{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:19:58Z","timestamp":1788326398926,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea government","doi-asserted-by":"publisher","award":["RS-2024-00353184"],"award-info":[{"award-number":["RS-2024-00353184"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-00353184"],"award-info":[{"award-number":["RS-2024-00353184"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000056","name":"Institute of Nursing Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000056","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Intracellular Ca2+ dysregulation and neurovascular dysfunction are increasingly recognized as important mechanisms underlying neurodegenerative disorders, including Alzheimer\u2019s disease (AD). Restoration of pathological Ca2+ imbalance has therefore emerged as a potential therapeutic strategy. Although ginsenoside compound K (CK) has demonstrated neuroprotective and anti-inflammatory properties, its role in Ca2+ homeostasis remains unclear. Methods: SH-SY5Y neuronal cells, U373 astrocytes, BV2 microglia, bEND brain endothelial cells, and MOVAS vascular smooth muscle cells were exposed to trimethyltin chloride (TMT, 5 \u03bcM, 24 h). Cell viability, real-time cell confluence, intracellular Ca2+ influx, and endoplasmic reticulum (ER) Ca2+ store release were evaluated. Ca2+ dynamics were analyzed using Fura-2 fluorescence, and signaling associated with CK-mediated Ca2+ regulation was investigated using pharmacological inhibitors. Orai1 protein expression was evaluated by Western blot analysis in SH-SY5Y and U373 cells. Results: TMT increased store-operated Ca2+ entry (SOCE)-mediated Ca2+ influx in SH-SY5Y neuronal cells without significant cytotoxicity. In contrast, TMT reduced both Ca2+ influx and cell viability in U373 astrocytes, BV2 microglia, and MOVAS cells, whereas bEND cells showed minimal changes. CK restored abnormal Ca2+ responses in a cell type-specific manner, reducing elevated Ca2+ influx in neuronal cells while restoring suppressed Ca2+ signaling in astrocytes. Consistent with these functional findings, Orai1 protein expression was increased by TMT in SH-SY5Y cells and attenuated by CK, whereas TMT reduced Orai1 expression in U373 cells, which was restored by CK. Pharmacological analyses suggested involvement of PKA- and LTCC-associated signaling in neuronal cells and PLC- and PLD-associated signaling in astrocytes. In both cell types, CK-associated Ca2+ responses were sensitive to NAC and the SOCE inhibitor BTP2, supporting ROS- and SOCE-associated mechanisms. Additional controls showed no significant inhibitor effects under control or CK-only conditions, strengthening the pharmacological interpretation of responses under TMT-containing conditions. Conclusions: TMT-induced Ca2+ dysregulation differed markedly by cell type. CK restored disrupted Ca2+ homeostasis in association with distinct pharmacological signaling profiles in neuronal and astrocytic cells. These findings suggest that CK may function as a cell type-specific Ca2+ homeostatic regulator under neurotoxic stress conditions and highlight the importance of differential Ca2+ regulation in neurodegenerative disease models.<\/jats:p>","DOI":"10.3390\/ph19091376","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:05:26Z","timestamp":1788224726000},"page":"1376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Compound K Differentially Regulates Neuronal and Astrocytic Ca2+ Homeostasis Under Trimethyltin-Induced Stress"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3560-6137","authenticated-orcid":false,"given":"Hayeong","family":"Jeon","sequence":"first","affiliation":[{"name":"Department of Basic Nursing Science, College of Nursing, Korea University, Seoul 02841, Republic of Korea"},{"name":"BK21 FOUR Program of Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9582-2899","authenticated-orcid":false,"given":"Yoo Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Basic Nursing Science, College of Nursing, Korea University, Seoul 02841, Republic of Korea"},{"name":"BK21 FOUR Program of Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2986-9688","authenticated-orcid":false,"given":"Geun Hee","family":"Seol","sequence":"additional","affiliation":[{"name":"Department of Basic Nursing Science, College of Nursing, Korea University, Seoul 02841, Republic of Korea"},{"name":"BK21 FOUR Program of Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70251","DOI":"10.1002\/trc2.70251","article-title":"Alzheimer\u2019s disease drug development pipeline: 2026","volume":"12","author":"Cummings","year":"2026","journal-title":"Alzheimer\u2019s Dement. 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