{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:02:09Z","timestamp":1790269329699,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2022J01315"],"award-info":[{"award-number":["2022J01315"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed in mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates the antidepressant-like mechanism of PSP by regulating microglial phenotype and signaling pathways in the prefrontal cortex of chronic restraint stress (CRS)-induced mice. PSP was extracted, purified, characterized, and orally administered to CRS mice. High-performance gel permeation chromatography (HPGPC) revealed that PSP has a molecular weight of 5.6 kDa. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that PSP exhibited a layered structure with densely packed, irregular surfaces. PSP treatment significantly increased sucrose preference (low: 71%, p &lt; 0.01; medium: 69%, p &lt; 0.05; high: 75%, p &lt; 0.001 vs. CRS: 58%) and reduced immobility time (low: 74 s, p &lt; 0.01; medium: 68 s, p &lt; 0.01; high: 79 s, p &lt; 0.05 vs. CRS: 129 s), indicating the alleviation of depressive-like behaviors. PSP inhibited microglial activation (PSP, 131\/mm2 vs. CRS, 173\/mm2, p = 0.057), reversing CRS-induced microglial hypertrophy and hyper-ramification. Furthermore, PSP inactivated microglial activation by inhibiting NLRP3\/ASC\/caspase-1\/IL-1\u03b2 signaling pathways, increasing BDNF synthesis and activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis (PSP, 80\/per DG vs. CRS, 49\/per DG, p &lt; 0.01). In conclusion, PSP exerts antidepressant-like effects through the regulation of microglial activity and neuroinflammatory pathways, indicating it as a potential natural compound for depression treatment.<\/jats:p>","DOI":"10.3390\/polym16162358","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T09:13:48Z","timestamp":1724145228000},"page":"2358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Polygonatum sibiricum Polysaccharides Alleviate Depressive-like Symptoms in Chronic Restraint Stress-Induced Mice via Microglial Regulation in Prefrontal Cortex"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhong-Yu","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong-Zhong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Heng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Xuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ting","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9052-8607","authenticated-orcid":false,"given":"Li-Tao","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"},{"name":"Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, China"},{"name":"Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1146\/annurev-clinpsy-072220-021440","article-title":"Major Depression and Its Recurrences: Life Course Matters","volume":"18","author":"Monroe","year":"2022","journal-title":"Annu. 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