Cryptochlorogenic acid (4-CQA) is a phenolic acid that has antioxidant and anti-inflammatory activities. Our preliminary study found that 4-CQA has a good effect on isoproterenol (ISO)-induced myocardial hypertrophy, while the mechanism remains largely unknown. This study aimed at delineating the metabolites and metabolic pathways of 4-CQA using liquid mass spectrometry and molecular biotechnology, exploring possible active metabolites and the mechanism of myocardial hypertrophy amelioration in H9c2 cells, and finally, investigating the pharmacokinetics of 4-CQA and its active metabolites . In summary, 56 potential effective metabolites were distinguished in rat urine, feces, plasma samples and heart tissue after intragastric administration of 4-CQA, and the main metabolic reaction types of 4-CQA included hydrogenation, methylation, glucuronidation, sulfation, hydration and their composite reactions in biotransformation. Besides, 4-CQA and its main active metabolites, caffeic acid and 4--feruloylquinic acid, significantly ameliorated pathological cardiac hypertrophy of H9c2 cells treated with ISO based on the Akt/mTOR/HIF-1α pathway. In addition, this study demonstrated that the prototype drugs 4-CQA and 4--ferulylquinic acid generally exhibit similar pharmacokinetic characteristics and caffeic acid presents relatively late peak time and low peak concentration in rats, which make them suitable candidate drugs.

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http://dx.doi.org/10.1039/d1fo03838aDOI Listing

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