Abstract
Ginsenosides Rh1 and Rg3, as the main bioactive components from Ginseng, are effective for prevention and treatment of cardiovascular diseases. Sheng-Mai-San (SMS), a classical complex prescription of traditional Chinese medicines, is composed of Radix Ginseng Rubra, Fructus Schisandrae, and Radix Ophiopogonis. In this research, a sensitive and specific liquid chromatography-mass spectrometric method was developed and validated for stereoselective determination and pharmacokinetic studies of 20(R)- and 20(S)-ginsenoside Rh1 and 20(R)- and 20(S)-ginsenoside Rg3 epimers in rat plasma after oral administration of Radix Ginseng Rubra or SMS extracts. The main pharmacokinetic parameters including Tmax, Cmax, t1/2, and AUC were calculated by noncompartment model. Compared with Radix Ginseng Rubra, SMS could significantly increase the content of ginsenosides Rh1 and Rg3 in the decocting process. Ginsenosides Rh1 and Rg3 following SMS treatment displayed higher Cmax, AUC(0–t), and AUC(0–∞) and longer t1/2 and tmax except for 20(R)-Rh1 in rat plasma. The results indicated SMS compound compatibility could influence the dissolution in vitro and the pharmacokinetic behaviors in vivo of ginsenosides Rh1 and Rg3, suggesting pharmacokinetic drug-drug interactions between ginsenosides Rh1 and Rg3 and other ingredients from Fructus Schisandrae and Radix Ophiopogonis. This study would provide valuable information for drug development and clinical application of SMS.
Highlights
Ginsenosides are glycosides with a dammarane skeleton and classified as protopanaxadiol or protopanaxatriol compounds
To obtain the maximum sensitivity, we investigated the effects of pH and additives with various mobile phases on the ionization efficiency of analytes
This study revealed that dissolution of ginsenosides in Radix Ginseng Rubra would change when decocted with Fructus Schisandrae and Radix Ophiopogonis
Summary
Ginsenosides are glycosides with a dammarane skeleton and classified as protopanaxadiol or protopanaxatriol compounds (except ginsenoside Ro). Ginsenosides are the major bioactive ingredients of Ginseng and exhibit many pharmacological activities including vasorelaxation, antioxidation, antiinflammation, and anticancer [1]. It was found that SMS possessed extensive biological and pharmacological activities, such as cardiovascular activities, antioxidative activities, and protective effects on tissue injury [3, 4]. SMS could protect against renal ischaemic damage during heat stroke by reducing iNOS-dependent NO and peroxynitrite production [5, 6]. Besides these, it could reduce hepatic lipids and lipid peroxidation [7]. Synergetic effects and interactions of multiple constituents usually exist in compound prescriptions.
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