Forsch Komplementmed. 2009 Aug; 16(4): 251-5Déglon-Fischer A, Barth J, Ausfeld-Hafter BOBJECTIVE: This study investigated the current supply of complementary and alternative medicine (CAM) in Swiss primary care. Information was collected on physicians' qualifications in CAM, frequency of patients' demand for CAM, physicians' supply and temporal resources for CAM as well as physicians' referrals to CAM. MATERIAL AND METHODS: 750 (500 German-speaking and 250 French-speaking) randomly selected Swiss female and male primary care physicians were asked to complete a questionnaire (response rate 50.4%). Sociodemographic data on professional training, place of residence, and sex were used to calculate a weighting factor to correct the responders' data in the analysis accordingly. RESULTS: 14.2% of the physicians were qualified in at least one CAM discipline. Around 30% (95% confidence interval 25.4-34.6%) of the physicians were asked for CAM by their patients more than once a week. Homeopathy and phytotherapy were the most frequently offered therapies, followed by traditional Chinese medicine (TCM)/acupuncture. 62.5% (57.6-67.4%) of the physicians refer their patients to CAM. Most patients were referred to TCM/acupuncture. Of the 37.2% (32.6-42.4%) of the physicians who do not refer their patients to CAM, around 40% (35.1-44.9%) offer it themselves. CONCLUSION: About three quarters of the physicians offer CAM themselves or refer their patients to CAM treatments. CAM is very important in primary medical care in Switzerland. Clear regulations for CAM are required in order to ensure a high quality in care.

J Ethnopharmacol. 2009 Sep 4; Zhang R, Hu Y, Yuan J, Wu DPuerariae radix, as an edible plant, has been used for centuries in China to treat alcohol-related problems, including alcoholic liver disease (ALD). However, the mechanisms of Puerariae radix on the liver protective effect have not been fully explored. Because an increased intestinal permeability is a major factor for ALD, the present study investigates whether Puerariae radix extract (PRE) inhibits ALD through prevention of alterations in intestinal permeability. Here, we used an animal model of chronic alcohol-induced liver injury that is associated with increased intestinal permeability. Male Wistar rats were given increasing alcohol doses from 2g/kg/d to 8g/kg/d and alcohol plus PRE via intragastric feeding for 10 weeks. Chronic alcohol exposure caused an elevation in serum alanine aminotransferase (ALT) as well as aspartate aminotransferase (AST) levels and a decrease in superoxide dismutase (SOD) activity, and hepatic damages including steatosis, inflammation, and necrosis, determined by serum enzymatic analysis and morphological analysis, respectively. The damage to small intestine induced by chronic alcohol treatment was examined by intestinal histological, immunohistochemical analysis, and permeability assays. Alcohol-induced hepatic pathological changes, elevations in ALT and AST, and a decrease in SOD activity were significantly inhibited in PRE treated animals. The inhibitory effect of PRE on alcohol-induced liver injury was associated with suppression of alcohol-induced the increase of intestinal permeability. The results showed that this beneficial effect of PRE on ALD could be partly explained by improving intestinal barrier dysfunction induced by alcohol.

J Med Biogr. 2009 Aug; 17(3): 144-8Breathnach CSJonathan Osborne was born in Dublin and educated in Trinity College Dublin, where he became Professor of Materia Medica. As physician to Sir Patrick Dun's and Mercer Hospitals he reported extensively on those patients who came under his care. In his native city he is remembered for the instruments he devised, for his studies on dropsies (particularly albuminuric nephritis), and for his therapeutic approach to epilepsy and neuralgia. It is his thorough analysis of a patient with conduction aphasia in 1833, however, which has stood the test of time.

J Org Chem. 2009 Aug 7; 74(15): 5656-9Ding X, Ye D, Liu F, Deng G, Liu G, Luo X, Jiang H, Liu HWe described a synthesis method by first using chlorotrimethylsilane as the activator to brominate the Ni(II) complex of the beta-alanine Schiff's base [beta-AlaNi(II)PABA] 1 and developed it to prepare beta-amino acids 5. The procedure involves a Suzuki coupling reaction between boric acids and the bromoenone 2, followed by hydrogenation and hydrolysis. This is the first report of the application of the Ni (II) complex [beta-AlaNi(II)PABA], which represents an attractive route to afford alpha-aryl-/heteroaryl-substituted beta-amino acids.

Forsch Komplementmed. 2009 Aug; 16(4): 256-61Milgrom LRThough homeopathy has been in successful and continuous use for well over 200 years, in the United Kingdom it is under growing pressure, from scientific detractors and sections of the media. As such, homeopathy's free National Health Service provision is threatened because it is derided as 'unproven', 'unscientific', and even 'deadly'. While refuting these and other detractions, this paper considers possible reasons for the current plight of homeopathy UK. Thus, the current attacks against homeopathy should be viewed more in the context of the globalised pharmaceutical industry which is itself in crisis, and a succession of UK governments seemingly supine in the face of legislation originating from the European Union.

Biomacromolecules. 2009 Aug 10; 10(8): 2175-82Gao Y, Zhang Z, Chen L, Gu W, Li YThe selective introduction of a trimethylammonium cationic group into the C-6 position of chitosan (Cs) was successfully performed by "click chemistry" for the first time, and the 6-N,N,N-trimethyltriazole-Cs (TCs) showed good solubility in water. TCs showed strong DNA binding ability and high protection of DNA against nuclease degradation assessed by gel electrophoresis assay. TCNs showed lower degree of flocculation than Cs/DNA self-assembled nanoparticles (CsNs) in the presence of medium containing serum within 60 min. The introduction of trimethyltriazole group led to significantly increased cellular uptake compared with unmodified Cs, which resulted in higher transfection efficiency in HEK 293 and MDA-MB-468 cells. TCs were noncytotoxic, and viability of cells exposure to TCNs for 24 h was over 80% even at 50 microg/mL of polymer. These results suggested that TCs could be an efficient and safe material for gene delivery.

Biol Pharm Bull. 2009 Sep; 32(9): 1533-7Sun X, Zhang X, Hu H, Lu Y, Chen J, Yasuda K, Wang HProliferation of hepatic stellate cells (HSCs) is central for the development of fibrosis during liver injury. Our aim in this study was to determine whether berberine could inhibit HSC proliferation in vitro and prevent experimental liver fibrosis in vivo. Activated rat hepatic stellate cells (CFSCs) were incubated with various concentrations (0-20 microg/ml) of berberine. After 48 h incubation, berberine significantly inhibited CFSC proliferation and induced cell cycle arrest in G1 phase. Real-time and Western blotting revealed that both p21 and p27 expression was markedly reduced by berberine. Berberine also decreased Akt phosphorylation and FoxO1 phosphorylation, which led to FoxO1 nuclear translocation. Berberine effectively prevented CCl(4)-induced liver fibrosis in mice, which was accompanied by a decrease in the number of activated HSCs. Thus, berberine was able to prevent liver fibrosis by inhibition of hepatic stellate cell proliferation.

Acta Pharmacol Sin. 2009 Sep; 30(9): 1359-68Zhou YB, Feng X, Wang LN, Du JQ, Zhou YY, Yu HP, Zang Y, Li JY, Li JAIM: To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. METHODS: Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis. RESULTS: LGH00031 inhibited CDC25B irreversibly in vitro in a dose-dependent manner, and impaired the proliferation of tumor cell lines. In synchronized HeLa cells, LGH00031 delayed the cell cycle progression at the G(2)/M phase. LGH00031 increased cyclin-dependent kinase 1 (CDK1) tyrosine 15 phosphorylation and cyclin B1 protein level. The activity of LGH00031 against CDC25B in vitro relied on the existence of 1,4-dithiothreitol (DTT) or dihydrolipoic acid and oxygen. The oxygen free radical scavenger catalase and superoxide dismutase reduced the inactivation of CDC25 by LGH00031, confirming that reactive oxygen species (ROS) mediate the inactivation process in vitro. LGH00031 accelerated cellular ROS production in a dose-dependent manner, and N-acetyl cysteine (NAC) markedly decreased the ROS production induced by LGH00031. Correspondingly, the LGH00031-induced decrease in cell viability and cell cycle arrest, cyclin B1 protein level, and phosphorylation of CDK1 tyrosine 15 were also rescued by NAC that decreased ROS production. CONCLUSION: The activity of LGH00031 at the molecular and cellular level is mediated by ROS.

J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Aug 21; Zhan Y, Chen X, Zhao X, Zhong DLeuprolide is a synthetic nonapeptide that has two basic amino acids, arginine and histidine, in its structure. By selection of an appropriate analytical column and optimizing the mobile phase composition, an improved analytical method has been developed and validated to determine leuprolide concentrations in human serum. After methanol-induced protein precipitation of serum samples and Oasis((R)) HLB cartridge solid-phase extraction, leuprolide and an internal standard (alarelin) were analyzed on a C(18) column interfaced with a triple quadrupole tandem mass spectrometer with positive electrospray ionization. The mobile phase consisted of acetonitrile-water-propionic acid (20:80:0.05). The analyte and internal standard were both detected in the selective reaction monitoring mode. The method exhibited a linear range of 0.018-45.2ng/mL for leuprolide. The intra- and inter-assay precisions were 11.5% or less relative standard deviation (R.S.D.), and accuracy was within +/-2.8% relative error (RE). The lower limit of quantification (LLOQ) was identifiable and reproducible at 0.018ng/mL, with acceptable precision and accuracy. The validated LC-MS/MS method was tested to a clinical pharmacokinetic study of leuprolide after a single subcutaneous injection of 1mg leuprolide acetate in healthy male Chinese volunteers.

J Phys Chem A. 2009 Aug 27; Wang J, Gu J, Leszczynski JConjugated polymers (CPs) contain one pi-conjugated backbone and functional groups that could be ionized in high dielectric media. These materials combine the semiconducting and photon harvesting properties of electronically delocalized polymers with the charge-mediated behavior of polyelectrolytes. CPs can be used as highly responsive optical sensors for chemical and biological targets. The density functional theory (DFT) and the time-dependent density functional theory (TDDFT) approach were employed to simulate the absorption and emission spectra of poly[9,9'-bis(6''-N,N,N-trimethylammonium)hexyl]fluorene-co-alt-4,7-(2,1,3-benzothiadiazole) dibromide] (PFBT) in the present study. The influences on the spectra of the monomer unit F(BT)F due to stacking with the fluorene (F) and 2,1,3-benzothiadiazole (BT) units have been explored. The results suggest that stacking lowers the excitation and emission energy, facilitating detections of the polymers.

Org Lett. 2009 Aug 24; Chen HD, He XF, Ai J, Geng MY, Yue JMTrigochilides A (1) and B (2), two highly modified daphnane-type diterpenoids with 12-carbon-containing polyketide appendages at C-16 forming a macro-lactone with C-3, were isolated from the twigs and leaves of Trigonostemon chinensis. Their structures were elucidated by spectroscopic analysis. Trigochilides A (1) showed modest cytotoxicity against two tumor cell lines.

Acta Pharmacol Sin. 2009 Aug 24; Zhang X, Zhou Y, Shen Y, Du LL, Chen JH, Leng Y, Shen JHAbstractAim:To design and synthese a novel class of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors, featuring the (phenylsulfonamido-methyl)pyridine and (phenylsulfonamido-methyl)thiazole framework.Methods:Our initial lead 4-(phenylsulfonamido-methyl)benzamides were modified. Inhibition of human and mouse 11beta-HSD1 enzymatic activities by the new compounds was determined by a scintillation proximity assay (SPA) using microsomes containing 11beta-HSD1.Results:Sixteen new compounds (6a-6h, 7a-7h) were designed, synthesized and bioassayed. In dose-response studies, several compounds showed strong inhibitory activities with IC(50) values at nanomolar or low nanomolar concentrations. Structure-activity relationships are also discussed with respect to molecular docking results.Conclusion:This study provides two promising new templates for 11beta-HSD1 inhibitors.Acta Pharmacologica Sinica advance online publication, 24 August 2009; doi: 10.1038/aps.2009.118.

J Phys Chem B. 2009 Aug 26; Lu Y, Wang Y, Xu Z, Yan X, Luo X, Jiang H, Zhu WThe hydrogen bond acceptor capability of halogens has long been underappreciated in the field of biology. In this work, we have surveyed structures of protein complexes with halogenated ligands to characterize geometrical preferences of C-X...H contacts and contributions of such interactions to protein-ligand binding affinity. Notably, F...H interactions in biomolecules exhibit a remarkably different behavior as compared to three other kinds of X...H (X = Cl, Br, I) interactions, which has been rationalized by means of ab initio calculations using simple model systems. The C-X...H contacts in biological systems are characterized as weak hydrogen bonding interactions. Furthermore, the electrophile "head on" and nucleophile "side on" interactions of halogens have been extensively investigated through the examination of interactions in protein structures and a two-layer ONIOM-based QM/MM method. In biomolecular systems, C-X...H contacts are recognized as secondary interaction contributions to C-X...O halogen bonds that play important roles in conferring specificity and affinity for halogenated ligands. The results presented here are within the context of their potential applications in drug design, including relevance to the development of accurate force fields for halogens.

The apparent success of homeopathy is often attributed to a collaborative, holistic, and empathic consultation and to the practitioner-patient relationship. Despite the practitioner's consultative style being shown to affect patient's health outcomes in conventional medicine, most research into the homeopathic consultation has focused on patients' experiences.

However, the practitioner is a crucial component of the therapeutic context and may therefore have an important part to play in optimizing health outcomes in homeopathy. Additionally, the mechanisms underlying therapist effects are still poorly understood in clinical medicine generally and particularly so in homeopathy.

AIM:
The aim of this research is to gain an in-depth understanding of homeopathic practitioners' perceptions and experiences of the consultation, and the process of engaging with the patient and prescribing the remedy. We propose to generate a theoretical model to explain the processes that underpin the homeopathic consultation.

DESIGN:
This is a qualitative study using grounded theory methodology. Two (2) phases of data collection will be involved. Phase 1 will involve face-to-face in-depth interviews with homeopaths. From these interviews, a theoretical model of the homeopathic consultation will be developed. Phase 2 of data collection will involve observations of homeopathic consultations and the use of practitioner diaries in order to test the emerging theoretical model from phase 1. Homeopaths will be sampled from the Faculty of Homeopathy and the Society of Homeopaths.

RESULTS: Results will be available in summer 2009.

CONCLUSIONS: The findings from this study will lead to the development of a theoretical model of how homeopaths view and enact the consultation process. Revealing this process may influence the training of new practitioners and improve the practice of experienced practitioners and will therefore be of benefit to patients. In addition, the findings may be of potential benefit to practitioners of other therapeutic consultations.


"Homeopathic practitioner's experiences of the homeopathic consultation: a protocol of a grounded theory study."
J Altern Complement Med. 2009 Apr; 15(4): 347-52Eyles C, Walker J, Brien S (Hubmed.org)

Med Law. 2009 Mar; 28(2): 269-82Laso LR, Alfonso-Galán MTThis paper discusses the question of whether anthroposophic medicinal products can be treated in the European Union as regards registration and marketing authorization, in the same way as homeopathic medicinal products. European Union legislation, European official pharmacopoeias, and bibliography in this regard have been revised. European Directives make a single reference in one of its whereas clauses to anthroposophic medicinal products "described in an official pharmacopoeia and prepared by a homeopathic method". It is referring to those which comply with these two conditions, but it happens that there is no anthroposophic medicinal product "described" in any European official pharmacopoeia. Legislators have known this and continue to be aware of it and have not agreed to extend (since 1992), the reference to anthroposophic products neither do they accept the inclusion of that peculiarity on the label of homeopathic medicinal products. Anthroposophy presents notable variations from homeopathy and it introduces philosophical and "spiritual" variables that are difficult to assess objectively. It is necessary for these products to show, using a scientific methodology, that they are truly bringing patients the therapeutic benefits they claim. In any case, their authorization and registration should not be at the expense of homeopathy, already a highly complex field in its own right.

Invest New Drugs. 2009 Aug 25; Zhang Z, Meng T, He J, Li M, Tong LJ, Xiong B, Lin L, Shen J, Miao ZH, Ding JTargeting cellular mitosis is an attractive antitumor strategy. Here, we reported MT7, a novel compound from the 6H-Pyrido[2',1':2,3]imidazo [4,5-c]isoquinolin- 5(6H)-one library generated by using the multi-component reaction strategy, as a new mitotic inhibitor. MT7 elicited apparent inhibition of cell proliferation by arresting mitosis specifically and reversibly in various tumor cell lines originating from different human tissues. Detailed mechanistic studies revealed that MT7 induced typical gene expression profiles related to mitotic arrest shown by cDNA microarray assays. Connectivity Map was used to analyze the microarray data and suggested that MT7 was possibly a tubulin inhibitor due to its similar gene expression profiles to those of the known tubulin inhibitors demecolcine, celastrol and paclitaxel. Further analyses demonstrated that MT7 inhibited the polymerization of cellular microtubules although it was not detectable to bind to purified tubulin. The inhibition of cellular tubulin polymerization by MT7 subsequently resulted in the disruption of mitotic spindle formation, activated the spindle assembly checkpoint and consequently arrested the cells at mitosis. The persistent mitotic arrest by the treatment with MT7 led the tested tumor cells to apoptosis. Our data indicate that MT7 could act as a promising lead for further optimization, in hopes of developing new anticancer therapeutics and being used to probe the biology of mitosis, specifically, the mode of interference with microtubules.

Danshen and gegen (D&G) have long been used in treatment of angina and other cardiac symptoms in Chinese materia medica. Recent pharmacological studies suggest their therapeutic values. We aimed to evaluate the efficacy and safety of Salvia miltiorrhiza (danshen) and Pueraria lobata (gegen) in secondary prevention.

METHODS:
One hundred (100) consecutive coronary patients (mean age 58 +/- 8 years) were randomized to adjunctive treatment with D&G combination (3 g) or placebo (6 capsules) for 24 weeks in double-blind parallel fashion, followed by optional open-label D&G (1.5 g/day) for 6 more months. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured using ultrasound.

RESULTS:
Baseline characteristics were similar between the 2 groups. After 24 weeks and compared with baseline, there were no significant changes in blood pressures, blood hematological and biochemical profiles, or folate and homocysteine levels in both groups,

CONCLUSIONS:
D&G adjunctive treatment in coronary patients was well tolerated and effective in improving vascular function and structure. These two herbs may become a novel agent for secondary prevention.



"The efficacy and tolerability of adjunctive alternative herbal medicine (Salvia miltiorrhiza and Pueraria lobata) on vascular function and structure in coronary patients"
J Altern Complement Med. 2009 Apr; 15(4): 415-21Tam WY, Chook P, Qiao M, Chan LT, Chan TY, Poon YK, Fung KP, Leung PC, Woo KS

Cancer Res. 2009 Aug 25; Wang Y, Ma X, Yan S, Shen S, Zhu H, Gu Y, Wang H, Qin G, Yu QConstitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs frequently in cancer cells and contributes to oncogenesis. Among the members of STAT family, STAT3 plays a pivotal role in the development and progression of human tumors. The STAT3-mediated signaling pathway has been recognized as a promising anticancer target. Here, we show that 17-Hydroxy-jolkinolide B (HJB), a diterpenoid from the Chinese medicinal herb Euphorbia fischeriana Steud, strongly inhibits interleukin (IL)-6-induced as well as constitutive STAT3 activation. Furthermore, we show that HJB directly targets the JAK family kinases, JAK1, JAK2, and TYK2, by inducing dimerization of the JAKs via cross-linking. Addition of DTT or glutathione prevents the JAK cross-linking and blocks the inhibitory effects of HJB on IL-6-induced STAT3 activation, suggesting that HJB may react with cystein residues of JAKs to form covalent bonds that inactivate JAKs. Liquid chromatography/mass spectrometry analysis confirmed that each HJB reacted with two thiols. The effect of HJB on the JAK/STAT3 pathway is specific as HJB has no effect on platelet-derived growth factor, epidermal growth factor, or insulin-like growth factor I signaling pathways. Finally, we show that HJB inhibits growth and induces apoptosis of tumor cells, particularly those tumor cells with constitutively activated STAT3. We propose that the natural compound HJB is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. [Cancer Res 2009;69(18):OF1-9].

Mov Disord. 2009 Aug 24; Kompoliti K, Fan W, Leurgans SThe aim of this study was to describe the use of complementary and alternative medicine (CAM) in patients with Tourette syndrome (TS) and explore associations with CAM use. In recent years CAM use has increased, but rates of CAM use in TS patients are not reported. Consecutive TS patients or their parent(s), seen in an academic movement disorder center, completed a questionnaire regarding their use of CAM. One hundred TS patients or parents completed the questionnaire, mean age 21.5 +/- 13.5, 76 males, 87 Caucasians. Sixty four patients had used at least one CAM modality. CAM treatments used were prayer (28), vitamins (21), massage (19), dietary supplements (15), chiropractic manipulations (12), meditation (10), diet alterations (nine), yoga (nine), acupuncture (eight), hypnosis (seven), homeopathy (six), and EEG biofeedback (six). Fifty six percent of patients using CAM reported some improvement. Users paid out of pocket for 47% of treatments pursued, and 19% of these payers received partial reimbursement by third party payer. Users and non-users did not differ in age, gender, race, income, educational level, general health, tic severity, medication use for TS, current satisfaction from medications or experience of side effects from medications. CAM use was associated with the presence of affective disorder (P = 0.004), but not with either ADHD or OCD. Among CAM users, 80% initiated CAM without informing their doctor. CAM is commonly used in children and adults with TS, and often without the neurologist's knowledge. Physicians should inquire about CAM to understand the spectrum of interventions that patients with TS use. (c) 2009 Movement Disorder Society.

Acta Pharmacol Sin. 2009 Aug 24; Chen L, Wang WY, Wang YPAbstractAim:To understand the effects of lithospermic acid (LA), a potent antioxidant from the water-soluble extract of Salvia miltiorrhiza, on the migration and proliferation of rat thoracic aorta vascular smooth muscle cells (VSMCs).Methods:VSMC migration, proliferation, DNA synthesis and cell cycle progression were investigated by transwell migration analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, bromodeoxyuridine (BrdU) incorporation assay, and flow cytometric detection, respectively. Intracellular reactive oxygen species (ROS) generation was detected using 2',7'-dichlorofluorescin diacetate (DCFH-DA). The expression of cyclin D1 protein and matrix metalloproteinase-9 (MMP-9) protein, as well as the phosphorylation state of ERK1/2, were determined using Western blots. The activity of MMP-9 and the expression of MMP-9 mRNA were assessed by gelatin zymography analysis and RT-PCR, respectively.Results:LA (25-100 mumol/L) inhibited both lipopolysaccharide (LPS)- and fetal bovine serum (FBS)-induced ROS generation and ERK1/2 phosphorylation. By down-regulating the expression of cyclin D(1) and arresting cell cycle progression at the G(1) phase, LA inhibited both VSMC proliferation and DNA synthesis as induced by 5% FBS. Furthermore, LA attenuated LPS-induced VSMC migration by inhibiting MMP-9 expression and its enzymatic activity.Conclusion:LA is able to inhibit FBS-induced VSMC proliferation and LPS-induced VSMC migration, which suggests that LA may have therapeutic effects in the prevention of atherosclerosis, restenosis and neointimal hyperplasia.Acta Pharmacologica Sinica advance online publication, 24 August 2009; doi: 10.1038/aps.2009.122.

Homeopathy. 2009 Jul; 98(3): 181-2Land ST

Homeopathy. 2009 Jul; 98(3): 135-6Güthlin C

Zhongguo Zhong Yao Za Zhi. 2009 May; 34(9): 1114-6Huang J, Yang J, Xue Q, Yu L, Zhang DOBJECTIVE: To study the chemical constituents of the whole plant of Viola yedoensis. METHOD: The compounds were isolated by various chromatographic techniques and their structures were elucidated by their physicochemical properties and the analysis of their spectral data. RESULT: Seven compounds were isolated and identified as esculetin (1), isoscopoletin (2), 6-hydroxymethyl-3-pyridinol (3),5,5-bi (6,7-dihydroxycoumarin) (4), 6,6,7,7-tetrahydroxy-5,8-bicoumarin (5), loliolide (6), dehydrololiolide (7). CONCLUSION: Compounds 2-7 were isolated from V. yedoensis for the first time.

J Nat Prod. 2009 Aug 19; Duan WJ, Yang JY, Chen LX, Zhang LJ, Jiang ZH, Cai XD, Zhang X, Qiu FEleven new monoterpenes, paeonidangenin (1), paeonidanin A (2), paeonidanin B (3), paeonidanin C (4), paeonidanin D (5), paeonidanin E (6), paeoniflorone (7), 4-O-methylbenzoylpaeoniflorin (8), 4-O-methylgalloylpaeoniflorin (9), 4-O-methyldebenzoylpaeoniflorin (10), and 4-O-methylalbiflorin (11), were isolated from the 60% ethanol extract of the roots of Paeonia albiflora. Their structures were determined primarily on the basis of 1D and 2D NMR techniques and MS studies. Paeonidanins D (5) and E (6) are unprecedented examples of "cage-like" monoterpene dimers. The inhibitory effects of the isolated compounds on nitric oxide production by lipopolysaccharide (LPS)-activated N9 microglia were evaluated.

Chem Biol Drug Des. 2009 Aug 19; Li F, Yin C, Chen J, Liu J, Xie X, Zhang AMono- and bis-indolomorphinans were synthesized through a multi-step synthetic approach from the alkaloid, thebaine, to further explore the C-ring SAR (structure-activity relationship) of morphinan scaffold. Both mono-indoles displayed good binding affinity and selectivity for the delta receptor, with compound 6b possessed the highest K(i) value of 1.45 nm at this receptor. Bisindolomorphinans 7a,b did not have appreciable affinity for both delta and kappa receptors, but moderate binding at the mu receptor was observed. Functional assays indicated that the newly synthesized mono-indole 6b was delta-agonist, opposite to the delta-antagonist profile of naltrindole. Bisindoles 7a,b were mu-agonists. This work further confirms that the phenol component in opioids is essential for higher binding to the opioid receptors. The different binding ability, receptor selectivity, and the functional activity profiles of naltrindole 2, monoindole 6b, and bisindole 7b clearly indicated that they interact with the opioid receptors in different modes.

J Pharm Biomed Anal. 2009 Jul 22; Sun N, Wen J, Lu G, Hong Z, Fan G, Wu Y, Sheng C, Zhang WIodiconazole is a very potent antifungal agent used to treat serious fungal infections. After transdermal administration, several factors affect the exposure of iodiconazole, resulting in large variability and demanding further elucidation of drug distribution. For determination of iodiconazole in dermal microdialysate, a new, efficient, reliable and robust ultra-fast liquid chromatography (UFLC, Shimadzu) assay using UV detection at 230nm has been developed and validated. Iodiconazole was separated on a Shimadzu Prominence UFLC C18 column (2.2mum, 50mmx2.0mm i.d.) using acetonitrile-0.025% triethylamine solution, adjusted to pH 3.6 with phosphoric acid (65:35, v/v), at a flow rate of 0.5ml/min. The retention time was 1.37min for iodiconazole and 1.78min for the internal standard, an isomeric compound of iodiconazole. Intra- and inter-day precision ranged from 5.3% to 7.8% and 3.7% to 8.4%, respectively. The UFLC method was used to measure iodiconazole concentrations in microdialysis samples obtained during the calibration of laboratory-made linear probes. The validation and sample analysis results show that the method is precise, accurate and well suited to support the dermal microdialysis experiments.

Life Sci. 2009 Aug 17; Wang SB, Yang XY, Tian S, Yang HG, Du GHAIMS: The present study was to evaluate the beneficial effect of salvianolic acid A (SAA) on the alterations in vascular reactivity of streptozotocin (STZ) diabetic rats. MAIN METHODS: Diabetes was induced by a single intraperitoneal injection of STZ (60mg/kg). Following 16weeks of SAA treatment (1mg/kg/day), thoracic aortic rings of rats were mounted in organ baths. Contractile responses to noradrenaline (NA) and KCl and relaxant responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed. KEY FINDINGS: Loss of weight, hyperglycemia, elevated content of malondialdehyde (MDA) and decline of total antioxidant capacity (TAC) were observed in diabetic rats. SAA could improve these metabolic and biochemical abnormalities. Compared to the control, the maximum contraction (E(max)) to NA, but not sensitivity (pD(2)), significantly elevated in diabetic aortas, which was prevented by SAA treatment. However, the response of rat aortas to KCl (E(max) and pD(2)) did not altered either in diabetic group or SAA treatment compared with that of normal control group. We also observed the significant decrease in relaxation to ACh rather than SNP in diabetic group compared with controls. And SAA treatment could revert the ACh response. Significance: It is concluded that oral administration of SAA can significantly improve glucose metabolism and inhibit oxidative injury as well as protect impaired vascular responsiveness in STZ-induced diabetic rats.

J Ethnopharmacol. 2009 Aug 12; Wang J, van der Heijden R, Spruit S, Hankermeier T, Chan K, van der Greef J, Xu G, Wang MChinese herbal Medicines, often referred as Chinese Materia Medica (CMM), are comprised of a complex multicomponent nature. The activities are aimed at the system level via interactions with a multitude of targets in the human body. This review aims at the toxicity aspects of CMM and its preparations at the different steps of production; harvesting, processing and the final formulation. The historic perspective and today's issues of the safety of CMM are introduced briefly, followed by the descriptions of the toxic CMM in the current Chinese pharmacopoeia (2005). Subsequently, several aspects of safety are illustrated using a typical example of a toxic CMM, Aconitum roots, and some recent findings of our own research are included to illustrate that proper processing and multi-herbs formulation can reduce the level of toxic components. This also explains that in CMM, some herbs, such as Aconitum, Ephedra species are never used as single herb for intervention and that aconite is only used when it is processed and in combination with specific matched other herbs. The formulation principle of multi-herbs intervention strategy is a systems approach for the treatment and prevention of disease. In this light, the role of systems toxicology in the safety and quality of Chinese herbal medicine is proposed as a promising method. Moreover the principles of practiced-based and evidence-based research are discussed from a symbiotic perspective.

Bioorg Med Chem Lett. 2009 Jul 28; Fu L, Jiang Z, Cai Z, Liu X, He H, Yang YA phosphate prodrug strategy was investigated to address the problem of poor aqueous solubility of pleuromutilin analogues. Water-soluble phosphate prodrugs 6a, 6b and 6c of pleuromutilin analogues were designed and synthesized. Three compounds all exhibited excellent aqueous solubility (>50mg/mL) at near-neutral pH and sufficient stability in buffer solution. In particular, the phenol pleuromutilin prodrug 6c displayed favourable pharmacokinetic profiles and comparable potency with vancomycin against MSSA and MRSA strains in vivo.

J Nat Prod. 2009 Aug 17; Xiao WL, Gong YQ, Wang RR, Weng ZY, Luo X, Li XN, Yang GY, He F, Pu JX, Yang LM, Zheng YT, Lu Y, Sun HDThree new nortriterpenoids, schigrandilactones A-C (1-3), along with eight known compounds, were isolated from an organic solvent extract of Schisandra grandiflora. Compounds 1 and 2 feature a spirocyclic moiety in their structures, and compound 3 was characterized with a new oxygenated pattern. The relative configurations of 1 and 3 were determined through single-crystal X-ray experiments. In addition, compounds 1 and 2 displayed cytotoxic activity against two human cancer cell lines, and compound 3 showed anti-HIV-1 inhibition in infected C8166 cells.

Toxicol Appl Pharmacol. 2009 Aug 11; Zhou J, Huang KAccumulating evidence suggests that peroxynitrite (ONOO(-)) is involved in the pathogenesis of insulin resistance. In the current study, we investigated whether insulin resistance in vivo could be mediated by nitration of proteins involved in the early steps of the insulin signal transduction pathway. Exogenous peroxynitrite donated by 3-morpholinosydnonimine hydrochloride (SIN-1) induced in vivo nitration of the insulin receptor beta subunit (IRbeta), insulin receptor substrate (IRS)-1 and protein kinase B/Akt (Akt) in skeletal muscle of mice, and dramatically reduced whole-body insulin sensitivity and muscle insulin signaling. Moreover, in high-fat diet (HFD)-fed insulin resistant mice, we observed enhanced nitration of IRbeta and IRS-1 in skeletal muscle, in parallel with impaired whole-body insulin sensitivity and muscle insulin signaling. Reversal of nitration of these proteins by treatment with the peroxynitrite decomposition catalyst FeTPPS yielded an improvement in whole-body insulin sensitivity and muscle insulin signaling in HFD-fed mice. Taken together, these findings provide new mechanistic insights for the involvement of peroxynitrite in the development of insulin resistance, and suggest that nitration of proteins involved in the early steps of insulin signal transduction is a novel molecular mechanism of HFD-induced muscle insulin resistance.

Acta Pharmacol Sin. 2009 Aug 17; Xue W, Hu JF, Yuan YH, Sun JD, Li BY, Zhang DM, Li CJ, Chen NHAbstractAim:The aim of this study was to investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (polygalasaponin XXXII, PGS32) isolated from the roots of Polygala tenuifolia Willd.Methods:The Morris water maze was used to evaluate the spatial learning and memory of mice. To detect the basic properties of synaptic transmission and long-term potentiation (LTP) in the dentate gyrus of rats, electrophysiological recordings were made of evoked potentials. Western blotting analysis and immunofluorescence assays were used to determine the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), synapsin I and the expression of brain derived neurotrophic factor (BDNF).Results:When administered at 0.125, 0.5, or 2 mg/kg, PGS32 could significantly prevent scopolamine-induced cognitive impairments in mice. Intracerebroventricular (icv) administration of PGS32 greatly enhanced basic synaptic transmission in the dentate gyrus of rats and induced LTP. In primary hippocampal neurons, as well as in the hippocampus of maze-trained mice, PGS32 activated the mitogen-activated protein (MAP) kinase cascade by promoting phosphorylation of ERK, CREB and synapsin I. The expression of BDNF was also greatly enhanced in the hippocampus.Conclusion:Our findings suggest that PGS32 can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade and enhancement of the level of BDNF. Therefore, PGS32 shows promise as a potential cognition-enhancing therapeutic drug.Acta Pharmacologica Sinica advance online publication, 17 August 2009; doi: 10.1038/aps.2009.112.

Evid Based Complement Alternat Med. 2009 Aug 17; Adler UC, Paiva NM, Cesar AT, Adler MS, Molina A, Padula AE, Calil HMHomeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day(-1) (up to 40 mg day(-1)) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Asberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = 0.654) and 8th weeks (P = 0.965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were -3.04 (95% CI -6.95, 0.86) and -2.4 (95% CI -6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression.

N Z Med J. 2009; 122(1297): 97Evans G

N Z Med J. 2009; 122(1295): 94-5Holt S, Gilbey A

Homeopathy. 2009 Jul; 98(3): 177-80Mathur MThis paper reviews the circumstances in which the concept of miasm evolved and how subsequent developments in medicine have improved our understanding of the cause of diseases. It concludes with an emphasis on the need to further refine the homeopathic concept of disease.

Phytochemistry. 2009 Aug 8; Zhang B, Yang SP, Yin S, Zhang CR, Wu Y, Yue JMFour limonoids, 1-O-deacetyl-6-deoxykhayanolide E (1), 1-O-deacetyl-2alpha-hydroxykhayanolide E (2), 3-acetyl-khayalactone (3), 11alpha-acetoxy-2alpha-hydroxy-6-deoxy-destigloylswietenine acetate (4), along with 12 known limonoids, were isolated from the stems of Khaya ivorensis. Their structures were elucidated on the basis of spectroscopic analysis.

J Org Chem. 2009 Aug 12; Zhang Q, Wang D, Wang X, Ding KEmploying (2-pyridyl)acetone as a new supporting ligand, the copper-catalyzed coupling reactions of aryl chlorides, aryl bromides, and aryl iodides with various phenols successfully proceeded in good yields under mild conditions. This reaction displays great functional groups compatibility and excellent reactive selectivity.

J Comb Chem. 2009 Jul 31; Jiang M, Li T, Meng L, Yang C, Xie Y, Ding JC-5 arylated 2/9-substituted pyrimido[5,4-b]indolizines were synthesized via palladium-catalyzed direct arylation. A variety of substituents on both pyrimido[5,4-b]indolizines and aryl/heteroaryl bromides are tolerated, providing rapid access to substituted pyrimido[5,4-b]indolizines in good to excellent yields.

Zhongguo Zhong Yao Za Zhi. 2009 May; 34(10): 1225-7Ouyang F, Liu Y, Xiao H, Yu H, Wang N, Yao XOBJECTIVE: To study the chemical constitutents of the 60% ethanol extract of the stems of Sambucus williamsii. METHOD: Compounds were isolated and purified by Diaion D101, silica gel,Sephadex LH-20, ODS column chromatography and preparative HPLC. Their structures were identified by spectroscopic methods. RESULT: Seven lignans were isolated and identified as erythro-guaiacylglycerol-beta-O-4'-sinapyl ether (1), 1-( 4'-hydroxy-3'-methoxyphenyl) -2- [4"-( 3-hydroxypropyl) -2", 6"-dimethoxyphenoxy] propane-1,3-diol (2), isolariciresinol (3), burselignan (4), lyoniresinol (5), 5-methoxy-isolariciresinol (6), cycloolivil (7). CONCLUSION: All these compounds were obtained from this genus for the first time.

Zhongguo Zhong Yao Za Zhi. 2009 May; 34(10): 1216-9Li X, Feng Z, Huo W, Li Y, Wang B, Zhu SOBJECTIVE: To establish a method to evaluate the in vitro release of Zhike Pingchuan sustained-release tablets. METHOD: The ephedrine, pseudoephedrine, scopolamine were chosen as marker components components, and the chromatographic conditions were chosen according to the separation of baseline and theoretical plate number for determining the marker in vitro release of Zhike Pingchuan sustained-release tablets; through the dissolution curves of the three active components, the release behavior was judged as well-balanced release or not. RESULT: Compared with conventional tablets, the Zhike Pingchuan sustained-release tablets had a well-balanced behavior in 10 h. CONCLUSION: The maker components of Zhike Pingchuan sustained-release tablets and two chromatographic conditions, which were used to determine the dissolution of the sustained-release tablets, could be chosen as evaluation methods for the in vitro release of Zhike Pingchuan sustained-release tablets.

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009 May; 29(5): 422-4Shi YT, Si CF, Liu BOBJECTIVE: To study the kinetogenic effects of serum containing Semen Arecae, Dandelion, Semen raphaniand Atractylodes macrocephala on the colonic smooth muscle cells of rats. METHODS: Serum containing Chinese materia medicas was made according to standard methods. Smooth muscle cells were isolated from the muscle layers of Wistar rat's colon, referred to modified Bitar's method. The contractile response of colonic smooth muscle cells to serum containing Chinese materia medicas (10%, 50%, 100% concentration) and other medicines (blank and 1 x 10(-3) mol/L acetylcholine) were separately observed. The contractility was presented by the decrease of the cell length between the drug groups and the control. RESULTS: Serum containing each Chinese materia medica can make dose-dependent contraction at different concentrations (P < 0.05), but the strongest effect of each serum had no significant difference (P > 0.05). CONCLUSION: Serum containing Semen Arecae, Dandelion, Semen raphani and Atractylodes macrocephala can make notable contraction on colonic smooth muscle cells in rats.

Rheumatol Int. 2009 Aug 12; Baranowsky J, Klose P, Musial F, Haeuser W, Dobos G, Langhorst JThe objectives of the study were identification, quality evaluation and summary of RCTs on complementary and alternative medicine as defined by the National Institute of Health with the exception of dietary and nutritional supplements. A computerized search of databases from 1990 (year of publication of the ACR criteria for fibromyalgia) to July 2007 was performed. The RCTs were assessed by a methodological quality score. A total of 23 RCTs issued from 1992 to 2007 on acupuncture, balneotherapy, thermotherapy, magnetic therapy, homeopathy, manual manipulation, mind-body medicine, diet therapy and music therapy were identified. The RCTs had an average group size of 25 with the number of groups ranging from two to four. The quality score assessment of the RCTs yielded a mean score of 51 out of 100. The average methodological quality of the identified studies was fairly low. Best evidence was found for balneotherapy/hydrotherapy in multiple studies. Positive results were also noted for homeopathy and mild infrared hyperthermia in 1 RCT in each field. Mindfulness meditation showed mostly positive results in two trials and acupuncture mixed results in multiple trials with a tendency toward positive results. Tendencies for improvement were furthermore noted in single trials of the Mesendieck system, connective tissue massage and to some degree for osteopathy and magnet therapy. No positive evidence could be identified for Qi Gong, biofeedback, and body awareness therapy.

Zhong Yao Cai. 2009 Apr; 32(4): 508-11Wang CF, Li RR, Huang LL, Zhong LQ, Yuan STOBJECTIVE: To study the chemical constituents of the flower buds of Daphne genkwa. METHODS: The constituents of petroleum ether and ethyl acetate-soluble portions were isolated and purified by means of chromatography, then they were identified by their physico-chemical characteristics and spectral features. RESULTS: Ten compounds were isolated and identified as octacosane (1), dotriacontane (2), beta-sitosterol (3), 4', 7-dimethoxy-5-hydroxyflovone (4), aurantiamide acetate (5), genkwanin (6), luteolin (7), apigenin (8), 3'-hydroxygenkwanin (9) and daphnoretin (10). CONCLUSION: Compound 1 and 2 are isolated from this plant for the first time.

J Tradit Chin Med. 2009 Jun; 29(2): 141-5Wang YZ, Xiao YQ, Zhang C, Sun XMOBJECTIVE: To explore the analgesic and anti-inflammatory effects of lappaconitine gelata (LA). METHODS: The writhing response induced by acetic acid, the pain response induced by formaldehyde and hot plate method in the mouse, and the paw edema induced by egg albumen in the rat and the ear edema induced by xylene in the mouse were used for investigation on the analgesic and anti-inflammatory effects of LA. RESULTS: The writhing response induced by acetic acid, the pain response induced by formaldehyde and hot plate methods was significantly inhibited by LA. In addition, the paw edema induced by egg albumen in the rat and the ear edema induced by xylene in the mouse were all significantly suppressed by LA. CONCLUSION: LA has the analgesic and anti-inflammatory effects.

Biomed Chromatogr. 2009 Aug 5; Huang H, Chen G, Lu Z, Zhang J, Guo DAOxyresveratrol (trans-2,4,3',5'-tetrahydroxystilbene) is a major compound isolated from Smilax china, a Chinese herbal medicine. The rat urine and bile samples were pretreated by solid-phase extraction method after oral administration at a dose of 100 mg/kg of oxyresveratrol. Seven metabolites were identified by LC-MS/MS method with electrospray ionization in negative ion mode. The results indicated that main metabolites of oxyresveratrol were monoglucuronided and monosulfated oxyresveratrol. Based on the results, the metabolic pathway of oxyresveratrol in rat urine and bile was proposed. Copyright (c) 2009 John Wiley & Sons, Ltd.

Homeopathy. 2009 Jul; 98(3): 149-53Waisse-Priven S, Jurj G, Lima Thomaz LC, Tierno SA, Filho WL, Sos A, de Souza MFThis study sought to assess the effectiveness of individualized homeopathic treatment on dermatological complaints in a public outpatient clinic. METHODS: Children and adults spontaneously seeking for homeopathic treatment for dermatological complaints were prescribed single individualized remedies and followed up for a minimum of 3 months; assessment was clinical and recorded graphically. RESULTS: Forty-nine patients met the inclusion criteria. Outcomes were positive (59%); no effect (4%); drop-out (37%), from which 6% was due to homeopathic aggravation. No manifestations of suppression were observed. CONCLUSIONS: Outcome studies are useful to point out to the effectiveness of individualized homeopathic treatment in dermatological complaints. Outcomes suggest that actions focusing on pathological categories do not lead to homeopathic suppression.

Phytother Res. 2009 Aug 4; Wu W, Xu X, Dai Y, Xia LThe objective of the present study was to investigate the effect of the saponin fraction from Clematis chinensis Osbeck roots (SFC) on an osteoarthritis model in rats and to explore its underlying mechanisms. Osteoarthritis was induced by intraarticular injection of monosodium iodoacetate (MIA) into knee joints of rats, and SFC and diclofenac were orally administered once a day for 28 consecutive days. Joint swelling, macroscopic observation, histological assessment and proteoglycan (PG) degradation were examined. In vitro, cultured rabbit chondrocytes were stimulated with MIA and sodium nitroprusside (SNP), respectively. The effects of SFC on MIA- and SNP-induced chondrocyte injury were examined by MTT assay. It was shown that SFC (50, 100, 200 mg/kg) dose-dependently reduced cartilage injury and PG degradation induced by MIA. Diclofenac (4 mg/kg) only slightly alleviated cartilage injury and PG degradation. SFC also prevented SNP- or MIA-induced rabbit chondrocyte impairment. These results indicate that SFC is effective in ameliorating joint destruction and cartilage erosion in MIA-induced osteoarthritic in rats, and the mechanisms of action for protecting articular cartilage are through preventing extracellular matrix degradation and chondrocyte injury. Copyright (c) 2009 John Wiley & Sons, Ltd.

Homeopathy. 2009 Jul; 98(3): 137-41Mousavi F, Mojaver YN, Asadzadeh M, Mirzazadeh MOBJECTIVE: The objectives of this study were to clinically determine the efficacy of individualised homeopathy in the treatment of minor recurrent aphthous ulceration (MiRAU). DESIGN & INTERVENTION: A randomized, single blind, placebo-controlled clinical trial of individualised homeopathy. One hundred patients with minor aphthous ulcer were treated with individualised homeopathic medicines or placebo and followed up for 6 days. Patients received two doses of individualised homeopathic medicines in the 6C potency as oral liquid at baseline and 12 h later. Pain intensity and ulcer size were recorded at baseline during and at the end of the trial (mornings of days 4 and 6). RESULT: All 100 patients completed treatment. Between group differences for pain intensity and ulcer size were statistically significant at day 4 and at day 6 (P

J Cell Mol Med. 2009 Jul 31; Xu X, Dai YIt was nearly one hundred years since heparin was discovered, but the role of this widely used anticoagulant is still remarkably thought-provoking now. During pathological processes such as atherosclerosis, inflammation, cancer and infection, phenomena of cell adhesion are ubiquitous and complicated. Heparin exerts anti-adhesion activity appearing as a common mechanism of its potential polypharmacology in those diseases. Furthermore, heparin can bind a variety of signaling molecules such growth factors, cell surface proteins of pathogens and most notably, cell adhesion molecules. These signaling molecules are involved in cell communication, acting as ligands, receptors, and second messengers. Considering that heparan sulfate glycosaminoglycan is increasingly recognized as a key mediator in many cellular processes, the structural similarity with heparan sulfate suggests that heparin is a multifunctional intervenor in cell communication.

Homeopathy. 2009 Jul; 98(3): 169-76Smit E, Oberholzer HM, Pretorius EImmunomodulators are substances which modify the immunity of an individual to favour a particular immunological response. The immune response and the function of the immune response regulation process are described, with special reference to cancer and autoimmune disease. Homeopathy and its role in immune regulation are discussed with special reference to Canova. Canova is a homeopathic product produced, according to the Hahnemannian homeopathic method, in Brazil. Its role in cancer, bone marrow and haematopoiesis as well as macrophage and monocyte activation is reviewed. Canova seems to stabilize platelet morphology in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). The data suggest that the future of immunomodulators and homeopathic products which appear to have an effect on the immune response requires a better understanding of the relative need for immune activation versus immune modulation. Homeopathic products specifically need more attention.

Homeopathy. 2009 Jul; 98(3): 142-8Rossi E, Endrizzi C, Panozzo MA, Bianchi A, Da Frè MOBJECTIVE: To evaluate the response to homeopathic treatment in a public homeopathic clinic of all patients attending between September 1998 until December 2005, and to analyze homeopathic practice. METHODS AND SETTING: Longitudinal observational study in a homeopathic clinic based in a public hospital in Lucca, Italy. Data relating to patient details, clinical diagnosis, remedy prescribed, potency of dosage, prescription strategy and identification of the case as acute-chronic-recurrent were analyzed. Clinical response was assessed by the Glasgow Homeopathic Hospital Outcome Score. RESULTS: Overall 74% of patients reported at least moderate improvement. Outcomes were better with longer treatment duration and younger age of patients. Respiratory, followed by dermatological and gastrointestinal pathologies responded best, psychological problems relatively poorly. CONCLUSIONS: Homeopathic therapy is associated with improvement in a range of chronic and recurring pathologies. Certain characteristics of patient and pathology influence the outcome.

Biol Pharm Bull. 2009 Aug; 32(8): 1359-63Tan CB, Gao M, Xu WR, Yang XY, Zhu XM, Du GHSalidroside is a major constituent of Rhodiola rosea L. that elicits beneficial effects for ischemic cardiovascular diseases. The aim of this study was to investigate the protective effects of salidroside on endothelial cells apoptosis induced by the hypoxia mimicking agent, cobalt chloride. After challenge with cobalt chloride for 24 h, loss of cell viability and excessive apoptotic cell death were observed in EA.hy926 endothelial cells, and the level of intracellular reactive oxygen species (ROS) increased concentration-dependently. However, the endothelial cell apoptosis and excessive ROS generation were attenuated markedly by salidroside pretreatment. In addition, salidroside inhibited activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) induced by cobalt chloride, decreased expression of Bax and rescued the balance of pro- and anti-apoptotic proteins. These findings suggest that salidroside protects endothelial cells from cobalt chloride-induced apoptosis as an antioxidant and by regulating Bcl-2 family. Salidroside may represent a novel therapeutic agent for the treatment and prevention of hypoxia and oxidative stress-related diseases.

Clin Chim Acta. 2009 Aug 1; Hu ZY, Zhao YS, Wu D, Cheng ZNBACKGROUND: We determined if if endogenous cortisol 6beta-hydroxylation clearance [CL(m(6beta))] could be used as a reliable index for in vivo CYP3A phenotyping (including both hepatic and intestinal CYP3A activity). Methods: In this study, 16 healthy volunteers received a single 7.5 mg oral dose of midazolam (MDZ). Blood samples were drawn up to 24 h after dosing. Urine samples were collected at various time periods after dosing. MDZ, 1-hydroxymidazolam (1-OHMDZ), cortisol (F) and 6beta-hydroxycortisol (6beta-OHF) in plasma or urine were determined by high-performance liquid chromatography with ultraviolet absorbance detection (HPLC-UV). RESULTS: CL(m(6beta)) was poorly correlated (P>0.2) with MDZ oral clearance [CL(oral(MDZ))] and the ratio of AUC(0-infinity(1-OHMDZ)) versus AUC(0-infinity(MDZ)) [MR((AUC))]. However, when examining the data obtained from male volunteers exclusively, strong correlations were observed between CL(m(6beta)) and CL(oral(MDZ)). Larger interindividual and intraindividual variability was observed in urinary ratio of 6beta-OHF/F compared with CL(m(6beta)). Conclusion: CL(m(6beta)) can not reflect the overall CYP3A activity accurately and quantitatively in the population.

Guang Pu Xue Yu Guang Pu Fen Xi. 2009 May; 29(5): 1427-30Miao S, Sun JY, Xie YH, Wang JB, Shi XP, Ding YY, Bi LL, Gao SB, Wang SWAn analysis method was developed to determine the chemical speciation of Cu, Zn, Fe and Mn in radix scutellariae decoction using atomic absorption spectroscopy(AAS). The decoction can be divided into suspension and soluble species by 0.45 microm filter membrane and the soluble species can be separated into organism and inorganic species by LSA-10 macroporous resin. These elements in water-soluble test samples can be divided into alcohol-soluble and water-soluble by adopting n-octyl alcohol-water allocation system in man-made gastric acidity. Then, the concentration of these elements was determined by AAS, which provided more chemical speciation information about these elements instead of the total amount of them only in radix scutellariae. Deteotion limit of Cu, Zn and Mn by using the method was all 0.01 microg x mL(-1) and was 0.02 microg x mL(-1) for Fe. The RSD was in the range of 1.5%-3.6% (n=11) and the recovery rate of soluble species and inorganic species were in range of 96.7%-105.0%. The method has been successfully applied to determine the chemical speciation of Cu, Zn, Fe and Mn in radix scutellariae, which was very important for overall study of radix scutellariae.

Toxicol In Vitro. 2009 Aug 1; Lu N, Zhou G, Pei D, Yi L, Gao ZThe major pathways of protein tyrosine nitration in vivo include peroxynitrite (ONOO(-)) and heme peroxidase -NO(2)(-)-H(2)O(2) dependent reaction in which free radicals and iron catalysis are involved. In this paper, we chose three classic antioxidants (GSH, a major intracellular antioxidant; Trolox, a phenolic antioxidant without chelating effect; and DFO, a good iron chelator), to study their efficiencies against ONOO(-) or Heme/NaNO(2)/H(2)O(2) - mediated nitrative/oxidative damage to human plasma proteins in vitro. Protein nitration was efficiently inhibited by the three antioxidants regardless of nitration pathways, whereas the efficiencies of antioxidants on protein oxidation depended on the concentration of antioxidants and categories of oxidant. In both models, GSH exhibited protective activity in protein oxidation and Trolox promoted the formation of plasma protein carbonyl groups at lower concentration (0.01mM and 0.1mM). DFO dose-dependently inhibited ONOO(-)-induced protein oxidation, while it enhanced Heme/NaNO(2)/H(2)O(2)-triggered protein oxidation at lower concentration. However, both DFO and Trolox exhibited protective effect on protein carbonyl formation when the higher concentration was used. The pro-oxidant or anti-oxidant effect for these antioxidants at different concentration, may provide useful information about the selection of the suitable antioxidant and dosage in experimental and clinical application.

PLoS One. 2009; 4(8): e6520Yang HZ, Cui B, Liu HZ, Mi S, Yan J, Yan HM, Hua F, Lin H, Cai WF, Xie WJ, Lv XX, Wang XX, Xin BM, Zhan QM, Hu ZWBACKGROUND: Metastasis is the most pivotal cause of mortality in cancer patients. Immune tolerance plays a crucial role in tumor progression and metastasis. METHODS AND FINDINGS: In this study, we investigated the potential roles and mechanisms of TLR2 signaling on tumor metastasis in a mouse model of intravenously injected B16 melanoma cells. Multiple subtypes of TLRs were expressed on B16 cells and several human cancer cell lines; TLR2 mediated the invasive activity of these cells. High metastatic B16 cells released more heat shock protein 60 than poor metastatic B16-F1 cells. Importantly, heat shock protein 60 released by tumor cells caused a persistent activation of TLR2 and was critical in the constitutive activation of transcription factor Stat3, leading to the release of immunosuppressive cytokines and chemokines. Moreover, targeting TLR2 markedly reduced pulmonary metastases and increased the survival of B16-bearing mice by reversing B16 cells induced immunosuppressive microenvironment and restoring tumor-killing cells such as CD8(+) T cells and M1 macrophages. Combining an anti-TLR2 antibody and a cytotoxic agent, gemcitabine, provided a further improvement in the survival of tumor-bearing mice. CONCLUSIONS AND SIGNIFICANCE: Our results demonstrate that TLR2 is an attractive target against metastasis and that targeting immunosuppressive microenvironment using anti-TLR2 antibody is a novel therapeutic strategy for combating a life-threatening metastasis.

Homeopathy. 2009 Jul; 98(3): 165-8Waisse-Priven S, Jurj G, Lima Thomaz LC, Tierno SA, Filho WL, Sos ABThis paper describes the successful outcome of homeopathic treatment in a case of resistant livedoid vasculopathy (LV). LV is a rare disease characterized by chronic recurrent and painful ulceration of the lower limbs, frequently associated to atrophie blanche (AB), probably due to procoagulant conditions. Most literature reports single or very few cases; response to treatment is difficult, even resistant. This patient suffered LV for 7 years before seeking homeopathic treatment; ulcers recurred frequently, at intervals less than 3 months, in spite of continual use of pentoxyfilline. Configuration of signs and symptoms strongly pointed out to the prescription of homeopathic remedy Sepia succus that promptly elicited significant improvement of LV and the patient's overall state (non suppressive treatment). Considerations are made on the value of single case reports and the reliability of prescriptions grounded on consistent signs and coherence among the manifold features of individual disease.

Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.

Homeopathy. 2009 Jul; 98(3): 160-4de Araújo FR, de Castro CM, Severo MS, Diniz Mde F, Viana MT, Evêncio LBOBJECTIVE: The purpose of this study was to assess the bacteriological response in alveolitis in rats treated with the homeopathic medicine Merc solubilis (Merc sol.) 12 cH. METHODS: The study was randomized and observer blind. The animals were anesthetized and the upper right incisor extracted resulting in alveolitis. Animals were randomly assigned to groups (n=18/group): Water control, Alcohol control and Merc sol. 12 cH. These groups were subsequently divided into 3 subgroups (n=6/subgroup): Early Euthanasia (EE), Mid Euthanasia (ME) and Late Euthanasia (LE), killed at the 6th, 15th and 21st days respectively. The perialveolar microbiota was collected by swab in Brain Heart Infusion (BHI) for seeding and bacterioscopy. After seeding, the Petri dishes were incubated at 37 degrees C for 48 h. RESULTS: Quantitative and qualitative changes were observed in the perialveolar microbiota when the groups were compared. Water control and Alcohol control had the highest counts of pathogenic bacteria, the microbiotica of the Merc sol. group remained closer to normal. CONCLUSIONS: Merc sol. 12 cH did not reduce bacterial growth, but the microbiotica remained within the parameters of normality, obtaining the best results at 21 days after treatment.

Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.

Homeopathy. 2009 Jul; 98(3): 154-9Patil CR, Salunkhe PS, Gaushal MH, Gadekar AR, Agrawal AM, Surana SJBACKGROUND: Toxicodendron pubescens is a botanical name of Rhus toxicodendron (Rhus tox). This plant is widely used in its homeopathically diluted form in the treatment of inflammatory and edematous conditions. In this study, various dilutions of Rhus tox including its crude form have been evaluated for their effects on immune response in the in vivo and in vitro experimental models. METHODS: Rhus tox in the form of mother tincture, 6cH, 30cH, 200cH and 1000cH dilutions was tested through in vivo models including sheep red blood cells (SRBCs) induced cellular and humoral immune response in C57/BL6 mice. The effects of Rhus tox dilutions were also evaluated in vitro on the functions of human polymorphonuclear (PMN) cells such as phagocytosis and intracellular killing of Candida albicans, chemotaxis, and reduction of nitroblue tetrazolium (NBT) dye. RESULTS: Rhus tox was found to intensify SRBCs induced antibody titer and delayed type hypersensitivity response in mice. Even higher dilutions such as 200cH and 1000cH were found to affect the immune response; however, the crude form, mother tincture, 6cH and 30cH dilutions revealed more potent effects than the 200cH and 1000cH dilutions. In in vitro assays, all the dilutions exerted stimulation of phagocytosis, candidacidal activity and chemotaxis of human PMN cells. The NBT dye reduction assay revealed that oxidative processes in the PMN cells are accelerated in the presence of Rhus tox. This study shows that Rhus tox possesses immunostimulatory activity in its crude form as well as in homeopathically diluted forms. These effects appeared to be concentration dependent as higher dilutions had less potent effects.

QJM. 2009 Jul 22; Aronson J

Cell Res. 2009 Jul 28; Yang H, Yu Y, Li WG, Xu TL, Jiang H

Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(8): 1005-6Zhang C, Xiao Y, Taniguchi M, Baba KOBJECTIVE: To study the chemical constituents in roots of Peucedanum praeruptorum. METHOD: The constituents were isolated by column chromatography on silica gel and ODS, and identified by spectroscopic methods. RESULT: Seven compounds, alpha-D-glucopyranose-1-hexadecanoate (1), D-mannitol monohexadecanoate (2), adenosine (3), butyric acid (4), eleutheroside B, (5), apiosylskimmin (6), and mannitol (7) were isolated and identified. CONCLUSION: Compounds 1-5 were isolated from this plant for the first time.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(8): 969-72Du M, Liu S, Li M, Jin R, Kang C, Li JOBJECTIVE: To investigate the regularity of Yulian Cataplasm in vitro release and transdermal behaviors. METHOD: Improved Franz diffusion devices was used with four index ingredients as evodiamine, rutaecarpine, palmatine and berberine that were determined by HPLC in one mobile phase. RESULT: The release rates of evodiamine, rutaecarpine, palmatine and berberine were 0.0239, 0.0156, 0.0725, 0.8191 mg x cm(-2) x h(-1/2), respectivley. The transdermal rates of evodiamine, rutaecarpine, palmatine and berberine were 1.256, 1.0302, 2.8029, 20.919 microg x cm(-2) x h(-1), respectively. CONCLUSION: The releasing process of all index is in accordance with Higuchi equation and the transdermal proccess is in accordance with zero-level equation.

Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.

Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(8): 1015-7Xiong Y, Gao H, Wang Z, Zhu JOBJECTIVE: To investigate ingredient differences of Lonicera japonica bud processed by different dryness techniques. METHOD: The HPLC fingerprint was used to evaluate the quality of L. japonica by various dryness process. The analysis was performed on a Kromasil C18 (4.6 mm x 250 mm, 5 microm). Acetonitril and water containing 0.4% H3PO4 were used as mobile phases with gradient elution. The flow rate was set at 1.0 mL x min(-1), the column temperature was set at 30 degrees C, and the detection wavelength was at 238 nm. RESULT: The HPLC-fingerprint profiles of L. japonica from six different dryness techniques were determined. A total of 17 common peaks were found, but their contents from various dryness techniques were significantly different. CONCLUSION: HPLC-fingerprint technique was one of potential Process Analytical Techniques (PAT) to explore the ingredient differences in dryness process.

Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.

Angew Chem Int Ed Engl. 2009 Jul 23; Zhao L, Xie F, Cheng G, Hu Y

Biomol NMR Assign. 2009 Jun; 3(1): 95-7Zhang F, Guo C, Lou L, Lin DLipocalin2 plays an important role in the innate immune system. In this article we report the backbone and side-chain resonance assignments of rat lipocalin2 (rLcn2). These assignments provide a basis for determining the structure and dynamics of rLcn2.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(7): 861-3Liu A, Xu L, Zou Z, Yang SOBJECTIVE: To isolate and identify chemical constituents of Cassia alata. METHOD: Compounds were separated and purified by column chromatography with silica gel and Sephadex LH-20, elucidated by spectroscopic methods including 1D and 2D NMR, IR and MS techniques. RESULT: Twelve compounds were isolated from C. alata, which were identified as chrysoeriol (1), kaempferol (2), quercetin (3), 5,7,4'-trihydroflavanone (4), kaempferol-3-O-beta-D-glucopyranoside (5), kaempferol-3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (6), 17-hydrotetratriacontane (7), n-dotriacontanol (8), n-triacontanol (9), palmitic acid ceryl ester (10), stearic acid (11), palmitic acid (12). CONCLUSION: Compounds 3-12 were isolated from C. alata for the first time.

Nat Prod Commun. 2009 Jun; 4(6): 825-30Huang HL, Zhang JQ, Chena GT, Lu ZQ, Sha N, Guo DAOxyresveratrol (trans-2,4,3',5'-tetrahydroxystilbene, OXY) and resveratrol (trans-3,5,4'-trihydroxystilbene, RES) are the two most important constituents of the traditional Chinese medicine Smilax china. A reversed-phase high-performance liquid chromatographic method was developed to determine OXY and RES in rat bile and urine after oral administration of Smilax china extract. The biological samples were analyzed by HPLC on Aglient Zorbax SB-C18 column (250 x 4.6 mm, 5 microm) at a wavelength 320 nm and at a flow rate of 1.0 mL/min. The method was accurate and reproducible for determination. The cumulative excretion of OXY and RES was 0.29% and 0.97% in bile samples, 0.84% and 0.65% in urine samples, respectively.

Nat Prod Commun. 2009 Jun; 4(6): 813-8Sha N, Huang HL, Zhang JQ, Chen GT, Tao SJ, Yang M, Li XN, Li P, Guo DAA simple, sensitive and specific high-performance liquid chromatography-UV (HPLC-UV) method has been developed to simultaneously quantify the eight major bioactive phenolic compounds in Chinese propolis, namely caffeic acid, isoferulic acid, 3,4-dimethoxycinnamic acid, pinobanksin 5-methyl ether, pinocembrin, benzyl caffeate, chrysin and galangin. This HPLC assay was performed on an Agilent Zorbax Extend-C18 (250 x 4.6 mm, 5 microm) column with a gradient of methanol and 0.2% aqueous acetic acid (v/v) in 50 min, at a flow rate of 1.0 mL/min, and detected at 290 nm. All calibration curves showed good linearity (r2 > 0.999) within the test ranges. The intra- and inter-day assay precision (RSD) of eight phenolic compounds were in the range of 0.07-4.92%. The recoveries were between 98.3% and 104.8%. This assay was applied to the evaluation of nineteen samples from different origins in China. The results indicated that the developed assay could be readily utilized for the quality control of propolis.

Nat Prod Commun. 2009 Jun; 4(6): 777-82Chong W, Feng XY, Zhen GZ, Dan L, Yue DThe objective of the present study was to investigate the effects of saponins from the anomalous fruits of Gleditsia sinensis on mast cell degranulation triggered by compound 48/80 and to determine possible structure-activity relationships. Among the eleven saponins tested, four effectively inhibited beta-hexosaminidase release from rat peritoneal mast cells. Studies of structure-activity relationships indicated that saponins with an aglycone of echinocystic acid instead of oleanolic acid were more effective. A sugar chain at C-3 was essential for the inhibitory effects, and a single sugar chain was the most effective. The length and structures of the oligosaccharide chain at C-28 were also critical for the activity of the compounds, and introduction of monoterpene units to the oligosaccharide chain substantially decreased the activity. To gain insight into the mechanisms responsible for preventing mast cell degranulation, the effects of saponins on intracellular cAMP were examined. After preincubation with mast cells for different times, the four active saponins significantly increased the intracellular cAMP content. These findings suggested that the four saponins might be the active constituents of the anomalous fruits of G. sinensis for antiallergic activities, and they prevented mast cell degranulation probably by elevating intracellular cAMP levels.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(7): 854-7Li Y, Yang S, Bai SOBJECTIVE: To investigate the chemical constituents of the roots of Angelica polymorpha. METHOD: Silica gel column chromatography was employed for the isolation and purification of chemical constituents. The structures were identified on the basis of spectral data and chemical evidence. RESULT: Fourteen compounds were isolated and identified as follows, 5-hydroxy-2-[(angeloyloxy) methyl] furan [3', 2': 6, 7] chromone (1), octacosanoic acid (2), isoimperatorin (3), 3'S-(-)-O-acetylhamaudol (4), bergapten (5), iso-oxypeucedanin (6), beta-sitosterol (7), angeliticin A (8) , saxalin (9), pabulenol (10), noreugenin (11), oxypeucedanin hydrate (12), daucosterol (13), sucrose (14). CONCLUSION: Compound 1 is a new chromone, named polymorchromone A. Compounds 2, 4, 11, 13, 14 were isolated from A. polymorpha for the first time.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(7): 924-8Hua Y, Huang L, Chen M, Xiao PThe authors propose suggestions for definition of classification position, classification standard, nomenclature and naming methods of chemotype on discussing the significance of chemotype of medicinal plants. This classification of chemotype should be established in infraspecific categories of "forma". Chemotype identification mainly has two aspects. One is that the main constituents are distinct or one or two components are half or more than half of the total chemical content. The main constituents come from the same biosynthetic pathway and have some genetic stability. The other is the chemical variation is genetic. The chemotype of medicinal plants study on the classification has important theoretical and practical value for quality assessment, resource development and the genuine medicinal research. It also can ensure the safe and effective of clinical medicine.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(7): 807-11Lv J, Guo L, Huang L, Liang L, Sun Y, Zhang X, Han X, Zhang HFor optimal adaptive cultivation region selection, we used ecology factors characterized Duolun region as model area to carry out the adaptive habitat division of Paeonia lactiflora. Similar priority comparison of ecology factors.in 91 cities were calculated by Fuzzy methods, then, distance of the ecology factors were transferred to spacial model by geography information system (,GIS) and modified by soil utilization map of China. The results showed that P. lactiflora were mainly distributed in the Daxing'an Mountain, Changbaishan and qinling range which were divided into six grades of suitable regions belonging to three geographical distributed units. The most similar areas to Duolun were Huade, Xilinhaote, Suolun and Zhangbei. P. lactiflora's distribution and quality are relevant with longitude and latitude, and temperature and rainfall.

Zhongguo Zhong Yao Za Zhi. 2009 Mar; 34(6): 744-7Jia Y, Yi H, Pen B, Li J, Yang HOBJECTIVE: To explore the anti-inflammatory effect and possible mechanism of Shuang-huang-lian (SHL) microemulsion. METHOD: Rat model of pleuritis was established by thoracic injecting 0.2 mL of 1% carrageenan. Rats in the treated groups were orally administered with SHL microemulsion prescription 1, 2, and oral liquid, while those in the positive control group were given aspirin. Rats in the normal group and the model group were given equal volume of water. Each groups were given their medicine for successive 6 days. Modeling was performed 30 mins after the 5th day medication. After 12 hrs of modeling, took suction of the pleurorrhea and measured the amount of tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), prostaglandin E2 (PGE2) and protein (pro). RESULT: Compared with the normal group, all the parameters were higher in model group (TNF-alpha and IL-8 P

Biomed Chromatogr. 2009 Jul 23; Geng F, He Y, Yang L, Wang ZAngiotensin-converting enzyme (ACE) plays an important role in the renin-angiotensin system and ACE activity is usually assayed in vitro by monitoring the transformation from a substrate to the product catalyzed by ACE. A rapid and sensitive analysis method or ACE activity by quantifying simultaneously the substrate hippuryl-histidyl-leucine and its product hippuric acid using an ultra-performance liquid chromatography coupled with electrospray ionization-mass spectrometry (UPLC-MS) was first developed and applied to assay the inhibitory activities against ACE of several natural phenolic compounds. The established UPLC-MS method showed obvious advantages over the conventional HPLC analysis in shortened running time (3.5 min), lower limit of detection (5 pg) and limit of quantification (18 pg), and high selectivity aided by MS detection in selected ion monitoring (SIM) mode. Among the six natural products screened, five compounds, caffeic acid, caffeoyl acetate, ferulic acid, chlorogenic acid and resveratrol indicated potent in vitro ACE inhibitory activity with IC(50) values of 2.527 +/- 0.032, 3.129 +/- 0.016, 10.898 +/- 0.430, 15.076 +/- 1.211 and 6.359 +/- 0.086 mm, respectively. A structure-activity relationship estimation suggested that the number and the situation of the hydroxyls on the benzene rings and the acrylic acid groups may play the most predominant role in their ACE inhibitory activity. Copyright (c) 2009 John Wiley & Sons, Ltd.

Zhongguo Zhong Yao Za Zhi. 2009 Apr; 34(7): 884-8Dong Y, Zhang Y, Yang Q, Li Y, Zhu XOBJECTIVE: To research the intestinal absorption characteristics of paeoniflorin in extractive Radix Paeoniae Alba in the different intestinal segment, and the interaction with P-glycoprotein. METHOD: Paeoniflorin, a representative component in extractive Radix Paeoniae Alba, on the intestinal absorption was studied in vitro using everted gut sacs model and detected by HPLC method. The absorption characteristics was evaluated by the absorption parameter. RESULT: The absorption of paeoniflorin was linearity at different intestine segment and dose, and the square of regrees correlation coefficient exceed 0.9 (R2 > 0.9), which consistent with zero order rate process. The Kalpha of paeoniflorin showed a dose-dependent increase along with the raised dose of extractive Radix Paeoniae Alba, indicated it was a mechanism of passive absorption. The absorption rate was jejunum > ileum > colon. Verapamil (100 micromol x L(-1)), a inhibitor of the P-glycoprotein, can remarkable increase the absorption of the paeoniflorin in ileum (P < 0.05). After administer the extractive Radix Paeoniae Alba for 5 days, the extraction of Rho123 is significantly increase in ileum (P < 0.01). CONCLUSION: The intestinal absorption of paeoniflorin is zero order rate process and passive absorption. Paeoniflorin is a substrate of P-glycoprotein, and extractive Radix Paeoniae Alba could induce the expression of the P-glycoprotein.

J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jul 17; Deng P, Chen X, Tang Y, Wang Y, Zhang H, Zhong DArotinoid acid (Ro 13-7410) is the third generation of synthetic retinoid, which was developed for the treatment of psoriasis and other hyperkeratotic skin disorders. The therapeutically active dose is less than 0.5mug/kg body weight/day. To investigate the pharmacokinetics of arotinoid acid, a sensitive and selective liquid chromatographic-tandem mass spectrometric method (LC-MS/MS) for the determination of arotinoid acid in human plasma was developed and validated. The sample processing was carried out in the dark to minimize photodegradation of the analytes. Arotinoid acid and the internal standard (IS), acitretin, were extracted from plasma samples using solid phase extraction with Oasis HLB cartridges. Chromatographic separation was achieved on a Zorbax Extend C(18) column (150mmx4.6mm, i.d., 5mum) using methanol:acetonitrile:5mM ammonium acetate (48:32:20, v/v/v) as the mobile phase at a flow rate of 0.8mL/min. The detection was carried out in multiple reaction monitoring (MRM) mode via negative electrospray ionization (ESI) interface. The lower limit of quantification (LLOQ) achieved was 37.1pg/mL with intra-day and inter-day precision (RSD) of 8.7% and 8.5%, and accuracy (RE) of 2.0%. Inter-day and intra-day RSD for three quality control levels (QCs) across validation runs were less than 11.0% and the accuracy ranged from 1.9% to 3.3%. The validated LC-MS/MS method was applied to a phase I clinical pharmacokinetic study after a single oral administration of 40mug arotinoid trometamol to healthy subjects.

J Alzheimers Dis. 2009 Jul 20; Hou Y, Yu YB, Liu G, Luo YSubstantial evidence supports a central role of Abeta in the pathogenesis of Alzheimer's disease (AD). We have demonstrated that FLZ, a synthetic cyclic analogue of natural squamosamide, exhibits neuroprotective actions in cells and mouse models, suggesting future investigation of FLZ as a candidate compound for the treatment of AD. In this study, we found that production of amyloid-beta (Abeta) was reduced by FLZ in Abeta-expressing neuroblastoma cells, which correlates with an increase in the soluble alpha-secretase derived fragment of the amyloid-beta protein precursor (sAbetaPPalpha) in the medium. Moreover, the active form of ADAM10 and AbetaPP were elevated at the cell surface of FLZ-treated cells, consistent with an enhanced co-localization of ADAM10 and AbetaPP on the membrane. Pretreatment with brefeldin, a protein trafficking inhibitor, blocked FLZ-induced translocation of ADAM10 to the cell surface and release of sAbetaPPalpha to the culture medium. Furthermore, oral administration of FLZ to APPswe/PS1 transgenic mice significantly reduced the levels of Abeta, parallel with activation of ADAM10, in the hippocampus. In silico prediction indicates that the structure of FLZ agree with the drug-like rules for absorption and permeability. These findings suggest that reducing Abeta production by FLZ may be mediated by its promotion of AbetaPP non-amyloidogenic alpha-secretase processing, and FLZ has therapeutic potential for the treatment of AD.

Zhongguo Zhong Yao Za Zhi. 2009 Mar; 34(6): 766-9Yan H, He W, Li X, Nie C, Wang L, Li X, Wu L, Tu POBJECTIVE: To establish a HPLC method to determine the carnosic acid in the stomach and intestine of rats and study its tissue distribution characteristics. METHOD: After intragastric administration of carnosic acid (90 mg x kg(-1)), rats for each time-point were sacrificed by decapitation. After removal of the blood, various tissues were rapidly removed and weighted, all tissues were treated with a series of pretreatment before HPLC. Chromatographic separation was achieved on a Kromasil C18 column (4.6 mm x 150 mm, 5 microm) protected by an ODS guard column at 25 degrees C, using acetonitrile-0.1% phosphoric acid solution (55:45) as mobile phase, at a flow rate of 1 mL x min(-1). The wavelength of the UV detector was set at 210 nm for carnosic acid and internal standard. RESULT: Good linearities were obtained in every tissue over a range of 0.3212-160.6 mg x L(-1). The recovery, intra-day and inter-day precision and accuracy of three concentrations of carnosic acid in tissues met the requirements of methodology. And the stability of the tissue samples were also validated. The results of distribution in stomach and intestine showed that the highest concentration was (307.1 +/- 119.2) microg x g(-1) in stomach and (33.32 +/- 17.70) microg x g(-1) in intestine after intragastric administration of carnosic acid. CONCLUSION: The HPLC method was established to determine the concentration of carnosic acid in tissues. This method is quick, precise, and reproducible. It is the first time to study the tissue distribution of carnosic acid in rats after intragastric administration.

Cancer Biol Ther. 2009 Sep 6; 8(17): Sun QM, Miao ZH, Lin LP, Gui M, Zhu CH, Xie H, Duan WH, Ding JAberrant activation of the epidermal growth factor receptor (EGFR) is closely associated with malignant progression of tumors. EGFR inhibitors have been used successfully in clinic in the treatment of solid tumors. In the present study, we revealed that BB, a new synthetic quinonazoline derivative, was a potent EGFR inhibitor. BB selectively inhibited EGFR with a IC(50) value of 50 +/- 37 nM, at least 32-fold more potent than suppressed all other 10 tested receptor tyrosine kinases including the same family member ErbB2 (IC(50) = 5.6 +/- 3.2 muM). BB effectively abrogated autophosphorylation of the EGF-stimulated EGFR and phosphorylation of its key downstream signaling molecules ERK and AKT in A549 cells. BB was shown to suppress EGF-stimulated proliferation of A549 cells with an apparently lower IC(50) value (0.33 +/- 0.07 muM) than that (2.7 +/- 0.4 muM) for the serum-stimulated cells. BB also inhibited the EGF-independent proliferation of a panel of tumor cells. In addition, BB exhibited anti-angiogenesis activity, as evidenced by antagonizing EGF-induced HMEC-1 migration in vitro, blocking HMEC-1 tube formation, and inhibiting microvessel sprouting from rat aortic rings. Most importantly, BB prominently inhibited in vivo tumorigenesis of NIH3T3 cells specifically driven by the activation-mutated EGFR genes. As reported, normal NIH3T3 cells lack tumorigenicity in nude mice. NIH3T3 cells transfected with the EGFR gene with activating mutation (A750P or L858R) produced rapidly growing xenografts in nude mice. BB, when given orally at 100 mg/kg consecutively for 2 weeks, prominently inhibited the growth of the xenografts and reduced the number of microvessels. Taken together, the data indicate that BB is a new selective EGFR inhibitor with potent antitumor activity, revealing its potential as a promising anticancer candidate.

Yao Xue Xue Bao. 2009 May; 44(5): 449-55Li XY, Chen XGProtein kinase C beta (PKCbeta) is a multifunctional serine/threonine protein kinase, which plays an important role in many cell signaling pathways. PKCbeta takes part in multiple physiological processes, including regulation of the cell cycle, differentiation, proliferation, apoptosis and angiogenesis. Increased PKCbeta activity has been observed in many human cancers, such as colon, breast and haematological malignancies. At present, Enzastaurin is mostly studied in preclinical and clinical studies, which is a selective PKCbeta inhibitor. This review focuses on the functional properties of PKCbeta, its role played in tumors and Enzastaurin.

Yao Xue Xue Bao. 2009 May; 44(5): 443-8Ying J, Lü Y, Du GHAmorphous is a special physical state of solid compounds that the positions of the molecules or atoms have no long-range order. Sometimes amorphous compounds have better bioavailability, or achieve ultra-fast absorption in situation of acute and intermittent symptoms than that of morphous compounds, thus change drug efficacy. Besides, different pharmaceutical preparing methods can lead to different characters. Research of amorphous compounds has been a hotspot, both in research field and industry world. However, there are challenges as amorphous compounds could be unstable; unexpected adverse drug reactions may also exist. In this review, recent progress in the research of amorphous pharmaceutical compounds both in the research field and the pharmaceutical industry is reviewed. Factors which can influence the efficacy of amorphous pharmaceuticals are summarized. The prospect of amorphous techniques is also discussed.

Microsc Res Tech. 2009 Jul 20; Choy SK, Tong CS, Zhao ZZThis article presents a novel and effective multistage system for classifying Chinese Materia Medica microscopic starch grain images. The proposed classification system is constructed based on the Gaussian mixture model-based clustering, the feature assignment algorithm, and the similarity measurement. Several features for each starch grain image are extracted and every class of drug is represented by a set of characteristic features. For each stage of the system, only one feature is chosen and assigned to that stage via the feature assignment algorithm, and the corresponding characteristic features are subdivided into smaller subsets based on clustering techniques. At the final stage, each subset contains a certain class of drugs (with corresponding characteristic features) and similarity measurement is carried out for starch grain classification. Three sets of the current state-of-the-art starch grain features including the granulometric size distribution, the chord length distribution, and the wavelet signature are used to construct the system. Experimental results on a database of 240 images of 24 classes of drugs reveal the superior performance of the multistage system. Comparison with the traditional starch grain classification approaches indicates that our proposed multistage method produces a marked improvement in classification performance. Microsc. Res. Tech. 2009. (c) 2009 Wiley-Liss, Inc.

J Cell Biochem. 2009 Jul 21; Ji L, Liu T, Chen Y, Wang ZPyrrolizidine alkaloid (PA) clivorine, isolated from traditional Chinese medicinal plant Ligularia hodgsonii Hook, has been shown to induce apoptosis in hepatocytes via mitochondrial-mediated apoptotic pathway in our previous research. The present study was designed to observe the protection of N-acetyl-cysteine (NAC) on clivorine-induced hepatocytes apoptosis. Our results showed that 5 mM NAC significantly reversed clivorine-induced cytotoxicity via MTT and Trypan Blue staining assay. DNA apoptotic fragmentation analysis and Western-blot results showed that NAC decreased clivorine-induced apoptotic DNA ladder and caspase-3 activation. Further results showed that NAC inhibited clivorine-induced Bcl-xL decrease, mitochondrial cytochrome c release and caspase-9 activation. Intracellular glutathione (GSH) is an important ubiquitous redox-active reducing sulfhydryl (--SH) tripeptide, and our results showed that clivorine (50 microM) decreased cellular GSH amounts and the ratio of GSH/GSSG in the time-dependent manner, while 5 mM NAC obviously reversed this depletion. Further results showed that GSH synthesis inhibitor BSO augmented clivorine-induced cytotoxicity, while exogenous GSH reversed its cytotoxicity on hepatocytes. Clivorine (50 microM) significantly induced cellular reactive oxygen species (ROS) generation. Further results showed that 50 microM Clivorine decreased glutathione peroxidase (GPx) activity and increased glutathione S transferase (GST) activity, which are both GSH-related antioxidant enzymes. Thioredoxin-1 (Trx) is also a ubiquitous redox-active reducing (--SH) protein, and clivorine (50 microM) decreased cellular expression of Trx in a time-dependent manner, while 5 mM NAC reversed this decrease. Taken together, our results demonstrate that the protection of NAC is major via maintaining cellular reduced environment and thus prevents clivorine-induced mitochondrial-mediated hepatocytes apoptosis. J. Cell. Biochem. (c) 2009 Wiley-Liss, Inc.