Neuroprotective Effects of Rhamnosyl Icariside II in 6-OHDA-Treated PC12 Cells and Zebrafish

This study evaluated the neuroprotective efficacy and molecular mechanisms of Rhamnosyl Icariside II (RIC), a rare secondary flavonoid glycoside from Epimedium Linn plants, in 6-hydroxydopamine-induced PC12 cell and zebrafish PD models. RIC demonstrated effective prophylactic protection and reparative effects, significantly improving PC12 cell viability in both the pretreatment and postinjury models. RIC alleviated oxidative stress by reducing lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels, while simultaneously increasing the activities of superoxide dismutase (SOD) and glutathione (GSH). RT-qPCR and Western blot analyses revealed that RIC inhibited the intrinsic mitochondrial apoptotic pathway by upregulating the antiapoptotic protein Bcl-2, suppressing the activation of pro-apoptotic Bax, cleaved caspase-3 and caspase-9, and inhibiting the release of cytochrome c from mitochondria. RIC effectively restored motor coordination impaired by 6-OHDA in the zebrafish PD model. Collectively, RIC exhibits significant neuroprotective potential through synergistic regulation of oxidative stress and modulation of the intrinsic mitochondrial apoptotic pathway. Therefore, this study suggests that RIC could be a promising option for the treatment or prevention of neurodegenerative disorders, particularly PD.