High performance liquid chromatographic–mass spectrometric determination of ginsenoside Rg3 and its metabolites in rat plasma using solid-phase extraction for pharmacokinetic studies

Xie, Huan; Wang, Guangji; Tucker, Ian G.; Zhao, Xiaochen; Xie, Yuanyuan; Li, Hao; Xi-ling, Jiang; Wang, Rui; Xu, Mei-Juang; Wang, Wei

doi:10.1016/j.jchromb.2004.12.028

Cited by 109 publications

(97 citation statements)

References 17 publications

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“…The ginsenosides 1-5, belonging to protopanaxatriol-type saponins, had different t max values, which should be due to the differences in the substituted groups. According to the PK investigations on 20(R)-ginsenoside Rg 3 (8) following oral administration of the single 8 to rats [31], the value of t max was (4.40˘1.67) h, suggesting promotion of absorption by oral administration of GTSSL. Namely, the t max of 8 after oral administration of GTSSL is shorter than that of single 8 administration, the oral administration of GTSSL containing 8 resulted in a shorter t max of 8 than when the single 8 was administered.…”

Section: Pharmacokinetics Of Gtsslmentioning

confidence: 99%

“…Compared to the previous PK studies of individual ginsenoside Rd [33,34], ginsenoside Rg 1 [35], 20(R)-and 20(S)-ginsenoside Rg 2 [8], and 20(R)-ginsenoside Rg 3 [31,36,37] after intravenous administration to animals or healthy volunteers, we have investigated three couples of 20(R)-and 20(S)-epimers simultaneously by LC-ESI-MS/MS, which possesses higher sensitivity and precision. On the contrary, the PK studies of individual ginsenoside was simple and uncomplicated, it is well-known that interactions from complex constituents of traditional Chinese medicines could substantially affect the PK profiles of targeted compounds, therefore, the research of PK on eight ginsenosides of GTSSL here will be useful for drug development in future.…”

Section: Pharmacokinetics Of Gtsslmentioning

confidence: 99%

See 1 more Smart Citation

Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics

Ma¹,

Zhang²,

Zhou³

et al. 2015

Molecules

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(8) in rat plasma. The established rapid method had high linearity, selectivity, sensitivity, accuracy, and precision. The method has been used successfully to study the pharmacokinetics of abovementioned eight ginsenosides for the first time. After an oral administration of total saponins in the stems-leaves of Panax ginseng C. A. Meyer (GTSSL) at a dose of 400 mg/kg, the ginsenosides 6, 7, and 8, belonging to protopanaxadiol-type saponins, exhibited relatively long t max values, suggesting that they were slowly absorbed, while the ginsenosides 1-5, belonging to protopanaxatriol-type saponins, had different t max values, which should be due to their differences in the substituted groups. Compounds 2 and 4, 3 and 5, 7 and 8 were three pairs of R/S epimerics at C-20, which was interesting that the t 1/2 of 20(S)-epimers were always longer than those of 20(R)-epimers. This pharmacokinetic identification of multiple ginsenosides of GTSSL in rat plasma provides a significant basis for better understanding the clinical application of GTSSL.

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Section: Pharmacokinetics Of Gtsslmentioning

confidence: 99%

Section: Pharmacokinetics Of Gtsslmentioning

confidence: 99%

Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics

Ma¹,

Zhang²,

Zhou³

et al. 2015

Molecules

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“…To investigate the chemical composition of GTS, a validated LC-MS method was employed to analyze the contents of eight major ginsenosides namely Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, and Rg2 (Xie et al 2005a). Briefly, stock solutions were prepared at 2 mg/ml in DMSO and diluted with 95% methanol before experiments.…”

Section: Analysis Of Ginsenosides By Lc-msmentioning

confidence: 99%

Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides

Liu

Zhang

et al. 2013

Journal of Endocrinology

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Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood. Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals. The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release. Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells. Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection. The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks. It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression. Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion. It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca 2C concentration. The metabolic inhibitor azide (3 mM), the K ATP channel opener diazoxide (340 mM), and the Ca 2C channel blocker nifedipine (20 mM) significantly reversed Rb1-mediated GLP1 secretion. All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro. The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion. Key Words" glucagon-like peptide-1 (GLP1)" ginsenosides " Rb1" type 2 diabetes " ginseng total saponins (GTS)

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“…The results showed that Rg3 had low bioavailability after oral administration. Xie presented a report mainly concerning the development of a liquid chromatography/mass spectrometry (LC/MS) method using solid-phase extraction for a pharmacokinetic study of Rg3 and its metabolites in rats [13] . Recently, a pharmacokinetic study of ginsenoside Rh2 in rats and dogs showed that Rh2 distributed mainly to the liver and gastrointestinal tissues in rats after oral dosing, and multiple dosing (7 days, 1 mg/kg bid) did not affect its pharmacokinetics in dogs [14] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of panaxatrol disuccinate sodium, a novel anti-cancer drug from Panax notoginseng, in healthy volunteers and patients with advanced solid tumors

et al. 2010

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npg IntroductionGinseng has long been known to be multifunctional as both a tonic and a sedative agent. Ginsenosides, the main bioactive components of Ginseng, have become a major focus in cancer research.Based on the properties of different sapogenins, ginsenosides are divided into 3 groups, 20(S)-protopanaxadiol, 20(S)-protopanaxatriol and oleanolic acid glycoside. Many ginsenosides have been found to have anti-cancer activity [1] and are involved in several anti-cancer mechanisms, such as inhibition of cell proliferation [2] , invasion [3] , induction of cell apoptosis [4] and anti-angiogenesis [5] . However, the antitumor mechanism of ginsenoside is not fully clear. Nakata H et al reported that ginsenoside Rh2 inhibited the growth of human ovarian cancer cells cultured in nude mice [6] . Quasipanaxatriol may reverse daunomycin resistance in P388/ADM cells by effectively blocking daunomycin efflux, leading to the accumulation of the drug in the cells [7] . Ginsenoside has been implicated in several signaling pathways, such as MAPK [8] , caspase [9] , NF-kappaB, and JNK pathways [10] . Furthermore, ginsenoside Rg3 ("Shenyi" Capsule) has shown effects on improving body immunity, decreasing toxic effects induced by chemotherapy Aim: To evaluate single-dose and multiple-dose pharmacokinetics of panaxatrol disuccinate sodium in healthy volunteers and patients with advanced solid tumors. Methods: In the single-dose pharmacokinetic study, 27 healthy volunteers received panaxatrol disuccinate sodium in three doses (70, 100, and 140 mg·m -2 ). In the multiple-dose pharmacokinetic study, Panaxatrol disuccinate sodium was administered to 8 patients at 100 mg·m -2 daily in a 30-day continuous intravenous injection. Determination of the panaxatrol disuccinate sodium plasma concentration was performed by an LC-MS method. The pharmacokinetic analysis system -Drug and Statistics (DAS) -was applied to assess plasma panaxatrol disuccinate sodium concentration-time data. Results: After a single intravenous dose of 70, 100, or 140 mg·m -2 was administered to subjects, panaxatrol disuccinate sodium distributed broadly, and the plasma concentration of panaxatrol disuccinate sodium declined rapidly. No significant differences were observed in the main pharmacokinetic parameters among the three dosing groups, including AUC 0-t , MRT 0-t , VRT 0-t , t 1/2Z , CL z/F , V z/F , and C 0 (P>0.05). In the multiple-dose pharmacokinetic study, the mean steady-state peak concentration (C max ), trough concentration (C min ), average concentration (C av ), mean steady state AUC (AUC ss ) and the degree of fluctuation were 13.96±15.48 mg·L -1 , 0.18±0.29 mg·L -1 , 0.15±0.29 mg·L -1 , 3.58±6.94 mg·L -1 ·h, and 148.00±117.18, respectively. At any given dose of panaxatrol disuccinate sodium, interindividual variability in the pharmacokinetic parameters was obvious. Conclusion: The effect of the dose level on single-dose pharmacokinetics of panaxatrol disuccinate sodium was not significant. No accumulation was observed with exposure to 100 mg·m -2 ...

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High performance liquid chromatographic–mass spectrometric determination of ginsenoside Rg3 and its metabolites in rat plasma using solid-phase extraction for pharmacokinetic studies

Cited by 109 publications

References 17 publications

Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics

Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics

Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides

Pharmacokinetics of panaxatrol disuccinate sodium, a novel anti-cancer drug from Panax notoginseng, in healthy volunteers and patients with advanced solid tumors

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