Green synthesis of puerarin acid esters and their oral absorption evaluation in vivo

Abstract

Design and synthesis of prodrugs is an effective strategy to develop new drugs. Puerarin is well-known for its pharmacological properties in the treatment of many cardiovascular and cerebrovascular related diseases. To cope with its poor liposolubility that limited practical applications, we successfully developed a new type of clean and efficient esterification medium for acylation modification of puerarin and studied the relative oral absorption, including pharmacokinetics, tissue distribution and metabolite after oral taking of puerarin acid esters in comparison with free puerarin in rats. In the 1-Ethyl-3-Methylimidazoliumacetate, puerarin had the good solubility, and the reaction showed great initial rate (46.71 mmol/(L*h)) and substrate conversion (63.91%). The results of oral absorption showed that the administration of long-chain fatty acid esters of puerarin, puerarin hexanoate and puerarin myristate, resulted in significantly higher levels of puerarin in the plasma and tissues, especially in the heart, cerebral cortex, hippocampus and corpus striatum. Overall, these findings collectively supported that puerarin acid esters administration led to greater circulating concentration of puerarin and had a reduced excretion rate, providing significant advantages and theoretical basis for their application in functional foods and pharmaceutical industries.