Salvia miltiorrhiza (SM) has been used in oriental medicine for its neuroprotective effects against cardiovascular diseases and ischemic stroke. In this study, we investigated the therapeutic mechanism underlying the effects of SM on stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Our results showed that SM administration significantly attenuated acute brain injury, including brain infarction and neurological deficits, 3 days after tMCAO. This was confirmed by our magnetic resonance imaging (MRI) study, which revealed a reduction in brain infarction with SM administration, as well as our magnetic resonance spectroscopy (MRS) study, which demonstrated the restoration of brain metabolites, including taurine, total creatine, and glutamate. The neuroprotective effects of SM were associated with the reduction in gliosis and upregulation of inflammatory cytokines, such as interleukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α), along with the upregulation of phosphorylated STAT3 in post-ischemic brains. SM also reduced the levels of 4-Hydroxynonenal (4-HNE) and malondialdehyde (MDA), which are markers of lipid peroxidation, induced by oxidative stress upregulation in the penumbra of the tMCAO mouse brain. SM administration attenuated ischemic neuronal injury by inhibiting ferroptosis. Additionally, post-ischemic brain synaptic loss and neuronal loss were alleviated by SM administration, as demonstrated by Western blot and Nissl staining. Moreover, daily administration of SM for 28 days after tMCAO significantly reduced neurological deficits and improved survival rates in tMCAO mice. SM administration also resulted in improvement in post-stroke cognitive impairment, as measured by the novel object recognition and passive avoidance tests in tMCAO mice. Our findings suggest that SM provides neuroprotection against ischemic stroke and has potential as a therapeutic agent.

Stroke is a major global health problem that causes significant mortality and long-term disability. Post-stroke neurological impairment is a complication that is often underestimated with the risk of persistent neurological deficits. Although traditional Chinese medicines have a long history of being used for stroke, their scientific efficacy remains unclear. Scutellaria baicalensis, an herbal component known for its anti-inflammatory and antioxidant properties, has traditionally been used to treat brain disorders. This study investigated the therapeutic effects of the Scutellaria baicalensis extraction (SB) during the acute stage of ischemic stroke using photothrombotic (PTB)-induced and transient middle cerebral artery occlusion (tMCAO) model mice. We found that SB mitigated ischemic brain injury, as evidenced by a significant reduction in the modified neurological severity score in the acute stage of PTB and both the acute and chronic stages of tMCAO. Furthermore, we elucidated the regulatory role of SB in the necroptosis and pyroptosis pathways during the acute stage of stroke, underscoring its protective effects. Behavioral assessments demonstrated the effectiveness of SB in ameliorating motor dysfunction and cognitive impairment compared to the group receiving the vehicle. Our findings highlight the potential of SB as a promising therapeutic candidate for stroke. SB was found to help modulate the programmed cell death pathways, promote neuroprotection, and facilitate functional recovery.