Bioorg Med Chem. 2009 Jun 16; Zhang J, Zhang H, Cai W, Yu L, Zhen X, Zhang AA series of new 1-aryl-3-benzazepine derivatives containing an arylpiperazinyl function as the N3 substituent were synthesized by combining a D(1) receptor agonistic pharmacophore and a 5-HT(1A) receptor pharmacophore through Click reaction. Interestingly, these compounds generally do not have good binding affinity at the D(1) receptor, but most compounds are potent at both D(2) and 5-HT(1A) receptors. Compound 8h, containing 1-m-tolyl-benzazepine scaffold and 2-methoxyphenylpiperazine core, displayed good affinity at all tested receptors, with K(i) values of 144, 80, and 133nM, for the D(1), D(2), and 5-HT(1A) receptors, respectively. Compound 13 with the triazole moiety formed differently from that in 8h showed the highest affinity at the D(2) receptor with K(i) value of 19nM. This compound also showed moderate affinity at the 5-HT(1A) (K(i), 105nM), and D(1) (K(i), 551nM) receptors. Functional assays indicated that both compounds 13 and 8h are antagonists at D(1) and D(2) receptors, whereas full agonistic activity at the 5-HT(1A) receptor was observed. In agreement with the binding affinity, compound 13 is a high efficacy D(2) antagonist and 5-HT(1A) agonist.

J Nat Prod. 2009 Jun 24; Lin BD, Zhang CR, Yang SP, Zhang S, Wu Y, Yue JMSixteen new D-ring-opened phragmalin limonoid orthoesters, swietenitins A-M (1-6, 8, 10, 12-16), 2-acetoxyswietenialide D (7), 2,11-diacetoxyswietenialide D (9), and 11-deoxyswietenialide D (11), and four known compounds were isolated from the twigs of Swietenia macrophylla. The structures of 1-16 were established on the basis of spectroscopic methods, and 1 and 2 were confirmed by single-crystal X-ray diffraction. The (1)H NMR-based conformational analysis on the epimeric compounds 1 and 2 provided a general approach to determine the absolute configuration of the 2,3-epoxy-2-methylbutyryloxy unit at C-3 borne by a large group of the known phragmalin-type limonoid orthoesters.

Phytomedicine. 2009 Jun 22; Kong WJ, Zhao YL, Xiao XH, Jin C, Li ZLTo control the quality of Rhizoma Coptidis, a method based on ultra performance liquid chromatography with photodiode array detector (UPLC-PAD) was developed for quantitative analysis of five active alkaloids and chemical fingerprint analysis. In quantitative analysis, the five alkaloids showed good regression (R > 0.999 2) within test ranges and the recovery of the method was in the range of 98.4- 100.8%. The limit of detections and quantifications for five alkaloids in PAD were less than 0.07 and 0.22mug/ml, respectively. In order to compare the UPLC fingerprints between Rhizoma Coptidis from different origins, the chemometrics procedures, including similarity analysis (SA), hierarchical clustering analysis (HCA), principal component analysis (PCA) were applied to classify the Rhizoma Coptidis samples according to their cultivated origins. Consistent results were obtained to show that Rhizoma Coptidis samples could be successfully grouped in accordance with the province of origin. Furthermore, five marker constituents were screened out to be the main chemical marker, which could be applied to accurate discrimination and quality control for Rhizoma Coptidis by quantitative analysis. This study revealed that UPLC-PAD method was simple, sensitive and reliable for quantitative and chemical fingerprint analysis, moreover, for the quality evaluation and control of Rhizoma Coptidis.

Chem Biodivers. 2009 Jun 23; 6(6): 858-863Yu ZG, Li J, Li ZY, Guo YWTwo new acetonyl-bearing sesquiterpenes, dysifragilisins A and B (1 and 2, resp.), have been isolated from the Hainan marine sponge Dysidea fragilis. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analyses and by comparison of their NMR data with those of structurally related compounds. A plausible biogenetic pathway is proposed for the origin of compounds 1 and 2.

Chem Biodivers. 2009 Jun 23; 6(6): 916-923Chen FY, Ye YP, Sun HX, Li XY, Shi HStemucronatoside L (SML), isolated from Stephanotis mucronata, could suppress the activation of T cells in vitro. However, the mechanisms responsible for its immunosuppressive activity remain poorly understood. The purpose of this study was to investigate whether SML could suppress Th1/Th2 immune responses and to characterize the cellular mechanisms involved. Effects of SML on T-lymphocyte subsets and the production of Th1 cytokines IL-2 and IFN-gamma, and Th2 cytokines IL-4 and IL-10 from ConA-stimulated mice splenocytes were detected by flow-cytometric analysis and ELISA method, respectively. Furthermore, effects of SML on mRNA expression level of Th1/Th2 cytokines and transcription factors T-bet and GATA-3 were evaluated by RT-PCR analysis. SML not only significantly decreased the percentage of CD4(+) T cells and the CD4(+)/CD8(+) ratio, but reduced the production of Th1/Th2 cytokines in a concentration-dependent manner. The mRNA expression levels of Th1/Th2 cytokines and transcription factors (T-bet and GATA-3) were also suppressed by SML. These results suggested that SML could simultaneously inhibit Th1/Th2 immune responses by suppressing gene expression of Th1/Th2 cytokines and transcription factors.

Yao Xue Xue Bao. 2009 Apr; 44(4): 436-9Chen RD, Zou JH, Jia JM, Dai JGSyringin is one of the main bioactive ingredients in Saussurea involucrata. In this study, various chromatographic techniques were employed to isolate and purify syringin in the polar extraction of cell suspension cultures of S. involucrata. The structure of syringin was characterized by the analysis of spectroscopic data. A quantitative analytical method for the content of syringin in cultures of S. involucrata was established with RP-HPLC. The method is convenient, accurate and reliable. All this results provided a basis for further studies on application of cell suspension cultures of S. involucrata for large-scale production of bioactive compound syringin.

Cancer Lett. 2009 Jun 16; Zhang Z, Wang S, Qiu H, Duan C, Ding K, Wang ZWaltonitone, a new ursane-type pentacyclic triterpene isolated from Gentian waltonii Burkill significantly inhibited human hepatocellular carcinoma BEL-7402 cells growth. Apoptosis induced by waltonitone was characterized by AO/EB staining and flow cytometric analysis. Apoptosis microarray assay results showed BCL-2 family genes might especially play an important role in waltonitone-induced apoptosis. RT-PCR and Western blotting analysis showed that waltonitone could induce tumor cell apoptosis via both death receptor and mitochondria pathways. Meanwhile, the inhibitory effect of waltonitone was examined in vivo using BEL-7402 tumor cells xenografted into athymic mice model. In summary, these studies demonstrated that waltonitone might inhibit hepatocellular carcinoma cells growth and induce apoptosis in vitro and in vivo.

Yao Xue Xue Bao. 2009 Apr; 44(4): 362-5Yuan YH, Sun JD, Hu JF, Chen NHThe aim of this study is to investigate the neurotoxic effect and mechanism of 1-methyl-4-phenylpyridinium (MPP+) on PC12 cells. MTT assay was used to investigate cell viability, Western blotting assay was performed to observe the protein level and phosphorylation, and dual-luciferase assay was used to study the transactivation. The experiment showed that MPP+ could decrease cell viability significantly in a dose-dependent manner and could decrease BDNF protein level, depress the phosphorylation of ERK, and attenuate the phosphorylation and transactivation of CREB, which is one of transcription factors of BDNF, but did not affect the activity of CaMK II in PC12 cells. So MPP+ might decrease BDNF protein level through MAPK/ERK signal pathway.

Exp Toxicol Pathol. 2009 Jun 18; Liu TY, Chen Y, Wang ZY, Ji LL, Wang ZTIsoline is a retronecine-type pyrrolizidine alkaloid (PA) isolated from the traditional Chinese medicinal herb Ligularia duciformis. The present investigation was carried out to evaluate isoline-induced oxidative injury in various important mouse organs. Various tissue samples were collected after mice were administrated with 100mg/kg isoline for 36h, and then lipid peroxidation (LPO) level, total antioxidant capacity, glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities were determined to evaluate the oxidative injury. Our results showed that the total antioxidant capacity of liver, brain and lung were all decreased after given isoline, and the LPO level was increased in liver and heart of isoline-treated mice. Further antioxidant-related enzyme activity assays showed that isoline (100mg/kg) decreased GPx activity in liver and heart, increased CAT activity in liver, brain and heart, and decreased the GST activity in lung. Taken together, our results demonstrate that isoline can induce different oxidative injury in various important mouse organs, and of which liver is the most sensitive organ.

Yao Xue Xue Bao. 2009 Apr; 44(4): 355-61Cao YL, Li SX, Chen H, Guo YConsistent non-nucleoside reverse-transcriptase inhibitors (NNRTIs) resistant HIV-1 strains occurred due to the clinical use for more than ten years of efavirenz (EFV), nevirapine (NVP), and delavirdine (DLV). In this study, we established nine cell-based pharmacological models according to most NNRTIs-resistant clinical tested strains, Resistant mutations were introduced into vector, pNL4-3.Luc.R-E-, by overlapping PCR. Then, pseudovirions were produced by co-transfection of VSV-G plasmid and pNL4-3.Luc.R-E- -mut. All nine recombinant VSVG/HIV-mut pseudovirions (VSVG/HIV-wt, VSVG/HIV(-K103N), VSVG/HIV(-Y181C), VSVG/HIV(-L100I,K103N), VSVG/HIV(-Y188L), VSVG/HIV(-K103N,Y181C), VSVG/HIV(-K103N,P225H), VSVG/HIV(-K103N,Y188L), VSVG/HIV(-K103N,G109A) and VSVG/HIV(-K103N,V108I)) had high efficient infectivity. Furthermore, they all showed resistant characteristics to EFV and NVP with IC50 changes consisting with clinical reports, not to nucleoside reverse-transcriptase inhibitors (AZT and d4T). This series safe cell-based model, which could be carried out in BSL-2 laboratory, can be used for evaluating NNRTIs candidates.

Acta Pharmacol Sin. 2009 Jun 22; Li QN, Liu HY, Xin XL, Pan QM, Wang L, Zhang J, Chen Q, Geng MY, Ding JAbstractAim:To elucidate the detailed mechanisms underlying the appreciable effects of JG3, a novel marine-derived oligosaccharide, on cell migration using a Chinese hamster ovary (CHO) cell line stably over-expressing heparanase.Methods:A retrovirus infection system was used to establish a CHO-K1 cell line stably transfected with heparanase. Immunocytochemistry was used to assess cell morphology. Flow cytometry was selected to analyze the activation of beta1-integrin, and Western blotting was used to analyze the downstream effects on the cell adhesion pathway. An affinity precipitation assay was used to determine activation of the small GTPases, Rac1, and RhoA.Results:JG3 abolished heparanase-driven formation of focal adhesions and cell spreading. Although JG3 failed to block the heparanase-triggered activation of beta1-integrin or the phosphorylation of Src, the oligosaccharide caused a significant dephosphorylation of FAK and subsequent inactivation of Erk. Furthermore, JG3 was found to arrest the activation of Rac1.Conclusion:All these findings help form an alternative view to understand the mechanisms underlying the inhibitory effects of JG3 on cell motility.Acta Pharmacologica Sinica advance online publication, 22 June 2009; doi: 10.1038/aps.2009.97.

Nat Med (Tokyo). 2009 Jun 24; Gao XH, Xu XX, Pan R, Li Y, Luo YB, Xia YF, Murata K, Matsuda H, Dai YSepsis remains the leading cause of death in intensive care units. Uncontrolled systemic inflammation and an impaired protein C pathway are two important contributors to sepsis pathophysiology. Based on the beneficial effects of the saponin fraction from Astragalus membranaceus roots (SAM) against inflammation, liver dysfunction, and endothelium injury, we investigated the potential protective roles and underlying mechanisms of SAM on polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. SAM, orally administered 1 h before and after CLP, significantly elevated the survival rate of mice. At 96 h after CLP operation, all mice in the model group died, whereas 33.3% of mice in the SAM (400 mg/kg)-treated group survived. SAM attenuated both inflammatory factors and their abilities to induce tissue dysfunction, which was mainly evidenced by decreased infiltration of polymorphonuclear leukocytes, tissue edema, and lung wet-to-dry weight ratio, lowered levels of myeloperoxidase (MPO), nitric oxide (NO), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in serum, as well as downregulated expressions of iNOS and IL-1beta mRNA in livers. Furthermore, we addressed the effects of SAM on the protein C (PC) pathway, closely linked with sepsis. In CLP-induced septic mice, SAM elevated the impaired expression of PC mRNA in livers. In vitro, SAM reversed the decreased expressions of thrombomodulin (TM) and endothelial PC receptor (EPCR) mRNA induced by lipopolysaccharide (LPS) in endothelial cells. These findings suggest that SAM is able to restore the impaired protein C pathway. Taken together, the current study demonstrates that SAM has protective effects on polymicrobial sepsis in mice. The mechanisms of action involve anti-inflammation and upregulation of the PC pathway.

Eur J Pharmacol. 2009 Jun 17; Tao R, Ye F, He Y, Tian J, Liu G, Ji T, Su YThis study was to explore the effects of a compound (BPG) from Balanophora polyandra Griff on metabolic syndrome in mice. The animal model, developed obesity, dyslipidemia and insulin resistance, were induced by high-fat-diet in C57BL/6 mice, and were treated orally with 100 mg/kg/day BPG and 15 mg/kg/day rosiglitazone, respectively. The age-matched C57BL/6 mice fed with standard chow were used as normal control. The blood glucose, the value of serum triglyceride and the content of triglyceride in the skeletal muscle were determined by biochemical methods. The protein expression was evaluated by western blot. BPG administration decreased body weight gain, adiposity index, serum triglyceride levels, and triglyceride accumulation in skeletal muscle significantly. At the same time, BPG administration also exhibited extensive effects on insulin resistance by improving orally glucose tolerance test, insulin tolerance test and glucose infusion rate in hyperinsulinemic-euglycemic clamp test. Furthermore, in skeletal muscle, BPG revered the defect expression of IRbeta, IRS-1 and PTP1B, and also decreased the expression of ACCbeta and increased the expression of p-AMPK in the high-fat-die-induced mice. All the results suggest that BPG improves metabolic syndrome may by the enhancement of insulin sensitivity and fatty acid oxidation.

Appl Microbiol Biotechnol. 2009 Jun 20; Kong WJ, Wang JB, Jin C, Zhao YL, Dai CM, Xiao XH, Li ZLUsing the 3114/3115 thermal activity monitor (TAM) air isothermal microcalorimeter, ampoule mode, the heat output of Candida albicans growth at 37 degrees C was measured, and the effect of emodin on C. albicans growth was evaluated by microcalorimetry coupled with chemometric methods. The similarities between the heat flow power (HFP)-time curves of C. albicans growth affected by different concentrations of emodin were calculated by similarity analysis (SA). In the correspondence analysis (CA) diagram of eight quantitative parameters taken from the HFP-time curves, it could be deduced that emodin had definite dose-effect relationship as the distance between different concentrations of it increased along with the dosage and the effect. From the principal component analysis (PCA) on eight quantitative parameters, the action of emodin on C. albicans growth could be easily evaluated by analyzing the change of values of the main two parameters, growth rate constant k (2) and maximum power output [Formula: see text]. The coherent results of SA, CA, and PCA showed that emodin at different concentrations had different effects on C. albicans growth metabolism: A low concentration (0-10 mug ml(-1)) poorly inhibited the growth of C. albicans, and a high concentration (15-35 mug ml(-1)) could notably inhibit growth of this fungus. This work provided a useful idea of the combination of microcalorimetry and chemometric analysis for investigating the effect of drug and other compounds on microbes.

J Cell Mol Med. 2009 Jun 16; Dai M, Miao ZH, Ren X, Tong LJ, Yang N, Li T, Lin LP, Shen YM, Ding JAbstract The macrolide compound MFTZ-1 has been identified as a novel topoisomerase II (Top2) inhibitor with potent in vitro and in vivo anti-tumor activities. In this study, we further examined the effects of MFTZ-1 on hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation, vascular endothelial growth factor (VEGF) secretion and angiogenesis. MFTZ-1 reduced HIF-1alpha accumulation driven by hypoxia or growth factors in human cancer cells. Mechanistic studies revealed that MFTZ-1 did not affect the degradation of HIF-1alpha protein or the level of HIF-1alpha mRNA. By contrast, MFTZ-1 apparently inhibited constitutive and inducible activation of both phosphatidylinositol-3-kinase (PI3K)-Akt and p42/p44 mitogen-activated protein kinase (MAPK) pathways. Further studies revealed that MFTZ-1 abrogated the HIF-1alpha-driven increase in VEGF mRNA and protein secretion. MFTZ-1 also lowered the basal level of VEGF secretion. The results reveal an important feature that MFTZ-1 can reduce constitutive, HIF-1alpha-independent VEGF secretion and concurrently antagonize inducible, HIF-1alpha-dependent VEGF secretion. Moreover, MFTZ-1 disrupted tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by hypoxia with low-concentration serum or by serum at normoxia, and inhibited HUVECs migration at normoxia. MFTZ-1 also prevented microvessel outgrowth from rat aortic ring. These data reflect the potent anti-angiogenesis of MFTZ-1 under different conditions. Furthermore, using specific small interfering RNA targeting Top2alpha or Top2-defective HL60/MX2 cells, we showed that MFTZ-1 affected HIF-1alpha accumulation and HUVECs tube formation irrelevant to its Top2 inhibition. Taken together, our data collectively reveal that MFTZ-1 reduces constitutive and inducible HIF-1alpha accumulation and VEGF secretion possibly via PI3K-Akt and MAPK pathways, eliciting anti-angiogenesis independently of its Top2 inhibition.

J Med Chem. 2009 Jun 16; Zhang L, Yan Y, Liu Z, Abliz Z, Liu GIn this paper, a peptide substrate (Pep8) of TSSK1 is identified. Using Pep8 as a substrate, two homogeneous and efficient assays for TSSK1 inhibitors screening have been developed, including luminescent kinase assay and LC-MS-based high-throughput assay. Two classes of compounds were identified that are able to efficiently inhibit phosphorylation catalyzed by TSSK1.

Cancer Res. 2009 Jun 16; Jeong CH, Bode AM, Pugliese A, Cho YY, Kim HG, Shim JH, Jeon YJ, Li H, Jiang H, Dong Z[6]-Gingerol, a natural component of ginger, exhibits anti-inflammatory and antitumorigenic activities. Despite its potential efficacy in cancer, the mechanism by which [6]-gingerol exerts its chemopreventive effects remains elusive. The leukotriene A4 hydrolase (LTA4H) protein is regarded as a relevant target for cancer therapy. Our in silico prediction using a reverse-docking approach revealed that LTA4H might be a potential target of [6]-gingerol. We supported our prediction by showing that [6]-gingerol suppresses anchorage-independent cancer cell growth by inhibiting LTA4H activity in HCT116 colorectal cancer cells. We showed that [6]-gingerol effectively suppressed tumor growth in vivo in nude mice, an effect that was mediated by inhibition of LTA4H activity. Collectively, these findings indicate a crucial role of LTA4H in cancer and also support the anticancer efficacy of [6]-gingerol targeting of LTA4H for the prevention of colorectal cancer. [Cancer Res 2009;69(13):5584-91].

Naturwissenschaften. 2009 Jun 17; Baumgartner S, Wolf M, Skrabal P, Bangerter F, Heusser P, Thurneysen A, Wolf UQuantitative meta-analyses of randomized clinical trials investigating the specific therapeutic efficacy of homeopathic remedies yielded statistically significant differences compared to placebo. Since the remedies used contained mostly only very low concentrations of pharmacologically active compounds, these effects cannot be accounted for within the framework of current pharmacology. Theories to explain clinical effects of homeopathic remedies are partially based upon changes in diluent structure. To investigate the latter, we measured for the first time high-field (600/500 MHz) (1)H T(1) and T(2) nuclear magnetic resonance relaxation times of H(2)O in homeopathic preparations with concurrent contamination control by inductively coupled plasma mass spectrometry (ICP-MS). Homeopathic preparations of quartz (10c-30c, n = 21, corresponding to iterative dilutions of 100(-10)-100(-30)), sulfur (13x-30x, n = 18, 10(-13)-10(-30)), and copper sulfate (11c-30c, n = 20, 100(-11)-100(-30)) were compared to n = 10 independent controls each (analogously agitated dilution medium) in randomized and blinded experiments. In none of the samples, the concentration of any element analyzed by ICP-MS exceeded 10 ppb. In the first measurement series (600 MHz), there was a significant increase in T(1) for all samples as a function of time, and there were no significant differences between homeopathic potencies and controls. In the second measurement series (500 MHz) 1 year after preparation, we observed statistically significant increased T(1) relaxation times for homeopathic sulfur preparations compared to controls. Fifteen out of 18 correlations between sample triplicates were higher for controls than for homeopathic preparations. No conclusive explanation for these phenomena can be given at present. Possible hypotheses involve differential leaching from the measurement vessel walls or a change in water molecule dynamics, i.e., in rotational correlation time and/or diffusion. Homeopathic preparations thus may exhibit specific physicochemical properties that need to be determined in detail in future investigations.

Zhongguo Zhong Yao Za Zhi. 2009 Mar; 34(5): 512-4Liang ACarrageenan is a collective term for polysaccharides prepared by alkaline extraction from red seaweed (Rhodophycae). Different carrageenans are widely used as food and medicinal ingredients and applied in chemical and biochemical researches. The studies in recent years showed that long-term administration of carrageenan in various animals can cause intestine mucous membrane damage or ulcerous colonitis, and produce or promote tumor growth. It is necessary to perform more epidemiological and essential studies to evaluate the safety of Carrageenan.

Zhongguo Zhong Yao Za Zhi. 2009 Mar; 34(5): 567-70Liu A, Xu L, Zou ZOBJECTIVE: To isolate and identify chemical constituents of Uvaria tonkinensis var. subglabra. METHOD: The column chromatographic techniques were applied to isolate constituents, and their structures were elucidated by means of spectral data analysis including 1D and 2D NMR, IR and MS techniques. RESULT: Seven compounds were isolated and identified as subglain C (1), beta-senepoxide (2) , 2, 4-dioxohexahydro-1, 3-diazepin (3), kaempferol-3, 7-di-O-alpha-L-rhamnoside (4), anolobine (5), (-)-lyoniresinol (6) and schizandriside (7). CONCLUSION: Compound 1 was the new natural product; compounds 2-7 were isolated for the first time from U. tonkinensis var. subglabra.

Bull Exp Biol Med. 2009 Mar; 147(3): 323-7Epstein OI, Dygai AM, Sergeeva SA, Zhdanov VV, Khrichkova TY, Stavrova LA, Zyuz'kov GN, Udut EV, Simanina EVThe possibility of using ultralow-dose cyclophosphamide for reducing the myelotoxicity of cyclophosphamide, injected in the maximum permissible dose, was studied in mice. Combined treatment by the cytostatic and its ultralow-dose preparation led to a lesser suppression of the erythroid, lymphocytic, and particularly granulocytic hemopoiesis stems. This effect is explained by stimulation of the secretory activity of hemopoiesis-inducing microenvironment and hence, of the functional activity of granulocytopoiesis under the effect of ultralow-dose cyclophosphamide.

Zhongguo Zhong Yao Za Zhi. 2009 Mar; 34(5): 564-6Wang W, Wang Z, Gao H, Hong YOBJECTIVE: To establish the quality standards of roasted ginger and charry ginger prepared from dried ginger. METHOD: The basic quality information of roasted ginger and charry ginger investigated by analysis of marketed samples. Ten batches of two roasted ginger and charry ginger were prepared in medium-scale from four main growth places by the processed criterion. The quality information includes contents of ash, acid-insoluble ash, water-soluble extract and 6-gingerol. The content of 6-gingerol were determined by HPLC method. RESULT: The contents of total ash, acid-insoluble ash and water-soluble extract in processed ginger from medium-scale production were 6.3% - 7.0%, 0.3% - 0.7% and 22.11% - 41.61%, and that in charry ginger were 5.0% - 6.0%, 0.4 - 0.6 % and 20.94% - 44.92%, respectively. The contents of 6-gingerol in roasted ginger from medium-scale production and market samples were 1.05 -5.34 mg x g(-1) and 1.01-4.81 mg x g(-1), and those indexes in charry ginger were 0.43-3.81 mg x g(-1) and 0.44-3.07 mg x g(-1), respectively. Total ash, acid-insoluble ash and water-soluble extract of the two ginger processed products had no obvious difference in batch-to-batch,but the contents of 6-gingerol were closely related to their growth places. CONCLUSION: The above data provide evidences for production and quality control of ginger processed products.

J Nat Prod. 2009 Jun 10; Wang XY, Ke CQ, Tang CP, Yuan D, Ye YFour new 9,10-dihydrophenanthrenes, juncuenins A-D (1-4), three new phenanthrenes, dehydrojuncuenins A-C (5-7), and three known compounds were isolated from the whole plants of Juncus setchuensis. The structures of the new compounds were established on the basis of detailed 1D and 2D NMR studies.

J Asian Nat Prod Res. 2009; 11(5): 401-9Jiang F, Wang XL, Wang NL, Yao XSTwo new flavonol glycosides, named icarisid B (1) and icarisid C (2), along with seven known flavonol glycosides were isolated from the bioassay-directed fractions of the aqueous extract of Epimedium koreanum Nakai. The structures of the two new compounds were established on the basis of chemical and spectroscopic methods (ESI-MS, 1D, and 2D NMR) as 5-hydroxyl-4'-methoxy-8-(gamma-hydroxyl-gamma,gamma-dimethyl)-propyl-3-O-alpha-L-rhamnopyranosyl-flavonol-7-O-beta-D-glucopyranoside (1) and 5-hydroxyl-4'-methoxy-8-(gamma-methoxy-gamma,gamma-dimethyl)-propyl-3-O-beta-D-glucopyranosyl(1 --> 3)-alpha-L-rhamnopyranosyl-flavonol-7-O-beta-D-glucopyranoside (2), respectively. All the nine compounds were tested for their effects on proliferation and alkaline phosphatase (ALP) activity using UMR106 cells. As a result, five compounds showed stimulating effects on both the proliferation and ALP activity, which suggested that they might be used as potential leading compounds to cure osteoporosis.

Bull Exp Biol Med. 2008 Dec; 146(6): 763-5Shishkina LN, Sergeev AN, Kabanov AS, Skarnovich MO, Evtin NK, Mazurkova NA, Sergeev AA, Belopolskaya MV, Kheyfets IA, Dugina JL, Tarasov SA, Sergeeva SA, Epstein OITherapeutic and preventive treatment of mice intranasally infected with a lethal dose of A/Aichi/2/68 (H3N2) influenza virus with anaferon (pediatric formulation) demonstrated an antiviral effect of the drug (increased percent of survivors and prolonged lifespan).

Bull Exp Biol Med. 2008 Dec; 146(6): 675-679Gainutdinov KL, Andrianov VV, Gainutdinova TK, Muranova LN, Obynochny AA, Timoshenko AK, Shtark MB, Epstein OI, Yurtaeva SV, Jafarova GGEPR-spectroscopy experiments (electron paramagnetic resonance) demonstrated a decrease in NO production in the nervous system and heart of edible snail Helix lucorum after formation of long-term sensitization, a neurobiological model of anxiety and depression. The protective effect of antibodies to Ca(2+)-binding protein S-100 in dilution of 10(-12)on the formation of long-term sensitization was accompanied by partial recovery of NO synthesis in the nervous system and heart. These findings indicate that the imbalance in Ca(2+)-binding protein S-100 can lead to inhibition or modulation of some processes during plastic reorganization in the body and especially during pathological processes.

J Cancer Res Clin Oncol. 2009 Jun 10; Su F, Li H, Yan C, Jia B, Zhang Y, Chen XBACKGROUND: Mitogen-activated protein/ERK kinase 1 (MEKK1) is a Ser/Thr protein kinase belonging to the MEKK/STE11 subgroup of the MAPKKK family and plays a key role in tumor metastasis. However, it remains unclear about its functions in pancreatic cancer. MATERIALS AND METHODS: We analyzed MEKK1 expression in 41 surgically resection pancreatic cancer patient's samples by immunohistochemistry and determined its role in BxPC3 cells via RNAi experiment. The abilities of invasion, motility, and adhesion of BxPC3 cells were detected by transwell assay, wound healing assay and adhesion assay, respectively. Gelatinase activity of MMPs in cultured cells was examined by gelatin zymography. RESULTS: Our data showed that MEKK1 expression is positively correlated with lymphatic metastases (P < 0.01). The abilities of invasion, motility, and adhesion of BxPC3 cells were inhibited significantly (P < 0.01) when MEKK1 was depleted with a specific siRNA. We observed that the activity of MMP2 was decreased in the MEKK1 depletion cell line (P < 0.05), accompanied with decreased phosphorylated ERK1/2. CONCLUSION: Our results indicated that the depletion of MEKK1 led to a potent inhibition on the invasion and migration of human pancreatic adenocarcinoma in vitro. It suggests that MEKK1 may be a potential target for development of anti-invasion and metastasis drugs.

Int J Pharm. 2009 Jun 6; Han SF, Yao TT, Zhang XX, Gan L, Zhu C, Yu HZ, Gan YThis study has explored the use of lipid-based formulations to enhance the oral bioavailability of the poorly water-soluble drug anethol trithione (ATT), and compared the performance of different formulations. Two groups of lipid-based formulations, sub-microemulsion (SME) and oil solution, were prepared using short (SCT), medium (MCT) and long (LCT) chain triglycerides respectively; aqueous suspension was used as the reference formulation. In vitro and in vivo studies were conducted to investigate the impact of lipid composition and formulation on drug absorption. In vitro digestion was used to analyze lipid digestion rates and drug distribution/solubilization. After in vitro digestion, the performance rank order for drug solubilization was SCT < MCT < LCT. SME formulations were digested more rapidly in vitro than oil solutions. The bioavailability of the drug from different formulations was investigated in rats. All six lipid-based formulations enhanced drug absorption compared to the aqueous suspension. For the SMEs, which were rapidly digested, in vivo bioavailability increased in accordance with the increase of solubilization data obtained by in vitro digestion, with the rank order SCT-SME < MCT-SME < LCT-SME. For the oil solutions, which were digested more slowly, there was no significant difference in drug bioavailability for the different formulations. In conclusion, lipid-based formulations can enhance the oral bioavailability of ATT, and for this BCS class II drug, both the lipid composition and type of lipid formulation are likely to govern in vivo performance.

J Asian Nat Prod Res. 2009; 11(5): 397-400Lu X, Xu N, Dai HF, Mei WL, Yang ZX, Pei YHThree new compounds, 4-hydroxyphenethyl-2'-hydroxypropanoate (1), 6-(1',2'-dimethyloxiran-1'-yl)-4-methoxy-3-methyl-2H-pyran-2-one (2), 6-(1-hydroxyethyl)-4-methoxy-3-methyl-2H-pyran-2-one (3), along with the two known compounds, nectriapyrone (4) and wermopyrone (5), have been isolated from the endophytic fungus of Cephalotaxus hainanensis. Their structures were determined on the basis of chemical and spectroscopic methods.

J Asian Nat Prod Res. 2009; 11(5): 426-32Li ZL, Li DY, Hua HM, Chen XH, Kim CSThree new flavone C-glycosides with the substitution of the unusual acyl, 2''-O-veratroylisoswertisin (1), 3''-O-2-methylbutyrylisoswertiajaponin (2), and 3''-O-2-methylbutyrylvitexin (3), together with the known compounds of 2''-O-2-methylbutyrylisoswertisin (4), 3''-O-2-methylbutyrylisoswertisin (5), and trollisin I (6) were isolated from the antibacterial fraction of the aqueous extract of the flowers of Trollius chinensis. The structural elucidations of these compounds were carried out by a detailed analysis of the NMR and MS spectra.

J Asian Nat Prod Res. 2009; 11(5): 433-8Gao HM, Liu JX, Wang ZM, Wang WHPhytolacacinoside A (1), a novel triterpenoid saponin, together with the seven known compounds, was isolated from 75% ethanol extract of the root of Phytolacca acinosa Roxb (Phytolaccaceae). Their structures were elucidated on the basis of analysis of spectroscopic data and physicochemical properties as 3-O-beta-[(beta-d-glucopyranosyl-(1 --> 4)-O-beta-D-xylopyranosyl)]-11beta-methoxy-jaligonic acid 30-methyl ester 28-O-beta-D-glucopyranoside (1), 3-O-beta-[(beta-D-glucopyranosyl-(1 --> 4)-O-beta-D-xylopyranosyl)]-jaligonic acid 30-methyl ester 28-O-beta-D-glucopyranoside (2, esculentoside G), 3-O-beta-[(beta-D-glucopyranosyl-(1 --> 4)-O-beta-D-xylopyranosyl)]-jaligonic acid 30-methyl ester (3, phytolaccoside E), 3-O-beta-D-xylopyranosyl-jaligonic acid 30-methyl ester (4, phytolaccoside B), hypaphorine (5), palmitic acid monoglyceride (6), beta-sitosterol (7), and daucosterol (8).

J Nat Prod. 2009 Jun 5; Shao Y, Zhang HK, Ding H, Quan HT, Lou LG, Hu LHA series of 3-demethoxycarbonyl-3-amide methyl anhydrovinblastine derivatives (5b-24b) was designed, synthesized, and evaluated for their proliferation inhibition activities against two tumor cell lines (A549 and HeLa). Most of the amide anhydrovinblastine derivatives exhibited potent cytotoxicity, with the size of the introduced substituents being the foremost factor in determining the resultant cytotoxic activity. Test results in vivo against sarcoma 180 of three potent compounds (6b, 12b, and 24b) indicated that the introduction of an amide group at the 22-position of anhydrovinblastine (1e) improved both potency and toxicity.

PLoS ONE. 2009; 4(6): e5811Chen XQ, Zhang J, Neumeyer JL, Jin GZ, Hu GY, Zhang A, Zhen X(+/-) SKF83959, like many other arylbenzazepines, elicits powerful neuroprotection in vitro and in vivo. The neuroprotective action of the compound was found to partially depend on its D(1)-like dopamine receptor agonistic activity. The precise mechanism for the (+/-) SKF83959-mediated neuroprotection remains elusive. We report here that (+/-) SKF83959 is a potent blocker for delayed rectifier K(+) channel. (+/-) SKF83959 inhibited the delayed rectifier K(+) current (I(K)) dose-dependently in rat hippocampal neurons. The IC(50) value for inhibition of I(K) was 41.9+/-2.3 microM (Hill coefficient = 1.81+/-0.13, n = 6), whereas that for inhibition of I(A) was 307.9+/-38.5 microM (Hill coefficient = 1.37+/-0.08, n = 6). Thus, (+/-) SKF83959 is 7.3-fold more potent in suppressing I(K) than I(A). Moreover, the inhibition of I(K) by (+/-) SKF83959 was voltage-dependent and not related to dopamine receptors. The rapidly onset of inhibition and recovery suggests that the inhibition resulted from a direct interaction of (+/-) SKF83959 with the K(+) channel. The intracellular application of (+/-) SKF83959 had no effects of on I(K), indicating that the compound most likely acts at the outer mouth of the pore of K(+) channel. We also tested the enantiomers of (+/-) SKF83959, R-(+) SKF83959 (MCL-201), and S-(-) SKF83959 (MCL-202), as well as SKF38393; all these compounds inhibited I(K). However, (+/-) SKF83959, at either 0.1 or 1 mM, exhibited the strongest inhibition on the currents among all tested drug. The present findings not only revealed a new potent blocker of I(K) , but also provided a novel mechanism for the neuroprotective action of arylbenzazepines such as (+/-) SKF83959.

Angew Chem Int Ed Engl. 2009 Jun 3; Yang L, Hill M, Wang M, Panjikar S, Stöckigt J

Acta Pharmacol Sin. 2009 Jun; 30(6): 740-751Yang KC, Jin GZ, Wu JNeuronal nicotinic acetylcholine receptors (nAChRs) are the superfamily of ligand-gated ion channels and widely expressed throughout the central and peripheral nervous systems. nAChRs play crucial roles in modulating a wide range of higher cognitive functions by mediating presynaptic, postsynaptic, and extrasynaptic signaling. Thus far, nine alpha (alpha2-alpha10) and three beta (beta2, beta3, and beta4) subunits have been identified in the CNS, and these subunits assemble to form a diversity of functional nAChRs. Although alpha4beta2- and alpha7-nAChRs are the two major functional nAChR types in the CNS, alpha6*-nAChRs are abundantly expressed in the midbrain dopaminergic (DAergic) system, including mesocorticolimbic and nigrostriatal pathways, and particularly present in presynaptic nerve terminals. Recently, functional and pharmacological profiles of alpha6*-nAChRs have been assessed with the use of alpha6 subunit blockers such as alpha-conotoxin MII and PIA, and also by using alpha6 subunit knockout mice. By modulating DA release in the nucleus accumbens (NAc) and modulating GABA release onto DAergic neurons in the ventral tegmental area (VTA), alpha6*-nAChRs may play important roles in the mediation of nicotine reward and addiction. Furthermore, alpha6*-nAChRs in the nigrostriatal DAergic system may be promising targets for selective preventative treatment of Parkinson's disease (PD). Thus, alpha6*-nAChRs may hold promise for future clinical treatment of human disorders, such as nicotine addiction and PD. In this review, we mainly focus on the recent advances in the understanding of alpha6*-nAChR function, pharmacology and pathophysiology.Acta Pharmacologica Sinica (2009) 30: 740-751; doi: 10.1038/aps.2009.63.

Org Lett. 2009 Jun 1; Mei K, Jin M, Zhang S, Li P, Liu W, Chen X, Xue F, Duan W, Wang WA highly enantioselective conjugate addition of nitroalkanes to enones has been developed. The process is efficiently catalyzed by a simple chiral cyclohexanediamine-derived primary amine thiourea with a broad substrate scope.

J AOAC Int. 2009 Mar-Apr; 92(2): 653-62Qiao YL, Zhang YH, Zhang W, Zhang JLA sensitive and reliable rapid resolution liquid chromatographic (RRLC) method coupled with diode array detection has been developed for the fingerprint analysis of raw and processed caowu (Aconitum kusnezoffii). The RRLC fingerprints were established with a Zorbax Extend C18 analytical column (4.6 x 50 mm, 1.8 microm) and gradient elution. Analysis run time was

J AOAC Int. 2009 Mar-Apr; 92(2): 663-71Qiao YL, Sheng YX, Wang LQ, Zhang JLA sensitive and specific method using rapid resolution liquid chromatography coupled with UV-Vis detection was developed for fingerprint analysis of Rhizoma coptidis and simultaneous determination of 4 alkaloids: jatrorrhizine, coptisine, palmatine, and berberine. Samples of R. coptidis grown under different cultivation conditions and from different habitats were analyzed. The analysis was performed using a reversed-phase octylsilyl (C8) column and gradient elution. The mobile phase consisted of acetonitrile and 20 mmol/L KH2PO4. Each analysis was completed within 3.5 min. The method showed good linearity within test ranges of 4.75-47.50 microg/mL for jatrorrhizine, 20.60-164.80 microg/mL for coptisine, 18.07-180.73 microg/mL for palmatine, and 89.70-717.57 microg/mL for berberine. The method showed good precision, repeatability, and stability for quantification of the 4 alkaloids. The lower limit of detection was 0.19 ng for jatrorrhizine, 0.21 ng for coptisine, 0.15 ng for palmatine, and 0.14 ng for berberine. The lower limit of quantification was 0.57 ng for jatrorrhizine, 0.82 ng for coptisine, 0.55 ng for palmatine, and 0.27 ng for berberine. The overall recovery ranged from 96.30 to 104.10% for the 4 alkaloids. The method is accurate, rapid, and convenient, and it is suitable for routine quality control of R. coptidis.

Chem Pharm Bull (Tokyo). 2009 Jun; 57(6): 625-7Wang G, Liu JS, Lin BB, Wang GK, Liu JKTwo new furanoid norditerpenes (1, 2) were isolated from the root tubers of Dioscorea bulbifera L. Their structures were established on the basis of extensive spectroscopic analysis.

Chem Pharm Bull (Tokyo). 2009 Jun; 57(6): 600-2Luo XM, Qi SH, Yin H, Gao CH, Zhang STwo new quinoldione alkaloids, methyl 2-(3-hydroxy-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetate (1) and 3-hydroxy-1-methyl-3-(2-oxopropyl)quinoline-2,4(1H,3H)-dione (2), and two quinolinone alkaloids previously synthesized but first isolated as natural products, N-methylflindersine (3) and 4-hydroxy-3-methoxy-1-methyl-2(1H)-quinolinone (4), were isolated from the stem bark of Micromelum falcatum, together with the known N-methylswietenidine-B (5). Their structures were established mainly on the basis of 1D- and 2D-NMR techniques. All compounds were evaluated for toxicity towards brine shrimp larvae, and 3 showed strong toxicity with an LD(50) value of 1.39 mug/ml.

Acta Pharmacol Sin. 2009 Jun 1; Qian J, Zhu CH, Tang S, Shen AJ, Ai J, Li J, Geng MY, Ding JAim:We aimed to investigate the potential modification of previously unrecognized surface glycoprotein(s) by alpha2,6-sialylation other than by integrins.Methods:The expression of beta-galactoside alpha2,6-sialyltransferase (ST6Gal-I) in the colon cancer cell line HCT116 was reduced by siRNA. The adhesion and Boyden chamber assay were used to detect the variation in cell motility. alpha2,6-Sialylation proteins were detected with lectin affinity assay. The mRNA expression, protein expression and downstream signaling modulation with siRNA were detected using reverse transcription-polymerase chain reaction, flow cytometry analysis, and Western blot.Results:In HCT116 cells, the knockdown of ST6Gal-I inhibited cell motility, but did not affect cell adhesion. This selectively altered cell migration was caused by the loss of alpha2,6-sialic acid structures on c-Met. Moreover, STAT3 was dephosphorylated at tyrosine 705 in ST6Gal-I-knockdown (ST6Gal-I-KD) HCT116 cells.Conclusion:c-Met is the substrate of ST6Gal-I. The hyposialylation of c-Met can abolish cell motility in ST6Gal-I-KD HCT116 cells.Acta Pharmacologica Sinica advance online publication, 1 June 2009; doi: 10.1038/aps.2009.84.