Silibinin protects the ischemic brain in mice by exerting anti-apoptotic effects via the EGFR/ERK pathway.

Apoptosis is a significant occurrence of cell death in the cerebral ischemia process, potentially revealing specific treatment points. Silibinin (SIL) has been proven to regulate a range of biological effects on inflammation, oxidative stress and apoptosis. Meanwhile, the epidermal growth factor receptor (EGFR) has been reported to impact cell apoptosis owing to its proliferative activity, which is in the opposite direction of apoptosis. This brings up the question of whether silibinin modulates apoptosis after cerebral ischemic injury and whether EGFR is involved in mediating this effect. We therefore examined the potential protective role of silibinin in ischemic brain and the underlying mechanisms. We assigned CD1 mice into groups and assessed neurological function via behavioral tests, infarct volume staining, and edema measurement. Neuronal vitality in the infarcted hemisphere was assessed using Nissl staining, while the level of apoptosis was evaluated by detecting cleaved Caspase-3, Bcl-2, and Bax. Penumbra vascular conditions were examined by immunofluorescence and two-photon imaging. Western Blot and immunohistochemistry detected EGFR/ERK level changes. An EGFR inhibitor was used to confirm the involvement of the EGFR/ERK pathway in the disease process. Our findings indicated that silibinin substantially diminished infarct volume and brain edema, reduced neuronal apoptosis following stroke, enhancing neurological function. These effects were accompanied by up-regulation of p-EGFR/EGFR, p-ERK/ERK, and Bcl-2, as well as down-regulation of Bax and cleaved-Caspase3 in ischemic brain tissue post-stroke, while inhibiting EGFR activation attenuated or reversed the anti-apoptotic effects of silibinin. We concluded that silibinin protected the brain after cerebral ischemia by exerting anti-apoptotic effects via the activation of EGFR/ERK signaling pathway.