{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:24:31Z","timestamp":1787077471798,"version":"build-2736575974"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) of Korea","doi-asserted-by":"crossref","award":["RS-2024-00353184"],"award-info":[{"award-number":["RS-2024-00353184"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Institute of Nursing Research, Korea University Grant"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Parkinson\u2019s disease is one of the most common neurodegenerative disorders, and the pesticide rotenone is widely used to model Parkinson\u2019s disease in experimental studies. Rotenone-induced mitochondrial dysfunction is associated with oxidative stress and intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\u1d62) dysregulation in neuronal systems. L-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels (LTCCs) contribute to Ca\u00b2\u2009\u207a\u2009influx under oxidative stress conditions, but pharmacological inhibition of LTCCs is limited by cardiovascular side effects. Phospholipase D (PLD) has also been implicated in cellular stress-associated signaling pathways. Ginsenosides are known to influence Ca\u00b2\u2009\u207a\u2009-related signaling; however, differences among ginsenosides in neuronal and microglial Ca\u00b2\u2009\u207a\u2009regulation have not been fully characterized. Therefore, this study aimed to investigate the effects of ginsenosides on intracellular Ca\u00b2\u2009\u207a\u2009homeostasis and oxidative stress of rotenone-exposed SH-SY5Y neuronal cells and BV2 microglial cells. Cell viability, superoxide dismutase (SOD) activity, interleukin-6 (IL-6) levels, intracellular Ca\u00b2\u2009\u207a\u2009influx, and malondialdehyde (MDA) levels were evaluated. Intracellular Ca\u00b2\u2009\u207a\u2009was measured using Fura-2 AM ratiometric fluorescence analysis. The effects of ginsenosides Rg1, Rg2, and Rd were examined using pharmacological inhibitors targeting PLD, LTCCs, and protein kinase A (PKA). Rotenone reduced cell viability and SOD activity, while increasing IL-6 levels, [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\u1d62 influx, and MDA levels in both cell types. Treatment with ginsenosides immediately before rotenone exposure attenuated rotenone-induced increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\u1d62 and MDA levels. Ca\u00b2\u2009\u207a\u2009responses in both SH-SY5Y and BV2 cells were sensitive to PLD inhibition. In SH-SY5Y cells, responses were additionally sensitive to LTCC inhibition, whereas BV2 cells showed weaker LTCC-associated pharmacological responses. Rd showed broader pharmacological sensitivity involving PLD-, LTCC-, and PKA-associated components, whereas Rg1 and Rg2 showed predominantly PLD-associated response patterns. These findings suggest that ginsenosides differentially modulate rotenone-associated Ca\u00b2\u2009\u207a\u2009dysregulation through PLD-associated pharmacological pathways in a cell type-dependent manner. Overall, the present findings demonstrate distinct pharmacological response profiles among structurally different ginsenosides under rotenone-induced oxidative stress conditions.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0356602","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:28:11Z","timestamp":1787074091000},"page":"e0356602","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential effects of ginsenosides on Ca2+ regulation in rotenone-treated neuronal and microglial cells"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9439-2571","authenticated-orcid":true,"given":"Jiwoo","family":"Shin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2986-9688","authenticated-orcid":true,"given":"Geun 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