Exploring the anti-stroke potential of our everyday diets

We have developed and consolidated a unique library of natural compounds derived from heart-healthy diets. Notably, we identified bioactive molecules from broccoli, khella, and licorice that can enhance the efficacy of thrombolytic therapy for stroke by up to threefold, without increasing the risk of intracranial bleeding (ACS Cent. Sci. 2024, 11k+ views). The electrophilic nature of these compounds enables them to selectively engage naturally evolved protein targets in our blood cells, mediating their cardiovascular protective effects.

To elucidate their molecular mechanisms, we synthesise specialized chemical probes and apply them in combination with advanced mass spectrometry through an approach known as activity-based protein profiling (ABPP). This platform has driven several ongoing projects in our lab, ranging from precision drug discovery to the development of tool compounds for investigating protein ubiquitination in blood cells, cardiomyocytes, tumors, and tumor-induced cardiovascular dysregulation.

Our research integrates diverse methodologies, including chemical synthesis (small molecules and peptides), in vitro cell culture, blood cell isolation, Western blotting and cell imaging, protein and gene expression analysis, mass spectrometry-based proteomics, and bioinformatic analysis.

Our mission is to better understand the therapeutic mechanisms of cardiovascular-protective natural supplements in platelets and the heart, and use this knowledge to develop next-generation precision medicine for the prevention and treatment of life-threatening thrombosis and ischaemic stroke.

Thrombotic complications are the leading cause of mortality and account for one in four deaths worldwide. Existing antithrombotic drugs such as aspirin and clopidogrel are less effective, with less than 15% of diabetic patients taking these medicines avoiding a fatal thrombotic event. Despite intense investigation over the past decades, the discovery of novel cardiovascular drugs has remained disappointingly low, mainly due to high bleeding risk. Therefore, there is a huge burden for novel and safe antithrombotic treatment, for which understanding the molecular differences between thrombosis and hemostasis is essential.

Recently, there is growing interest in developing natural supplements for cardiovascular-protective therapies, driven by their favourable safety profiles and clinical evidence in mitigating chemotherapy-induced cardiovascular complications. In particular, electrophilic small molecules found in healthy diets and herbs, which are historically safe and possess long-lasting effects due to their electrophilic nature - making them valuable for both therapy and mechanistic studies.