[Show abstract][Hide abstract] ABSTRACT: Astragaloside is a saponin widely used in traditional Chinese medicine and has been reported to be a potent multidrug resistance (MDR) reversal agent. The present study investigated the role of astragaloside Ⅳ (ASIV) in the regulation of P‑glycoprotein (P‑gp, encoded by the mdr1 gene) and its effect on the reversal of MDR. The activity of ASIV was evaluated using human hepatic cancer cells Bel‑7402 and the corresponding 5‑fluorouracil (5‑FU) resistant cells Bel‑7402/FU. ASIV (0.08 mg/ml) potentiated the cytotoxicity of 5‑FU which was demonstrated using the MTT assay on Bel‑7402/FU cells. ASIV reduced the expression of P‑gp as was revealed by immunocytochemistry. Accumulation and efflux studies with the P‑gp substrate, rhodamine 123 (Rh123), demonstrated that ASIV inhibited P‑gp‑mediated drug efflux. Furthermore, it was demonstrated that ASⅣ enhanced the drug accumulation of 5‑FU using a high performance liquid chromatography (HPLC) assay for drug resistant cells. Furthermore, ASIV may downregulate the expression of P‑gp, which was examined using western blot analysis and polymerase chain reaction. In conclusion, the results of the present study indicated that ASIV reverses the drug resistance of Bel‑7402/FU cells by downregulating the expression of mdr1. ASIV may represent a potent modulator of P‑gp‑mediated MDR in hepatic cancer therapy.
Molecular Medicine Reports 03/2014; 9(6). DOI:10.3892/mmr.2014.2074 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -To evaluate the influence of the single nucleotide polymorphism (SNP) rs 6265 in the brain-derived neurotrophic factor (BDNF) gene and of 21 SNPs of the glial cell line-derived neurotrophic factor (GDNF) gene on the efficacy of paroxetine in patients with major depressive disorder (MDD).
-Genotyping for BDNF and GDNF polymorphisms was performed in 298 MDD patients who started 20 mg paroxetine per day and had their plasma concentrations measured after 6 weeks. The SNPs were selected from the HapMap Chinese ethnic group and literature reports. Changes in the severity of MDD were assessed with the Hamilton Depression Rating Scale (HAM-D) at baseline and at a 6-week follow-up. Paroxetine plasma concentration was measured using high-performance liquid chromatography with fluorescence detection (HPLC-FD). The Sequenom MassArray system was used for genotyping.
-At the 6-week follow-up, 219 of the 298 patients (73.5%) were responders and 79 patients (26.5%) were non-responders to paroxetine treatment. The lower threshold concentration of paroxetine for response was 50 ng/mL and a linear relationship was found between paroxetine plasma concentration and clinical response. The allele types for the SNPs rs 6265 (p < 0.001), rs 2973049 (p = 0.005), and rs 2216711 (p = 0.006) demonstrated significant associations with paroxetine treatment remission at week 6.
-Genetic variants in the BDNF and GDNF regions may be indicators of treatment response to paroxetine in MDD patients.
Therapeutic drug monitoring 02/2014; 36(5). DOI:10.1097/FTD.0000000000000062 · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Curdione, one of the major sesquiterpene compounds from Rhizoma Curcumae, has been shown to exhibit multiple bioactive properties. In this study, we investigated the anti-platelet aggregation and antithrombotic activities of curdione with different methods both in vitro and in vivo. The purpose of the study was to explore an inhibitor of platelet aggregation, which promised to be a preventive or therapeutic agent for various vascular diseases.
Curdione was isolated from the essential oil of Curcuma wenyujin using the silica gel column chromatography method. The effects of curdione on human platelet aggregation induced by thrombin (0.3 U/ml), platelet-activating factor (PAF, 0.375 μg/ml), adenosine diphosphate (ADP, 10 μM) and arachidonic acid (AA, 0.1mg/ml) were tested in vitro, and the potential mechanisms underlying such activities were investigated. We also tested the antithrombotic effect of curdione in a tail thrombosis model.
Curdione preferentially inhibited PAF- and thrombin- induced platelet aggregation in a concentration-dependent manner (IC(50): 60-80 μM), whereas much higher concentrations of curdione were required to inhibit platelet aggregation induced by ADP and AA. Curdione also inhibited P-selectin expression in PAF-activated platelets. Moreover, curdione caused an increase in cAMP levels and attenuated intracellular Ca(2+) mobilization in PAF-activated platelets. In vivo, we also found that curdione showed significant antithrombotic activity. Therefore, we conclude that the inhibitory mechanism of curdione on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca(2+) mobilization. Furthermore, the effect observed in the tail thrombosis model might be explained completely by increased vasodilation. These results indicate that curdione may be one of the main bioactive constituents in Rhizoma Curcumae that removes blood stasis.
Thrombosis Research 05/2012; 130(3):409-14. DOI:10.1016/j.thromres.2012.04.005 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two polysaccharides (APS-I and APS-II) were isolated from the water extract of Radix Astragali and purified through ethanol precipitation, deproteination and by ion-exchange and gel-filtration chromatography. Their molecular weight was determined using high performance liquid chromatography and gel permeation chromatography (HPLC-GPC) and their monosaccharide composition was analyzed by TLC and HPLC methods, using a refractive index detector (RID) and an NH(2) column. It was shown that APS-I consisted of arabinose and glucose and APS-II consisted of rhamnose, arabinose and glucose, in a molar ratio of 1:3.45 and 1:6.25:17.86, respectively. The molecular weights (Mw) of APS-I and APS-II were 1,699,100 Da and 1,197,600 Da, respectively.