Quercetin-loaded mixed micelles exhibit enhanced cytotoxic efficacy in non-small cell lung cancer in vitro.

In the present study, quercetin (QUR)-loaded mixed micelles (QUR-M) were prepared with the aim of improving the physicochemical and anticancer efficacy of QUR in lung cancer cells. The mixed micelles comprised tocopheryl polyethylene glycol 1000 succinate (TPGS) and a 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine derivative of polyethylene glycol. The nanosized QUR-M exhibited a pH-responsive and controlled release of QUR that is likely to be beneficial in cancer treatment. The results of an MTT assay clearly demonstrated that the anticancer effect of QUR-M in A549 cancer cells was stronger compared with that of free QUR at 24 and 48 h time points. The half-maximal inhibitory concentrations of QUR and QUR-M were observed to be 12.45 and 6.42 µg/ml, respectively. When stained with Hoechst 33342 and observed using a confocal laser scanning microscope, A549 cells treated with QUR-M exhibited severe chromatin condensation and apoptotic body formation of the nuclei. Overall, high intracellular uptake, sustained drug release and the presence of TPGS in the mixed micelles may result in an increased inhibitory effect against cell proliferation and improved therapeutic efficacy in lung cancers.

High-mobility group box 1 expression and lymph node metastasis in intrahepatic cholangiocarcinoma.

AIM: To evaluate the prognostic value of high-mobility group box 1 (HMGB1) expression in intrahepatic cholangiocarcinoma (IHCC) and the possible underlying mechanism. METHODS: Tissue microarray was constructed from 65 IHCC patients. Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C (VEGF-C). Real-time PCR and Western blot analyses were used to study transcript and protein levels. The interaction between HMGB1 and VEGF-C was evaluated by siRNA, real-time PCR, and enzyme-linked immuno assays. The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed by χ (2) test, and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Cox-regression model, respectively. RESULTS: Overall, overexpression of HMGB1 was found in 38/65 (58.8%) IHCCs, whereas VEGF-C overexpression was present in 30/65 (46.2%) cases. Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density (P = 0.031, r = 0.268) and VEGF-C expression (P = 0.041, r = 0.254). With univariate analysis, both HMGB1 (P = 0.001) and VEGF-C (P = 0.004) were identified to be significantly associated with overall survival rate. Multivariate analysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs (P = 0.005). siRNA knockdown of HMGB1 inhibited transforming growth factor-ß-induced epithelial-mesenchymal transition (EMT) by elevating E-Cadherin expression and reducing expression of N-Cadherin, Vimentin and Snail in RBE cells. Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C, whereas the recombinant HMGB1 increased the VEGF-C level in RBE cells (both P < 0.05), which suggested that HMGB1 could promote lymphatic microvessel density, and subsequently lymphatic invasion, via promoting VEGF-C expression. CONCLUSION: Our results define an important role of HMGB1 in the progression of cholangiocarcinoma, and HMGB1 may serve as a prognostic marker for IHCC patients.

The analgesic activity and possible mechanisms of deacetyl asperulosidic acid methyl ester from Ji shi teng in mice.

Deacetyl Asperulosidic Acid Methyl Ester (DAAME) from Ji shi teng was evaluated on analgesic activity in mice using chemical and thermal models of nociception. Given intraperitoneally, DAAME, at doses of 40 and 80 mg/kg, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin/capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. In the open-field test and the rotarod test, DAAME couldn't impair the motor performance, indicating that the observed antinociception was unlikely due to motor abnormality. In a measurement of core body temperature, DAAME (80 mg/kg) did not affect temperature within 80 min. Moreover, DAAME-induced antinociception in the capsaicin test and the hot plate test was significantly antagonized by glibenclamide. The results suggested that DAAME-produced antinociception was possibly involved in the ATP sensitive K+ channels in the capsaicin test and the hot plate test, which merited exploring further.

Analgesic activity of the aqueous fraction from the ethanolic extract of Chrysanthemum indicum in mice.

The aqueous fraction (AF) of an ethanolic extract from Chrysanthemum indicum was evaluated for analgesic activity in mice using chemical and thermal models of nociception. Given orally, AF at doses of 300 and 600 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin/capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. In the pentobarbital sodium-induced sleeping time test and the open-field test, AF neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed analgesic activity was unlikely due to sedation or motor abnormality. In a measurement of core body temperature, AF did not affect temperature within 80 min. Moreover, the effective dose (600 mg/kg) also showed no toxicity within 7 days. These results suggested further that AF produced analgesic activity possibly related to the flavonoid glycosides and phenolic glycosides in this fraction.

Mechanisms involved in the antinociception of petroleum ether fraction from the EtOH extract of Chrysanthemum indicum in mice.

The petroleum ether fraction (PEF) from the EtOH extract of flowers and buds of Chrysanthemum indicum was evaluated on antinociception in mice using chemical and thermal models of nociception. PEF administered orally at doses of 188 and 376 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and the hot plate test. In the pentobarbital sodium-induced sleep time test and the open-field test, PEF neither enhanced the pentobarbital sodium-induced sleep time nor impaired the motor performance, indicating that the observed antinociception was unrelated to sedation or motor abnormality. In a measurement of core body temperature, PEF did not affect temperature within 80 min. Moreover, PEF-induced antinociception in the capsaicin test was insensitive to naloxone, yohimbine or methylene blue, but was significantly antagonized by atropine and glibenclamide. These results suggested that PEF-produced antinociception might be involvement in the ATP sensitive K+ channels and the mAChRs-ATP sensitive K+ channels pathway. In additional, the antinociception of PEF might attribute to the synergic effects of these two compounds, 2-[[2-[2-[(2-ethylcyclopropyl)methyl] cyclop Cyclopropaneoctanoic and n-hexadecanoic acid, or the property of a single compound, which merited exploring further.

Antitumor activity of two gelsemine metabolites in rat liver microsomes.

Gelsemine is one of the major alkaloids from Gelsemium elegans Benth., which has been used as an antitumor remedy in clinic. In this paper, metabolism of gelsemine has been investigated in vitro in phenobarbital-treated rat liver microsomes. The metabolites of gelsemine were separated and evaluated using the flash silica gel column, preparative HPLC, using NMR and MS methods. According to the spectral data, two metabolites, M1 and M2, were identified as 4-N-demethylgelsemine and 21-oxogelsemine, respectively. By the MTT method in vitro, the antitumor activities between gelsemine and its metabolites were compared in the HepG2 and HeLa cell lines. Moreover, the main metabolic pathway was further proposed.

Two new alkaloids from Gelsemium elegans.

Two new alkaloids, named gelsenine (1) and 11-methoxyhumantenmine (2), were isolated from the whole plant of Gelsemium elegans. The structures were elucidated on the basis of 1D NMR, 2D NMR, and MS methods.

[Tissue distribution of solid lipid nanoparticles loaded garlic oil in rats].

OBJECTIVE: To investigate the tissue distribution of the diallyl disulfide (DADS) and diallyl trisulfide (DATS) in solid lipid nanoparticles loaded garlic oil (GO-SLN) in rats. METHOD: The gas chromatography-electron capture detection (GC-ECD) method was established to determined the DADS and DATS simultaneously in the biological samples of rats after administration of 0.5 mL garlic oil injection or GO-SLN (containing about 10 mg garlic oil) via jugular vein cannula. The conditions for gas chromatographic separation were as follows. The oven temperature was set at 110 degrees C and maintained for 15 min. Temperatures at the injection port and detector were 180 degrees C and 300 degrees C, respectively. Ultra-pure nitrogen (purity > 99.999%, Shenyang Kerui Special Gases Co. Ltd., China) was used as a carrier gas and made-up gas at flow-rates of 1 mL x min(-1) and 60 mL x min(-1), respectively. All injections were carried out in the split injection mode with a split ratio of 1:10. RESULT: The GC-ECD method was fit for determing the concentration of DADS and DATS in garlic oil. The distribution character of GO-SLN in rats had changed to some extent and the concentration of GO-SLN in tissues was higher than that of GO-Injection. CONCLUSION: The SLN can elevate the passive targeting of drugs and lengthen their action time in tissues.

[Study on the preparation of venenum bufonis beta-cyclodextrin inclusion complexes].

OBJECTIVE: To study the preparation of Venenum Bufonis beta-cyclodextrin inclusion complexes. METHOD: An optimal condition was established by the uniform design. Under the optimal conditions the Venenum Bufonis beta-cyclodextrin inclusion complexes were prepared with 5 different methods. RESULT: The ball grinding method was superior to other four methods. The bufadienolide inclusion rate of Venenum Bufonis beta-cyclodextrin prepared with ball grinding method was 85.42%. CONCLUSION: Ball grinding method is the best method for the preparation of Venenum Bufonis beta-cyclodextrin inclusion complexes.