In vivo pharmacokinetics comparisons of icariin, emodin and psoralen from Gan-kang granules and extracts of Herba Epimedii, Nepal dock root, Ficus hirta yahl

Li, Yihui; Duan, Juping; Guo, Tingting; Xie, Weifeng; Yan, Shineng; Li, Bo; Zhou, Yanqin; Chen, Yuxiang

doi:10.1016/j.jep.2009.05.008

Cited by 50 publications

(23 citation statements)

References 15 publications

(8 reference statements)

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“…The inhibitory activity of PRN or IPRN on rat cyp1a2 without preincubation was relatively moderate, with IC 50 values of 10.4 mM and 7.1 mM, respectively. From the available literature, typical plasma concentrations of PRN and IPRN were less than 400 ng/ml after the clinical dose of herbal medications containing PRN and IPRN (Gu et al, 2009;Li et al, 2009). This concentration is lower than the IC 50 values in rats but is much higher than the IC 50 values in humans.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies

et al. 2013

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Naturally occurring furanocoumarin compounds psoralen (PRN) and isopsoralen (IPRN) are bioactive constituents found in herbaceous plants. They are widely used as active ingredients in several Chinese herbal medicines. In this study, the CYP1A2 inhibitory potential of PRN and IPRN was investigated in rats in vitro and in vivo as well as in human liver microsomes. Both compounds exhibited reversible and time-dependent inhibition toward rat microsomal cyp1a2. The IC 50 , k inact , and K I values were 10.4 6 1.4 mM, 0.060 6 0.002 min 21 , and 1.13 6 0.12 mM for PRN, and 7.1 6 0.6 mM, 0.10 6 0.01 min 21 , and 1.95 6 0.31 mM for IPRN, respectively. In human liver microsomal incubations, potent reversible CYP1A2 inhibition was observed for both compounds, with IC 50 values of 0.26 6 0.01 mM and 0.22 6 0.03 mM for PRN and IPRN, respectively. However, time-dependent inhibition was only observed for IPRN, with k inact and K I values of 0.050 6 0.002 min 21 and 0.40 6 0.06 mM, respectively. Coadministration with PRN or IPRN significantly inhibited cyp1a2 activity in rats, with the area under the curve (AUC) of phenacetin increasing more than 5-fold. Simcyp simulation predicted that PRN would cause 1.71-and 2.12-fold increases in the phenacetin AUC in healthy volunteers and smokers, respectively. IPRN, on the other hand, would result in 3.24-and 5.01-fold increases in phenacetin AUCs in healthy volunteers and smokers, respectively. These findings represent the first detailed report comparing the potential drug-drug interactions of PRN and IPRN, and provide useful information for balancing safe and efficacious doses of PRN and IPRN.

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies

et al. 2013

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“…34,35 However, the application of emodin-based therapeutics is hampered by its poor pharmacokinetics. 36 In past years, various delivery systems, including liposome, solid lipid nanoparticles (SLN), silver nanoparticles and polyvinylpyrrolidone blended nanofibrous have been developed to enhance emodin availability. 37–40 Using emodin as a model drug, we test the feasibility of using PBA-NPs as a carrier to deliver polyphenolic drugs based on the formation of boronate ester bonds between PBA groups and diols.…”

Section: Resultsmentioning

confidence: 99%

Development of phenylboronic acid-functionalized nanoparticles for emodin delivery

et al. 2015

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Stable and monodisperse phenylboronic acid-functionalized nanoparticles (PBA-NPs) were fabricated using 3-((acrylamido)methyl)phenylboronic acid homopolymer (PBAH) via solvent displacement technique. The effect of operating parameters, including stirring time, initial polymer concentration and the proportion of methanol on the self-assembly process were systematically investigated. The diameters of the PBA-NPs were increased as increasing the initial PBAH concentration and the proportion of methanol. Likewise, there was a linear dependence between the size of self-assembled nanoparticles and the polymer concentration. Moreover, the dissipative particle dynamics (DPD) simulation technique was used to investigate the mechanism of self-assembly behavior of PBAH, which indicated that the interior of PBA-NPs was hydrophobic and compact, and the boronic acid groups were displayed on both the outermost and interior of PBA-NPs. The resulting PBA-NPs could successfully encapsulate emodin through PBA-diol interaction and the encapsulation efficiency (EE%) and drug loading content (DLC%) of drug-loaded PBA-NPs were 78% and 2.1%, respectively. Owing to the acid-labile feature of the boronate linkage, a reduction in environmental pH from pH 7.4 to 5.0 could trigger the disassociation of the boronate ester bonds, which could accelerate the drug release from PBA-Emodin-NPs. Besides, PBA-Emodin-NPs showed a much higher cytotoxicity to HepG2 cells (cancer cells) than that to MC-3T3-E1 cells (normal cells). These results imply that PBA-NPs would be a promising scaffold for the delivery of polyphenolic drugs.

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“…However, only the constituents absorbed to blood and their metabolites possess the probability to exert pharmacological activities through the oral administration way. Generally, the compound compatibility of TCM influences the absorption, distribution, metabolism, and excretion in vivo of active ingredients [8, 9]. Synergetic effects and interactions of multiple constituents exist in the complex prescription, and some ingredients considered to be inactive could promote the absorption of effective constituents to blood [19].…”

Section: Discussionmentioning

confidence: 99%

“…Synergetic effects and interactions of multiple constituents usually exist in compound prescriptions. The absorption, distribution, metabolism, and excretion of active ingredients in herbs are often influenced by other herbs [8, 9]. Pharmacokinetic study is an effective strategy to understand the mechanism of drug-drug interactions in clinical application [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Comparison of 20(R)- and 20(S)-Ginsenoside Rh1 and 20(R)- and 20(S)-Ginsenoside Rg3 in Rat Plasma following Oral Administration of Radix Ginseng Rubra and Sheng-Mai-San Extracts

Fan

Zhu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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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.

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In vivo pharmacokinetics comparisons of icariin, emodin and psoralen from Gan-kang granules and extracts of Herba Epimedii, Nepal dock root, Ficus hirta yahl

Cited by 50 publications

References 15 publications

Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies

Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies

Development of phenylboronic acid-functionalized nanoparticles for emodin delivery

Pharmacokinetic Comparison of 20(R)- and 20(S)-Ginsenoside Rh1 and 20(R)- and 20(S)-Ginsenoside Rg3 in Rat Plasma following Oral Administration of Radix Ginseng Rubra and Sheng-Mai-San Extracts

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