Evid Based Complement Alternat Med. 2009 May 27; Wolf U, Wolf M, Heusser P, Thurneysen A, Baumgartner SHomeopathic preparations are used in homeopathy and anthroposophic medicine. Although there is evidence of effectiveness in several clinical studies, including double-blinded randomized controlled trials, their nature and mode of action could not be explained with current scientific approaches yet. Several physical methods have already been applied to investigate homeopathic preparations but it is yet unclear which methods are best suited to identify characteristic physicochemical properties of homeopathic preparations. The aim of this study was to investigate homeopathic preparations with UV-spectroscopy. In a blinded, randomized, controlled experiment homeopathic preparations of copper sulfate (CuSO(4); 11c-30c), quartz (SiO(2); 10c-30c, i.e. centesimal dilution steps) and sulfur (S; 11x-30x, i.e. decimal dilution steps) and controls (one-time succussed diluent) were investigated using UV-spectroscopy and tested for contamination by inductively coupled plasma mass spectrometry (ICP-MS). The UV transmission for homeopathic preparations of CuSO(4) preparations was significantly lower than in controls. The transmission seemed to be also lower for both SiO(2) and S, but not significant. The mean effect size (95% confidence interval) was similar for the homeopathic preparations: CuSO(4) (pooled data) 0.0544% (0.0260-0.0827%), SiO(2) 0.0323% (-0.0064% to 0.0710%) and S 0.0281% (-0.0520% to 0.1082%). UV transmission values of homeopathic preparations had a significantly higher variability compared to controls. In none of the samples the concentration of any element analyzed by ICP-MS exceeded 100 ppb. Lower transmission of UV light may indicate that homeopathic preparations are less structured or more dynamic than their succussed pure solvent.

Hepatol Res. 2009 Mar 10; Yao XM, Chen H, Li YAim: Bicyclol is a synthetic anti-hepatitis drug with anti-oxidative property. The purpose of this study was to investigate the effect of bicyclol on hepatic ischemia/reperfusion (I/R) injury and related mechanisms. Methods: Rats were subjected to 90 min of hepatic ischemia followed by reperfusion for 1, 3, 6 and 24 h. Three doses of bicyclol were orally administered before ischemia. Liver injury was evaluated by biochemical and histopathological examinations. Liver malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) contents, and plasma endotoxin levels were spectrophotometrically measured. The expressions of inflammatory and anti-inflammatory cytokines were detected by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Liver intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemistry, and the expressions of nuclear factor (NF)-kappaB, inhibitor of NF-kappaB (IkappaB) and toll-like receptor 4 (TLR4) were determined by western blot. Results: Bicyclol significantly inhibited the elevations of serum alanine aminotransferase, total bilirubin and plasma endotoxin levels, alleviated the formation of liver MDA and nitrite/nitrate, restored impaired antioxidant SOD, attenuated hepatic necrosis and neutrophil infiltration, and also improved the 7-day survival in I/R rats. Additionally, bicyclol markedly downregulated the overexpression of ICAM-1, modulated the expression of inflammatory/anti-inflammatory cytokines and inhibited the expression of NF-kappaB and TLR4 in I/R rats. Conclusion: Bicyclol had a remarkable protective effect on hepatic I/R injury, which was partially due to inhibiting the expression of TLR4 and NF-kappaB via its ability to attenuate oxidative stress and endotoxin.

Homeopathy. 2009 Apr; 98(2): 122-4Land ST

Homeopathy. 2009 Apr; 98(2): 132-3Thomas DM

J Altern Complement Med. 2009 May; 15(5): 465-7Smith CW

Vet Rec. 2009 May 16; 164(20): 634-5Baker SJ, Baker GJ

J Comb Chem. 2009 May 26; Wang DM, Sun MN, Liu GThis paper reports a versatile, good-yielding, solution-phase method that is a substituent diversity-directed synthesis of 1H-indoles (6-13, 17-20) and 1-hydroxyindoles (14, 15) starting from commercially available 1,5-difluoro-2,4-dinitrobenzene. The synthetic products possessed the maximum six diversity points.

ChemMedChem. 2009 May 8; Chen F, Gao AH, Li J, Nan FJ

J Asian Nat Prod Res. 2009; 11(4): 289-93Zhang YW, Sun WX, Li X, Zhao CC, Meng DL, Li NTwo new compounds were isolated from the whole plant of Helichrysum arenarium (L.) Moench. By means of spectroscopic data (IR, UV, 1D and 2D NMR, HR-MS, ESI-MS, and NOESY) and chemical evidence, the structures were established as 6,7-dimethoxy-4-hydroxy-1-naphthoic acid (1) and (Z)-5-hydroxy-7-methoxy-4-[3-methyl-4-(O-beta-D-xylopyranosyl)but-2-enyl]isobenzofuran-1(3H)-one (2).

J Pharm Biomed Anal. 2009 Apr 17; Yang D, Yu C, Li S, Liu G, Lu Y, Wang YA sensitive and specific LC-CMS/MS method was developed for the quantification of changrolin, an anti-arrhythmic drug, in rat plasma using tiapride as internal standard. Liquid-liquid extraction was employed for sample preparation and analyzed using a multiple reaction monitoring mode with electrospray positive ionization source. The calibration curve for changrolin was linear over the range 5-1600ng/mL with coefficients of correlation >0.99. The intra- and inter-batch precision was less than 8.6%, and accuracy ranged from 94.6% to 104.5%. This validated LC-MS/MS method was successfully applied to a bioavailability study of oral and intravenous administration of changrolin with 20mg/kg dosage in SD rats.

Cancer Sci. 2009 Apr; 100(4): 782-5Gao H, Lu Q, Liu X, Cong H, Zhao L, Wang H, Lin D1H nuclear magnetic resonance (NMR)-based metabonomics was used to characterize metabolic profiles of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We found compared to healthy humans, LC and HCC sera had higher levels of acetate, Nacetylglycoproteins, pyruvate, glutamine, alpha-ketoglutarate, glycerol, tyrosine, 1-methylhistidine and phenylalanine, together with lower levels of low-density lipoprotein, isoleucine, valine, acetoacetate, creatine, choline and unsaturated lipids. Scores plot of pattern recognition analysis were capable of distinguishing LC and HCC patients from healthy humans. These results indicate that serum NMR spectra combined with pattern recognition analysis techniques offer an efficient, convenient way of depicting tumor biochemistry, which may be of great benefit to early diagnosis of human malignant diseases using single blood samples.

Steroids. 2009 May 14; Zhang T, Liu H, Liu XT, Chen XQ, Wang QTwo new steroidal saponins, padelaosides A (1) and B (2), along with two other known steroidal saponins (3 and 4) were isolated from the rhizomes of Paris delavayi. Their structures were elucidated by 1D and 2D NMR techniques, HRFTMS, physical data and chemical methods. The two different absolute configurations of fucose, assigned as L and D, that were found on compounds 1 and 2, respectively, were simultaneously reported in a natural medicine for the first time.

J Nat Prod. 2009 May 4; Li XN, Pu JX, Du X, Yang LM, An HM, Lei C, He F, Luo X, Zheng YT, Lu Y, Xiao WL, Sun HDFourteen new lignans, tiegusanins A-N (1-14), together with 13 known compounds were isolated from the aerial parts of Schisandra propinqua var. sinensis. The structures and absolute configurations of 1-13 were established using a combination of spectroscopic techniques. Compound 14 was obtained as a racemate. When evaluated for inhibitory activity against HIV-1, tiegusanin G (7) showed anti-HIV-1 activity with an EC(50) value of 7.9 muM and a therapeutic index (TI) of more than 25.

Yao Xue Xue Bao. 2009 Mar; 44(3): 314-20Guo YS, Guo ZRDual dopamine D2/5-HT2A receptor antagonists have potent activity and are referred to atypical antipsychotics due to their lower propensity to elicit EPS and their moderate efficacy toward negative symptoms. However, an on-going challenge in developing atypical antipsychotics drugs is to maintain the favorable profiles and avoid of cardiovascular risk. In this paper, comparative pharmacophore analysis of dual dopamine D2/5-HT2A receptor antagonists, hERG K+ channel blockers, and alA adrenoceptor antagonists is carried out, and the results could give some insight into multi-target drug design.

Yao Xue Xue Bao. 2009 Mar; 44(3): 264-9Chen XG, Zhang YMalignant tumor, one of the most refractory diseases, plays a threaten role in human health, the therapy and research on malignant tumor have taken a long way to go. The anti-tumor drugs which are the essential therapy strategies upgrade with the development of new anti-tumor targets and the research on tumor pathogenesis. Aurora kinase and Pin1, the novel anti-tumor targets, maintain the important relationship with tumor. Many new compounds designed on these targets have excellent anti-tumor effects and also enter into phase I or phase II clinical trial.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(3): 282-5Li X, Yan H, Pang X, Sha N, Hua H, Wu L, Guo DOBJECTIVE: To study the chemical constituents of the flavonoids from Sophora tonkinensis. METHOD: The compounds were isolated by chromatography on silica gel, Sephadex LH-20 column and identified by spectroscopic analysis. RESULT: Eight compounds were isolated and their structures were identified as tonkinochromane I (1), glabrol (3), lupinifolin (2), tonkinensisol (4), 8-C-prenylkaempferol (5), 7,2'-dihydroxy-4'-methoxy-isoflavanol (6), formononetin (7), and genistein (8), respectively. CONCLUSION: Compound 1 was a new compound. And compound 6 was firstly isolated from the genus Sophora. Compounds 2, 3 and 5 were isolated from S. tonkinensis for the first time.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(3): 286-90Cui X, Chen H, Chen ROBJECTIVE: To isolate and identify the Diels-Alder type adducts from stem barks of Morus yunanensis. METHOD: The compounds were isolated and purified by silicagel, Sephadex LH-20 and RP-18 colum chromatography. Their chemical structures were elucidated on the basis ofphysicochemical properties and spectral data. RESULT: Nine compounds were isolated and identified as: kuwanon G (1), sanggenol M (2), mulberrofuran J (3), guangsangon B (4), resveratrol (5), kuwanon X (6), kuwanon P (7), mulberrofuran O (8), mulberrofuran Q (9). CONCLUSION: All the compounds are isolated from the plant for the first time, and compounds 4, 5 have anti-inflammation activities with inhibitory ratios of 57.3%, 50.5% respectively at a concentration of 10 microg mL(-1).

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(4): 382-5Qian D, Huang L, Cui G, Chen MOBJECTIVE: To study the genetic relationship of Astragalus membranaceus var. mongholicus in different producing area and provide theoretical basis for the evaluation of Astragalus germplasm resources. METHOD: Through quence-related amplified polymorphism (SRAP) analysis, the systematic diagram of genetic relationship was constructed by UPGMA method. RESULT: A total of 141 SRAP markers were scored. By the use of UPGMA cluster analysis with genetic distance, Astragalus could be divided into two provenance plots of Gansu and Shanxi. CONCLUSION: The genetic differentiation among populations of A. membranaceus var. mongholicus is remarkable. SRAP marker could be efficiently used for the study of the genetic relationship of Astragalus.

Yao Xue Xue Bao. 2009 Mar; 44(3): 303-8Wen H, Yang J, Zhang JJ, Wang YF, Ji CX, Yang GZBased on the pharmacophore information and the analysis of structure-activity relationship of SSRIs and SNRIs, a series of substituted aromatic heterocyclic arylamidine derivatives were designed and synthesized in order to search for lead compounds with dual activity. All of them were new compounds, and their structures were confirmed by 1H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibitory activity and some compounds exhibited NE reuptake inhibitory activity. These aromatic heterocyclic arylamidine designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(4): 379-81Liu F, Wu X, Zhang D, Luo Q, Chen S, Yin D, Zeng WOBJECTIVE: To study the biological character of Hepialus introduced from Yunnan province. METHOD: H. jianchuanensis introduced from Yunnan was bred artificially to observe its biological character. RESULT: The pupa duration was about 40 d, pupa emergence lasted for one day, female to male ratio was about 1.2:1, the mating peak was 19:30-20:30, the adults duration was about 25 d, the average life time of female was 5-6 d and that of male 6-7 d, the average number of the producing egg was about 300, the average weight of the 100 eggs was 10.33 mg. Lasting period of the larva is 350 d and the infancy larva showed the character of the polyphagy and cold endurance. CONCLUSION: Results indicate that there are some differences in the whole duration, weight of the 100 eggs and the number of the eggs left in the abdomen between H. jianchuanensis and others bred at the Kangding base.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(4): 472-5Liu T, Liang A, Yi Y, Li C, Zhao Y, Hao R, Cao COBJECTIVE: To compare the sensitivity of Brown Norway rats (BN) with Guinea pigs (GP) as allergen assessment animal models. METHOD: BN rats and GP were randomly assigned to 1 control group, 2 Bovine serum albumin group (BSA), respectively. Animals in BSA groups of BN rats and GPs were sensitized by intraperitoneal injection of 0.6% BSA 1 ml on day 1, 3, 5, respectively, and irritated by intravenous injection of 2.4% BSA 1 ml on day 7 and day 14 after the last sensitization, while the same volume of normal saline was given to control group on each time point mentioned above. The allergic reactions were scored within 1 h after each irritation treatment, and the sera of both BN rats and GPs were collected to detect IgE concentration by using ELISA. The sera were also applied for passive cutaneous anaphylaxis test (PCA test) in SD rats. RESULT: No obvious allergic reactions were observed in BSA group of GPs after each irritation treat, however, the score of allergic response in BSA group of BN rats was evidently higher than that in control group after first irritation. PCA test by using sera from BSA group of BN rats after both irritations showed the strong positive result characterized as large amount of subcutaneous effusions of Evans blue in SD rats, however, the sera from BSA group of GP were negative in PCA test. Serum IgE concentration did not increase after each irritation in BSA group of both BN rats and GP. CONCLUSION: BN rats were more sensitive than GPs on initiative systemic anaphylaxis test and passive cutaneous anaphylaxis test. Meanwhile, BN rats has an advantage in experimental treatment compared with Guinea pigs.

Yao Xue Xue Bao. 2009 Mar; 44(3): 309-13Huan Y, Shen ZFThe aim of this project is to establish a GLP-1 signaling pathway targeted cell model, for screening the new class of GLP-1 receptor agonists as anti-diabetic candidates. Firstly construct a recombined plasmid with multi-copied specific response element (RIP-CRE) regulated by GLP-1 signaling pathway and E-GFP reporter gene. Transient transfect this recombined plasmid into islet cell NIT-1, then detect the responsibility of transfected cell to GLP-1 analogue, Exendin 4. For secondly, use stable transfection and monocloning cell culture to obtain a GLP-1 signaling-specific cell line. It indicates that this cell model can response to Exendin 4, which response can be completely inhibited by GLP-1 receptor antagonist, Exendin 9-39, further showing GLP-1 receptor specific activity with a cAMP-PKA-independently mechanism. Establishment of this novel cell model can be used in high-throughput drug screening of peptides or small molecular GLP-1 analogues.

Yao Xue Xue Bao. 2009 Mar; 44(3): 276-81Guo YS, Guo ZRDrugs designed to act on individual molecular targets usually can not combat multigenic diseases such as cancer, or diseases that affect multiple tissues or cell types such as diabetes. Increasingly, it is being recognised that a balanced modulation of several targets can provide a superior therapeutic effect and side effect profile compared to the action of a selective ligand. The multi-target drugs which impact multiple targets simultaneously are better at controlling complex disease systems and are less prone to drug resistance. Here, we compare the disadvantage of the selective ligands and the predominance of multi-targets drugs in detail and introduce the approaches of designing multiple ligands and the procedure of optimization particularly. A key challenge in the design of multiple ligands is attaining a balanced activity at each target of interest while simultaneously achieving a wider selectivity and a suitable pharmacokinetic profile. On this point, the multi-target approach represents a new challenge for medicinal chemists, pharmacologists, toxicologists, and biochemists.

Yao Xue Xue Bao. 2009 Mar; 44(3): 209-18Guo ZRPhysiology-based and target-based drug discovery constitutes two principal approaches in drug innovation, which are mutually complementary and collaborative. With the target-based approach, a lot of new molecular entities have been marketed as drugs. However, many complicated diseases such as cancer, metabolic disorders, and CNS diseases can not be effectively treated or cured with one medicine acting on a single target. As simultaneous intervention of two (or multiple) targets relevant to a disease has shown improved therapeutic efficacy, the innovation of dual-target drugs has become an active field. Dual-target drug can modulate two receptors, inhibit two enzymes, act on an enzyme and a receptor, or affect an ion channel and a transporter. From viewpoint of molecular design, there are three approaches to construct a dual-target drug molecule. A connective molecule can simply be realized by combining two active molecules or their pharmacophores with a linker; while an integrated molecule comes into an entity either by fusing or by merging the common structural or pharmacophoric features of two active molecules, depending on the extent of the common features. The latter approach facilitates the reduction of molecular size and molecular weight and the optimal overlap between the pharmacodynamic and pharmacokinetic spaces, which will certainly elevate the probability of being a drug.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(3): 255-9Chen D, Peng R, Li L, Sun N, Zhong G, Cai YOBJECTIVE: To study the genetic diversity of Codonopsis tangshen. METHOD: Eighteen germplasmic resources of C. tangshen were analyzed by SRAP and ISSR molecular markers. The systematic diagram of genetic relationship was made by TREECONW software and clustered by UPGMA method. RESULT: Twenty-nine SRAP primer combination amplified 329 bands with 266 (80.85%) polymorphic and 21 ISSR primers amplified 223 bands with 166 (74.44%) polymorphic. The average genetic similarity coefficient was 0.7121 (by SRAPs) and 0.7781 (by ISSRs). Both SRAP and ISSR analyses revealed a high level of genetic diversity in C. tangshen. By cluster analysis, the geographical distribution was not distinctive. The significant positive correlation between SRAPs and ISSRs was observed (r=0.802, P

Eur J Pharmacol. 2009 May 12; Wang SB, Tian S, Yang F, Yang HG, Yang XY, Du GHThe present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(3): 312-8Liang A, Wang J, Xue B, Li C, Liu T, Zhao Y, Cao C, Yi YOBJECTIVE: To investigate hepatoxicity and nephrotoxicity of cinnabar to provide the scientific basis for safe uses in clinic. METHOD: Maximally tolerated dose of cinnabar (MTD) was tested by single oral administration. Chronic toxicity of cinnabar at different dose level (0.025, 0.05, 0.1, 0.4, 0.8 g x kg(-1) x d(-1)) corresponding to 1/2, 1, 2, 8, 16 times of clinic doses of cinnabar was investigated. The rats were treated with the cinnabar through oral administration once a day for successive 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of cinnabar and no-observed adverse effect level (NOAEL) were evaluated. RESULT: For the content of 98.1% total Hg and 21.5 microg x g(-1) absoluble Hg, MTD of cinnabar with oral administration was 24 g x kg(-1) (corresponding to 516 microg x kg(-1) absoluble Hg), equivalent to 3,000 times of clinical daily dose for an adult, and no obvious adverse effect was showed at this dose. Cinnabar can cause kidney and liver pathological changes when it is repeatedly administrated for over 30 days. The kidney was more sensitive to cinnabar than liver. Based on repeated dose toxicity study, NOAELs were 0.1, 0.05 g x kg(-1) x d(-1)) respectively for 30 day and 90 day treatment, and those were approximately accumulative intake of absoluble Hg 64.5 microg x kg(-1) and 96.76 microg x kg(-1). Thus, for safe use of cinnabar, the acceptable daily intake (ADI) of cinnabar was 0.0009-0.0017 g x kg(-1) x d(-1), namely daily dose 0.05-0.1 g for an adult with body weight about 60 kg. Considering the difference of drug sensitivity and lifecircle between human and rats, we suggest that cinnabar which contains absoluble Hg < or = 21 microg x g(-1) should be used for no longer than 2 weeks at daily dose 0.05-0.1 g. CONCLUSION: Long term use of cinnabar can cause kidney and liver pathological change, so the dose and administration duration should be limited. The suggestion is as follows: cinnabar which contains absoluble Hg < or = 21 microg x g(-1) should be used less than 2 weeks at the daily dose below 0.05-0.1 g.

Mol Cell Biochem. 2009 May 3; Sun X, Zhang XD, Cheng G, Hu YH, Wang HYHepatic stellate cells (HSCs) play an important role in the development of hepatic fibrosis. Heat shock protein 90 (Hsp90) is essential for the maturation and activity of a varied group of proteins involved in signal transduction and cell cycle regulation. In this study, we found that two Hsp90 inhibitors, VER-49009 and its analog VER-49009M, inhibited the proliferation of hepatic stellate cell line CFSC cells, and both of them induced G2 phase arrest in CFSC cells. Akt expression was decreased by the treatment of Hsp90 inhibitors in CFSC cells. Based on these findings, we propose that the inhibition of Hsp90 might be a rational approach in the prevention of liver fibrosis.

Tyrosine nitration by peroxynitrite can affect signal transduction pathways involving tyrosine phosphorylation.

The present study was undertaken to investigate the effects of peroxynitrite-induced protein tyrosine nitration on insulin-stimulated tyrosine phosphorylation in HepG2 cells. We show here that exposure of HepG2 cells to peroxynitrite led to a dose-dependent increase in tyrosine nitration of cellular proteins, mainly membrane and nuclear proteins.

Furthermore, peroxynitrite induced differential responses in tyrosine phosphorylation of membrane proteins as well as cytosolic proteins according to peroxynitrite concentrations used.

Our findings indicate at low concentrations peroxynitrite upregulates the insulin signaling and may operate as a signaling molecule, but at higher concentrations peroxynitrite downregulates the insulin signaling and may be involved in insulin resistance, suggesting peroxynitrite plays a dual role in regulation of the insulin signaling.


"Effects of peroxynitrite-induced protein tyrosine nitration on insulin-stimulated tyrosine phosphorylation in HepG2 cells."
Mol Cell Biochem. 2009 May 8; Zhou J, Li H, Zeng J, Huang K

Curr Top Med Chem. 2009; 9(4): 348-61Ye D, Wang J, Yu K, Zhou Y, Jiang H, Chen K, Liu HPotassium ion (K(+)) channels consist of a ubiquitous family of membrane proteins that play critical roles in a wide variety of physiological processes, such as the regulation of neuronal excitability, muscle contraction, cell proliferation, and insulin secretion. Due to their pivotal functions in biological systems, K(+) channels have long been attractive targets for the rational drug design on the basis of their structures and interaction mechanisms. Various small-molecular compounds and toxins have been discovered to act as K(+) channel modulators. In the present review, we will first briefly discuss current knowledge of the structures and functions of K(+) channels, and then review the recent strategies for the discovery of K(+) channel modulators, focusing especially on the virtual screening approaches and chemical synthesis technologies.

Neuroscience. 2009 May 11; Rui L, Mei G, Guifen Q, Tiantai Z, Xi L, Jian Y, Guanhua DLuteolin is an important member of the flavonoid family. It exhibits strongly anti-inflammatory, anti-oxidant and phytoestrogen-like activities. In the present study, we examined the anti-amnesic and protective effects of luteolin against Ass(25-35) -induced toxicity in mice. Mice were given an intracerebroventricular injection of aggregated Ass(25-35) peptide. The learning and memory impairments, ultrastructural changes of cerebral cortex, cerebrovascular dysfunction and neuronal changes were detected after oral administration of luteolin continuously for 8 days. Our results demonstrate that oral administration of luteolin for 8 days for those Ass(25-35) -induced amnesic mice conferred robust neurovascular protection in Ass(25-35) -induced amnesia, involving the improvement of the spatial learning and memory capabilities, the modulation of microvascular function, the increase of regional cerebral blood flow values, the clearance of ROS, the improvement of cholinergic neuronal system, and the raise of BNDF level and its receptor TrkB expression in cerebral cortex.

LRT-PCR was used to detect expression level of VP16 mRNA and IFN-gamma mRNA in Herpes simplex virus type-1 infected mice brains at 4th day, 7th day, 10th day, 14th day, 21st day post infection and investigate the effects of the Gardenia extracts-T9 on viral replication and host immunity.

The results showed that expression of VP16 mRNA in Gardenia extracts-T9 high dose and low dose group were both lower than that in virus control group at same time point. Relative VP16 mRNA expression in low dose group decreased at 21st day and relative VP16 mRNA expression in high dose group decreased continuously.

Relative expression of IFN-gamma mRNA in high dose and low dose groups were both higher than that in virus control group at all time point except the 4th day. IFN-gamma mRNA in low dose group increased from the 4th day till the 14th day, and after the 14th day, the expression decreased slightly.

Relative IFN-gamma mRNA in high dose group maintained increasing from 4th day till 21st day. Base on these results, we conclude that Gardenia extracts-T9 might exert the inhibition effect of viral replication by upregulating expression of IFN-gamma mRNA.

"Effect of the gardenia extracts-T9 on viral replication and IFN-gamma mRNA in Herpes simplex virus type-1 infected mice brains"
Bing Du Xue Bao. 2009 Jan; 25(1): 41-6Shi YJ, Huang Y, Jiang J, Guo SS, Su D, Zhao Y, Gao YJ, Cui X

Biomed Chromatogr. 2009 May 14; Cui L, Wen J, Zhou T, Wang S, Fan GAn ion-pair reverse-phase high performance liquid chromatographic method with UV-vis detection has been developed for the determination of total free iodine in rabbit plasma after vaginal administration of povidone-iodine (PVP-I). Sample preparation was done by protein precipitation with acetonitrile in 96-well format and aspirin was used as the internal standard. The 100 microL sodium thiosulfate solution (5 g L(-1)) was added to 100 microL plasma sample before protein precipitation, to convert the total free iodine in plasma to iodide (I(-)). Separation was performed on a C(18) column (200 x 4.6 mm i.d., 5 microm). The mobile phase consisting of a mixture of water phase (containing 10 mmol L(-1) 18-crown-6 ether, 5 mmol L(-1) octylamine and 5 mmol L(-1) sodium dihydrogen phosphate, pH adjusted to 6.0 with phosphoric acid) and acetonitrile in the ratio 70:30 (v/v) was delivered isocraticly at a flow rate of 1.0 mL min(-1). The method was sensitive with a lower limit of quantification of 0.005 microg mL(-1), with good linearity (r(2) > 0.9990) over the linear range of 0.005-2 microg mL(-1). All the validation data, such as linearity, accuracy and precision, were within the required limits. The method was successfully applied to study the pharmacokinetic of PVP-I in rabbits after vaginal administration. Copyright (c) 2009 John Wiley & Sons, Ltd.

J Ethnopharmacol. 2009 Mar 25; Zhang L, Hu JJ, Lin JW, Fang WS, Du GHAIM OF THE STUDY: This study evaluates the anti-inflammatory and analgesic activities of the ethanol and aqueous extracts of a Tibetan herb Pterocephalus hookeri (C.B. Clarke) Höeck to provide experimental evidence for its traditional use such as cold, flu and rheumatoid arthritis. MATERIALS AND METHODS: Investigations on the analgesic effects of P. hookeri (C.B. Clarke) Höeck were carried out, including hot-plate test and acetic acid-induced writhing. The anti-inflammatory activities were observed by utilizing the following models: carrageenin-induced edema of the hind paw of rats, cotton pellet-induced granuloma formation in rats, acetic acid-induced permeability, and xylene-induced ear edema in mice. The effects of the administration of indomethacin were also studied. RESULTS: It has been shown that the ethanol and aqueous extracts significantly increased the hot-plate pain threshold and reduced acetic acid-induced writhing response in mice. The ethanol and aqueous extracts remarkably inhibited the increase in vascular permeability induced by acetic acid and ear edema induced by xylene. The ethanol extract also significantly decreased the carrageenin-induced rat paw edema perimeter and inhibited the increase of granuloma weight. CONCLUSION: The results show that the ethanol and aqueous extracts have both central and peripheral analgesic activities and as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.

Fitoterapia. 2009 May 7; Bao L, Yao X, Xu J, Guo X, Liu H, Kurihara HThe ethanol extract of Pithecellobium clypearia Benth (PCE) was characterized to be rich in polyphenols by HPLC analysis, and investigated for its anti-inflammatory and anti-allergic activities. In our assay, PCE showed anti-inflammatory activity in both acute and auto-immune inflammation animal models. Administration of PCE can effectively inhibit the croton oil-induced ear edema and capillary permeability, the carrageenin-induced paw edema, and the liver injury caused by propionibacterium acnes plus lipopolysaccharide. PCE was also found to possess anti-allergic activity in inhibiting the DNFB-induced delayed hypersensitivity reaction. Meanwhile, seven main components (1-7) from PCE were studied for their effect on histamine release stimulated by compound 48/80 from rat peritoneal mast cells in vitro. Compound 2 ((-)-epigallocatechin-7-gallate), 3 ((-)-5, 7, 3', 4', 5'-pentahydroxyflavan), and 5 ((-)-tetra hydroxyflavan-7-gallate) showed significant inhibition effect on histamine release.

Phytomedicine. 2009 May 6; Sun M, Zhang JJ, Shan JZ, Zhang H, Jin CY, Xu S, Wang YLDanhong Injection (DHI), a Chinese Materia Medica standardized product extracted from Radix Salviae Miltiorrhizae and Flos Carthami tinctorii, has the actions of promoting blood circulation and resolving stasis to promote regeneration. The clinical therapeutic effects of DHI on traumatic intracranial hematoma (TICH) were observed. Eighty patients with TICH were randomly assigned to trial group and a control group (40 patients per group), and all were administered with routine medication. Additionally, DIH was administered intravenously to patients in the trial group. Pre and post-treatment GCS was observed in the two groups, along with GOS after therapy. The intracranial hematoma absorption, hemorheological changes, and changes in coagulation indexes pre- and post-treatment were evaluated. The results indicated that GCS and GOS after therapy for the trial group were superior to those for the control group (p

Environ Toxicol. 2009 May 12; Ji L, Liu T, Wang ZPyrrolizidine alkaloids (PAs) are well-known natural hepatotoxins. In this study, we investigated the protection of epidermal growth factor (EGF) against the hepatotoxicity of clivorine, which is an otonecine-type PA from traditional Chinese medicine Ligularia hodgsonii Hook. Cell viability assay and cell morphology observation showed that EGF (1 ng/mL) reversed clivorine-induced cytotoxicity on human normal liver L-02 cells. EGF (1 ng/mL) also inhibited clivorine-induced DNA fragmentation and caspase-3 cleavage. Our previous study has showed that antiapoptotic Bcl-xL degradation and mitochondrial-mediated apoptosis was involved in clivorine-induced hepatotoxicity. In this study, we found that EGF (1 ng/mL) inhibited clivorine-induced antiapoptotic Bcl-xL protein decrease, caspase-9 activation, and release of cytosolic cytochrome C. We further investigated the effects of vascular epidermal growth factor, basic fibroblast growth factor, and insulin-like growth factor-1 on clivorine-induced cytotoxicity, and there is no significant protection observed. Our results suggest that EGF exerts its protective effects against clivorine-induced hepatotoxicity probably by modulating mitochondrial-mediated apoptotic signal pathway. (c) 2009 Wiley Periodicals, Inc. Environ Toxicol, 2009.

Food Chem Toxicol. 2009 May 4; Ma C, Yue QX, Guan SH, Wu WY, Yang M, Jiang BH, Liu X, Guo DACyclophosphamide (Cy) could induce immuno-suppression such as thymus atrophy and inhibition of lymphocyte proliferation response in mice. But;the mechanism of its effect is still not clear. Polysaccharides isolated from spore of Garnoderma lucidum (GL-SP) could;at least partly;restore the immunological effects against Cy-induced immuno-suppression. In the present study;a two-dimensional gel electrophoresis (2-DE)-based comparative proteomic method was conducted to identify the possible target-related proteins of Cy in mice thymus including those could be influenced by GL-SP. Fifteen proteins differentially expressed in Cy-treated mice compared with control were identified. Among the fifteen proteins;combined use of GL-SP with Cy could not affect Cy-induced expression change of three proteins;totally prevented Cy-induced expression change of six proteins;partly prevented Cy-induced expression change of four proteins and further enhanced Cy-induced expression change of two proteins. Results of the present study shed light on the mechanism of Cy-induced immuno-suppression as well as the protective effect of GL-SP against toxicity of Cy.

Mol Pharm. 2008 Nov-Dec; 5(6): 1044-54Gao Y, Chen L, Gu W, Xi Y, Lin L, Li YDocetaxel is one of the most promising chemotherapeutic agents for the treatment of metastatic breast cancer, but it shows fearful side effects. We hypothesized that a novel targeted nanoassembly (TNA) could provide efficient intracellular drug delivery in breast tumor cells overexpressing epidermal growth factor (EGF) receptor and thus improve the efficacy and reduce the side effects of docetaxel. We prepared the novel docetaxel loaded TNAs formed by polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) and modified with EGF. Compared with nontargeted nanoassemblies (NNAs), TNAs showed obvious improvement of cell-specific uptake and internalization, and revealed more cytotoxicity against MDA-MB-468 cells by inducing more late apoptosis and subG1 cells at low drug concentration, or more G2/M arrest at high drug concentration than NNAs or Taxotere. In BALB/c mice bearing breast tumor xenografts, TNAs showed stronger inhibition of tumor growth compared with NNAs (relative tumor volume in mice treated with 5 mg/kg TNAs = 0.99 and 10 mg/kg NNAs = 1.71, p < 0.05) or Taxotere (relative tumor volume in mice treated with 5 mg/kg TNAs = 0.99 and 10 mg/kg Taxotere = 4.20, p < 0.01). In particular, tumor disappeared completely in the TNA group at a dose of 10 mg/kg. The maximum tolerated dose (MTD) of TNAs was about four times higher than that of Taxotere. TNAs also demonstrated a much longer circulation time in vivo and more drug accumulation in tumor in a murine breast cancer model than Taxotere. TNA treatment also prolonged survival of mice. These results suggested that TNAs could have more potential as a delivery system for breast cancer chemotherapy.

J Cell Biol. 2009 May 11; Shen S, Zhang P, Lovchik MA, Li Y, Tang L, Chen Z, Zeng R, Ma D, Yuan J, Yu QPromoting the degradation of Hsp90 client proteins by inhibiting Hsp90, an important protein chaperone, has been shown to be a promising new anticancer strategy. In this study, we show that an oxazoline analogue of apratoxin A (oz-apraA), a cyclodepsipeptide isolated from a marine cyanobacterium, promotes the degradation of Hsp90 clients through chaperone-mediated autophagy (CMA). We identify a KFERQ-like motif as a conserved pentapeptide sequence in the kinase domain of epidermal growth factor receptor (EGFR) necessary for recognition as a CMA substrate. Mutation of this motif prevents EGFR degradation by CMA and promotes the degradation of EGFR through the proteasomal pathway in oz-apraA-treated cells. Oz-apraA binds to Hsc70/Hsp70. We propose that apratoxin A inhibits Hsp90 function by stabilizing the interaction of Hsp90 client proteins with Hsc70/Hsp70 and thus prevents their interactions with Hsp90. Our study provides the first examples for the ability of CMA to mediate degradation of membrane receptors and cross talks of CMA and proteasomal degradation mechanisms.

Toxicol Lett. 2009 Apr 25; 186(2): 111-4Li Y, Qi XM, Xue X, Wu XF, Wu YF, Chen M, Xing GZ, Luan Y, Ren JOBJECTIVE: Many nonsteroidal anti-inflammatory drugs (NSAIDs) with diphenylamine structure induce severe hepatotoxicities. We evaluated the role of diphenylamine structure in liver injuries induced by these NSAIDs. METHODS: Effects of diphenylamine, diclofenac and tolfenamic acid on mitochondrial permeability transition (MPT) and efflux of calcium in isolated liver mitochondria as well as on cellular ATP content and mitochondrial membrane depolarization in rat primary hepatocyte cultures were examined. RESULTS: Diclofenac and tolfenamic acid induced cyclosporine A (CsA)-sensitive mitochondrial swelling and membrane depolarization in isolated liver mitochondria. Only diclofenac caused the release of calcium in isolated liver mitochondria. Diphenylamine had no effects on isolated liver mitochondria. All three compounds decreased ATP content and induced mitochondrial membrane depolarization. CsA attenuated these effects, suggesting MPT might be involved in the hepatotoxicities caused by diphenylamine, diclofenac and tolfenamic acid. SKF-525A, a general inhibitor of CYP450, markedly inhibited the injury induced by diphenylamine, but not diclofenac or tolfenamic acid. CONCLUSION: The hepatotoxicities caused by diclofenac and tolfenamic acid may be attributed to the mitochondrial dysfunction induced by these drugs instead of the diphenylamine structure per se.

Acta Pharmacol Sin. 2009 May; 30(5): 522-9Fang F, Liu GTAIM: The aim of the present study was to assess the effects of N-[2-(4-hydroxyphenyl)ethyl]-2-(2,5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl) acrylamide (compound FLZ), a novel synthetic analogue of squamosamide, on the dysfunction of rat brain mitochondria induced by Abeta(25-35) in vitro. METHODS: Isolated rat brain mitochondria were incubated with aged Abeta(25-35) for 30 min in the presence and absence of FLZ (1-100 micromol/L). The activities of key mitochondrial enzymes, the production of hydrogen peroxide (H(2)O(2)) and superoxide anion (O2*-), and the levels of glutathione (GSH) in mitochondria were examined. Mitochondrial swelling and the release of cytochrome c from mitochondria were assessed by biochemical and Western blot methods, respectively. RESULTS: Incubation of mitochondria with aged Abeta(25-35) inhibited the activities of alpha-ketoglutarate dehydrogenase (alpha-KGDH), pyruvate dehydrogenase (PDH) and respiratory chain complex IV. It also resulted in increased H(2)O(2) and (O2*-) production, and decreased the GSH level in mitochondria. Furthermore, it induced mitochondrial swelling and cytochrome c release from the mitochondria. The addition of FLZ (100 micromol/L) prior to treatment with Abeta(25-35) significantly prevented these toxic effects of Abeta(25-35) on the mitochondria. CONCLUSION: FLZ has a protective effect against Abeta(25-35)-induced mitochondrial dysfunction in vitro.

Planta Med. 2009 May 8; Jiang B, Wu W, Li M, Xu L, Sun K, Yang M, Guan S, Liu X, Guo DAAcute myocardial infarction (AMI) remains the leading cause of mortality in the world. Early intervention using salvianolic acids (SA) can substantially improve clinical outcomes. However, in spite of the great achievements that have been made in elucidating the protective effects of SA on AMI, the effects of SA on the contractile performance of the left ventricle (LV) and the underlying mechanism are still not so clear. In the present study, AMI was introduced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Administration of SA significantly decreased infarct size, improved LV function and appearance of the myocardium and decreased myocardial malondialdehyde levels compared with the AMI group. Furthermore, treatment with SA significantly downregulated the mRNA expression level and activity of matrix metalloproteinase-9 (MMP-9), but did not regulate the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression level at the infarct area. Lisinopril (an angiotensin converting enzyme inhibitor), which holds potential effects on cardioprotection, was chosen as the positive control in this study. Lisinopril elevated LV function and appearance of the myocardium, decreased malondialdehyde levels without an influence on infarct size, and regulated the MMP-9 enzyme level but not the MMP-9 mRNA and TIMP-1 protein levels. These findings suggest that early SA treatment is effective to improve LV function; and SA may exert preventative effects against myocardial remodeling after infarction.

Toxicology. 2009 May 6; Yu HY, Wang BL, Zhao J, Yao XM, Gu Y, Li YPeroxisome proliferators-activated receptor alpha (PPARalpha) and oxidative stress are two important pathological factors in non-alcoholic fatty liver disease (NAFLD). Tetracycline-induced fatty liver was partly due to the disturbance of mitochondrial fatty acids beta-oxidation regulated by PPARalpha. Bicyclol was found to protect against high fat diet-induced fatty liver through modulating PPARalpha and clearing reactive oxygen species (ROS). The present study was performed to further investigate the effect of bicyclol on tetracycline-induced fatty liver and related mechanism in mice. Bicyclol (75, 150, 300mg/kg) was given orally three times in two consecutive days. Tetracycline (200mg/kg) was injected intraperitoneally 1h after the last administration of bicyclol. Oxidative stress, mitochondrial function, PPARalpha and its target genes were evaluated by biochemical and RT-PCR analysis. The activity of CYP4A was assessed by liquid chromatography/mass spectrometry (LC/MS) method. Bicyclol significantly protected against tetracycline-induced fatty liver by reducing the accumulation of hepatic lipids and elevation of serum aminotransferase. In addition, bicyclol remarkably alleviated the over-production of thiobarbituric acid-reactive substance. The reduced activity of mitochondrial respiratory chain (MRC) complex I&IV and mitochondrial permeability transition (MPT) were also improved by bicyclol. Furthermore, bicyclol inhibited the decrease of PPARalpha expression and its target genes, including long-chain acyl CoA dehydrogenase (LCAD), acetyl CoA oxidase (AOX) and CYP4A at mRNA and enzyme activity level. Bicyclol protected against tetracycline-induced fatty liver mainly through modulating the disturbance of PPARalpha pathway and ameliorating mitochondrial function.

Phytomedicine. 2009 May 7; Sun JY, Yang H, Miao S, Li JP, Wang SW, Zhu MZ, Xie YH, Wang JB, Liu Z, Yang QSwainsonine, an extract from Astragalus membranaceus, is known for its anti-cancer effects and could prevent metastases. In order to investigate the effects and mechanisms of swainsonine in C6 glioma cells, we carry out correlated experiments in vitro and in vivo. After treatment with swainsonine, the effective dose and IC(50) value of swainsonine in the C6 glioma cell were examined using the MTT assay. Cell cycle distribution and apoptotic rates were analyzed using FCM and [Ca(2+)](i) was measured by LSCM. Expressions of p16 and p53 protein were evaluated by immunocytochemical methods. Simultaneously, glioma-bearing rats were administered swainsonine at doses of 2, 4 and 8mg/kg body wt. The inhibition rate was calculated and pathological sections were observed. The results indicated that the growth of C6 glioma cells is inhibited by swainsonine in vitro, with an IC(50) value within 24h of 0.05mug/ml. Increases in swainsonine correlate with S phase percentages of 11.3%, 11.6% and 12.4%, respectively. Moreover, the expression of apoptosis inhibiting p53 and p16 protein decreases gradually. Tumor weight in vivo decreased clearly and HE dyeing of tumor tissue showed gray, its texture was soft, with necrosis and hemorrhagic concentrated inward. Swainsonine could inhibit the proliferation of C6 glioma cells in vitro and the growth of C6 glioma in vivo. The mechanisms of swainsonine-induced apoptosis may relate with the expression of apoptosis-related genes and overloading-[Ca(2+)](i)-induced endoplasmic reticulum stress.

J Appl Microbiol. 2009 Apr 22; Kong WJ, Zhao YL, Xiao XH, Li ZL, Jin C, Li HBAbstract Aims: This study investigated the anti-fungal activity of coptisine on Candida albicans growth. Methods and Results: The metabolic power-time curves of Candida albicans growth at 37 degrees C affected by coptisine were measured by microcalorimetry using an LKB-2277 Bioactivity Monitor with stop-flow mode. Then, the diameter of inhibitory zones in the agar layer was observed using agar cup method, and the minimal inhibitory concentration (MIC) of coptisine on Candida albicans growth was determined by serial dilution method. From the principal component analysis on nine quantitative parameters obtained from the power-time curves, we could easily evaluate the anti-fungal activity of coptisine by analysing the change of values of the main two parameters, growth rate constant k and maximum power output in the log phase P(m, log). The results showed that coptisine had strong anti-fungal activity: at a low concentration (45 mug ml(-1)) began to inhibit the growth of Candida albicans and at a high concentration (500 mug ml(-1)) completely inhibited Candida albicans growth. Coptisine gave big inhibitory zones with diameters between 11 and 43 mm within test range, and the MIC of it was 1000 mug ml(-1). Conclusions: Coptisine had strong anti-fungal activity on Candida albicans growth. The method of microcalorimetry applied for the assay of anti-fungal activity of coptisine was quantitative, sensitive and simple. Significance and Impact of the Study: This work will provide useful information for the development of chemical biology policy in the use of anti-microbials in food and drug production.

Homeopathy. 2008 Oct; 97(4): 167-8Fisher P

Homeopathy. 2008 Oct; 97(4): 220-2Land ST

Homeopathy. 2009 Apr; 98(2): 127-8; author reply 129Wilson P

Homeopathy. 2009 Apr; 98(2): 130-1; author reply 132Thomas DM

J Asian Nat Prod Res. 2009; 11(3): 274-80Jiao XZ, Wang LP, Xiao Q, Xie P, Liang XTA new approach for the synthesis of the (+)-conagenin has been achieved based on Evans asymmetry syn-aldol reaction and the self-regeneration of stereocenters strategy.

J Nat Prod. 2009 Apr 29; Wang HB, Gu WF, Chu WJ, Zhang S, Tang XC, Qin GWFour new "cage-like" monoterpene glucosides (1-4) were isolated from Paeonia lactiflora. The structures of these compounds were established by spectroscopic methods, mainly 1D and 2D NMR, and mass spectrometric analysis. Compound 4 exhibited moderate cell-protective activity against hydrogen peroxide-induced PC12 cell damage.

J Asian Nat Prod Res. 2009; 11(3): 281-7Xue P, Wang LP, Jiao XZ, Jiang YJ, Xiao Q, Luo ZG, Xie P, Liang XT( - )-Talaumidin (1) and ( - )-galbelgin (2) have been synthesized via 4-pentenoic acid as a starting material with the overall yield of about 17.8 and 16.9%, respectively. The key steps include Evans asymmetry anti-aldol reaction, TBS protection, hydroboration, oxidation, Friedel-Crafts arylation, etc.

Bioorg Med Chem Lett. 2009 Mar 28; Duan H, Zheng J, Lai Q, Liu Z, Tian G, Wang Z, Li J, Shen JIn our efforts to minimize the side effects associated with low selectivity against the other PDE isozymes, a novel class of 2-phenylquinazolin-4(3H)-one derivatives were designed and prepared as potent PDE5 inhibitors with high selectivity against PDE6. The syntheses and SAR studies of such molecules were reported.

Magn Reson Chem. 2009 Apr 28; Feng J, Zhao WFour new oligosaccharides (1-4), one new pregnane glycoside (5), and one new cardiac glycoside (6) were isolated from the roots of Periploca forrestii Schltr. (Asclepiadaceae), a traditional Chinese medicine used for the treatment of rheumatoid arthritis and wounds. Their structures were characterized on the basis of extensive analysis of NMR ((1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, HMBC, TOCSY and ROESY) spectra. Copyright (c) 2009 John Wiley & Sons, Ltd.

Homeopathy. 2008 Oct; 97(4): 178-84Steinsbekk A, Nilsen TV, Rise MBOBJECTIVES: To study the characteristics of people visiting homeopaths in a total adult population in Norway. METHODS: Data from a total population cross sectional health survey conducted in 1995-1997 in Central Norway (HUNT 2) with 65,495 participants. Variables included in the analysis were age, marital status, education, being a social welfare recipient, lifestyle (daily smoker), Hospital Anxiety and Depression Scale (HADS-T), global health perception, self-reported health complaints and a variety of diseases. Significance level p

J Asian Nat Prod Res. 2009; 11(3): 243-9Yuan T, Yang SP, Zhang HY, Liao SG, Wang W, Wu Y, Tang XC, Yue JMTwo new depsidones, livistones A (1) and B (2), and a new benzofurane, livistone C (3), together with the 11 known compounds including three stilbenes (4-6), four steroids, three flavan-3-ols, and an alkaloid were isolated from the fruits of Livistona chinensis. The structures of the new compounds were determined by spectroscopic methods. Compounds 1, 4-6 exhibited remarkable cell protective activities against H(2)O(2)-induced SH-SY5Y cell damage.

The review of the literature and some media data referring to chosen methods of unconventional treatment, its history of the development in Poland and around the world has been made in this paper (homeopathy, waxing of ears, bio-energy therapy) and the increasing interest among the treated patients has been shown.

It is essential that the doctors (including laryngologists) while carrying out the interview should take the unconventional way of treatment of patients into consideration.

This may explain the registering of patients to appropriate treatment in the advanced state of illness, which is particularly unprofitable in cancer-afflicted states.


"Selected issues regarding implementing alternative medicine with special reference to the patients with laryngological problems"
Pol Merkur Lekarski. 2009 Mar; 26(153): 239-44Glińska A, Sieczka J, Tarnowska C, Maj P

Forsch Komplementmed. 2009 Apr; 16(2): 105-10Möllinger H, Schneider R, Walach HIntroduction: Homeopathy uses information gathered from healthy volunteers taking homeopathic substances (pathogenetic trials) for clinical treatment. It is controversial whether such studies produce symptoms different from those produced by placebo. Objective: To test whether homeopathic preparations produce different symptoms than placebo in healthy volunteers. Methods: Three armed, double-blind, placebo controlled randomised experimental pathogenetic study in 25 healthy volunteers who took either one of two homeopathic remedies, Natrum muriaticum and Arsenicum album in 30CH or identical placebo. Main outcome parameter was the number of remedy-specific symptoms per group. Results: On average, 6 symptoms typical for Arsenicum album were experienced by participants taking arsenicum album, 5 symptoms typical for Natrum muriaticum by those taking natrum muriaticum, and 11 non-specific symptoms by those in the placebo group. Differences were significant overall (Kruskall Wallis test, p = 0.0002,) and significantly different from placebo (Mann-Whitney test, p = 0.001). Conclusion: Homeopathic remedies produce different symptoms than placebo.

J Altern Complement Med. 2009 May 7; Shaikh SH, Malik F, James H, Abdul HAbstract Objectives: The objective of this study was to evaluate the extent of use of complementary and alternative systems of medicine by different segments of society and to identify the diseases in which they have been found to be effective. Methods: This was a questionnaire-based descriptive study carried out from April 2002 to March 2004, in selected urban and rural areas of four provinces of Pakistan representing general strata of population from various socioeconomic conditions. Results: The overall trend in Pakistan shows that 51.7% (CI 54.3-49.1) chose complementary and alternative medicine (CAM) while 48.3% (CI 50.71-48.89) chose biomedicine. Of those who chose CAM, 20% (CI 21-19) also used biomedicine as well; 16% (CI 16.8-15.2) homeopathy, 12.4% (CI 13.02-11.78) unani medicine, 2.1% (CI 2.20-1.99) mind-body medicine (faith healing), 0.9% biologically based practices (home remedies, diet and nutrition) 0.05% energy medicine (Reiki), 0.05% Traditional Chinese Medicine, and 0.02% aromatherapy. Conclusions: About half of the studied population used CAM. The population estimates of use of CAM are within the range reported elsewhere. It reflects an increasing popularity of CAM in Pakistan as well. Combined use of biomedicine with CAM was common and often patients did not reveal the use of CAM to the biomedicine practitioners.

J Altern Complement Med. 2009 May 7; Lachance LL, Hawthorne V, Brien S, Hyland ME, Lewith GT, Verhoef MJ, Warber S, Zick SAbstract Assessing complementary and alternative medicine (CAM) use remains difficult due to many problems, not the least of which is defining therapies and modalities that should be considered as CAM. Members of the International Society for Complementary Medicine Research (ISCMR) participated in a Delphi process to identify a core listing of common CAM therapies presently in use in Western countries. Lists of practitioner-based and self-administered CAM were constructed based on previous population-based surveys and ranked by ISCMR researchers by perceived level of importance. A total of 64 (49%) ISCMR members responded to the first round of the Delphi process, and 39 of these (61%) responded during the second round. There was agreement across all geographic regions (United States, United Kingdom, Canada, and Western Europe) for the inclusion of herbal medicine, acupuncture, homeopathy, Traditional Chinese Medicine (TCM), chiropractic, naturopathy, osteopathy, Ayurvedic medicine, and massage therapy in the core practitioner-based CAM list, and for homeopathy products, herbal supplements, TCM products, naturopathic products, and nutritional products in the self-administered list. This Delphi process, along with the existing literature, has demonstrated that (1) separate lists are required to measure practitioner-based and self-administered CAM; (2) timeframes should include both ever use and recent use; (3) researchers should measure and report prevalence estimates for each individual therapy so that direct comparisons can be made across studies, time, and populations; (4) the list of CAM therapies should include a core list and additionally those therapies appropriate to the geographic region, population, and the specific research questions addressed, and (5) intended populations and samples studied should be defined by the researcher so that the generalizability of findings can be assessed. Ultimately, it is important to find out what CAM modality people are using and if they are being helped by these interventions.

Forsch Komplementmed. 2009 Apr; 16(2): 111-6Münstedt K, Schroter C, Brüggmann D, Tinneberg HR, von Georgi RBACKGROUND: This nationwide study aimed to assess the use of complementary and alternative medicine (CAM) methods in German departments of obstetrics. METHODS: All German departments of obstetrics were identified and were sent a questionnaire designed to assess which CAM methods, if any, they used during childbirth, how frequently, and why. SPSS software was used for statistical analyses (Spearman's bivariate correlation, cross-tabulation, and Pearson's chi-square test). RESULTS: The questionnaires were returned by 40.3% (381/946) of the identified departments. The most commonly used CAM therapy was acupuncture (available in 97.3% (366/376) of departments) followed by homeopathy (offered in 93.4%) and aromatherapy (available in 76.6%). Most decisions regarding CAM use were made by midwives; only decisions on acupuncture were taken by obstetricians and midwives. Reasons given for using CAM were patient demand and perceived efficacy of CAM, particularly by midwives. Obstetricians were only partly convinced of the efficacy of CAM methods and their conviction varied with the type of unit they worked in. CONCLUSIONS: CAM methods are widely used in German departments of obstetrics despite lacking evidence of effectiveness. Efficacy, side effects and consequences of CAM use should be assessed using the mandatory German quality assurance measures and birth surveys. CAM use elsewhere also merits further study.

Zhongguo Zhong Yao Za Zhi. 2009 Jan; 34(1): 14-7Wang X, Cui G, Gao W, Huang LThis paper introduced a new method of "ingredient difference phonetypical cloning" for functional gene clone of medicinal plants, which might solve the difficulties in isolating genes encoding enzymes for the biosynthesis of secondary metabolites by usual ways. Concepts, mechanisms and methods were systematically introduced and possibility was proved by experiments. The method showed the extra superiority of for the isolation of the genes belonged to unknown metabolic pathway and little information about its sequences. The method provides a new way to isolate functional gene cloning from Chinese herbs and a fundament for the further study on medicinal plant genetic engineering.

Homeopathy. 2008 Oct; 97(4): 206-13Teixeira MZ, Leal SM, Ceschin VMHomeopathy has been used for more than two hundred years to treat chronic disease using various approaches in a wide range of diseases. However, for acute disease and critical illness, application has been limited by inadequate training of homeopathic physicians and the small number of pertinent clinical studies. In view of the difficulty of practising homeopathy in Intensive Care Units (ICU), a protocol was developed to facilitate description of objective homeopathic symptoms with a ranking of symptoms appropriate for these situations (Protocol for Objective Homeopathic Semiology). Examples of favorable results with individualized homeopathic treatments for a series of cases of Systemic Inflammatory Response Syndrome (sepsis) are described.

Homeopathy. 2008 Oct; 97(4): 190-5Valentim-Zabott M, Vargas L, Ribeiro RP, Piau R, Torres MB, Rönnau M, Souza JCThis study aimed to evaluate the effects of the homeopathic complex Homeopatila RS (REAL Homeopathy, Brazil), in the performance, sexual proportion and gills and liver histology of the Nile tilapia fish (Oreochromis niloticus L.). 4,800 post-larvae were treated for 45 days, in 12 tanks (500 L), in a closed environment, with density of 400 larvae per tank. Three treatments were given: alcohol 30%, negative control (C); hormonal, positive control, 17 alpha-methyltestosterone (H); homeopathic, Homeopatila RS, in ethanol (HH), with four replications. Mean values for length, weight, liver somatic index, condition factor, survival rate, average values of histological alterations and sexual proportion were determined. Analysis revealed significant differences (p

High performance liquid chromatography coupled with on-line electrospray tandem mass spectrometry (HPLC/ESI-MS/MS) was used to identify C21 steroidal glycosides in the roots of Cynanchum atratum.

The structures of C21 steroidal glycosides were deduced from mass fragments features in positive and negative mode. The constituents of C. atratum were separated and detected. 7 compounds were identified by comparing their ESI-MS/MS data with the reference compounds and 2 compounds were inferred solely by the ESI-MS/MS data.

The method is sensitive, and provides good separation and rapid qualitative characterization of C21 steroidal glycosides in the roots of C. atratum


"Study on C21 steroidal glycosides of Cynanchum atratum by LC-MS"
Zhongguo Zhong Yao Za Zhi. 2009 Jan; 34(2): 186-8Zhao X, Bai H, Liu Y, Li W, Wang Y, Liu A, Koike K

Homeopathy. 2008 Oct; 97(4): 185-9Pinto S, Rao AV, Rao AOBJECTIVE: This study attempts to evaluate the status of oxidative stress in osteoarthritis (OA), by measuring some parameters of oxidant stress and antioxidant defenses in blood, before and after homeopathy treatment, and to asses the role, if any, of homeopathic treatment in modulating free radical toxicity in OA. METHODS: Erythrocyte lipid peroxidation (LP), erythrocyte antioxidants viz., glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CT) and plasma antioxidants viz., ceruloplasmin, glutathione-S-transferase (GST), vitamin C, total antioxidant activity (AOA) were determined in eighty one patients with OA and fifty three normals. Forty seven patients, who were treated with homeopathic remedies were considered for the follow-up studies. LOCATION: Father Muller Homeopathic Hospital, Mangalore, South Karnataka, India. RESULTS: Erythrocyte LP (0 hour, p

Homeopathy. 2008 Oct; 97(4): 169-77Rutten AL, Stolper CFBACKGROUND: There is a discrepancy between the outcome of a meta-analysis published in 1997 of 89 trials of homeopathy by Linde et al and an analysis of 110 trials by Shang et al published in 2005, these reached opposite conclusions. Important data were not mentioned in Shang et al's paper, but only provided subsequently. QUESTIONS: What was the outcome of Shang et al's predefined hypotheses? Were the homeopathic and conventional trials comparable? Was subgroup selection justified? The possible role of ineffective treatments. Was the conclusion about effect justified? Were essential data missing in the original article? METHODS: Analysis of post-publication data. Re-extraction and analysis of 21 higher quality trials selected by Shang et al with sensitivity analysis for the influence of single indications. Analysis of comparability. Sensitivity analysis of influence of subjective choices, like quality of single indications and of cut-off values for 'larger samples'. RESULTS: The quality of trials of homeopathy was better than of conventional trials. Regarding smaller trials, homeopathy accounted for 14 out of 83 and conventional medicine 2 out of 78 good quality trials with n

Homeopathy. 2008 Oct; 97(4): 196-201Botha I, Ross AHBACKGROUND: Trituration of base substances, commonly to the 3cH level, is the cornerstone of the homeopathic pharmaceutical process or insoluble solutions. Becker and Ehrler claim that trituration to 4cH gives a new, spiritual dimension to the homoeopathic medicine picture. AIM AND METHOD: This study sought to establish whether the claim that C4-derived potencies possess different physicochemical qualities to the homoeopathic medicines derived from a 3cH trituration is valid. All potencies were produced by hand according to the German Homoeopathic Pharmacopoeia (GHP). Five different samples were analysed using Nuclear Magnetic Resonance (NMR) Spectroscopy. RESULTS: The results indicated a significant difference between the 12cH samples of potassium dichromate (Kalium bichromicum) produced from 3cH and 4cH triturations. This was especially prominent in the chemical shift values of all four peaks and the relative integration levels of the H(2)O, OH and CH(3) peaks when comparing two sample groups. CONCLUSION: Trituration plays a part in the development of physicochemical properties specific to homoeopathic medicines. The higher the level of trituration, the more pronounced is the alteration of the physical structure of the active ingredient. The study concludes that 4cH potencies are physicochemically distinct from 3cH-derived potencies (as currently employed).

Homeopathy. 2009 Apr; 98(2): 107-13Thompson TD, Thompson EAUK medical students spend 25% of their curricular time on elective "Student Selected Components" (SSCs). We report one in homeopathic medicine run jointly by the University of Bristol and the Bristol Homeopathic Hospital. The SSC was an intensive four week course using a variety of learning methods, grounded in the Faculty of Homeopathy's Primary Health Care Examination (PHCE) Certificate syllabus. Students were exposed to specialist clinics and the prescribing methods used in them. They received tuition from a veterinarian, a psychiatrist, a medical historian, a professional homeopath and an expert in the evidence base of complementary medicine. Educational methods included interactive lectures, out-patient clinics, recorded video cases, live cases via video link, a "dream proving" and a reflective diary. At the end of the course students sat and passed the Faculty's PHC examination. Assessment also included an in-depth case report in which most students revealed understanding of the course. Though students were uncertain about the nature of the healing stimulus, many were affected by the healing responses they witnessed and the intellectual challenge of remedy selection. Some professed interest in further training and all wished to see the Bristol Homeopathic Hospital (BHH) develop as a centre for holistic care. For some the experience was "transformative learning". We conclude that this approach to a foundation training in homeopathy is feasible and effective.

Homeopathy. 2009 Apr; 98(2): 114-21Teixeira MZBACKGROUND: Samuel Hahnemann noticed that palliative treatments for the symptoms of chronic diseases, after an initial improvement, provoked symptoms similar but stronger symptoms to those initially suppressed. He regarded this as a consequence of the vital reaction of the organism: an automatic and instinctive capacity to return to the initial health condition altered by medicines. Using this homeostatic conception of the organism as a treatment rationale, Hahnemann proposed the therapy of similarity, administering to the patients medicines capable of causing, in healthy individuals, similar symptoms to the natural disease. Based on experimental observations, he proposed that the primary action of the drug was followed by the secondary and opposite action of the organism, inaugurating homeopathic pharmacology, and alerting to the harmful consequences of palliative medicines in susceptible individuals. Such iatrogenic events can be observed in contemporary medicine, after the withdrawal of modern enantiopathic medicines, according to the study of the rebound effect or paradoxical reaction of the organism. METHOD: This study reviews the recent studies which describe suicidality after the suspension or discontinuation of second generation antidepressants according to the hypothesis of the paradoxical reaction of the organism. CONCLUSIONS: Rebound and withdrawal effects, including suicidality occur with antidepressant drugs. They are relatively rare but more intense than the primary action of the drug. The probability of such effects is influenced by patient factors including age and diagnosis, and drug factors including half-life.

To study the protective effect of Sarcandra glabra extract (SGE) on immune system in restrained mice.

METHOD:
The male C57BL/6 mice were randomly divided into normal control group, stress control group, 125, 500 mg x kg(-1) SGE group. The spleen lymphocyte suspensions of each group were prepared. The parameters of spleen T cells subsets, NK cell and NKT cell proportion and number was detected by Flow cytometry.

RESULT:
SGE regulated the balance of T cell subsets, increased the percent of NK cells and NKT cell proportion and number in restrained mice.

CONCLUSION:
SGE has immunologic protective effect in restrained mice probably via the amelioration of immune cells proportion and number.


"Effects of Sarcandra glabra extract on immune activity in restraint stress mice"
Zhongguo Zhong Yao Za Zhi. 2009 Jan; 34(1): 100-3He R, Wang M, Li Y, Dai Y, Duan Y, Yao X, Kurihara H

Zhongguo Zhong Yao Za Zhi. 2009 Jan; 34(2): 148-51Chen Y, Chen F, Wei W, Zhang X, Feng Q, Jin ROBJECTIVE: To study the preparation ofnanostructured lipid carriers loaded with supercritical carbon dioxide fluid extraction of Xionggui powder. METHOD: Prepared nanostructured lipid carriers (NLC) loaded with supercritical carbon dioxide fluid extraction of Xionggui powder (XG-CO2-SFE) with a microemulsion ultrasonication method , established the best prescription of XG-CO2-SFE-NLC by orthogonal design methods with entrapment efficiency of nanoparticles as index, and investigated their physicochemical characterizations. RESULT: The best prescription was m(phospholipid) : m(S-40) : m(lipid carriers) = 5 : 2 : 1, the entrapment efficiency of nanopartices was 86.8%, results revealed that nanoparticles were sphere like with the mean size of 92.6 nm and the mean zeta potential was -20.68 mV. CONCLUSION: The prep aration method of the XG-CO2-SFE-NLC is appropriate.

Rev Med Chil. 2009 Jan; 137(1): 115-20Avello L M, Avendaño O C, Mennickent C SHomeopathic medicine is a type of therapy that appeared in Europe at the end of the eighteenth century. At the present time, it is widely accepted in developed countries as a form of alternative medicine. In Chile, health regulation includes homeopathy as pharmaceutical products and homeopathy is also considered a form of complementary medicine, that is well accepted by the public. The scientific rationale of homeopathy is based on an empiric type of thought that goes from the general to the particular. The symptoms that are valued are those that are particular to each sick individual. It uses diluted solutions of plants, minerals, animals and even venoms. There are basically two hypotheses to explain its mechanisms of action: The "immunological memory" and the "memory of water" or the transmission of electromagnetic information of the water. There still is needed to perform new studies to scientifically assess homeopathy and its usefulness, as an accepted alternative therapy.

Homeopathy. 2008 Oct; 97(4): 214-9Rutten ALHow can Randomised Controlled Trials (RCTs) change our beliefs? The fact that they do update prior beliefs to different posterior beliefs is explained by Bayesian philosophy. Crucial points in Bayesian analysis include setting the first prior expectation right and sequential updating of the prior in the light of new evidence. Bayesian analysis depends highly on the evidence included. RCT evidence can only falsify the placebo hypothesis, it cannot indicate which mechanism of action could be responsible for an intrinsic effect and therefore cannot overturn existing beliefs. Bayesian reasoning could structure further discussion, but subjectivity is an inherent element of this process. In the case of homeopathy the first prior is not a common prior shared by all parties to the debate, but a paradigm, this prevents common updating of beliefs. Only by keeping an open mind towards other paradigms and all possible hypotheses can a low Bayesian prior be elevated to the point of accepting a new paradigm, this is more relevant than Bayesian calculations.

Homeopathic medicine is a type of therapy that appeared in Europe at the end of the eighteenth century. At the present time, it is widely accepted in developed countries as a form of alternative medicine.

In Chile, health regulation includes homeopathy as pharmaceutical producís and homeopathy is also considered a form of complementary medicine, that is well accepted by the public. The scientific rationale of homeopathy is based on an empine type of thought that goes from the general to the particular.

The symptoms that are valued are those that are particular to each sick individual. It uses diluted solutions of plants, minerals, animáis and even venoms.

There are basically two hypotheses to explain its mechanisms ofaction: The "immunological memory" and the "memory of water" or the transmission of electromagnetic information of the water.

There still is needed to perform new studies to scientifically assess homeopathy and its usefulness, as an accepted alternative therapy .


"General Aspects Of Homeopathy"
Rev Med Chil. 2009 Jan; 137(1): 115-20Avello L M, Avendaño O C, Mennickent C S

Phytomedicine. 2009 Apr 27; Wang Y, Shi JG, Wang MZ, Che CT, Yeung JHIn this study, six major xanthones, isolated and identified from Halenia elliptica were investigated for their vasodilatory actions in isolated rat coronary artery. The xanthones, including 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1), 1-hydroxy-2,3,4,7-tetramethoxy-xanthone (HM-2), 1-hydroxy-2,3,4,5-tetramethoxy-xanthone (HM-3), 1,7-dihydroxy-2,3,4,5-tetramethoxy-xanthone (HM-4), 1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) and 1,7-dihydroxy-2,3-dimethoxy-xanthone (HM-7) caused vasodilation in the coronary artery pre-contracted with 1muM 5-hydroxytryptamine (5-HT), with EC(50) values ranging from 1.4+/-0.1muM (HM-1) to 6.6+/-1.4muM (HM-2). The EC(50) values of the other xanthones were between those of HM-1 and HM-2. Removal of endothelium of the coronary artery led to decreases in the vasorelaxant effects of HM-1, HM-7 but not HM-2, HM-3, HM-4 and HM-5. Our results showed that xanthones isolated from Halenia elliptica are vasoactive substances which exhibit either endothelium-dependent or endothelium-independent mechanisms in rat coronary artery. The potency and mechanism(s) of the vasorelaxant effects of these xanthones may be relevant to the structure-activity differences in the level and the position of the substituent groups with the primary xanthone structure.

Biomed Chromatogr. 2009 Apr 29; Tan W, Wang BL, Hu JP, Sheng L, Li YA simple, rapid and sensitive method was developed for determination of bicyclol, a new synthetic anti-hepatitis drug, in rat plasma from the mesenteric vein using a high-performance liquid chromatography system coupled to a positive ion electrospray-mass spectrometric analysis. Bicyclol and internal standard (biphenyldicarboxylate, DDB) were isolated from plasma by liquid-liquid extraction, then separated on a Zorbax SB-C(18) column (3.5 microm, 2.1 x 100 mm) with mobile phase of methanol-water (60:40, v/v) at a flow rate of 0.2 mL/min. Detection was performed on a Trap XCT mass spectrometer equipped with an electrospray ionization (ESI) source operated in selected ion monitoring mode. Positive ion ESI was used to form sodium adduct molecular ions at m/z 413 for bicyclol and m/z 441 for DDB, respectively. A linear detection response was obtained for bicyclol ranging from 3.3 to 333.3 ng/mL and the lower limit of quantitation was 3.3 ng/mL. The coefficients of variation for intra- and inter-day precisions were 1.1-7.7 and 2.0-6.6%, respectively. The percentage of absolute recovery of bicyclol was 85.3-94.6%. All analytes proved to be stable during all sample storage, preparation and analytic procedures. The method was successfully applied to determine the plasma concentration of bicyclol in mesenteric vein after intestinal perfusion. Copyright (c) 2009 John Wiley & Sons, Ltd.

Homeopathy. 2008 Oct; 97(4): 202-5Soto FR, Vuaden ER, Coelho C, Benites NR, Bonamin LV, de Azevedo SSAIM: To evaluate the zootechnic performance and occurrence of diarrhea in piglets in the week post-weaning comparing supplementation with sucrose saline which contained or did not contain added homeopathic medicine. METHOD: Animals were randomly divided into three groups of 24 piglets each. The control group did not receive any treatment. Another group received sucrose saline, and the third group received sucrose saline with homeopathic medicine added, in the period of zero to seven days post-weaning. The homeopathic treatment consisted of Echinacea angustifolia, Avena sativa, Ignatia amara, Calcarea carbonica, all 6cH. Piglets were weighed daily for weight gain or loss, and observed for diarrhea and feed intake. RESULTS: Animals receiving sucrose saline alone and sucrose saline with homeopathy had less weight loss than control (p=0.017, p=0.0001 respectively). There was no statistical difference in relation to overall incidence of diarrhea or food consumption. These data suggest that the supplementation with sucrose saline with added homeopathic medicine in the first seven days post-weaning may be an useful option to reduce weight loss in weaned piglets.

Ageing Res Rev. 2009 Apr 20; Sun L, Bai Y, Du GDue to ageing populations and improvements in survival, increasing numbers of patients suffering from ischemic cardiovascular disease are not amenable to revascularization. Hence, interests are currently focused on "therapeutic angiogenesis", which is the clinical use of growth factors to enhance or promote the development of collateral blood vessels in ischemic tissue. Several growth factors (or genes encoding these growth factors) are now available for therapeutic vascular growth in normal and ischemic tissues. However, the successes of angiogenic therapy observed in pre-clinical studies have not been realized in clinical trials. Most animal studies demonstrating the physiologic effectiveness of angiogenic therapies have been performed in normal young animals, while clinical trials typically enroll older patients with various endothelial disruptive risk factors. The promising results of trials using endothelial function-improving strategies support the hypothesis that the decreased effectiveness of growth factor therapy due to endothelial dysfunction could be a principle reason for failure of trials using growth factors. We will have a retrospection of therapeutic angiogenesis trials and discuss the mechanisms that contribute to an impaired angiogenic response in the setting of endothelial dysfunction. We also briefly explore endothelial function-improving procedures that have the potentially therapeutic benefit of enhancing the angiogenic response.

J Pharmacol Exp Ther. 2009 Apr 18; Quan H, Liu H, Li C, Lou LCombretastatin A4 (CA4) is a novel vascular-disrupting agent that has shown promising anticancer effects through its inhibition of microtubule assembly and subsequent disruption of tumor blood flow. In this report, we demonstrate that U0126, a selective inhibitor of mitogen-activated protein kinase kinase (MEK), significantly enhances the cytotoxicity of CA4 in BEL-7402 cells, independent of MEK inhibition. This independence is evidenced by the fact that another, more specific MEK inhibitor, PD0325901, does not have the same effect as U0126. The disassembled microtubules are able to reassemble in the later stages of CA4 treatment, due to the inactivating glucuronidation of CA4. U0126, but not PD0325901, inhibits CA4 glucuronidation, thereby blocking microtubule reassembly and enhancing CA4-induced G2/M cell cycle arrest. Consistent with this, U0126 significantly enhances CA4-induced cytotoxicity for cells in which CA4 glucuronidation occurs, but not for cells in which such glucuronidation does not occur. These results suggest that great caution should be exercised when interpreting data obtained using U0126, or when CA4 is combined with inhibitors of glucuronidation in clinical practice. More importantly, these findings indicate that the combination of CA4 with inhibitors of glucuronidation may be a novel and rational strategy for cancer therapy.

J Pharm Biomed Anal. 2009 Mar 20; Wang XH, Xie PS, Lam CW, Yan YZ, Yu QXThe after-harvesting sun-dried process of Angelicae dahuricae radix (Chinese name: Baizhi) was previously the traditional treatment for commodity. Over recent decades the natural drying process for some fleshy roots or rhizomes of Chinese materia medica has been replaced by sulfur-fumigation for curtailing the drying duration and pest control. We used high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC) fingerprinting analysis to investigate the potential damaging effect of the sulfur-fumigating process. The experimental conditions were as follows. HPTLC analysis was carried out on pre-coated silica-gel 60 plate, twice development was performed with two solvent systems (mobile phase) A, chloroform-ethyl acetate (10:1) and B, hexane-chloroform-ether (4:1:2); the fluorescent images were observed under UV 365nm. HPLC was preceeded on Zorbax SB-C(18) column; the linear gradient elution was conducted with mobile phase prepared from methanol-0.5% acetic acid; column temperature was at 25 degrees C; the detection wavelength was 250nm. We found serious degradation of the majority of coumarins in sulfur-fumigated Baizhi. The destructive effect was manifested by the defaced chromatographic profile and verified by imitating the sulfur dioxide reaction with the constituents in Baizhi in the laboratory. It is suggested that sulfur-fumigation process is an unacceptable approach for processing herbal drugs.

J Ethnopharmacol. 2009 Apr 16; Wang J, Zhao Y, Xiao X, Li H, Zhao H, Zhang P, Jin CAIM OF THE STUDY: Rhubarb is well-used to treat chronic renal failure(CRF) in China and Japan, but recent studies reported that the anthraquinone derivatives contained in rhubarb had nephrotoxicity. In this investigation an attempt was made to assess the value and toxic potential of rhubarb to treat CRF. MATERIALS AND METHODS: Histopathologic and biochemical tests combined with toxicokinetic analysis were performed to investigate the nephrotoxic potential and protective effect of rhubarb extract. RESULTS: In normal rat groups, no death was observed and no renal lesion was found after repetitive administration of rhubarb for 3 weeks. The survival rate, pathologic conditions and biochemical indexes of CRF rats treated with rhubarb at two dosages were all improved and significant amelioration was found in the low dosage group compared to the untreated CRF group. Rhein was the mainly absorbable anthraquinone derivative into systemic circulation after oral administration and the area under curve of rhein in CRF groups was lower than that in normal groups at same dosage. CONCLUSIONS: After 3 weeks of administration of rhubarb extract, there was evidence of protective effect to CRF rats, while incidences of hepatotoxicity with minimal to mild hyaline droplets were also observed in normal rats.

Zhongguo Zhong Yao Za Zhi. 2009 Jan; 34(2): 138-42Chen D, Li L, Peng R, Wu Y, Cai YOBJECTIVE: The genetic difference among Scrophularia ningpoensis cultivars were analyzed in molecular level. METHOD: Ninety-two individuls of three S. ningpoensis cultivars were employed to be analyzed by the approach of Sequence-related Amplified Polymorphism (SRAP).The parameters were calculated by POPGENE1.31 and the relationship was constructed based on UPGMA method. RESULT: 1) A total of 227 bands were scored and 199 bands of them were polymorphic. 2) The result is showed that there is a medium level of genetic diversity among three cultivars. At species level: percentage of polymorphic loci PPB=52.42%, effective number of alleles N(e)=1.2812, Nei's gene diversity H=0.1671 and Shannon's information index H(sp)= 0.2526; At cultivar level: PPB=21.44%, N(e)=1.1216, Nei's gene diversity H=0.0725 and Shannon's information index H(pop)= 0.1083. 3) The Nei's coefficient of genetic differentiation was 0.5625, which was consistent with the Shannon's coefficient of genetic differentiation (0.5713). Most of the genetic variation existed among cultivars. 4) The gene flow (N(m)=0.3889) was less among cultivars, indicating that the degree of genetic differentiation was higher. 5) Genetic similarity coefficient were changed from 0.8082 to 0.9133. By clustering analysis, the classified result of SRAP marker between traditional modal character was almost same. CONCLUSION: The genetic diversity of samples of S. ningpoensis is medium. The genetic difference among cultivar is higher than that within cultivar.

J Org Chem. 2009 Apr 21; Zhu K, He J, Li S, Liu M, Wang F, Zhang M, Abliz Z, Yang HB, Li N, Huang FTwo bis(m-phenylene)-32-crown-10 derivatives containing two pyridyl or carboxyl groups were made. They were used to prepare three bis(m-phenylene)-32-crown-10-based discrete rhomboids by coordination-driven self-assembly with high yields. The formation of these crown ether-based rhomboids was confirmed by NMR, UV-vis, CSI-TOF-MS, and elemental analysis. The complexation of these crown ether-based assemblies with paraquat (N,N'-dimethyl-4,4'-bipyridinium) was studied. The complexation of neutral bis(crown ether) rhomboid 1 with paraquat was found to be statistical with a 1:2 stoichiometry. The average apparent association constant K(av) of the complexation of rhomboid 1 with paraquat was found to be about 8.8(+/-0.8) x 10(3) M(-1) in acetone, about 17 times higher than the reported association constant value for the complexation of the corresponding simple bis(m-phenylene)-32-crown-10 with paraquat. This is possibly because the carboxylate groups provide additional noncovalent interactions between the host and guest. No obvious complexation was observed between the cationic rhomboids and paraquat when studied by NMR, UV-vis, and CSI-TOF-MS analysis. This could be attributed to the combination of the charge repulsion between cationic pyridinium rings and cationic platinum atoms and the weak pi-pi stacking and charge transfer interactions between the phenyl rings and the pyridinium rings caused by the electron-withdrawing effect of the cationic platinum atoms.