Salvia miltiorrhiza (Danshen) is the most frequently used medicinal herbs for treatment of cardio- and cerebrovascular disease. As one of its main component, caffeic acid was be proved to have antibacterial, anti-oxidant and anti-age dementia effects. In the previous study, the author's team found that guide herb borneol in Compound Danshen Formula can improve the bioavailability of the main components of minister herb Danshen significantly, slow down its metabolic rate, and promote the permeability of the blood-brain barrier for components in Danshen. Based on this, we chose herb pairs Danshen-Borneol which were in one group of the "Liang Guanxi" composition in the Compound Danshen Formula, and then synthesized the "Liang Guanxi" Jun-Shi compound-bornyl caffeiante utilizing the modern medicinal chemistry technique, and found that compared with caffeic acid, bornyl caffeiante could more quickly exert the effect in vivo, maintain the effective concentration for more longer time, and show more better tissue selectivity to some extent, thus it was be concerned will be helpful to taking its therapeutic effects. In the metabolic study, HPLC-Q-TOF-MS technique was utilized to comprehensively characterizing the metabolic profiles of plasma, feces and urine in rats administered with bornyl Caffeiante. As a result, there are 31 drug prototypes and metabolites were detected and intentatively identified by reference substance, literature and database retrieve. Phase I including hydrolysis, oxidation and reduction products and phase II metabolism includes methylation, sulfation, glucuronidation, sulfonation and glycine mainly involved in the metabolism of bornyl caffeinate. Glucuronidation, sulfation, O-methylation and reduction were the main metabolic pathways of bornyl caffeate in rat. In short, we designed and synthesized the compound bornyl caffeate which belonged to ‘Liang Guanxi’ Jun-Shi compound, and then finished its pharmacokinetic and metabolic study thereby providing valuable information for the rational of its druggability and new idea of innovative drug discovery from Compound Danshen foumula .
References
[1] Xiaojuan Chao, Xixin He, YilinYang, et al. Design, synthesis and pharmacological evaluation of novel tacrine–caffeic acid hybrids as multi-targeted compounds against Alzheimer’s disease.Bioorganic & Medicinal Chemistry Letters 2012,22: 6498-6502
[2] Xiaohui Zheng *，Pu Jia，Yajun Bai. Research strategy for Combination of Traditional Chinese Medicine Molecular Chemistry based on the traditional theory of ‘Jun-Chen-Zuo-Shi’. Journal of Northwest University(Natural Science Edition), 2015, 45(3): 406-412
[3] Alson Sylvain G, Jansen Olivia,Cieckiewicz Ewa,et al . In-vitro and in-vivo antimalarial activity of caffeic acid and some of its derivatives. The Journal of pharmacy and pharmacology,2018, DOI:10.1111/jphp.12982.
[4] Jingyan Han. Study on the mechanism of inhibitory action of caffeic acid for hepatic microcirculatory disturbance and liver damage. Chinese Journal of Pathophysiology, 2015,10:1873.