{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:22Z","timestamp":1787028562096,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"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":["81603289"],"award-info":[{"award-number":["81603289"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81603251"],"award-info":[{"award-number":["81603251"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["202304051001020"],"award-info":[{"award-number":["202304051001020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20210302123470"],"award-info":[{"award-number":["20210302123470"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20210302123237"],"award-info":[{"award-number":["20210302123237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["202204021301063"],"award-info":[{"award-number":["202204021301063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["202105D121009"],"award-info":[{"award-number":["202105D121009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["YDZJSX2021C025"],"award-info":[{"award-number":["YDZJSX2021C025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["81603289"],"award-info":[{"award-number":["81603289"]}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["81603251"],"award-info":[{"award-number":["81603251"]}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["202304051001020"],"award-info":[{"award-number":["202304051001020"]}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["20210302123470"],"award-info":[{"award-number":["20210302123470"]}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["20210302123237"],"award-info":[{"award-number":["20210302123237"]}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["202204021301063"],"award-info":[{"award-number":["202204021301063"]}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["202105D121009"],"award-info":[{"award-number":["202105D121009"]}]},{"name":"Special Fund for Science and Technology Innovation Teams of Shanxi Province","award":["YDZJSX2021C025"],"award-info":[{"award-number":["YDZJSX2021C025"]}]},{"name":"Natural Science Foundation of Shanxi","award":["81603289"],"award-info":[{"award-number":["81603289"]}]},{"name":"Natural Science Foundation of Shanxi","award":["81603251"],"award-info":[{"award-number":["81603251"]}]},{"name":"Natural Science Foundation of Shanxi","award":["202304051001020"],"award-info":[{"award-number":["202304051001020"]}]},{"name":"Natural Science Foundation of Shanxi","award":["20210302123470"],"award-info":[{"award-number":["20210302123470"]}]},{"name":"Natural Science Foundation of Shanxi","award":["20210302123237"],"award-info":[{"award-number":["20210302123237"]}]},{"name":"Natural Science Foundation of Shanxi","award":["202204021301063"],"award-info":[{"award-number":["202204021301063"]}]},{"name":"Natural Science Foundation of Shanxi","award":["202105D121009"],"award-info":[{"award-number":["202105D121009"]}]},{"name":"Natural Science Foundation of Shanxi","award":["YDZJSX2021C025"],"award-info":[{"award-number":["YDZJSX2021C025"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["81603289"],"award-info":[{"award-number":["81603289"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["81603251"],"award-info":[{"award-number":["81603251"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["202304051001020"],"award-info":[{"award-number":["202304051001020"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["20210302123470"],"award-info":[{"award-number":["20210302123470"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["20210302123237"],"award-info":[{"award-number":["20210302123237"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["202204021301063"],"award-info":[{"award-number":["202204021301063"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["202105D121009"],"award-info":[{"award-number":["202105D121009"]}]},{"name":"Science and Technology Achievements Transformation Project of Shanxi Province","award":["YDZJSX2021C025"],"award-info":[{"award-number":["YDZJSX2021C025"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["81603289"],"award-info":[{"award-number":["81603289"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["81603251"],"award-info":[{"award-number":["81603251"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["202304051001020"],"award-info":[{"award-number":["202304051001020"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["20210302123470"],"award-info":[{"award-number":["20210302123470"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["20210302123237"],"award-info":[{"award-number":["20210302123237"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["202204021301063"],"award-info":[{"award-number":["202204021301063"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["202105D121009"],"award-info":[{"award-number":["202105D121009"]}]},{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education of Shanxi University","award":["YDZJSX2021C025"],"award-info":[{"award-number":["YDZJSX2021C025"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["81603289"],"award-info":[{"award-number":["81603289"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["81603251"],"award-info":[{"award-number":["81603251"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["202304051001020"],"award-info":[{"award-number":["202304051001020"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["20210302123470"],"award-info":[{"award-number":["20210302123470"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["20210302123237"],"award-info":[{"award-number":["20210302123237"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["202204021301063"],"award-info":[{"award-number":["202204021301063"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["202105D121009"],"award-info":[{"award-number":["202105D121009"]}]},{"name":"Central Guide Local Science and Technology Development Fund Project of Shanxi Provincial Science and Technology Department","award":["YDZJSX2021C025"],"award-info":[{"award-number":["YDZJSX2021C025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ziziphi Spinosae Semen saponins (ZSSS) show sedative\u2013hypnotic activity but have very low bioavailability, potentially due to their conversion into bioactive metabolites by gut microbiota. In this study, the biotransformation of ZSSS by gut microbiota from healthy humans and patients with insomnia in vitro was analyzed. A total of 21 prototype compounds and 49 metabolites were identified using UHPLC-Q-Orbitrap-MS. Deglycosylation, deoxygenation, dehydration, and deacylation were detected in both healthy individuals and insomniacs. However, oxidation and hydrogenation were uniquely observed in insomniacs. ZSSS can enhance beneficial bacteria, such as Veillonella, Dialister, and Bacteroides. ZSSS can promote the synthesis of short-chain fatty acids (SCFAs), especially acetic acid, propionic acid, and butyric acid. Furthermore, it was found that the sedative\u2013hypnotic activity of ZSSS was enhanced after biotransformation, as determined by a sodium pentobarbital-induced sleeping test (SPST), open-field behavior test (OFBT), and molecular docking experiment (MDE). These results collectively offer valuable insight into the mechanism of action of ZSSS.<\/jats:p>","DOI":"10.3390\/ijms26094011","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:18:02Z","timestamp":1745475482000},"page":"4011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Vitro Biotransformation of Ziziphi Spinosae Semen Saponins by Gut Microbiota from Healthy and Insomniac Groups"],"prefix":"10.3390","volume":"26","author":[{"given":"Xiaofang","family":"Cui","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"He","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huizhu","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangping","family":"Pei","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yan","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-8878","authenticated-orcid":false,"given":"Chenhui","family":"Du","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.phymed.2017.07.004","article-title":"Ziziphus spinosa seeds for insomnia: A review of chemistry and psychopharmacology","volume":"34","author":"Shergis","year":"2017","journal-title":"Phytomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, D.D., Ho, C.T., and Bai, N.S. (2022). Ziziphi Spinosae Semen: An updated review on pharmacological activity, quality control, and application. J. Food Biochem., 46.","DOI":"10.1111\/jfbc.14153"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8331","DOI":"10.1021\/acs.jafc.7b02748","article-title":"Gastrointestinal Absorption and Metabolic Dynamics of Jujuboside A, A Saponin Derived from the Seed of Ziziphus jujuba","volume":"65","author":"Song","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.1039\/C5AY00413F","article-title":"Development and validation of an UPLC-MS\/MS method for determination of jujuboside B in rat plasma and its application in pharmacokinetic and bioavailability studies","volume":"7","author":"Zheng","year":"2015","journal-title":"Anal. Methods"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41586-019-1291-3","article-title":"Mapping human microbiome drug metabolism by gut bacteria and their genes","volume":"570","author":"Zimmermann","year":"2019","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nri.2017.7","article-title":"Dysbiosis and the immune system","volume":"17","author":"Levy","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1080\/10942912.2012.749410","article-title":"Degradation kinetics of jujuboside A by rat intestinal flora and identification of the metabolites by HPLC-MS\/MS","volume":"17","author":"Zhang","year":"2014","journal-title":"Int. J. Food Prop."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1039\/D0FO00098A","article-title":"Targets and underlying mechanisms related to the sedative and hypnotic activities of saponin extracts from semen Ziziphus jujube","volume":"11","author":"Shen","year":"2022","journal-title":"Food Funct."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.jcice.2008.03.013","article-title":"Insights into the suanzaoren mechanism-From constructing the 3D structure of GABA-A receptor to its binding interaction analysis","volume":"39","author":"Chen","year":"2008","journal-title":"J. Chin. Inst. Eng."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, Q.H., Chen, B., Sheng, D.S., Yang, J.J., Fu, S.J., Wang, J.W., Zhao, C.Y., Wang, Y.H., Gai, X.Z., and Wang, J.F. (2022). Multiomics Analysis Reveals Aberrant Metabolism and Immunity Linked Gut Microbiota with Insomnia. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.00998-22"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1039\/C4AY00800F","article-title":"Analysis of six bioactive components in Semen Ziziphi Spinosae by UPLC-ELSD and UPLC-Q\/TOF-MS","volume":"6","author":"Zhao","year":"2014","journal-title":"Anal. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yan, Y., Liu, J.X., Zhang, M., Zhang, Y.J., Shi, B.Y., Qin, X.M., and Du, C.H. (2022). A strategy to explore the quality markers of Ziziphi Spinosae semen by combining metabolic in vivo study with network pharmacology. Biomed. Chromatogr., 37.","DOI":"10.1002\/bmc.5530"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jpba.2016.01.047","article-title":"Rapid characterization of Ziziphi Spinosae Semen by UPLC\/Qtof MS with novel informatics platform and its application in evaluation of two seeds from Ziziphus species","volume":"122","author":"Zhang","year":"2016","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101834","DOI":"10.1016\/j.clinre.2021.101834","article-title":"The gut microbiome as a target for adjuvant therapy in insomnia disorder","volume":"46","author":"Kang","year":"2022","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1080\/14786419.2014.910663","article-title":"Anti-depressive activities and biotransformation of timosaponin B-III and its derivatives","volume":"28","author":"Jiang","year":"2014","journal-title":"Nat. Prod. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1021\/acs.jafc.6b04498","article-title":"Biotransformation of total saponins in Siraitia Fructus by human intestinal microbiota of normal and type 2 diabetic patients: Comprehensive metabolite identification and metabolic profile elucidation using LC-Q-TOF\/MS","volume":"65","author":"Zhou","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/1574-6941.12127","article-title":"Diversity of human small intestinal Streptococcus and Veillonella populations","volume":"85","author":"Bogert","year":"2013","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, Q., Wang, B., Qiu, H.Y., Yan, X.J., Cheng, L., Wang, Q.Q., and Chen, S.L. (2021). Chronic jet lag exacerbates Jejunal and colonic microenvironment in mice. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.648175"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3390\/clockssleep2030022","article-title":"MicroRNA: A Key Player for the Interplay of Circadian Rhythm Abnormalities, Sleep Disorders and Neurodegenerative Diseases","volume":"2","author":"Kinoshita","year":"2020","journal-title":"Clocks Sleep"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S2215-0366(18)30139-1","article-title":"Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: A cross-sectional study of 91105 participants from the UK Biobank","volume":"5","author":"Lyall","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Silva, Y.P., Bernardi, A., and Frozza, R.L. (2020). The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00025"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1128\/microbiolspec.BAI-0023-2019","article-title":"Shigella pathogenesis: New insights through advanced methodologies","volume":"7","author":"Schnupf","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.26599\/FSHW.2022.9250162","article-title":"Probiotics Administration Alleviates Cognitive Impairment and Circadian Rhythm Disturbance Induced by Sleep Deprivation","volume":"13","author":"Tian","year":"2024","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"153157","DOI":"10.1016\/j.phymed.2019.153157","article-title":"Fructo-oligosaccharides from Morinda officinalis remodeled gut microbiota and alleviated depression features in a stress rat model","volume":"67","author":"Chi","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yang, X.Q., Xiao, H.S., Zeng, Y., Huang, L.L., Ji, K., Deng, D.Y., Yang, W.Y., and Liu, L. (2021). Tianwang buxin granules influence the intestinal flora in perimenopausal insomnia. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/9979511"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"R\u00edos-Covi\u00e1n, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., Reyes-Gavil\u00e1n, C.G.L., and de Salazar, N. (2016). Intestinal short chain fatty acids and their link with diet and human health. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00185"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116215","DOI":"10.1016\/j.jep.2023.116215","article-title":"Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis","volume":"308","author":"Li","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.chom.2015.03.006","article-title":"Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism","volume":"17","author":"Leone","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.redox.2017.03.006","article-title":"Butyrate induces ROS-mediated apoptosis by modulating miR-22\/SIRT-1 pathway in hepatic cancer cells","volume":"12","author":"Pant","year":"2017","journal-title":"Redox Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liu, L.X., Li, Q.Q., Yang, Y.Q., and Guo, A.W. (2021). Biological function of short-chain fatty acids and its regulation on intestinal health of poultry. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.736739"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/1751-7915.13282","article-title":"Caecal infusion of the short-chain fatty acid propionate affects the microbiota and expression of inflammatory cytokines in the colon in a fistula pig model","volume":"11","author":"Zhang","year":"2018","journal-title":"Micro. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrmicro3344","article-title":"The gut microbiota, bacterial metabolites and colorectal cancer","volume":"12","author":"Louis","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fu, K., Ma, C., Wang, C., Zhou, H.L., Gong, L.H., Zhang, Y.Y., and Li, Y.X. (2022). Forsythiaside A alleviated carbon tetrachloride-induced liver fibrosis by modulating gut microbiota composition to increase short-chain fatty acids and restoring bile acids metabolism disorder. Biomed. Pharmacother., 151.","DOI":"10.1016\/j.biopha.2022.113185"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.molmed.2021.07.004","article-title":"Microbiota and sleep: Awakening the gut feeling","volume":"27","author":"Sen","year":"2021","journal-title":"Trends Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bian, Z.H., Zhang, W.M., Tang, J.Y., Fei, Q.Q., Hu, M.M., Chen, X.W., Su, L.L., Fei, C.H., Ji, D., and Mao, C.Q. (2021). Mechanisms Underlying the Action of Ziziphi Spinosae Semen in the Treatment of Insomnia: A Study Involving Network Pharmacology and Experimental Validation. Front. Pharmacol., 24.","DOI":"10.3389\/fphar.2021.752211"},{"key":"ref_36","first-page":"1936","article-title":"Investigation of effective components screening of Ziziphi Spinosae Semen based on serum pharmacochemistry and network pharmacology","volume":"48","author":"Li","year":"2017","journal-title":"Chin. Tradit. Herbal. Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"126651","DOI":"10.1016\/j.foodchem.2020.126651","article-title":"Metabolic profile and underlying antioxidant improvement of Ziziphi Spinosae Folium by human intestinal bacteria","volume":"320","author":"Yan","year":"2020","journal-title":"Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jff.2019.02.030","article-title":"In vitro fermentation of novel microwave-synthesized non-digestible oligosaccharides and their impact on the composition and metabolites of human gut microbiota","volume":"55","author":"Wang","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jep.2014.12.041","article-title":"Biological evaluation and molecular docking of baicalin and scutellarin as Helicobacter pylori urease inhibitors","volume":"162","author":"Yu","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41586-018-0832-5","article-title":"GABAA receptor signalling mechanisms revealed by structural pharmacology","volume":"565","author":"Masiulis","year":"2019","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gomes, I.S., Santana, C.A., Marcolino, L.S., Lima, L.H.F., Melo-Minardi, R.C., Dias, R.S., Paula, S.O., and Silveira, S.A. (2022). Computational prediction of potential inhibitors for SARS-COV-2 main protease based on machine learning, docking, MM-PBSA calculations, and metadynamics. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267471"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Buey, B., Forc\u00e9n, A., Grasa, L., Layunta, E., Mesonero, J.E., and Latorre, E. (2023). Gut Microbiota-Derived Short-Chain Fatty Acids: Novel Regulators of Intestinal Serotonin Transporter. Life, 13.","DOI":"10.3390\/life13051085"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Feng, W.Y., Yang, Z.H., Liu, Y.X., Chen, R., Song, Z.H., Pan, G.Y., Wang, Y.H., Guo, Z.H., Ding, X.Y., and Chen, L. (2023). Gut microbiota: A new target of traditional Chinese medicine for insomnia. Biomed. Pharmacother., 160.","DOI":"10.1016\/j.biopha.2023.114344"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4011\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:20:31Z","timestamp":1760030431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26094011"],"URL":"https:\/\/doi.org\/10.3390\/ijms26094011","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,24]]}}}