{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:03Z","timestamp":1785411363102,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"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":["82071478"],"award-info":[{"award-number":["82071478"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82071478"],"award-info":[{"award-number":["82071478"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Joint Fund Project of the NSF of Hubei Province","award":["2023AFD123"],"award-info":[{"award-number":["2023AFD123"]}]},{"name":"Joint Fund Project of the NSF of Hubei Province","award":["2025AFD596"],"award-info":[{"award-number":["2025AFD596"]}]},{"name":"Clinical Research Project of Shenzhen Medical Research Fund from Shenzhen Medical Academy of Research and Translation","award":["C2401001"],"award-info":[{"award-number":["C2401001"]}]},{"name":"Guided Project of Hubei Provincial Department of Education's Scientific Research Plan","award":["B2020200"],"award-info":[{"award-number":["B2020200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Estrogen deficiency is an established risk factor for menopausal brain dysfunctions in women. Urgent exploration of drugs is needed to improve estrogen deficiency-related brain dysfunctions without the side effects of estrogen supplements. Three-month-old rats had bilateral ovariectomy (OVX) performed and were treated with emodin (EMO, 80 mg\/kg\/day) and 17 \u03b2-estradiol (EST, 0.5 mg\/kg\/day). Brain functions were evaluated by cognition and emotion-related behavioral tests. Levels of glucagon-like peptide-1 (GLP-1) and estrogen in blood, mRNA levels of estrogen receptor (ER) \u03b1, ER\u03b2, GLP-1 receptor (GLP-1R), proprotein convertase subtilisin\/kexin type 1 (PCSK1) and proglucagon (proGCG) in intestinal segments, and brain ER\u03b1 and GLP-1R levels were evaluated. Contractions of isolated intestinal segments were recorded. Additionally, an ER\u03b2 antagonist, PHTPP (200 \u03bcg\/kg\/day), was used to clarify the role of ER\u03b2. EST and EMO significantly ameliorated cognition deficit and depressive behaviors in OVX rats, and reduced neuronal loss and synaptic abnormalities in the hippocampus and prefrontal cortex. The blood GLP-1 levels of sham operation rats (sham, 3.09 pg\/mL), EMO-treated (2.57 pg\/mL) and EST-treated OVX rats (2.64 pg\/mL), were higher than that of OVX rats (1.03 pg\/mL). EMO had no effect on the blood estrogen level. Furthermore, EMO up-regulated mRNA levels of ER\u03b2 in ileum, colon, and cerebral GLP-1R level, while EST increased mRNA levels of ER\u03b2 in colon and cerebral ER\u03b1 level. In vitro intestinal segment spontaneous contraction tests revealed that EMO reduced contraction amplitudes in isolated intestinal segments from OVX rats, with the ileum and proximal colon showing greater sensitivity to EMO. The ileum and colon segments from OVX rats were less sensitive to EST as compared to those of normal rats. Upon PHTPP intervention, the up-regulated intestinal mRNA levels of ER\u03b2, PCSK1, proGCG, blood GLP-1 level by EMO, and the beneficial effects of EMO in abnormal behaviors of OVX rats were significantly inhibited. Overall, it was found that EMO up-regulated blood GLP-1 level via intestinal Er\u03b2-dependent mechanism and increased brain GLP-1R level, which may be involved in the neuroprotection of EMO in OVX animals.<\/jats:p>","DOI":"10.3390\/ijms27083414","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:01:52Z","timestamp":1775822512000},"page":"3414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emodin Promoted Intestinal Secretion of GLP-1 and Limited Cognitive Deficits in Young Bilateral Ovariectomized Rats"],"prefix":"10.3390","volume":"27","author":[{"given":"Xin-Yuan","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Neurological Disease of Hubei Province and National Education Ministry, Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yuan","family":"Ye","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Disease of Hubei Province and National Education Ministry, Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Disease of Hubei Province and National Education Ministry, Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"National Famous Traditional Chinese Medicine Professor Sun Guojie Inheritance Studio, Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Disease of Hubei Province and National Education Ministry, Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Disease of Hubei Province and National Education Ministry, Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"National Famous Traditional Chinese Medicine Professor Sun Guojie Inheritance Studio, Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"National Famous Traditional Chinese Medicine Professor Sun Guojie Inheritance Studio, Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-9077","authenticated-orcid":false,"given":"Yan-Jun","family":"Du","sequence":"additional","affiliation":[{"name":"National Famous Traditional Chinese Medicine Professor Sun Guojie Inheritance Studio, Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Yan","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Renal Diseases Occurrence and Intervention of Hubei Province, Medical College, Hubei Polytechnic University, Huangshi 435003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Disease of Hubei Province and National Education Ministry, Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"National Famous Traditional Chinese Medicine Professor Sun Guojie Inheritance Studio, Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16056","DOI":"10.1523\/JNEUROSCI.4097-11.2011","article-title":"Rapid estrogen signaling in the brain: Implications for the fine-tuning of neuronal circuitry","volume":"31","author":"Srivastava","year":"2011","journal-title":"J. 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