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Stroke is the second most common cause of death and the leading cause of adult disability worldwide. Recombinant tissue-type plasminogen activator (rt-PA) treatment and endovascular thrombectomy are the only effective treatment, there are no other options available. Consuming vegetables, fruits, herbs, and tea has been proven to offer various health benefits such as their anti-inflammatory, anti-ROS, and anti-cancer properties, among others. Multiple epidemiological and clinical studies have also shown a correlation between the consumption of natural plant-based foods and a reduced risk of ischemic stroke. Therefore, incorporating these foods into one's diet has become a promising strategy for preventing and treating ischemic stroke. 

In the study, we used an inhibitor and siRNA approach to demonstrate that Clinacanthus nutans(C.nutans), a widely-used medicinal plant, increases the expression of PPAR-γ, which in turn inhibits hypoxia-induced apoptosis in primary cortical neurons. Further ChIP assays showed that C.nutans enhances C/EBPβ binding to the promoter region of PPAR-γ, thereby increasing its transcription. Additionally, we found that C.nutans blocks NF-B nuclear translocation and reduces the transcriptional activity of the pro-inflammatory cytokine IL-1β. All of our findings were observed in both in vitro and in vivo experiments. 

In addition, Ergothioneine (Ergo), a naturally occurring amino acid and a thiol metabolite of histidine betaine, has the ability to safeguard the brain from ischemic damage by mediating NRF2 and NF-kB nuclear translocation. Ergo boosts the production of antioxidant proteins, thereby reducing oxidative stress. On the other hand, it impedes the formation of NLRP3 inflammasome and lowers the release of IL-1β and IL-18. Moreover, Ergo is involved in tissue repair and regeneration to promote functional recovery. 

These findings suggest that both C. nutans and Ergo are promising targets for preventing and treating stroke.

Taiwan International Graduate Program in Molecular Medicine, 
National Yang-Ming University and Academia Sinica
Doctoral Dissertation