{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:16:40Z","timestamp":1788545800712,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Huanggang City Demonstration and Pilot Project for the Inheritance, Innovation, and Development of Traditional Chinese Medicine","award":["No. 42110022237T000000135"],"award-info":[{"award-number":["No. 42110022237T000000135"]}]},{"name":"Special Fund for the Construction of the Modern Agricultural Industrial Technology System","award":["CARS-21"],"award-info":[{"award-number":["CARS-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objective: To investigate the therapeutic effects and safety profile of Wanshi Shachong Xiaoji Pills (WSXPs) on a functional dyspepsia (FD) mouse model and to preliminarily explore its potential mechanism and impact on associated hepatic metabolism. Methods: An FD model was established in mice using L-arginine. Gastrointestinal motility was assessed by measuring gastric emptying and intestinal propulsion rates. Serum levels of gastrointestinal hormones (MTL, GAS, VIP, CCK) and gut microbiota composition were analyzed. A one-month repeated-dose toxicity study was conducted in normal mice to evaluate safety. The effects of WSXPs on lipid metabolism and inflammation were further examined in a hepatocyte steatosis model in vitro, and network pharmacology was employed to predict potential mechanisms. Results: WSXPs significantly alleviated FD symptoms by improving gastrointestinal motility, bidirectionally regulating gut hormone levels, and increasing the abundance of beneficial bacteria (Akkermansia muciniphila). Long-term administration showed no significant toxicity. In vitro, WSXPS reduced lipid accumulation and inflammation in hepatocytes. Network analysis identified the PI3K-Akt signaling pathway as a potentially central common target, providing a hypothesis for future mechanistic studies. Conclusions: WSXPs effectively improve FD symptoms, modulates gut microbiota, and exhibits potential benefits on hepatic lipid metabolism in vitro, possibly via the PI3K-Akt pathway. This hepatocyte-level finding, combined with its in vivo efficacy in FD, suggests a promising avenue for future research into its potential applications in metabolic-associated conditions. This study provides a scientific foundation for the further development and clinical application of WSXPs in treating FD.<\/jats:p>","DOI":"10.3390\/ph19030448","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:45:39Z","timestamp":1773153939000},"page":"448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Wanshi Shachong Xiaoji Pills Alleviate Functional Dyspepsia in Mice and Exhibit Lipid-Lowering Effects in a Hepatocyte Steatosis Model"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3985-3302","authenticated-orcid":false,"given":"Xiaoyue","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0660-5076","authenticated-orcid":false,"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junming","family":"Tu","sequence":"additional","affiliation":[{"name":"Huanggang Academy of Agricultural Sciences, Huanggang 438000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Huanggang Academy of Agricultural Sciences, Huanggang 438000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanfan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Duan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuxian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"},{"name":"Hubei Engineering Research Center of Good Agricultural Practices (GAP) Production for Chinese Herbal Medicines, Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmao","family":"You","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Cultivation of Chinese Herbal Medicines, Ministry of Agriculture and Rural Affairs, Institute of Chinese Herbal 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Gastroenterol. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9330","DOI":"10.3748\/wjg.v20.i28.9330","article-title":"Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations","volume":"20","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Volari\u0107, M., \u0160ojat, D., Majnari\u0107, L.T., and Vu\u010di\u0107, D. (2024). The Association between Functional Dyspepsia and Metabolic Syndrome-The State of the Art. Int. J. Environ. Res. Public Health, 21.","DOI":"10.3390\/ijerph21020237"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Juanola, O., Mart\u00ednez-L\u00f3pez, S., Franc\u00e9s, R., and G\u00f3mez-Hurtado, I. (2021). Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18105227"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4103\/2277-9175.180988","article-title":"Dietary fat intake and functional dyspepsia","volume":"5","author":"Khodarahmi","year":"2016","journal-title":"Adv. Biomed. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/nrgastro.2012.246","article-title":"Dietary and lifestyle factors in functional dyspepsia","volume":"10","author":"Azpiroz","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.bbrc.2019.11.158","article-title":"High-fat diet-derived free fatty acids impair the intestinal immune system and increase sensitivity to intestinal epithelial damage","volume":"522","author":"Tanaka","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s00535-016-1291-0","article-title":"Fatty acids in a high-fat diet potentially induce gastric parietal-cell damage and metaplasia in mice","volume":"52","author":"Hirata","year":"2017","journal-title":"J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109199","DOI":"10.1016\/j.cbi.2020.109199","article-title":"High fat diet-triggered non-alcoholic fatty liver disease: A review of proposed mechanisms","volume":"330","author":"Lian","year":"2020","journal-title":"Chem.-Biol. Interact."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.3748\/wjg.v26.i40.6141","article-title":"Role of gut microbiota via the gut-liver-brain axis in digestive diseases","volume":"26","author":"Ding","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_12","first-page":"117","article-title":"Impacts on the appetite regulating factors of infantile anorexia treated with acupuncture at Sifeng (EX-UE 10)","volume":"33","author":"Fu","year":"2013","journal-title":"Chin. Acupunct. Moxibustion"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lozano, F. (2014). Basic Theories of Traditional Chinese Medicine, Springer.","DOI":"10.1007\/978-1-4614-5275-1_2"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hao, L., Yu, Z., Sun, J., Li, Z., Li, J., Deng, Y., Huang, H., Huo, H., Li, H., and Huang, L. (2024). Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1385159"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/jmf.2016.3791","article-title":"Antiobesity Effects of Sansa (Crataegi fructus) on 3T3-L1 Cells and on High-Fat-High-Cholesterol Diet-Induced Obese Rats","volume":"20","author":"Lee","year":"2017","journal-title":"J. Med. Food"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mao, Y., Song, Y., Pan, S., Li, N., Wang, W.X., Feng, B.B., and Zhang, J.H. (2022). Effect of Codonopsis Radix and Polygonati Rhizoma on the regulation of the IRS1\/PI3K\/AKT signaling pathway in type 2 diabetic mice. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1068555"},{"key":"ref_17","first-page":"157540","article-title":"Codonopsis Radix: A comprehensive review for its ethnopharmacology, phytochemistry, pharmacodynamics, pharmacokinetics, toxicity and potential clinical applications","volume":"149","author":"Bai","year":"2025","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.fct.2018.05.051","article-title":"Phytochemicals, pharmacology, clinical application, patents, and products of Amomi fructus","volume":"119","author":"Suo","year":"2018","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1089\/jmf.2019.4430","article-title":"Maillard Reaction Products of Stir Fried Hordei Fructus Germinatus Are Important for Its Efficacy in Treating Functional Dyspepsia","volume":"23","author":"Wu","year":"2020","journal-title":"J. Med. Food"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"114524","DOI":"10.1016\/j.jep.2021.114524","article-title":"The rich pharmacological activities of Magnolia officinalis and secondary effects based on significant intestinal contributions","volume":"281","author":"Niu","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15203","DOI":"10.1038\/s41598-023-42358-w","article-title":"Honokiol affects the composition of gut microbiota and the metabolism of lipid and bile acid in methionine-choline deficiency diet-induced NASH mice","volume":"13","author":"Zhai","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.3748\/wjg.v23.i32.5977","article-title":"New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase II trial","volume":"23","author":"Jeong","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_23","unstructured":"(2025, March 02). Center for Drug Evaluation (CDE), National Medical Products Administration (NMPA), China. (13 May 2014). Technical Guidelines for Repeated Dose Toxicity Testing. Available online: https:\/\/www.cde.org.cn\/zdyz\/domesticinfopage?zdyzIdCODE=eb1121e208d156f8fb0384d1e77edb8f."},{"key":"ref_24","first-page":"623","article-title":"Role of nitric oxide in the control of the gastric motility within the nucleus ambiguus of rats","volume":"63","author":"Sun","year":"2012","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6135","DOI":"10.1038\/s41598-026-37006-y","article-title":"Comparative study of palmitoleic acid, sea buckthorn oil, and lovastatin in hepatocellular steatosis model","volume":"16","author":"Szustak","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fujio-Vejar, S., Vasquez, Y., Morales, P., Magne, F., Vera-Wolf, P., Ugalde, J.A., Navarrete, P., and Gotteland, M. (2017). The Gut Microbiota of Healthy Chilean Subjects Reveals a High Abundance of the Phylum Verrucomicrobia. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01221"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e159621","DOI":"10.1128\/spectrum.01596-21","article-title":"Akkermansia muciniphila Ameliorates Acetaminophen-Induced Liver Injury by Regulating Gut Microbial Composition and Metabolism","volume":"10","author":"Xia","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1016\/j.clnu.2022.08.029","article-title":"Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases","volume":"41","author":"Liu","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111198","DOI":"10.1016\/j.nut.2021.111198","article-title":"Sodium acetate, propionate, and butyrate reduce fat accumulation in mice via modulating appetite and relevant genes","volume":"87\u201388","author":"Jiao","year":"2021","journal-title":"Nutrition"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13099-021-00446-0","article-title":"Gut microbiota influence in type 2 diabetes mellitus (T2DM)","volume":"13","author":"Cunningham","year":"2021","journal-title":"Gut Pathog."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s12035-023-03602-6","article-title":"Akkermansia muciniphila Improves Depressive-Like Symptoms by Modulating the Level of 5-HT Neurotransmitters in the Gut and Brain of Mice","volume":"61","author":"Guo","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1892441","DOI":"10.1080\/19490976.2021.1892441","article-title":"Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development","volume":"13","author":"Kim","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114244","DOI":"10.1016\/j.biopha.2023.114244","article-title":"Targeting PI3K\/AKT signaling pathway in obesity","volume":"159","author":"Savova","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"155912","DOI":"10.1016\/j.metabol.2024.155912","article-title":"Deciphering the molecular pathways of saroglitazar: A dual PPAR \u03b1\/\u03b3 agonist for managing metabolic NAFLD","volume":"155","author":"Ezhilarasan","year":"2024","journal-title":"Metabolism"},{"key":"ref_35","first-page":"489","article-title":"Therapeutic effect of pachymic acid on Helicobacter pylori-associated gastritis in rats by regulating the PI3K\/AKT\/NF-\u03baB signaling pathway","volume":"44","author":"Xu","year":"2024","journal-title":"Basic Clin. Med."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/448\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:52:09Z","timestamp":1773154329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030448"],"URL":"https:\/\/doi.org\/10.3390\/ph19030448","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]}}}