Modulating intracellular calcium dynamics with alkaloids: A novel strategy against oxidative neurodegeneration
Serap NİĞDELİOĞLU DOLANBAY
TL;DR
This study explores how alkaloids from a methanol extract protect neurons by restoring calcium balance and reducing oxidative stress.
Contribution
The study introduces a novel strategy using alkaloids to modulate calcium dynamics and combat oxidative neurodegeneration.
Findings
MAE pretreatment significantly reduced H₂O₂-induced intracellular Ca2+ accumulation in fPC12 cells.
MAE downregulated key calcium channels and regulatory proteins involved in calcium signaling.
Molecular docking confirmed strong binding of MAE alkaloids to calcium-handling proteins like SERCA and IP3R.
Abstract
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 H₂O₂-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…
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Taxonomy
TopicsBerberine and alkaloids research · Alkaloids: synthesis and pharmacology · Cannabis and Cannabinoid Research