A new spirostanol saponin from the rhizomes of Paris mairei

A new spirostanol steroidal saponin, named maireioside A （1）, together with three known steroidal saponins, hypoglaucin G （2）, parisaponin I （3）, and diosgenin-3-O-α-L-rhamnopyranosyl （1→4）-[α-L-rhamnopyranosyl （1→2）]-β-D-glucopyranoside （4）, were isolated from the rhizomes of Paris mairei. The structure elucidation was accomplished by 1D and 2D NMR methods, HR-ESI-MS, and hydrolysis. C 2009 Qiang Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Comparative pharmacokinetics of bergenin,a main active constituent of Saxifraga stolonifera Curt.,in normal and hepatic injury rats after oral administration

Bergenin, isolated from the herb of Saxifrage stolonifera Curt.(Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, rapid, and sensitive RP-HPLC method for determination of bergenin in rat plasma and compare its oral pharmacokinetic behaviors in normal and CCl_4-induced hepatic injury rats. With norisoboldine as an internal standard, chromatographic separation was performed on a C_(18) analytical column with acetonitrile and water(11 : 89, V/V) containing 0.1% formic acid as the mobile phase. A good linearity was obtained over the range of 100^(–1)0 000 ng·m L^(–1). The lower limit of quantification was 50 ng·m L~(^(–1)). The developed method was successfully applied to a study of the pharmacokinetic difference of bergenin(100 mg·kg^(–1)) between normal and hepatic injury rats after oral administration. Marked alterations of pharmacokinetic parameters in hepatic injury rats were observed. Compared to normal rats, the AUC_((0–∞)) of bergenin in hepatic injury rats was elevated to 2.11-fold and C_(max) was increased by 130%, whereas CL value was only 55% of the normal rats, suggesting that the systemic exposure of bergenin was significantly increased under hepatic injury status.

A LC-ESI-MS method for the simultaneous determination of madecassoside and its metabolite madecassic acid in rat plasma: comparison pharmacokinetics in normal and collagen-induced arthritic rats

To develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric(LC-ESI-MS) method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis(CIA) rats. Glycyrrhetinic acid was used as the internal standard(IS). Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1%(V/V) formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring(SIM) mode. In normal and CIA rats, madecassoside(30 mg·kg-1) was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10–1 000 ng·mL-1 with the square regression coefficient(r) of 0.998 9, while for madecassic acid, the linear range was 10–500 ng·mL-1 with the square regression coefficient(r) of 0.996 1. The lower limit of quantification was 10 ng·mL-1 for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between –0.95% and 6.30% for madecassoside and between –1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were > 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, cmax and AUC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA rats compared with normal rats. Along with repeated administration of madecassoside, the differences of pharmacokinetic parameters of both madecassoside and madecassic acid between CIA and normal rats gradually subsided. The pharmacokinetic characteristics of both madecassoside and madecassic acid in rats were significantly altered by arthritis status, and the differences of pharmacokinetic parameters between arthritis and normal rats coincide with the severity of arthritis.