"19","author":"Blackshaw","year":"2007","journal-title":"Neurogastroenterol. Motil."},{"key":"B2","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3389\/fnins.2015.00413","article-title":"Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology","volume":"9","author":"Browning","year":"2015","journal-title":"Front. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1053\/j.gastro.2016.02.029","article-title":"Pharmacological, pharmacokinetic, and pharmacogenomic aspects of functional gastrointestinal disorders","volume":"150","author":"Camilleri","year":"2016","journal-title":"Gastroenterology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"115034","DOI":"10.1016\/j.jep.2022.115034","article-title":"Bupleurum chinense DC improves CUMS-induced depressive symptoms in rats through upregulation of the cAMP\/PKA\/CREB signalling pathway","volume":"289","author":"Chang","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.cgh.2013.03.026","article-title":"Decreased Basal and postprandial plasma serotonin levels in patients with functional dyspepsia","volume":"11","author":"Cheung","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.phymed.2010.08.010","article-title":"Pharmacological mechanism responsible for the Atractylodes japonica-induced distal colonic contraction in rats","volume":"18","author":"Choi","year":"2011","journal-title":"Phytomedicine"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1111\/nmo.12667","article-title":"Mechanisms contributing to visceral hypersensitivity: Focus on splanchnic afferent nerve signaling","volume":"27","author":"Deiteren","year":"2015","journal-title":"Neurogastroenterol. Motil."},{"key":"B8","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s12272-021-01342-6","article-title":"Atractylenolides (I, II, and III): A review of their pharmacology and pharmacokinetics","volume":"44","author":"Deng","year":"2021","journal-title":"Arch. Pharm. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1038\/ajg.2014.231","article-title":"Fasting and postprandial gastric sensorimotor activity in functional dyspepsia: Postprandial distress vs. epigastric pain syndrome","volume":"109","author":"Di Stefano","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"17081","DOI":"10.1038\/nrdp.2017.81","article-title":"Functional dyspepsia","volume":"3","author":"Enck","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B11","doi-asserted-by":"publisher","first-page":"109777","DOI":"10.1016\/j.foodres.2020.109777","article-title":"Polysaccharides from Atractylodes macrocephala Koidz. Ameliorate ulcerative colitis via extensive modification of gut microbiota and host metabolism","volume":"138","author":"Feng","year":"2020","journal-title":"Food Res. Int."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1016\/S0140-6736(20)30469-4","article-title":"Functional dyspepsia","volume":"396","author":"Ford","year":"2020","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1097\/MED.0b013e32835bc703","article-title":"5-Hydroxytryptamine (serotonin) in the gastrointestinal tract","volume":"20","author":"Gershon","year":"2013","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1365-2036.2004.02180.x","article-title":"Review article: Serotonin receptors and transporters - roles in normal and abnormal gastrointestinal motility","volume":"20","author":"Gershon","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B15","first-page":"1071","article-title":"Long-term efficacy and safety research on functional dyspepsia treated with electroacupuncture and Zhizhu Kuanzhong capsule","volume":"31","author":"Guo","year":"2011","journal-title":"Zhongguo Zhen Jiu"},{"key":"B16","doi-asserted-by":"crossref","first-page":"108S","DOI":"10.1023\/A:1026610418663","article-title":"Serotonin receptor physiology: Relation to emesis","volume":"44","author":"Hasler","year":"1999","journal-title":"Dig. Dis. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"953205","DOI":"10.3389\/fphar.2022.953205","article-title":"Best Practice in the chemical characterisation of extracts used in pharmacological and toxicological research-The ConPhyMP-Guidelines","volume":"13","author":"Heinrich","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1517\/14728222.8.2.107","article-title":"Gastrointestinal pain in functional bowel disorders: Sensory neurons as novel drug targets","volume":"8","author":"Holzer","year":"2004","journal-title":"Expert Opin. Ther. Targets"},{"key":"B19","doi-asserted-by":"publisher","first-page":"945624","DOI":"10.3389\/fphar.2022.945624","article-title":"Hesperidin promotes gastric motility in rats with functional dyspepsia by regulating Drp1-mediated ICC mitophagy","volume":"13","author":"Jia","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"581","DOI":"10.3109\/13880209.2013.854396","article-title":"The effects of Fructus Aurantii extract on the 5-hydroxytryptamine and vasoactive intestinal peptide contents of the rat gastrointestinal tract","volume":"52","author":"Jiang","year":"2014","journal-title":"Pharm. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"14490","DOI":"10.3390\/molecules171214490","article-title":"Polyphenolic profile and biological activity of Chinese hawthorn (Crataegus pinnatifida BUNGE) fruits","volume":"17","author":"Jurikova","year":"2012","journal-title":"Mol. (Basel, Switz."},{"key":"B22","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.phrs.2018.06.017","article-title":"What is the role of endogenous gut serotonin in the control of gastrointestinal motility?","volume":"140","author":"Keating","year":"2019","journal-title":"Pharmacol. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1111\/nmo.12617","article-title":"Serotonin and colonic motility","volume":"27","author":"Kendig","year":"2015","journal-title":"Neurogastroenterol. Motil."},{"key":"B24","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.jep.2012.02.031","article-title":"Effects of an Atractylodes lancea rhizome extract and a volatile component beta-eudesmol on gastrointestinal motility in mice","volume":"141","author":"Kimura","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"8998","DOI":"10.1523\/JNEUROSCI.6684-10.2011","article-title":"Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development\/survival of enteric dopaminergic neurons","volume":"31","author":"Li","year":"2011","journal-title":"J. Neurosci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e9731","DOI":"10.1097\/MD.0000000000009731","article-title":"Effect of Zhizhu Kuanzhong capsule on functional dyspepsia: Protocol for a systematic review and meta-analysis of randomized controlled trials","volume":"97","author":"Lin","year":"2018","journal-title":"Med. Baltim."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1053\/j.gastro.2008.02.093","article-title":"A rat model of chronic gastric sensorimotor dysfunction resulting from transient neonatal gastric irritation","volume":"134","author":"Liu","year":"2008","journal-title":"Gastroenterology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s00535-021-01843-7","article-title":"Evidence-based clinical practice guidelines for functional dyspepsia 2021","volume":"57","author":"Miwa","year":"2022","journal-title":"J. Gastroenterol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fnsys.2018.00010","article-title":"Meal-sensing signaling pathways in functional dyspepsia","volume":"12","author":"Page","year":"2018","journal-title":"Front. Syst. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"115578","DOI":"10.1016\/j.jep.2022.115578","article-title":"Bidirectional effects and mechanisms of traditional Chinese medicine","volume":"298","author":"Peng","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"Reagan-Shaw","year":"2008","journal-title":"FASEB J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.jep.2013.12.022","article-title":"What is in a name? The need for accurate scientific nomenclature for plants","volume":"152","author":"Rivera","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/s0016-5085(99)70171-x","article-title":"Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients","volume":"116","author":"Samsom","year":"1999","journal-title":"Gastroenterology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s11894-022-00843-8","article-title":"Role of traditional Chinese herbal medicines in functional gastrointestinal and motility disorders","volume":"24","author":"Sankararaman","year":"2022","journal-title":"Curr. Gastroenterol. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1007\/s40265-020-01362-4","article-title":"Functional dyspepsia: Diagnostic and therapeutic approaches","volume":"80","author":"Sayuk","year":"2020","journal-title":"Drugs"},{"key":"B36","doi-asserted-by":"publisher","first-page":"E1464","DOI":"10.3390\/nu11071464","article-title":"The intestinal fate of Citrus flavanones and their effects on gastrointestinal health","volume":"11","author":"Stevens","year":"2019","journal-title":"Nutrients"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1053\/j.gastro.2004.05.030","article-title":"Pathophysiology and treatment of functional dyspepsia","volume":"127","author":"Tack","year":"2004","journal-title":"Gastroenterology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1053\/gast.2001.27180","article-title":"Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia","volume":"121","author":"Tack","year":"2001","journal-title":"Gastroenterology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1136\/gutjnl-2016-312230","article-title":"Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: A consensus of experts","volume":"67","author":"Tack","year":"2018","journal-title":"Gut"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1053\/j.gastro.2005.11.059","article-title":"Functional gastroduodenal disorders","volume":"130","author":"Tack","year":"2006","journal-title":"Gastroenterology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"349","DOI":"10.5009\/gnl16055","article-title":"Functional dyspepsia: Advances in diagnosis and therapy","volume":"11","author":"Talley","year":"2017","journal-title":"Gut Liver"},{"key":"B42","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1097\/MOG.0000000000000306","article-title":"Functional dyspepsia","volume":"32","author":"Talley","year":"2016","journal-title":"Curr. Opin. Gastroenterol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/j.1365-2982.2005.00716.x","article-title":"5-Hydroxytryptamine effects in the gut: The 3, 4, and 7 receptors","volume":"17","author":"Tonini","year":"2005","journal-title":"Neurogastroenterol. Motil."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1053\/j.gastro.2007.03.037","article-title":"Regional cerebral blood flow during gastric balloon distention in functional dyspepsia","volume":"132","author":"Vandenberghe","year":"2007","journal-title":"Gastroenterology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1136\/gut.2004.052605","article-title":"Dyspeptic patients with visceral hypersensitivity: Sensitisation of pain specific or multimodal pathways?","volume":"54","author":"Vandenberghe","year":"2005","journal-title":"Gut"},{"key":"B46","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/nrgastro.2012.255","article-title":"Changes in gastrointestinal tract function and structure in functional dyspepsia","volume":"10","author":"Vanheel","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"9358","DOI":"10.3748\/wjg.v21.i31.9358","article-title":"Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons","volume":"21","author":"Wang","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3748\/wjg.v18.i6.522","article-title":"Hyperpolarization-activated cyclic nucleotide-gated cation channel subtypes differentially modulate the excitability of murine small intestinal afferents","volume":"18","author":"Wang","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1136\/gutjnl-2019-318536","article-title":"Novel concepts in the pathophysiology and treatment of functional dyspepsia","volume":"69","author":"Wauters","year":"2020","journal-title":"Gut"},{"key":"B50","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s11655-018-2846-0","article-title":"Effect of Zhizhu Kuanzhong capsules on treatment of functional dyspepsia: A meta-analysis of randomized controlled trials","volume":"25","author":"Wen","year":"2019","journal-title":"Chin. J. Integr. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.3390\/molecules19021685","article-title":"Crataegus pinnatifida: Chemical constituents, pharmacology, and potential applications","volume":"19","author":"Wu","year":"2014","journal-title":"Molecules"},{"key":"B52","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1186\/s13063-022-06396-5","article-title":"Zhizhu Kuanzhong capsule in treating patients with functional dyspepsia postprandial distress syndrome: Study protocol for a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial","volume":"23","author":"Xiao","year":"2022","journal-title":"Trials"},{"key":"B53","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1111\/jgh.14467","article-title":"The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome","volume":"34","author":"Xiao","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.jep.2015.10.001","article-title":"Traditional Chinese medicine Zhiqiao-Houpu herb-pair induce bidirectional effects on gastric motility in rats","volume":"175","author":"Xiong","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"4778","DOI":"10.19540\/j.cnki.cjcmm.20220520.501","article-title":"Four Chinese patent medicines for regulating stomach for functional dyspepsia: A rapid health technology assessment","volume":"47","author":"Xu","year":"2022","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B56","doi-asserted-by":"publisher","first-page":"727154","DOI":"10.3389\/fphar.2021.727154","article-title":"A review of the Ethnopharmacology, phytochemistry, pharmacology, application, quality control, processing, toxicology, and pharmacokinetics of the dried rhizome of Atractylodes macrocephala","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.fitote.2013.10.010","article-title":"Synergy effects of herb extracts: Pharmacokinetics and pharmacodynamic basis","volume":"92","author":"Yang","year":"2014","journal-title":"Fitoterapia"},{"key":"B58","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/s0254-6272(13)60039-4","article-title":"Clinical curative effect of electroacupuncture combined with zhizhukuanzhong capsules for treating gastroesophageal reflux disease","volume":"32","author":"Zhang","year":"2012","journal-title":"J. Tradit. Chin. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"13644","DOI":"10.1096\/fj.201901192R","article-title":"EphrinB2\/ephB2-mediated myenteric synaptic plasticity: Mechanisms underlying the persistent muscle hypercontractility and pain in postinfectious IBS","volume":"33","author":"Zhang","year":"2019","journal-title":"FASEB J."},{"key":"B60","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jep.2018.08.023","article-title":"The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz. A review","volume":"226","author":"Zhu","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"5623","DOI":"10.2147\/DDDT.S260703","article-title":"Paeoniflorin alleviates abnormalities in rats with functional dyspepsia by stimulating the release of acetylcholine","volume":"14","author":"Zou","year":"2020","journal-title":"Drug Des. devel. Ther."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1026660\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T05:20:00Z","timestamp":1668662400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1026660\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,17]]},"references-count":61,"alternative-id":["10.3389\/fphar.2022.1026660"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.1026660","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,17]]},"article-number":"1026660"}}