Abstract
Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT) might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC) optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines.Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates.Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI) values.Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different drugs which might provide useful information for research of signal cascades in platelet.
Highlights
Anti-platelet therapy is an essential component of treatment in patients with coronary artery disease, especially those underwent percutaneous coronary intervention (Abbott, 2017; Majithia and Bhatt, 2017)
By using the in vitro Adenosine 5′-diphosphate (ADP)-induced Platelet-rich plasma (PRP) aggregation assay, anti-platelet activities of aspirin, ticagrelor and representative components of herbal medicines listed in Supplemental Table 1
Feedback system control (FSC) analysis was conducted based on drugs with experimentally determined IC50 values
Summary
Anti-platelet therapy is an essential component of treatment in patients with coronary artery disease, especially those underwent percutaneous coronary intervention (Abbott, 2017; Majithia and Bhatt, 2017). Dual antiplatelet therapy (DAPT), a combination of aspirin and P2Y12 receptor antagonist, clopidogrel or ticagrelor, is popularly used in clinic. For patients underwent percutaneous coronary intervention, an arbitrary recommendation for 12 months of DAPT after drug eluting stent implantation was issued by Cardiology Guideline Committees (Roffi et al, 2016). For these patients who have to take at least 12 months of DAPT, the finetuning of platelet activation and inhibition is very important because either bleeding or thrombosis would cause severe events in clinic. Popularly used herbal medicines and/or food additives with possible anti-platelet activities should be taken as a factor which could not be ignored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
