Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

Abstract

ABSTRACT:The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in rat urine via intragastrical oral administration was investigated. In total, 19 metabolites (M1-M19) were identified. Among these, 16 metabolites were characterized by high-performance liquid chromatography solid-phase extraction-tube transfer-NMR, and seven metabolites were further isolated from the treated urine to enable further structural determination. Twelve of these are new compounds. The phase I metabolites of 1 were formed via various oxidations at positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C-14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were glucuronide conjugates from the parent compound or phase I metabolites. The major metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2-hydroxymethylpterosin E (M14), and (؎)-pterosin B (M19). Quantitative HPLC analysis of metabolites, based on similar UV absorption and use of the regression equation of 1, indicated that ϳ71% 1 was excreted as metabolites in rat urine.

Isolation and characterisation of 13 pterosins and pterosides from bracken (Pteridium aquilinum (L.) Kuhn) rhizome

“…However, another cyclic lactone pterosin, (S)-12-hydroxy-2-hydroxymethylpterosin E 14, 12-lactone, with one extra methylene has been reported as a metabolic product of (2S)-pterosin A in rat urine via oral administration (100 mg/kg) (Lee et al, 2012). Other metabolites of (2S)-pterosin A were compounds 14, 27 and 29, which we isolated for the first time from plant material.…”

“…One-and two-dimensional NMR experiments combined with mass spectrometry were used to identify thirteen novel natural products (1-13) (Supplementary Information 1) belonging to the sesquiterpenoid family. The structures of twenty two previously reported pterosins and pterosides 14, 27, 29 (Lee et al, 2012), 15-18, 30-33, 35 (Kuroyanagi et al, 1979), 19-25 (Fukuoka et al, 1978), 26 (Kuraishi et al, 1985;Tanaka et al, 1982), 28 (Murakami et al, 1980), 34 (Castillo et al, 2003) were determined by the comparison of their spectroscopic data with those reported in the literature . The structures of compound 1-13 are shown in Figs.…”

“…UV spectrum of compound 13 in CH3OH. (Lee et al, 2012), 16, 30, 32 (Kuroyanagi et al, 1979), 19-25 (Fukuoka et al, 1978) and 34 (Castillo et al, 2003) obtained from bracken rhizomes with their absolute stereochemistry. In Fig.…”

Identification of the metabolites of TCM prescription Sinisan, found in miniature pig urine via intragastric administration

“…Pharmacological studies have demonstrated its effectiveness against inflammatory diseases such as hepatitis, gastritis, neuralgia, and appendagitis [1][2][3][4]. Although the major bioactive components in Sinisan crude drug, such as liquiritin (P2), albiflorin (11), paeoniflorin (13), naringin (23), neohesperidin (27), glycyrrhizin (49), saikosaponins a (50), and d (P7), have been studied [4][5][6], it is necessary to figure out the in vivo metabolic profile for characterizing the fate of active components and to elucidate the in vivo functions of the metabolites.…”

Secondary Metabolites (Pterosin F and B) From Pteridium aquilinum

“…These compounds are stored in the root cells for subsequent This (root exudates) is the more probable means by which fern allelochemicals are released into the soil, which explains the higher inhibitory activity (both on germination and growth) of extracts, which also inhibited the root growth of P. pratensis. This probably indicates interferences between P. aquilinum allelochemicals and growth phytohormones [3]. For example, depending on the pH of the soil, ptaquiloside may decompose according to the following reaction scheme (Figure 4).…”