{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:51:21Z","timestamp":1791859881957,"version":"4.3.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Calcium homeostasis plays a pivotal role in neuronal function, and its dysregulation is closely associated with oxidative stress-induced neurotoxicity. This study investigated the protective effects of a methanol alkaloid extract (MAE), rich in allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide, on H\u2082O\u2082-induced calcium dysregulation in fPC12 cells. Flow cytometry analysis revealed that MAE pretreatment significantly attenuated intracellular Ca2+ accumulation caused by oxidative stress. In line with this, MAE markedly downregulated the mRNA and protein expression levels of CACNA1C (Cav1.2 subunit) and CACNA1D (Cav1.3 subunit), two L-type voltage-gated calcium channels responsible for calcium influx. Furthermore, MAE suppressed the expression of key calcium regulatory proteins, including CALM1, CaMK2A, PMCA (ATP2B1), SERCA (ATP2A1), RyR1, and IP3R (ITPR1), as confirmed by ELISA and Western Blot analysis. Protein\u2013protein interaction (PPI) network analysis demonstrated a highly interconnected and functionally enriched network among these targets, indicating coordinated regulation of calcium signaling pathways. Molecular docking studies supported these findings by showing strong binding affinities of MAE\u2019s isoquinoline alkaloids, particularly tetrahydropalmatine, to SERCA (ATP2A1) and IP3R (ITPR1). These interactions suggest a direct modulatory effect on calcium-handling proteins. Overall, this study provides experimental and in silico evidence that MAE exerts multifaceted neuroprotective effects by restoring calcium homeostasis and modulating oxidative stress responses, highlighting its therapeutic potential in calcium-related neurodegenerative conditions.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf100","type":"journal-article","created":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T14:45:48Z","timestamp":1753627548000},"source":"Crossref","is-referenced-by-count":2,"title":["Modulating intracellular calcium dynamics with alkaloids: A novel strategy against oxidative neurodegeneration"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1238-0894","authenticated-orcid":false,"given":"Serap","family":"N\u0130\u011eDEL\u0130O\u011eLU DOLANBAY","sequence":"first","affiliation":[{"name":"Gazi University, Faculty of Science, Department of Biology , Teknikokullar, Ankara 06500 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