Conversion of puerarin into its 7-O-glycoside derivatives by Microbacterium oxydans (CGMCC 1788) to improve its water solubility and pharmacokinetic properties

Abstract

Microbacterium oxydans strain NJ 6 isolated from soil samples converted puerarin into two novel compounds, puerarin-7-O-glucoside and puerarin-7-O-isomaltoside, via an unreported O-glycosylation of the phenolic hydroxyl group at the 7-position of puerarin. Sucrose, maltotriose, and maltose could be used as glucosyl donors for glycosylation of puerarin, but uridine-diphosphate glucose, glucose, fructose, lactose, cyclodextrin, and starch could not. Regardless of the position of B-ring in the (iso)flavonoids core structure, the glycosylation of the phenolic hydroxyl group at the 7-position of (iso)flavonoids was governed by the presence or absence of a glucosyl residue at 8-C. The apparent solubility of puerarin-7-O-glucoside and puerarin-7-O-isomaltoside was approximately 18 and 100 times that of natural puerarin, respectively. Like parent puerarin, puerarin-7-O-glucoside maintained its physiological ability to relax the contractions of isolated rat thoracic aortic rings in vitro induced by phenylephrine. However, puerarin-7-O-glucoside was able to maintain higher plasma concentrations and have a longer mean residence time in the blood than the parent puerarin.

Immobilization of puerarin glycosidase from Microbacterium oxydans CGMCC 1788 increases puerarin transformation efficiency

“…We have previously reported that puerarin is transformed to two products, puerarin-7-O-glucoside and puerarin-7-O-fructoside, when it is transformed by free enzyme or bacterial cells permeabilized with organic solvent (Jiang et al, 2008;Yu et al, 2010). However, we showed that the main transformation product by immobilized puerarin glycosidase is puerarin-7-O-glucoside.…”

“…However, the transformation by resting cells is limited by low transformation efficiency and long transformation time because extracellular puerarin diffuses slowly into the intracellular space through the barrier of the cell membrane. When the intracellular puerarin reaches a certain concentration, it is transformed by M. oxydans CGMCC 1788 glycosidase to glycosylated puerarin that is then secreted through the cell membrane to the extracellular solution (Jiang et al, 2008;Yu et al, 2010). In order to increase the transformation efficiency and shorten the transformation time, free glycosidase extracted from disrupted cells of M. oxydans CGMCC 1788 has been used to transform puerarin (Yu et al, 2010).…”

“…However, the pharmacological development of puerarin is limited by its low water solubility and bioavailability (Ren et al, 2006). Thus, significant effort has been made to chemically or biologically modify the structure of puerarin to obtain novel puerarin derivatives with higher water solubility and biological activity (Li et al, 2004;Huang et al, 2008;Jiang et al, 2008;Yu et al, 2010;Ko et al, 2012). Previous studies have shown that transformation of flavonoid substances in the form of aglycon to glycosides improves not only their physical and chemical properties, such as water solubility, taste and sweetness but also their pharmacological activities, including circulation, metabolism, and concentration in body fluids (Lee et al, 1999;Kren et al, 2001;Daines et al, 2004;Blanchard et al, 2006;Hyung et al, 2006;Salas et al, 2007).…”

“…Previous studies have shown that transformation of flavonoid substances in the form of aglycon to glycosides improves not only their physical and chemical properties, such as water solubility, taste and sweetness but also their pharmacological activities, including circulation, metabolism, and concentration in body fluids (Lee et al, 1999;Kren et al, 2001;Daines et al, 2004;Blanchard et al, 2006;Hyung et al, 2006;Salas et al, 2007). Jiang et al (2008) and Yu et al (2010) from our laboratory have previously reported that puerarin is transformed to puerarin-7-O-glucoside and puerarin-7-O-fructoside, respectively, under different condi-…”

Enzymatic Synthesis of Polyphenol Glycosides by Amylosucrase

“…이런 문제점은 폴리페놀의 당화과정 (glycosylation)을 통하여 합성된 배당체를 이용하여 극복할 수 있다. 배당체의 합성은 화학적 방법으로 가능하지만, 이런 방법은 고온, 고압을 포함하는 조건이 필수적이고 합성된 아 노머(anomer) 물질의 분리 및 환경문제 등을 야기하여 [18] 최 근에는 생물체가 지니는 당 전이 능력을 갖는 효소를 이용한 당 전이 반응(transglycosylation)을 통하여 빠르고 쉽게 생산 하고 있다 [8,13] (Fig. 2).…”