Interaction between gemfibrozil and warfarin: case report and review of the literature.

Pharmacotherapy. 2009 Jun; 29(6): 744-8Dixon DL, Williams VGAbstract Possible procoagulant effects can occur when lipid-lowering fibric acid derivatives, such as gemfibrozil and fenofibrate, are taken concomitantly with warfarin. Although there are several detailed reports of fenofibrate potentiating the anticoagulant effects of warfarin, few case reports have been published regarding an interaction between gemfibrozil and warfarin. We describe a 62-year-old man who was taking warfarin for paroxysmal atrial fibrillation and came to the anticoagulation clinic for a routine follow-up. For 9 months, the patient's international normalized ratio (INR) had been stable (target range 2.0-3.0) with warfarin 45 mg/week. At this clinic visit, however, his INR was supratherapeutic at 5.8; the only identified change in his drug therapy was the addition of gemfibrozil 600 mg twice/day, started 3 weeks earlier. The patient denied any changes in his dietary intake of vitamin K, alcohol use, or addition of nonprescription or herbal agents. Recent laboratory tests revealed no signs of thyroid abnormalities and only an insignificant elevation in his alanine aminotransferase level. His warfarin dose was decreased to 35-37.5 mg/week (a 22% reduction), and a therapeutic INR was maintained until gemfibrozil was later discontinued because of myalgia. After consecutive subtherapeutic INRs, his warfarin dose was increased to 45 mg/week and a therapeutic INR was maintained. Use of the Drug Interaction Probability Scale indicated that the likelihood of the gemfibrozil-warfarin interaction was probable. The exact mechanism of the proposed interactions between fibric acid derivatives and warfarin remains unknown but may be multifactorial through inhibition of cytochrome P450 isoenzymes, displacement from protein binding sites, or changes in coagulation factor synthesis. Regardless of the fibric acid derivative chosen, an empiric dosage reduction of 20% and close INR monitoring are warranted in patients receiving warfarin.

Anti-allergic effects of herbal product from Allium cepa (bulb).

J Med Food. 2009 Apr; 12(2): 374-82Kaiser P, Youssouf MS, Tasduq SA, Singh S, Sharma SC, Singh GD, Gupta VK, Gupta BD, Johri RKAllium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.

Integration of complementary medical treatments with rehabilitation from the perspectives of patients and their caregivers: A qualitative inquiry.

Clin Rehabil. 2009 May 15; Chang LH, Wang JObjective: This article uses a qualitative design and examines how patients and their caregivers integrate pluralistic health practices into rehabilitation from their perspectives. Design: Ethnography was used as the framework for research design. Data were collected via participant observation, taped in-depth interviews and regular chart review, and all interviews were transcribed verbatim. Setting: An inpatient rehabilitation unit in Taiwan. Subjects: Twenty-one patients, their caregivers and their rehabilitation professionals. Results: The patients and their caregivers used pluralistic illness explanations and treatments to make sense of their suffering, to control healing and to find the hope that rehabilitation professionals often deliberately avoided giving. Spiritual healing and therapies related to Traditional Chinese Medicine, such as functional food and herbal medicines, were popular alternative therapeutics. Although the patients and their caregivers perceived opposition from the medical staff on the unit, they used a variety of covert strategies to integrate their pluralistic illness explanations and treatments into their daily routines without openly challenging the rehabilitation primacy. Conclusion: Aware of the rehabilitation staff's opposition, the patients and caregivers resorted to a variety of underground strategies to conceal their use of complementary medical treatments.

Histological patterns in drug-induced liver disease.

J Clin Pathol. 2009 Jun; 62(6): 481-92Ramachandran R, Kakar SThe diagnosis of drug-induced liver injury (DILI) is a challenging problem, often confounded by incomplete clinical information and the difficulty of eliciting exposure to herbal products, over-the-counter agents and toxins. The task is further rendered difficult on biopsy, as drugs can mimic all the patterns found in primary liver disease. Acute hepatitis, with or without cholestasis, is the most common histological pattern of DILI, and drugs such as acetaminophen are the leading causes of acute liver failure. Most cases of DILI resolve on discontinuation of the drug, but recovery can take months or rarely the disease can progress despite drug withdrawal. Drugs such as methotrexate can lead to chronic hepatitis and cirrhosis, while others such as minocycline, nitrofurantoin and methyldopa are implicated in autoimmune hepatitis. Prolonged cholestasis and ductopenia resembling primary chronic biliary disease can occur. Drug-induced steatohepatitis is also an uncommon pattern, but is well described with drugs such as amiodarone and irinotecan. In the presence of risk factors such as obesity and diabetes, some drugs such as tamoxifen, oestrogens and nifedipine can precipitate or exacerbate steatohepatitis. Other observed patterns include granulomatous hepatitis, vascular injury (eg, sinusoidal obstruction syndrome), Ito cell lipidosis and neoplasms (eg, adenomas).

In vitro anti-fibrotic activities of herbal compounds and herbs.

Nephrol Dial Transplant. 2009 May 27; Hu Q, Noor M, Wong YF, Hylands PJ, Simmonds MS, Xu Q, Jiang D, Hendry BM, Xu QBACKGROUND: We recently developed high-throughput assays of inflammation-independent anti-fibrotic activities based on TGF-beta1-induced total collagen accumulation and nodule formation in normal rat kidney fibroblasts. METHODS: These assays were applied to examine the anti-fibrotic activities of 21 compounds isolated from plants used in Chinese medicine and methanol extracts of 12 Chinese herbs. Lactate dehydrogenase release assay and cell detachment index were used to monitor cytotoxicity. Changes in fibrogenic molecular markers were observed by reverse transcriptase quantitative polymerase chain reaction and high-content imaging analysis of immunofluorescence. RESULTS: Three flavonoids (quercetin, baicalein and baicalin) and two non-flavonoids (salvianolic acid B and emodin) demonstrated anti-fibrotic activities in both total collagen accumulation and nodule formation assays. The remaining 16 compounds had little anti-fibrotic effect or were cytotoxic. The anti-fibrotic compounds suppressed collagen I expression at both mRNA and protein levels and also variably suppressed alpha-smooth muscle actin expression and bromodeoxyuridine incorporation. Methanol extracts of Scutellaria baicalensis Georgi, Salvia miltiorrhiza Bunge and Rheum palmatum L., which are rich sources of baicalein, baicalin, salvianolic acid B and emodin, respectively, also showed in vitro anti-fibrotic activities. CONCLUSIONS: Five herbal compounds and three herbal extracts have in vitro anti-fibrotic activities. These data warrant further studies on these anti-fibrotic entities and suggest it a promising strategy to discover new anti-fibrotic drugs by screening more plant materials.

Hypoglycemic effect of quassinoids from Brucea javanica (L.) Merr (Simaroubaceae) seeds.

J Ethnopharmacol. 2009 May 8; Noorshahida A, Wong TW, Choo CYETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Brucea javanica (L.) Merr (Simaroubaceae) are recommended by traditional practitioners for the treatment of diabetes mellitus. Aim of the Study: To identify the compounds responsible for blood glucose lowering effect and evaluate the acute toxicity of the compounds. MATERIALS AND METHODS: Extracts, fractions and subfractions were administered to normoglycemic mice and the blood glucose concentration was monitored for 8h. Bioactive compounds isolated through column chromatography were administered to normoglycemic mice and streptozotocin (STZ) rats with monitoring of blood glucose concentration at 0-8h. The acute toxicity was evaluated in mice. RESULTS: Bioactivity guided fractionation led to the isolation of bruceines E (1) and D (2). Normoglycemic mice administered with 1mg/kg of 1 and 2 exhibited significant blood glucose concentration reduction of 40.07+/-11.45% and 48.82+/-13.34 %, respectively. STZ induced diabetic rats administered with 1 and 2 exhibited significant blood glucose concentration reduction of 73.57+/-13.64% and 87.99+/-2.91%, respectively. CONCLUSION: The reduction of blood glucose concentration by both bruceines were comparable to glibenclamide and they might act as an insulin secretagogue. The presence of a hydroxyl moiety at C(2) in 1 reduced the toxic effect by nine fold compared to 2.

Herbal Medicines in the Management of Urolithiasis: Alternative or Complementary?

Planta Med. 2009 May 14; Butterweck V, Khan SRKidney stone formation or urolithiasis is a complex process that results from a succession of several physicochemical events including supersaturation, nucleation, growth, aggregation, and retention within the kidneys. Epidemiological data have shown that calcium oxalate is the predominant mineral in a majority of kidney stones. Among the treatments used are extracorporeal shock wave lithotripsy (ESWL) and drug treatment. Even improved and besides the high cost that imposes, compelling data now suggest that exposure to shock waves in therapeutic doses may cause acute renal injury, decrease in renal function and an increase in stone recurrence. In addition, persistent residual stone fragments and the possibility of infection after ESWL represent a serious problem in the treatment of stones. Furthermore, in spite of substantial progress in the study of the biological and physical manifestations of kidney stones, there is no satisfactory drug to use in clinical therapy. Data from IN VITRO, IN VIVO and clinical trials reveal that phytotherapeutic agents could be useful as either an alternative or an adjunctive therapy in the management of urolithiasis. The present review therefore critically evaluates the potential usefulness of herbal medicines in the management of urolithiasis.

Yi-gan san as adjunctive therapy for treatment-resistant schizophrenia: an open-label study.

Clin Neuropharmacol. 2009 Jan-Feb; 32(1): 6-9Miyaoka T, Furuya M, Yasuda H, Hayashida M, Nishida A, Inagaki T, Horiguchi JBACKGROUD:: Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS; yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in patients with dementia and borderline personality disorder. We aimed at evaluating both the efficacy and safety of YGS in patients with treatment-resistant schizophrenia. METHODS:: Thirty-four patients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (YGS-free) group (n = 25) and treated in a 4-week open-label study with YGS at an average daily dosage of 6.7 +/- 2.5 g (range, 2.5-7.5 g). Psychometric instruments used to assess efficacy included the Positive and Negative Syndrome Scale for Schizophrenia and the Drug-Induced Extrapyramidal Symptom Scale. RESULTS:: A significant decrease was observed at 2 weeks and at 4 weeks in each Positive and Negative Syndrome Scale for Schizophrenia subscale score in the YGS group, but this was not observed in the control group. However, the Drug-Induced Extrapyramidal Symptom Scale total score did not change in both groups. CONCLUSIONS:: In this open-label pilot study, patients treated with YGS showed a statistically significant reduction on clinician-rated scales. The present findings suggest that an adjunction of YGS might be effective for treatment-resistant schizophrenia.

Chinese slimming capsules containing sibutramine sold over the internet: a case series.

Dtsch Arztebl Int. 2009 Mar; 106(13): 218-22Müller D, Weinmann W, Hermanns-Clausen MBACKGROUND: In recent years, the market for dietary supplements has grown. International products are readily available for purchase over the Internet. We report 17 cases of poisoning with a single product, said to be of purely herbal origin, that was bought over the Internet. A complete declaration of the ingredients was not available. METHODS: We performed a retrospective study of cases of poisoning documented by the Göttingen and Freiburg poison information centers from 2005 to 2008. In 4 cases, we were able to perform toxicological analyses of leftover capsules and urine samples. RESULTS: The manifestations of poisoning in the 17 documented cases included malaise, tachycardia, headache, agitation, arterial hypertension, nausea, vomiting, dyspnea, insomnia, left-sided chest pressure, elevated temperature, and, in two cases, psychosis after the substance was combined with atomoxetine and methylphenidate and with citalopram, olanzapine, and chlorprothixene. The frequency of cases rose markedly in the last year of the study. The toxicological analyses of all samples studied revealed sibutramine. The dose in each capsule was nearly twice the maximum daily dose sibutramine in the medication containing this substance that is licensed for use in Germany. CONCLUSIONS: Products available without a prescription whose contents are claimed to be purely herbal may nonetheless contain synthetic substances in concentrations far above the therapeutic range and may be a cause of poisoning. When taking the history of a patient possibly suffering from an intoxication, the physician should ask specifically about drugs, dietary supplements, and so-called lifestyle products that were obtained without a prescription. It would be desirable for the contents of all such products to be declared, as required by law, so that their suitability for the market can be checked.

Emerging significance of flavonoids as p-glycoprotein inhibitors in cancer chemotherapy.

J Pharm Pharm Sci. 2009; 12(1): 46-78Bansal T, Jaggi M, Khar R, Talegaonkar SChemotherapy forms the mainstay of cancer treatment particularly for patients who do not respond to local excision or radiation treatment. However, cancer treatment by drugs is seriously limited by P-glycoprotein (P-gp) associated multi-drug resistance (MDR) in various tumor cells. On the other hand, it is now widely recognized that P-gp also influences drug transport across various biological membranes. P-gp transporter is widely present in the luminal surface of enterocytes, biliary canalicular surface of hepatocytes, apical surface of proximal tubular cells of kidney, endothelial cells of blood brain barrier, etc. thus affecting absorption, distribution, metabolism and excretion of xenobiotics. Clinical significance of above mentioned carrier is appreciated from the fact that more than fifty percent of existing anti-cancer drugs undergo inhibitable and saturable P-gp mediated efflux. Consequently, there is an increasing trend to optimize pharmacokinetics, enhance antitumour activity and reduce systemic toxicity of existing anti-cancer drugs by inhibiting P-gp mediated transport. Although a wide variety of P-gp inhibitors have been discovered, research efforts are underway to identify the most appropriate one. Flavonoids (polyphenolic herbal constituents) form the third generation, non-pharmaceutical category of P-gp inhibitors. The effects produced by some of these components are found to be comparable to those of well-known P-gp inhibitors verapamil and cyclosporine. Identification of effective P-gp modulator among herbal compounds have an added advantage of being safe, thereby making them ideal candidates for bioavailability enhancement, tissue-penetration (e.g. blood brain barrier (BBB)), decreasing biliary excretion and multi-drug resistance modulating agents. The dual effects, i.e. P-gp modulation and antitumor activity, of these herbal derivatives may synergistically act in cancer chemotherapy. This paper presents an overview of the investigations on the feasibility and application of flavonoids as P-gp modulators for improved efficacy of anti-cancer drugs like taxanes, anthracyclines, epipodophyllotoxins, camptothecins and vinca alkaloids. The review also focuses on flavonoid-drug interactions as well as the reversal activity of flavonoids useful against MDR. In addition, the experimental models which could be used for investigation on P-gp mediated efflux are also discussed.

Uses of medicinal plants by Haitian immigrants and their descendants in the Province of Camaguey, Cuba.

J Ethnobiol Ethnomed. 2009 May 18; 5(1): 16Volpato G, Godinez D, Beyra A, Barreto AABSTRACT: BACKGROUND: Haitian immigrants played an important role shaping Cuban culture and traditional ethnobotanical knowledge. An ethnobotanical investigation was conducted to collect information on medicinal plant use by Haitians immigrants and their descendants in the Province of Camaguey, Cuba. METHODS: Information was obtained from semi-structured interviews with Haitian immigrants and their descendants, direct observations, and by reviewing reports of traditional Haitian medicine in the literature. RESULTS: Informants reported using 123 plant species belonging to 112 genera in 63 families. Haitian immigrants and their descendants mainly decoct or infuse aerial parts and ingest them, but medicinal baths are also relevant. Some 22 herbal mixtures are reported, including formulas for a preparation obtained using the fruit of Crescentia cujete. Cultural aspects related to traditional plant posology are also addressed, as well as changes and adaptation of Haitian medicinal knowledge with emigration and integration over time. CONCLUSIONS: The rapid disappearance of Haitian immigrants' traditional culture due to integration and urbanization suggests that unrecorded ethnomedicinal information may be lost forever. Given this, as well as the poor availability of ethnobotanical data relating to traditional Haitian medicine, there is an urgent need to record this knowledge.

Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats.

J Ethnopharmacol. 2009 May 4; 123(1): 22-6Singh J, Kakkar PETHNOPHARMACOLOGICAL RELEVANCE: Berberis aristata DC root is used in traditional medicine for a number of ailments including metabolic disorders. AIM OF THE STUDY: The aim of the present study was to explore the antihyperglycemic and antioxidant potential of 50% aqueous ethanolic root extract of Berberis aristata (BA) in alloxan induced diabetic rats. MATERIALS AND METHODS: BA root extract (250 mg/kg) was administered to diabetic rats and standard drug glybenclamide (0.6 mg/kg) to group serving as positive control. Effect of extract on antioxidant and carbohydrate metabolism regulating enzymes of liver was studied in diabetic rats along with its safety parameters. RESULTS: The main constituents of root were identified as berberine, berbamine and palmatine through HPTLC. The extract besides being safe, lowered the blood glucose significantly without any hypoglycemic effect on their control counterparts. It increased CAT, SOD, GPx, GR activity significantly and reduced lipid peroxidation (41.6%) and protein carbonylation (30.15%). It also increased the glucokinase and glucose-6-phosphate dehydrogenase activities and decreased glucose-6-phosphatase activity in diabetic rats which play a critical role in glucose homeostasis. CONCLUSION: Thus, the extract of Berberis aristata (root) has strong potential to regulate glucose homeostasis through decreased gluconeogenesis and oxidative stress.

Optimising resolution for a preparative separation of Chinese herbal medicine using a surrogate model sample system.

J Chromatogr A. 2009 May 3; Ye H, Ignatova S, Peng A, Chen L, Sutherland IThis paper builds on previous modelling research with short single layer columns to develop rapid methods for optimising high-performance counter-current chromatography at constant stationary phase retention. Benzyl alcohol and p-cresol are used as model compounds to rapidly optimise first flow and then rotational speed operating conditions at a preparative scale with long columns for a given phase system using a Dynamic Extractions Midi-DE centrifuge. The transfer to a high value extract such as the crude ethanol extract of Chinese herbal medicine Millettia pachycarpa Benth. is then demonstrated and validated using the same phase system. The results show that constant stationary phase modelling of flow and speed with long multilayer columns works well as a cheap, quick and effective method of optimising operating conditions for the chosen phase system-hexane-ethyl acetate-methanol-water (1:0.8:1:0.6, v/v). Optimum conditions for resolution were a flow of 20ml/min and speed of 1200rpm, but for throughput were 80ml/min at the same speed. The results show that 80ml/min gave the best throughputs for tephrosin (518mg/h), pyranoisoflavone (47.2mg/h) and dehydrodeguelin (10.4mg/h), whereas for deguelin (100.5mg/h), the best flow rate was 40ml/min.

Head lice.

Clin Evid (Online). 2009; 2009: Burgess IFINTRODUCTION: Head lice can only be diagnosed by finding live lice, as eggs take 7 days to hatch and may appear viable for weeks after death of the egg. Infestation may be more likely in school children, with risks increased in children with more siblings, longer hair, and of lower socioeconomic group. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for head lice? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: dimeticone, herbal and essential oils, insecticide combinations, lindane, malathion, mechanical removal by combing ('bug busting'), oral trimethoprim-sulfamethoxazone (co-trimoxazole, TMP-SMX), permethrin, phenothrin, and pyrethrum.

A promising approach for understanding the mechanism of Traditional Chinese Medicine by the aggregation morphology.

J Ethnopharmacol. 2009 Jun 22; 123(2): 267-74Hu J, Wu Z, Yan J, Pang W, Liang D, Xu XOBJECTIVE: Previous work has found that the Traditional Chinese Medicine (TCM) form aggregates in the aqueous solution, and the activities of two Chinese herbal formulae against three cardiovascular targets were aggregates-related. This paper further studied the molecular morphology composed of aggregation and single active molecule in TCM. METHODS: We take Pueraria lobata (Willd.) Ohwi (PUE) as an example. By means of dynamic light scattering (DLS), transmission electron microscopy (TEM), and high performance liquid chromatography-mass spectrometry (HPLC-MS), the mechanism and active components of the aggregates in PUE have been studies. Besides the relationship between aggregation and therapeutic activities in the vivo level has been studied by hemorheological method. RESULTS: Puerarin, daidzein, daidzin, genistein, these cardiovascular bioactive compounds existed in the aggregates. Three kinds of aggregation processes by the bioactive molecules in the solution were elucidated: (1) the aggregation of single molecule oneself; (2) the aggregation between different single molecules; (3) the aggregation between different single molecules and the primary metabolites. Furthermore, the therapeutic activity of PUE solution was aggregates-related in vivo level. CONCLUSIONS: The aggregation morphology of molecules in TCM might be a promising way to study the mechanism of TCM, even to develop an approach of new nanomedicine of TCM.

Potential Role of Borreria hispida in Ameliorating Cardiovascular Risk Factors.

J Cardiovasc Pharmacol. 2009 May 18; Vasanthi HR, Mukherjee S, Lekli I, Ray D, Veeraraghavan G, Das DKBorreria hispida (BHE), a weed of Rubiaceae family, is being used from time immemorial as an alternative therapy for diabetes. To evaluate the scientific background of using BHE as therapy to reduce cardiovascular risk, a group of rats were given BHE for a period of 30 days, whereas control animals were given the vehicle only. The animals were sacrificed, the hearts were isolated, and perfused with buffer. All the hearts were subjected to 30-minute ischemia followed by 2-hour reperfusion. Compared with vehicle-treated rats, BHE-treated rat hearts showed improved post-ischemic ventricular function and exhibited reduced myocardial infarct size and cardiomyocyte apoptosis. The level of cytochrome c expression and caspase 3 activation was also reduced. BHE elevated antiapoptotic proteins Bcl-2 and heme oxygenase-1 and stimulated the phosphorylation of survival protein Akt simultaneously decreasing the apoptotic proteins Bax and Src. In addition, BHE enhanced the protein expression of peroxisome proliferator-activated receptor-gamma, peroxisome proliferator-activated receptor-delta, and Glut-4, probably revealing the antiobese and antidiabetic potential of BHE. These results indicate that treatment with BHE improves cardiac function and ameliorates various risk factors associated with cardiac disease, suggesting that BHE can be considered as a potential plant-based nutraceutical and pharmaceutical agent for the management of cardiovascular diseases.

An herbal decoction of Radix astragali and Radix angelicae sinensis promotes hematopoiesis and thrombopoiesis.

J Ethnopharmacol. 2009 Apr 11; Yang M, Chan GC, Deng R, Ng MH, Cheng SW, Lau CP, Ye JY, Wang L, Liu CETHNOPHARMACOLOGICAL RELEVANCE: A decoction containing Radix angelicae sinensis and Radix astragali (Danggui Buxue Tang, DBT) has been used to raise the "Qi" and nourish the "Blood". However, its effects on haematopoiesis and particularly thrombopoiesis have not been studied. AIMS: This study aims to examine the effects of DBT on hematopoiesis and thrombopoiesis. MATERIALS AND METHODS: A myelosuppression mouse model was treated with DBT (10mg/kg/day). Peripheral blood cells from DBT and thrombopoietin-treated samples were counted on days 0, 7, 14 and 21. Then CFU assays were used to determine the effects of DBT on the megakaryocytic progenitor cells and other lineages. Last, analyses of annexin V, caspase-3, and mitochondrial membrane potential were conducted in megakaryocytic cell line M-07e. RESULTS: Morphological examination showed that DBT treatment significantly increased the recovery of the megakaryocytic series. DBT significantly enhanced the platelet recovery and CFU-MK formation in vivo. DBT significantly promoted CFU-MK and CFU-F formation. Last, we observed the antiapoptotic effects of DBT on M-07e cells. CONCLUSION: DBT might promote haematopoiesis and thrombopoiesis in the mouse model through (i) directly promoting the growth of megakaryocytes; (ii) indirectly promoting the growth of bone marrow stromal cells; (iii) inhibiting apoptosis of megakaryocytes.

Reprint of The Herbal Alternatives for Menopause (HALT) Study: background and study design.

Maturitas. 2008 Sep-Oct; 61(1-2): 181-93Newton KM, Reed SD, Grothaus L, Ehrlich K, Guiltinan J, Ludman E, LaCroix AZWe designed a randomized double-blind randomized trial to examine the short and long-term effects of alternative approaches commonly used to manage menopause symptoms. Women were randomly assigned to: (1) black cohosh 160 mg daily; (2) multibotanical (50 mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron) four capsules daily; (3) multibotanical plus telephone counseling to increase dietary soy; (4) conjugated equine estrogen 0.625 mg +/- 2.5 mg medroxyprogesterone acetate; or (5) placebo. Working with a skilled CAM provider helped us choose interventions that reflected naturopathic practices worthy of study. Mass mailing, with careful tracking and rapid responses to recruitment rates, was an effective and cost-effective recruitment strategy. Creativity was necessary to construct methods for blinding capsules and the dietary soy intervention. Independent testing of herbal products was vital to confirming their constituents. The Data and Safety and Monitoring Committee, and project officers at the funding agency, were critical partners in designing responses to unanticipated Women's Health Initiative findings published during the HALT trial. Careful monitoring of adverse events may provide much needed information about side effects of herbal products and supplements. Despite inherent challenges, the study of alternative therapies for menopause symptoms is a rewarding and important area deserving of further inquiry.

Glycyrrhizin, the main active compound in licorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signaling.

Biochem J. 2009 May 14; Schröfelbauer B, Raffetseder J, Hauner M, Wolkerstorfer A, Ernst W, Szolar OHThe triterpene glycoside glycyrrhizin (GL) is the main active compound in licorice. It is used as a herbal medicine owing to its anti-cancer, anti-viral, and anti-inflammatory properties. Its mode of action however remains widely unknown. In this study, we aimed to elucidate the molecular mechanism of GL in attenuating inflammatory responses in macrophages. Using microarray analysis, we found that GL caused a broad block in the induction of pro-inflammatory mediators induced by the toll-like receptor 9 (TLR9) agonist CpG-DNA in RAW 264.7 cells. Furthermore, we found that GL also strongly attenuated inflammatory responses induced by TLR3 and TLR4 ligands. The inhibition was accompanied by reduced activation not only of the NF-kappaB pathway but also of the parallel MAPKs signaling cascade upon stimulation with TLR9 and TLR4 agonists. Further analysis of upstream events revealed that GL treatment reduced cellular attachment and/or uptake of CpG-DNA and strongly impaired TLR4 internalization. Moreover, we found that the anti-inflammatory effects were specific for membrane-dependent receptormediated stimuli, as GL was ineffective in blocking Tnfa induction upon stimulation with phorbol myristate acetate (PMA), a receptor and membrane-independent stimulus. These observations suggest that the broad anti-inflammatory activity of GL is mediated by the interaction with the lipid bilayer thereby attenuating receptor-mediated signaling.

Effects of Bambusae caulis in Liquamen on the development of atopic dermatitis-like skin lesions in hairless mice.

J Ethnopharmacol. 2009 Jun 22; 123(2): 195-200Qi XF, Kim DH, Yoon YS, Li JH, Jin D, Deung YK, Lee KJETHNOPHARMACOLOGICAL RELEVANCE: Bambusae caulis in Liquamen (BCL) is a nutritious liquid extracted from heat-treated fresh bamboo stems. It is an important traditional herbal medicine used to treat coughs and asthma in East Asia. In recent years, it has been studied for its anti-inflammatory, anti-allergenic, and immune-regulating properties. AIM OF THE STUDY: To examine whether BCL suppresses the development of 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in hairless mice. MATERIALS AND METHODS: The effects of BCL were analyzed by measuring transepidermal water loss (TEWL), melanin content, and erythema in the skin, leukocyte numbers and IgE levels in the serum, and mRNA expression of relevant cytokines in the spleen. RESULTS: The transdermal administration of BCL to hairless mice inhibited the development of DNCB-induced AD-like skin lesions by suppressing TEWL, melanin production and erythema of skin, the number of leukocytes and the level of IgE in serum, and the mRNA expression of IL-4, IL-13, and TNF-alpha in the spleen. However, BCL administration increased the expression of IFN-gamma in the spleen. CONCLUSIONS: These findings indicate that BCL suppresses the development of DNCB-induced AD-like skin lesions in hairless mice, suggesting that BCL may be a potential therapeutic agent for AD in a clinical setting.

Chrysanthemum indicum Linné extract inhibits the inflammatory response by suppressing NF-kappaB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophages.

J Ethnopharmacol. 2009 Apr 21; 122(3): 473-7Cheon MS, Yoon T, Lee do Y, Choi G, Moon BC, Lee AY, Choo BK, Kim HKAIMS OF STUDY: Although the flowers of Chrysanthemum indicum Linné (Asteraceae) have long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of a 70% ethanolic extract of C. indicum (CIE) on the activities of cellular signaling molecules that mediate inflammatory responses. MATERIALS AND METHODS: Production of NO, PGE(2), TNF-alpha, and IL-1beta by ELISA, mRNA and protein expression of iNOS and COX-2, phosphorylation of MAPKs, and activation of NF-kappaB by RT-PCR and Western blotting were examined in LPS-induced RAW 264.7 macrophages. RESULTS: The CIE strongly inhibited NO, PGE(2), TNF-alpha, and IL-1beta production, and also significantly inhibited mRNA and protein expression of iNOS and COX-2 in LPS-induced RAW 264.7 macrophages, in a dose-dependent manner. Furthermore, the CIE clearly suppressed nuclear translocation of NF-kappaB p65 subunits, which correlated with an inhibitory effect on IkappaBalpha phosphorylation. The CIE also attenuated the activation of ERK1/2 and JNK in a dose-dependent manner. CONCLUSION: Our results suggest that the anti-inflammatory properties of CIE might result from the inhibition of inflammatory mediators, such as NO, PGE(2), TNF-alpha, and IL-1beta, via suppression of MAPKs and NF-kappaB-dependent pathways.

Effects of Kang-Jia-Wan, a Chinese medicinal herb officinal, on apoptosis induction in goiter of rats.

J Ethnopharmacol. 2009 Apr 21; 122(3): 533-40Han Y, Gao L, Sun N, Zhang J, Zhang W, Zhou X, Zhang H, Zhao JETHNOPHARMACOLOGICAL RELEVANCE: Kang-Jia-Wan (KJW), a traditional Chinese herbal medicine, is widely used to treat goiter in the clinics in China. AIM: The mechanisms by which KJW treats goiter are unclear. It is known that insufficient apoptosis of thyrocytes is involved in the formation of goiter. Here, we investigated whether KJW could induce apoptosis in goiter of rats given methimazole (MMI). MATERIALS AND METHODS: Fifty-six Wistar rats were randomly separated into four groups: normal, MMI, MMI+low-dose KJW and MMI+hig h-dose KJW. Except for the normal group (20 rats), all groups (each with 12 rats) were given 0.04% (w/v) MMI in their drinking water. One week later, the rats in MMI+low- and high-dose KJW groups were orally supplemented with KJW at 250 mg/kg d(-1) and 1000 mg/kg d(-1), respectively. RESULTS: After KJW treatment for 12 weeks, the relative thyroid weight (mg/100g body weight) of the MMI+high-dose KJW group decreased significantly. Features of apoptosis were also apparent in thyroid tissues of rats given KJW treatment. Importantly, KJW markedly increased the caspase-3 and Fas protein expression, in a dose-dependent manner, in the thyroid specimens. CONCLUSIONS: These results showed that KJW played a therapeutic role via apoptosis induction in the goitrous glands.

Status of herbal medicines in the treatment of diabetes: a review.

Curr Diabetes Rev. 2009 May; 5(2): 102-11Samad A, Shams MS, Ullah Z, Wais M, Nazish I, Sultana Y, Aqil MDiabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by defective insulin secretion, resistance to insulin action, or a combination of both. DM has reached epidemic proportions in the US and more recently worldwide. The morbidity and mortality associated with diabetes is anticipated to account for a substantial proportion of health care expenditures. Although there are several drug treatments currently available, the need for new herbal agents for treatment of diabetes are required. The treatment goals for patients with diabetes have evolved significantly over the last 80 years, from preventing imminent mortality, to alleviating symptoms, to the now recognized objective of normalization or near normalization of glucose levels with the intent of forestalling diabetic complications. The present review stated several findings from an extensive literature search of natural plants that have been assessed for the anti diabetic activity over past 80 years. An attempt has been made to summarize the information in order to highlight those chemical entities and plant species which are of worthy for further investigation as leads to the drug developments. Over 100 plant species from wide range of families containing various chemical classes of compounds have been cited here which are worthy for the researchers and the industrialist concerned to diabetes.

Characteristics and nutritional and cardiovascular-health properties of seaweeds.

J Med Food. 2009 Apr; 12(2): 236-58Bocanegra A, Bastida S, Benedí J, Ródenas S, Sánchez-Muniz FJWhile marine algae have traditionally formed part of the Oriental diet, their major use in Western countries has been in the phytocolloid industry. Only a few coastal communities outside Asia have customarily used seaweeds as components of special dishes. Of late, however, seaweeds have gained importance as foodstuffs in Western countries and most recently as components of functional foods because of their high dietary fiber, mineral, vitamin, and phytochemical content, low energy levels, and high concentrations of certain polyunsaturated fatty acids. The present paper reviews the available data for some of the components of the major edible algae and studies several factors that can affect their physiochemical properties (e.g., hydration, water and oil-holding capacity, fermentability, binding capacity, etc.) and, in turn, their nutritional importance. The effects of marine alga consumption on growth and body weight, mineral availability, lipid metabolism, blood pressure, and antioxidant properties are reviewed, together with preliminary data on the effects of some functional foods containing seaweeds on lipid metabolism and gene expression of enzymes engaged in antioxidant protection. This review concludes with some remarks regarding the danger of the improper use of seaweeds in herbal medications. In addition, as the properties of algae are highly dependent on their individual composition, any generalization regarding these properties may be considered misleading and scientifically inappropriate.

Effect of ShanZha, a Chinese herbal product, on obesity and dyslipidemia in hamsters receiving high-fat diet.

J Ethnopharmacol. 2009 May 16; Kou DH, Yeh CH, Shieh PC, Cheng KC, Chen FA, Cheng JTAIM: The present study is designed to investigate the effect of ShanZha (Crataegus pinnatifida) on obesity or dyslipidemia induced by high fat diet in hamsters and characterize the role of PPARalpha in this action of ShanZha. MATERIALS AND METHODS: We induced dyslipidemia and obesity in hamsters using high fat diet and treated hamsters with ShanZha or vehicle for 7 days. We measured the body weight, adipose tissue weights, and food intake of hamsters. Plasma total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) were determined at the beginning and end of this treatment. Effect of ShanZha on adipogenesis was examined in vitro and change of PPARalpha was analyzed using Western blot. RESULTS: The food intake, body weights, and weights of both brown and white adipose tissues were markedly reduced in hamsters receiving ShanZha as compared with the vehicle-treated control. Plasma levels of TC, TG and LDL-C were decreased by this ShanZha treatment while HDL-C was elevated. The effects of ShanZha were reversed by the combined treatment with PPARalpha antagonist, MK886. ShanZha inhibited the fat droplet accumulation in 3T3-L1 adipocytes in a dose-dependent manner and this effect was abolished by MK886. Western blot results showed activation of PPARalpha by ShanZha in hamster adipose tissue. CONCLUSION: We suggest that ShanZha could activate PPARalpha to improve dyslipidemia or obesity.

Chemistry and pharmacology of Rhaponticum carthamoides: A review.

Phytochemistry. 2009 May 18; Kokoska L, Janovska DRhaponticum carthamoides (Willd.) Iljin is a perennial herb, commonly known as a maral root or Russian leuzea, which has been used for centuries in eastern parts of Russia for its marked medicinal properties. This review based on 117 literary sources, with many of them being originally published in non-English languages (mainly in Russian), discusses the current knowledge of traditional uses, chemistry, biological effects and toxicity of this species. Several different classes of compounds were previously isolated from various parts of R. carthamoides of which the main groups are steroids, particularly ecdysteroids, and phenolics (flavonoids and phenolic acids) accompanied with polyacetylenes, sesquiterpene lactones, triterpenoid glycosides and terpenes (essential oil). A comprehensive account of the chemical constituents is given in this review (figures of 120 structures are shown). Various types of preparations, extracts and individual compounds derived from this species have been found to possess a broad spectrum of pharmacological effects on several organs such as the brain, blood, cardiovascular and nervous systems as well as on different biochemical processes and physiological functions including proteosynthesis, work capacity, reproduction, and sexual function. Moreover, the extracts and preparations from the plant, which are hopefully safe, exhibited various additional biological effects e.g. antioxidant, immunomodulatory, anticancerogenic, antimicrobial, antiparasitic and insect antifeedant or repellent activities. The results of data analysis on the chemical, pharmacological and toxicological characteristics of R. carthamoides support the view that this species has beneficial therapeutic properties and indicate its potential as an effective adaptogenic herbal remedy. Finally, some suggestions for further research on chemical and pharmacological properties are given in this review.

Flavonol tetraglycosides from fruits of Styphnolobium japonicum (Leguminosae) and the authentication of Fructus Sophorae and Flos Sophorae.

Phytochemistry. 2009 May 15; Kite GC, Veitch NC, Boalch ME, Lewis GP, Leon CJ, Simmonds MSThe dried fruits and seeds of Styphnolobium japonicum (L.) Schott (syn. Sophora japonica L.) are used in traditional Chinese medicine and known as Fructus Sophorae or Huai Jiao. The major flavonoids in these fruits and seeds were studied by LC-MS and other spectroscopic techniques to aid the chemical authentication of Fructus Sophorae. Among the flavonoids were two previously unreported kaempferol glycosides: kaempferol 3-O-beta-glucopyranosyl(1-->2)-beta-galactopyranoside-7-O-alpha-rhamnopyranoside and kaempferol 3-O-beta-xylopyranosyl(1-->3)-alpha-rhamnopyranosyl(1-->6)[beta-glucopyranosyl(1-->2)]-beta-glucopyranoside, the structures of which were determined by NMR. Two further tetraglycosides were identified for the first time in S. japonicum as kaempferol 3-O-beta-glucopyranosyl(1-->2)[alpha-rhamnopyranosyl(1-->6)]-beta-glucopyranoside-7-O-alpha-rhamnopyranoside and kaempferol 3-O-beta-glucopyranosyl(1-->2)[alpha-rhamnopyranosyl(1-->6)]-beta-galactopyranoside-7-O-alpha-rhamnopyranoside; the latter was the main flavonoid in mature seeds. The chromatographic profiles of 27 recorded flavonoids were relatively consistent among fruits of similar ages collected from five trees of S. japonicum, and those of maturing unripe and ripe fruits were similar to a market sample of Fructus Sophorae, and thus provide useful markers for authentication of this herbal ingredient. The flower buds (Huai Mi) and flowers (Huai Hua) of S. japonicum (collectively Flos Sophorae) contained rutin as the main flavonoid and lacked the flavone glycosides that were present in flower buds and flowers of Sophora flavescens Ait., reported to be occasional substitutes for Flos Sophorae. The single major flavonoid in fruits of S. flavescens was determined as 3'-hydroxydaidzein.

Antimicrobial and brine shrimp toxicity of some plants used in traditional medicine in Bukoba District, north-western Tanzania.

Tanzan J Health Res. 2009 Jan; 11(1): 23-8Moshi MJ, Innocent E, Masimba PJ, Otieno DF, Weisheit A, Mbabazi P, Lynes M, Meachem K, Hamilton A, Urassa IHerbal medicines constitute a potentially important resource for new and safe drugs for the management of microbial infections and other diseases. In this study, dichloromethane, ethylacetate and ethanol extracts of Canarium schweinfurthii Engl., Dissotis brazzae Cong., Iboza urticifolia (Bak) E.A.Bruce, Isoglosa lacteal Lindau, Strombosia Scheffleri Engl., and Whitfieldia elongate T. Anders were tested for antimicrobial activity and brine shrimp toxicity. The objective was to validate claims that they are used to treat bacterial infections, diarrhoea and heal wounds among the Haya tribe of north-western Tanzania. At least one extract of each plant showed antibacterial activity. Dichloromethane extracts were the most active while ethanol extracts were the least active. Extracts of Whitfieldia elongate and Isoglossa lacteal were the most and least active with MICs in the range 0.08-0.62 mg/ml and 15.6-62.5 mg/ml, respectively. The dichloromethane extract of Whitfieldia elongate exhibited strong antifungal activity against Cryptococcus neoformans. Against brine shrimp larvae, the extracts from the six plants exhibited a low to very low toxicity with LC50 values ranging from 15.35-374.0 microg/ml. However, ethanol extracts of Dissotis brazzae and Strombosia scheffleri had LC50 values of >1000 microg/ml. The seemingly innocuous nature and relatively good antibacterial activity against skin infections and gastrointestinal pathogenic bacteria support the traditional uses of the plants and deserve more detailed studies.

Use of physiologically based biokinetic (PBBK) modeling to study estragole bioactivation and detoxification in humans as compared to male rats.

Toxicol Sci. 2009 May 15; Punt A, Paini A, Boersma MG, Freidig AP, Delatour T, Scholz G, Schilter B, van Bladeren PJ, Rietjens IMThe extent of bioactivation of the herbal constituent estragole to its ultimate carcinogenic metabolite, 1'-sulfooxyestragole depends on the relative levels of both bioactivation and detoxification pathways. The present study investigated the kinetics of the metabolic reactions of both estragole and its proximate carcinogenic metabolite 1'-hydroxyestragole in humans in incubations with relevant tissue fractions. Based on the kinetic data obtained a PBBK model for estragole in human was defined to predict the relative extent of bioactivation and detoxification at different dose levels of estragole. The outcomes of the model were subsequently compared to those previously predicted by a PBBK model for estragole in male rat to evaluate the occurrence of species differences in metabolic activation. The results obtained reveal that formation of 1'-oxoestragole, which represents a minor metabolic route for 1'-hydroxyestragole in rat, is the main detoxification pathway of 1'-hydroxyestragole in humans. Due to a high level of this 1'-hydroxyestragole oxidation pathway in human liver, the predicted species differences in formation of 1'-sulfooxyestragole remain relatively low, with the predicted formation of 1'-sulfooxyestragole being 2-fold higher in human compared to male rat, even though the formation of its precursor 1'-hydroxyestragole was predicted to be 4-fold higher in human. Overall, it is concluded that in spite of significant differences in the relative extent of different metabolic pathways between human and male rat there is a minor influence of species differences on the ultimate overall bioactivation of estragole to 1'-sulfooxyestragole.

The Effects of Ginkgo Biloba Extract EGb 761 on Mechanical and Cold Allodynia in a Rat Model of Neuropathic Pain.

Anesth Analg. 2009 Jun; 108(6): 1958-63Kim YS, Park HJ, Kim TK, Moon DE, Lee HJBACKGROUND: Neuropathic pain is chronic pain that is caused by an injury to the peripheral or central nervous system. The symptoms of neuropathic pain are continuing pain, hyperalgesia, and allodynia. Ginkgo biloba extract is an oriental herbal medicine that has various pharmacological actions. We examined the effect of Ginkgo biloba extract, EGb 761, on the mechanical and cold allodynia in a rat model of neuropathic pain. METHODS: Male Sprague-Dawley rats were prepared by tightly ligating the left L5 and L6 spinal nerves. All the rats developed mechanical and cold allodynia 7 days after surgery. Fifty neuropathic rats were assigned into five groups for the intraperitoneal administration of drugs. The study was double-blind and the order of the treatments was randomized. Normal saline and EGb 761 (50, 100, 150, and 200 mg/kg) were administered, respectively, to the individual groups. We examined mechanical and cold allodynia at preadministration and at 15, 30, 60, 90, 120, 150, and 180 min after intraperitoneal drug administration. Mechanical allodynia was quantified by measuring the paw withdrawal threshold to stimuli with von Frey filaments of 1.0, 1.4, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, 15.0, and 26.0 g. Cold allodynia was quantified by measuring the frequency of foot lift with applying 100% acetone. We measured the locomotor function of the neuropathic rats by using the rotarod test to reveal if EGb 761 has side effects, such as sedation or reduced motor coordination. RESULTS: The control group showed no differences for mechanical and cold allodynia. For the EGb 761 groups, the paw withdrawal thresholds to mechanical stimuli and withdrawal frequencies to cold stimuli were significantly reduced versus the preadministration values and versus the control group. The duration of antiallodynic effects increased in a dose-dependent fashion, and these were maintained for 120 min at the highest dose (P < 0.05). Only at the highest dose (200 mg/kg) did EGb 761 reduce the rotarod performance time. CONCLUSION: We conclude that Ginkgo biloba extract, EGb 761, attenuates mechanical and cold allodynia in a rat model of neuropathic pain, and it may be useful for the management of neuropathic pain.

MotherSafe: Review of three years of counselling by an Australian teratology Information Service.

Aust N Z J Obstet Gynaecol. 2009 Apr; 49(2): 168-72Lim JM, Sullivan E, Kennedy DBACKGROUND: MotherSafe was established in January 2000 at the Royal Hospital for Women as Australia's first 'purpose-built' Teratogen Information Service and since then has received over 75,000 calls regarding exposures during pregnancy and lactation. AIM: To describe the patterns of use of MotherSafe over a three-year period. METHODS: Retrospective descriptive epidemiological study using data from the database established at MotherSafe. Records from all the calls logged at MotherSafe between January 2005 and December 2007 were analysed to determine total number of calls, demographic characteristics of callers, including age, caller category and postcode, reason for call, source of referral and type of exposure. RESULTS: A total of 47,138 calls were recorded to the MotherSafe service from January 2005 to December 2007. The majority of calls were regarding exposures in pregnancy (55%) and breast-feeding (38%). Average age of patients was 32.3 years. Of the calls made, 81.9% (38,485 of 46,968) were by consumers (the pregnant or lactating woman herself or a relative). The most common primary exposure categories were: over-the-counter medications (11.3%), psychotropic medication (9.0%), herbal or vitamin products (8.2%), antibiotics (7.0%), gastrointestinal medications (6.8%) and topical products (6.6%). Forty per cent of callers enquired about multiple exposures. CONCLUSIONS: The utilisation of MotherSafe by consumers and general practitioners continues to increase, reflecting the strong demand for a teratogen counselling service that provides high-quality, evidence-based information on exposures during pregnancy and lactation.

MAPK activation is necessary to the apoptotic death of KB cells induced by the essential oil isolated from Artemisia iwayomogi.

J Ethnopharmacol. 2009 Jun 22; 123(2): 308-14Cha JD, Jeong MR, Kim HY, Lee JC, Lee KYAIM OF THE STUDY: Artemisia iwayomogi is a perennial small herbal plant that has long been used as a chemopreventive agent in traditional Korean medicine. Previously, the purified essential oil was isolated from Artemisia iwayomogi, herein named AIEO, and found to contain the active components responsible for the chemopreventive potential of the herb. MATERIALS AND METHODS: This study examined whether or not AIEO has potential chemopreventative effects against cancer using the human oral epidermoid carcinoma cell line, KB cells. The possible mechanism of AIEO-induced apoptosis was also examined. RESULTS: The results showed that AIEO induces the apoptotic death of KB cells, which is mediated by mitogen-activated protein kinases (MAPKs). In addition, AIEO not only induced an imbalance between the mitochondrial Bcl-2 and Bax levels with the concomitant release of Cytochrome c into the cytosol but also induced the activation of caspases and the cleavage of PARP. This induction was significantly suppressed by MAPK inhibitors. Moreover, pretreating the cells with each of the caspase or MAPK-specific inhibitors apparently inhibited AIEO-induced cytotoxicity of KB cells. CONCLUSIONS: These results strongly suggest that AIEO might have cancer chemopreventive and therapeutic potential, which is closely related to its ability to activate the MAPK-mediated signaling pathways with the subsequent induction of a mitochondria- and caspase-dependent mechanism.

Advances of Molecular Clinical Pharmacology in Gastroenterology and Hepatology.

Am J Ther. 2009 May 8; Prandota JDuring developmental age, differences in pharmacodynamic reactions to several drugs may reflect polymorphisms of genes encoding drug-transporting proteins, receptors, drug targets, and gene products, whose disturbed activity sometimes plays an important role in certain diseases. Administration of drugs with a narrow therapeutic index may quite easily be associated with changes in pharmacokinetics and development of adverse drug reactions, which occasionally may cause fatalities. In such cases, polypragmasy and resulting drug interactions may enhance effects of changes in drug-metabolizing enzymes' activities. Phenotyping and genotyping of patients slowly are finding their place in some therapeutic regimens used in clinical gastroenterology and hepatology. At present, some assays to measure, for example, thiopurine S-methyltransferase activity are already commercially available. Polymorphisms of CYP450 enzymes, interleukins, and altered gene expression play an important role in some patients' various gastrointestinal tract and liver diseases. Herbal drugs also affect proinflammatory and antiinflammatory cytokine and nitric oxide balance in the body. Therapeutic use of recombined proteins, such as infliximab, natalizumab, onercept, humanized antibody to integrin alpha-4 beta-7, or IFN-beta in some large-bowel diseases increased therapeutic efficacy. IFN-alpha used in the patients with chronic hepatitis C improved cellular immunity in these subjects and exerted antiviral activity. Practical application of progress in pharmacogenetics, pharmacokinetics, pharmacodynamics, and use of bioproducts in novel therapeutic regimens has opened therapeutic frontiers and increased clinical safety.

Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam.

Phytother Res. 2009 May 13; Carrasco MC, Vallejo JR, Pardo-de-Santayana M, Peral D, Martín MA, Altimiras JThere is an increasing interest in the health risks related to the use of herbal remedies. Although most consumers think that phytomedicines are safe and without side effects, interactions between complementary alternative and conventional medicines are being described. The aim of this clinical case report is to highlight the importance of the safe use of herbal remedies by providing a clinical interaction study between pharmaceutical medicines and herbal medicinal products. The case of a patient self-medicated with Valeriana officinalis L. and Passiflora incarnata L. while he was on lorazepam treatment is described. Handshaking, dizziness, throbbing and muscular fatigue were reported within the 32 h before clinical diagnosis. The analysis of family medical history ruled out essential tremor, Parkinson's disease, Wilson's disease and other symptom-related pathologies. His medical history revealed a generalized anxiety disorder and medicinal plant consumption but no neurological disorder. Appropriate physical examination was carried out. An additive or synergistic effect is suspected to have produced these symptoms. The active principles of Valerian and passionflower might increase the inhibitory activity of benzodiazepines binding to the GABA receptors, causing severe secondary effects. Due to the increase in herbal product self-medication, the use of herbal remedies should be registered while taking the personal clinical history. Multidisciplinary teams should be created to raise studies on medicinal plants with impact on medical praxis. Copyright (c) 2009 John Wiley & Sons, Ltd.

Evaluation of the wash resistance of three types of manufactured insecticidal nets in comparison to conventionally treated nets.

Acta Trop. 2009 Apr 11; Kayedi MH, Lines JD, Haghdoost AAThe present study evaluated the efficacy and wash resistance of several commercial deltamethrin-treated nets (PermaNet, from factory (PN-F) and market (PN-M), Yorkool (Y) and AZ net) that were claimed by the manufacturers to be Long-Lasting Insecticide Treated Nets (LLITNs), compared to ITNs conventionally treated with deltamethrin (23-27mg/m(2), using one K-O Tab((R)) tablet (KO) per net). Montpellier washing technique was used for washing the pieces of the nets. Insecticidal activity was assessed on dried pieces of nets after 0, 2, 5, 8, 11, 15, 18 and 21 washes, using two types of bioassay (mean median knock down times and mortality 24h after a 3-min exposure) and reared female Anopheles stephensi. To evaluate the effect of heat on diffusion of insecticide from inside of the nets to the surface of them, some Permanet nets were heated. For all the types of nets tested the median knock down time (MKDT) increased approximately linearly with number of washes. The slopes of the lines (increase of MKDT per wash) were low with the PN-F and PN-M, intermediate with Y and equally high with KO and AZ. No significant differences can be claimed with the 3-min exposure tests. The slopes of the regression lines did not differ significantly between the heated and unheated samples. It is concluded that diffusion at ambient temperature is fast enough to rapidly compensate for the loss of insecticide on the surface with no need to artificially stimulate diffusion by heating.

[Self-medication and the elderly. The reality of the home medicine cabinet.]

Aten Primaria. 2009 May 12; Vacas Rodilla E, Castellà Dagà I, Sánchez Giralt M, Pujol Algué A, Pallarés Comalada MC, Balagué Corbera MOBJECTIVE: To estimate the prevalence of self-medication in the elderly, to describe the characteristics of self-medication and home medicine cabinets. DESIGN: Cross-sectional descriptive study. SETTING: An urban primary health care (PHC) centre in Spain. PARTICIPANTS: A total of 240 patients 75 years of age or older. MAIN MEASUREMENTS: A structured questionnaire filled in by home care nurses from April to June 2006. Self-medication was classified into 4 sub-groups: pharmacological or herbal, exclusively pharmacological, exclusively herbal and pharmacological and herbal. The study variables were: age, sex, living alone, number of chronic diseases, number of chronic prescriptions and medicine cabinet characteristics (drugs accumulation, expired drugs, chronic drugs out of prescription, location of medicine chest and periodic review). Other variables were: drug types, source, and acute/chronic reason for self-medication. RESULTS: Self-medication frequency was 31,2% (95% CI, 26-36), with 22.9% (95% CI, 17.5-27.5) being pharmacological and 15.4% (95% CI, 23.1-17.3), herbal. The drugs most used in self-medication were analgesics (30.9%) and cold remedies (27.2%). The pharmacy was the most usual source (49.3%). A total of 41.6% contained drugs that were out of chronic prescription, and 34.4% accumulated more than three boxes of the same medication. CONCLUSIONS: There is a significant prevalence of self-medication among the elderly. Accumulating drugs in homes is a very extensive practice. Pharmacists and PHC professionals need to be trained in the responsible use of chronic and self-medication. Although self-care has to be encouraged, PHC professionals must make their patients aware of the harmful effects of self-medication.

The use of herbal medicines by people with cancer: a qualitative study.

BMC Complement Altern Med. 2009 May 14; 9(1): 14Gratus C, Wilson S, Greenfield SM, Damery SL, Warmington SA, Grieve R, Steven NM, Routledge PABSTRACT: BACKGROUND: Between 7% and 48% of cancer patients report taking herbal medicines after diagnosis. Because of the possibility of unwanted side effects or interactions with conventional treatments, people with cancer are generally advised to tell the professionals treating them if they are taking any form of medication, including herbal medicines and supplements. Studies suggest that only about half do so, and that the professionals themselves have at best very limited knowledge and feel unable to give informed advice. This study is intended to inform the future development of information resources for cancer patients, survivors and healthcare professionals including tools for use before or during consultation to make it easier for patients to mention, and for healthcare professionals to ask about, use of herbal medications. Methods/design This is a three-phase study. In phase 1, a systematic review of the literature on self-medication with herbal medicines among UK populations living with cancer will establish the current evidence base on use of herbal medicine, sources of information, characteristics and motivations. This will allow us to better understand what aspects need further investigation and inform the topic guide for a qualitative study (phase 2). Six focus groups of six to eight cancer patients who have used at least one herbal preparation since diagnosis will explore behaviour, beliefs, knowledge, information sources and needs in an informal conversational setting. Informed by the findings of the systematic review and qualitative study, in phase 3 we will construct and pilot a questionnaire for a future large-scale survey to quantify and prioritise people's beliefs, needs and information preferences DISCUSSION: Despite known interactions with conventional cancer treatments and contraindications for some herbal remedies with specific cancers, reliable information resources for patients are very limited. Identifying cancer patients' information needs and preferences is the first step in creating a suitable resource for both the public and the professionals advising them.

The use of natural products for sleep: A common practice?

Sleep Med. 2009 May 6; Sánchez-Ortuño MM, Bélanger L, Ivers H, Leblanc M, Morin CMBACKGROUND: Despite a paucity of data on efficacy and safety of natural (herbal and dietary) products, their use appears to be widespread. This study aimed at examining the frequency of natural products' use for sleep and their correlates in a population-based sample. METHODS: A randomly selected sample of adults (n=997; 59.9% women) from the province of Quebec completed a postal survey on sleep, use of sleep-promoting products (natural products, prescribed medication, over-the-counter medication and alcohol), physical and mental health, lifestyle habits and demographics. RESULTS: A total of 18.5% of participants reported having used natural products as sleep aids in the past 12months, with chamomile being the most popular product. Participants who exclusively used natural products as sleep aids (10.3% of the sample) were predominantly females, younger and had a higher educational level than those using prescribed medications. Natural products users reported engaging in more health-promoting behaviors than the nonusers of sleep aids and, despite the presence of subthreshold insomnia symptoms (mean Insomnia Severity Index score=9.33), they tended to perceive themselves as healthier when compared with prescribed medication users and nonusers of sleep aids. CONCLUSIONS: The use of natural products as sleep aids is a common practice. Often associated with a general health-promoting lifestyle, it may reflect the common perception that natural products are necessarily beneficial for sleep and without risks.

Antidiabetic effect of Ficus bengalensis aerial roots in experimental animals.

J Ethnopharmacol. 2009 May 4; 123(1): 110-4Singh RK, Mehta S, Jaiswal D, Rai PK, Watal GETHNOPHARMACOLOGICAL RELEVANCE: Herbal preparations of Ficus bengalensis had been considered as effective, economical and safe ethnomedicines for various ailments in Indian traditional system of medicine. AIM OF STUDY: The present study was aimed to explore scientifically the antidiabetic potential of Ficus bengalensis aerial roots as its bark had already been reported to possess antidiabetic efficacy. MATERIALS AND METHODS: Effect of variable doses of aqueous extract of Ficus bengalensis aerial roots on blood glucose level (BGL) of normal-, sub- and mild-diabetic models have been studied and the results were compared with the reference drug Glipizide and elemental Mg and Ca intake as glycemic elements. RESULTS: The dose of 300 mg kg(-1) showed the maximum fall of 43.8 and 40.7% in BGL during FBG and glucose tolerance test (GTT) studies of normal rats, respectively. The same dose showed a marked reduction in BGL of 54.3% in sub- and 51.7% in mild-diabetic rats during GTT. The concentration of Mg (1.02%) and Ca (0.85%) identified through laser induced breakdown spectroscopy (LIBS) in the most effective dose could be responsible for this high percentage fall in BGL as they take part in glucose metabolism. CONCLUSION: The hypoglycemic effect in normoglycemic and antidiabetic effect in sub- and mild-diabetic models of aqueous extract of aerial roots of Ficus bengalensis are due to the presence of these glycemic elements in high concentration with respect to other elements.

[Effects of Baihe Recipe on expressions of vascular endothelial growth factor and p53 proteins in tumor tissues of nude mice bearing orthotopically transplanted gastric carcinoma BGC-823.]

Zhong Xi Yi Jie He Xue Bao. 2009 May; 7(5): 458-62Dong ZP, Hu ZQ, Peng W, Shu ZJ, Cao YM, Lu LObjective: To investigate the effects of Baihe Recipe, a compound traditional Chinese herbal medicine, on growth and metastasis of orthotopically transplanted gastric carcinoma and the expressions of vascular endothelial growth factor (VEGF) and p53 proteins in the tumor tissues in nude mice. Methods: Forty-five nude mice orthotopically transplanted with BGC-823 human gastric cancer cells were randomly divided into three groups: Baihe Recipe group, 5-fluorouracil (5-FU) group and untreated group. The mice in the Baihe Recipe group received intragastric administration of 0.5 mL Baihe Recipe (crude drug content was 0.2 g/mL) for 6 weeks, and the mice in the untreated group received 0.5 mL normal saline. The mice in the 5-FU group received an intraperitoneal injection of 5-FU dilution (0.2 mL, 60 mg/kg per week, for 3 weeks). All mice were sacrificed after 6-week treatment. The weights of tumor and the growth-inhibiting rate were measured and the expressions of VEGF and p53 proteins were detected by immunohistochemical method. Results: The growth inhibition rates in the Baihe Recipe and 5-FU groups were 52.86% and 42.87% respectively. The incidence rates of metastasis to perigastric and hepatic portal lymph nodes, and to liver and peritoneum in the Baihe Recipe and 5-FU groups were lower than those in the untreated group. The metastasis rates in Baihe Recipe group, 5-FU group and untreated group were 33.33%, 35.71% and 80.00% respectively, with significant difference (P

[Effects of Niupo Zhibao Pellet on high-mobility group box-1 protein expression in lung tissues of endotoxin shock rats.]

Zhong Xi Yi Jie He Xue Bao. 2009 May; 7(5): 441-6Li H, DU SH, Zhang SX, Deng RD, Li C, Li YW, Chen DF, Zhou JHObjective: To observe the effects of Niupo Zhibao Pellet, a compound traditional Chinese herbal medicine, on high-mobility group box-1 protein (HMGB1) expression in lung tissues of rats with endotoxin shock. Methods: Thirty SPF Sprague-Dawley rats were randomly divided into control group, lipopolysaccharide (LPS) group and Niupo Zhibao Pellet group. Rats in Niupo Zhibao Pellet group were consecutively administered 7 days with 3 mL (1 g/L) Niupo Zhibao Pellet saline suspension every day by intragastric administration. Endotoxin shock was induced in rats of the LPS and Niupo Zhibao Pellet groups by intravenous injection of LPS (1.5 mg/kg) and intraperitoneal injection of D-galactosamine (100 mg/kg). Expression of HMGB1 in lung tissues was measured by immunohistochemical method with diaminobenzidine (DAB) coloration, fluorescein isothiocyanate (FITC) labeling, and by Western blotting. Results: Expression of HMGB1 in lung tissues in the LPS group was increased and that in Niupo Zhibao Pellet group was higher than that in the LPS group and the control group. HMGB1 was presented in the cytoplasm of positive cells in the LPS group, but in the nucleus of positive cells in the Niupo Zhibao Pellet group. However, HMGB1 was little expressed in the lung tissues of normal rats. Conclusion: Niupo Zhibao Pellet can increase HMGB1 expression and locate HMGB1 in the nucleus but not the cytoplasm, which may be one of its mechanisms in reducing endotoxin shock.

[Dual regulation of cell cycles by Shuanghuang Shengbai Granule in Lewis-bearing mice with chemotherapy-induced myelosuppression and its mechanism.]

Zhong Xi Yi Jie He Xue Bao. 2009 May; 7(5): 453-7Wang LF, Xu ZY, Jin CJ, Sha HF, Wang ZQ, Zhou WD, Zhang M, Wu J, Bai BObjective: To explore the dual regulatory effects of Shuanghuang Shengbai Granule, a compound traditional Chinese herbal medicine, on cell cycle in Lewis-bearing mice with chemotherapy-induced myelosuppression. Methods: Thrity Lewis-bearing mice were randomly divided into control group, untreated group and treated group. A model of myelosuppression was established by peritoneal injection of cyclophosphamide to Lewis-bearing mice. Mice in the treated group were treated with Shuanghaung Shengbai Granule for 6 days. Cell cycle progressions of cells collected from bone marrow and tumor tissues were assayed by flow cytometry, and proliferation index (PI) was also calculated. Expressions of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6) and cyclin D1 in bone marrow and tumor tissues were detected by Western blotting and immunohistochemical method. Results: Percentages of bone marrow and tumor cells in G0/G1 phase in the untreated group were lower than those in the control group; however, the PI of untreated group was higher than that of the control group. The expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues in the untreated group were increased as compared with the control group. Compared with the untreated group and the control group, the percentage of bone marrow cells in G(0)/G(1) phase was decreased, and the PI of bone marrow cells and the expressions of CDK4, CDK6 and cyclin D1 were increased in bone marrow in the treated group. However, the percentage of tumor cells in G(0)/G(1) phase in the treated group was increased, and the PI of tumor cells and the expressions of CDK4, CDK6 and cyclin D1 in tumor tissues were decreased as compared with the untreated and control groups. Conclusion: Shuanghuang Shengbai Granule may have a function of cell cycle dual regulation in Lewis-bearing mice with chemotherapy-induced myelosuppression by regulating the expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues.

Impact of immigration on complementary and alternative medicine use in Hispanic patients.

J Am Board Fam Med. 2009 May-Jun; 22(3): 337-8White B, Knox L, Zepeda M, Mull D, Nunez FBACKGROUND: Although previous research has demonstrated frequent complementary and alternative medicine (CAM) use by Hispanic patients, it remains unclear whether the status of immigration plays a role in the frequency and reasons for use. METHODS: A survey of 164 patients from a federally qualified health center in South Central Los Angeles was used; the health center serves a predominantly Latino immigrant patient population. The study included the following variables: patient age; sex; place of birth; number of years living in the United States; CAM use within the last year; and, if positive CAM use, what type(s) and for what condition(s). RESULTS: Sixty-six percent of patients had used a CAM substance within the past year. Ninety-seven percent of the patients were immigrants (primarily from Mexico, El Salvador, and Guatemala). Differences in CAM use between recently arrived (< or =9 years) and long-term immigrants (> or =10 years) were not significant. Ninety-four percent of patients using CAM reported using herbal/tea/plant-based substances, with the most frequent reason for CAM use being digestive problems. Although most CAM substances were obtained from a market (64%), a not insignificant number of CAM substances were grown at home (23%). CONCLUSIONS: Time since immigration does not seem to impact the frequency of CAM use by Hispanic immigrant patients. Herbal/tea/plant-based substances are frequently used in the Hispanic patient population, often for digestive complaints.

Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer.

J Ethnopharmacol. 2009 May 4; 123(1): 155-62Lau TW, Lam FF, Lau KM, Chan YW, Lee KM, Sahota DS, Ho YY, Fung KP, Leung PC, Lau CBETHNOPHARMACOLOGICAL RELEVANCE: Radix Rehmanniae (RR) has a very long history of usage in traditional Chinese medicine and is usually one of the principal herb found in many herbal formulae used in diabetic foot ulcer. AIM OF THE STUDY: RR aqueous extract was investigated for its wound healing effects in a diabetic foot ulcer rat model and its detailed mechanism of actions. MATERIALS AND METHODS: A previously established diabetic foot ulcer rat model was used to assess the effect of RR extract on wound area reduction, tissue regeneration and angiogenesis. Carrageenan-induced inflammation rat model was used for inflammation study; and diabetic control was evaluated using a neonatal streptozotocin-induced diabetic rat model. RESULTS: In the RR treated group, a trend of reduction of the wound area was observed from days 8 to 18 and a significant difference (as compared with control group) was found on day 8. The ulcer healing effect of RR extract was further supported by better developed scars and epithelialization as well as good formation of capillaries with enhanced VEGF expression. Carrageenan-induced inflammation was also significantly alleviated with RR extract. CONCLUSIONS: Our results demonstrated for the first time that Radix Rehmanniae was effective in promoting diabetic foot ulcer healing in rats through the processes of tissue regeneration, angiogenesis and inflammation control, but not glycemia control. The present study provided scientific basis to support the traditional use of Radix Rehmanniae in diabetic foot ulcer.

Mao's heritage: Medicinal plant knowledge among the Bai in Shaxi, China, at a crossroads between distinct local and common widespread practice.

J Ethnopharmacol. 2009 Jun 22; 123(2): 213-28Weckerle CS, Ineichen R, Huber FK, Yang YETHNOPHARMACOLOGICAL RELEVANCE: The study focuses on medicinal plant knowledge among the Bai in the Shaxi Valley, Northwest Yunnan, where no ethnobotanical study has been conducted so far. In an area of high biodiversity, distinct medicinal plant knowledge is documented and the influence of herbals on local knowledge is revealed. AIM OF THE STUDY: To analyse current medicinal plant knowledge among the Bai in the context of the influence of the Han culture and mainstream Chinese herbal medicine. MATERIALS AND METHODS: During fieldwork in summer 2005, semistructured interviews were conducted with 68 stakeholders, and voucher specimens of all plants mentioned were prepared. RESULTS: A total of 176 medicinal plant species were documented and 1133 use-reports have been collected. Overall, 91.5% of the documented plants are already established as known drugs, and are mentioned in books on medicinal plants in Yunnan and China. Furthermore, the way in which they are used largely coincides. Fourteen plant species represent novel recordings, 9 of which were independently mentioned by three or more informants. CONCLUSIONS: The medicinal plant knowledge of the Bai is strongly influenced by mainstream Chinese herbal medicine and especially by medicinal plant books from the 1970s, which were distributed under Mao Zedong's directive to improve rural health care. We conclude that these herbals have exerted, and continue to exert, a strong influence on the standardisation of plant knowledge among rural populations in China. However, distinct local use of plants also exists, indicating that plant knowledge specific to the Bai people is alive and practiced.

Assessing Quality of Case Series Studies: Development and Validation of an Instrument by Herbal Medicine CAM Researchers.

J Altern Complement Med. 2009 May 11; Yang AW, Li CG, Da Costa C, Allan G, Reece J, Xue CCAbstract Objectives: When higher level of evidence is absent, findings of case series studies can be used to generate hypotheses for further research. However, to date, there has been no established instrument for determining their quality. This study was to develop and validate an instrument to assess the quality of case series studies on herbal medicines. Design: A draft instrument was developed based on items generated by judges. Raters (including judges), consisting of herbal medicine researchers, herbal medicine practitioners, and other professionals, used the draft instrument to assess the quality of sample case series reports. The number of quality assessment items was then reduced as much as possible in the instrument while maintaining its reliability and validity. Content and construct validity, and inter-rater agreement of the instrument were used as the main outcome measures. Results: Seven (7) judges from different backgrounds independently generated 68 nonredundant items for inclusion in the initial draft instrument. The content validity of these items was assessed by all judges for consensus using a seven-point scale, and a 24-item second-draft instrument was derived. The wording and sequence of these items were further revised and then used by 20 raters (including seven judges) to assess the quality of 35 case series reports. A 13-item instrument was finally developed. All raters, including the judges, demonstrated a high level of consistency on quality of the reports by using this instrument, despite their different backgrounds. Conclusions: High-level consistency can be achieved by using this instrument to assess the quality of case series studies. This instrument may facilitate the improvement of reporting quality of case series studies.

Echinacea metabolism and drug interactions: The case for standardization of a complementary medicine.

Life Sci. 2009 May 7; Toselli F, Matthias A, Gillam EMThe herbal medicine, Echinacea, is used for treatment and prevention of upper respiratory tract infections. Among the phytochemicals found in Echinacea, the bioavailable alkylamides are thought to be the compounds responsible for its effects on the human immune system. Cytochrome P450 enzymes (P450s) appear to be the principal system responsible for the metabolism of Echinacea components and most of the main hepatic and some extrahepatic isoforms appear to be involved. Epoxide formation, N-dealkylation and hydroxylation appear to be the main metabolic pathways mediated by P450s. Interactions with P450s determine the circulating concentrations and duration of action of these phytochemicals as well as any potential interactions with other chemicals. Most research to date has focussed on the potential of Echinacea to interact with other drugs. Literature reports are equivocal and comparisons between studies are difficult as the phytochemical composition of the preparations examined is rarely assessed. Certain alkylamides containing a terminal acetylene appear to exert a time- and NADPH-dependent inhibition on the metabolism of other compounds. However as there are no industry standardization requirements, differences in the relative concentrations of individual alkylamides between preparations could alter the potential for interactions. A thorough phytochemical analysis of samples investigated is necessary in further studies so that sound conclusions can be drawn regarding the potential for interindividual variation in pharmacokinetics and therapeutic effects and interactions with other chemicals. Moreover standardization of alkylamide content may allow the exploitation of beneficial interactions between alkylamide components to enhance the therapeutic effect of this widely used complementary medicine.

New perspectives for synergy research with the "omic"-technologies.

Phytomedicine. 2009 May 8; Ulrich-Merzenich G, Panek D, Zeitler H, Wagner H, Vetter HSynergistic effects, understood as true overadditive effects, are often observed in experimental and clinical studies using phytopharmaceuticals. The introduction of the "omic"-technologies is now opening new perspectives in rationalizing these effects and making use of them in the development of a new generation of phytopharmaceuticals. This review describes possible mechanism of synergistic actions of herbal drugs by mono- and multitargeting and by the activation of signal cascades. It examins the possibilities of the standardization of single and multi component plant extracts and the prediction and assessment of the toxicity and safety of plant extracts with the support of the "omic"-technologies. It further discusses the use of phytopharmaceuticals in the context of an "individualized medicine". It makes proposals how to use the "omic"-technologies to rationalize and develop combination therapies of phytopharmaceuticals and synthetic drugs to minimize adverse reactions (ARs) or improve the therapeutic efficacy. Examples of clinical studies are given which explore already the potential of such co-medications. Modern medical therapy has acknowledged for quite some time the usefulness of combination therapies in the treatment of multifactorial diseases like cancer, cardiovascular or rheumatic diseases. The term "synergy" is rarely used in this context, the combinatory mechanisms of actions seldom completely understood and the potentially occurring adverse reactions feared. A systematic exploitation of synergy effects of phytomedical interventions alone or in combination with synthetic drugs should lead in a long term perspective to the discovery and development of more rational evidence-based interventions in the prevention and therapy of multifactorial diseases and should thereby enrich modern pharmacotherapy.

Preventive action of Kai Xin San aqueous extract on depressive-like symptoms and cognition deficit induced by chronic mild stress.

Exp Biol Med (Maywood). 2009 May 8; Dang H, Sun L, Liu X, Peng B, Wang Q, Jia W, Chen Y, Pan A, Xiao PKai Xin San (KXS), a traditional Chinese herbal medicine, has been used clinically for the treatment of depressive disorders and cognitive impairment for centuries. However, the effects of KXS on cognitive dysfunction induced by depression have not been evaluated scientifically. The present study aimed to explore the antidepressant-like and nootropic effects of an aqueous extract of KXS (at doses of 0.3, 0.9, and 2.7g/kg/day) using chronic mild stress (CMS) as a model of depression. Depressive symptoms were analyzed using the sucrose-preference and novelty-induced inhibition of feeding tests. Cognitive function was evaluated using a two-way active avoidance task. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels, acetylcholinesterase (AChE) protein expression in the hippocampus, and monoamine neurotransmitter concentrations in the prefrontal cortex and hippocampus were also determined to elucidate the neurochemical mechanisms. Expereimental results showed that KXS aqueous extract significantly ameliorated the CMS-induced depressive symptoms, including the reduced preference index and prolonged latency to novelty-suppressed feeding. Simultaneously, KXS significantly reversed the CMS-induced decrease in the numbers of active avoidance and active movement distances and increase in the numbers of the passive avoidance and passive movement distances, thereby producing nootropic effects in the two-way active avoidance test. KXS also inhibited the increased AChE expression in the hippocampus, up-regulated the decreased monoamine neurotransmitter concentrations of both brain areas and reduced the elevated ACTH concentrations in the serum induced by CMS. Taken together, these results indicate that KXS exerts its antidepressant-like and nootropic effects in the CMS model by modulating the HPA axis, monoamine neurotransmitter and cholinergic systems.

Lead poisoning from an Ayurvedic herbal medicine in a patient with chronic kidney disease.

Nat Rev Nephrol. 2009 May; 5(5): 297-300Prakash S, Hernandez GT, Dujaili I, Bhalla VBACKGROUND: A 60-year-old man with a history of diabetes and hypertension was referred to a nephrology clinic for investigation of his elevated serum creatinine level. INVESTIGATIONS: Physical examination; laboratory investigations, including measurement of whole-blood lead level, body lead burden and urine albumin:creatinine ratio; history of lead exposure and use of herbal medical products; and renal ultrasonography. DIAGNOSIS: Stage 3 chronic kidney disease that was probably worsened by consumption of lead in the form of an Ayurvedic herbal remedy. MANAGEMENT: Cessation of the herbal product, followed by lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid. The patient's whole-body lead burden and blood lead level decreased to acceptable levels and his serum creatinine value was within the normal range at final follow-up.

Inhibitory Effect of Glycoprotein Isolated from Cudrania tricuspidata Bureau on Expression of Inflammation-Related Cytokine in Bisphenol A-Treated HMC-1 Cells.

Inflammation. 2009 May 5; Shim JU, Lim KTCudrania tricuspidata is one of the most omnipresent traditional herbal drugs for anti-inflammation and anti-tumor. The purpose of the present study was to determine whether the CTB glycoprotein regulates the inflammatory reaction stimulated by bisphenol A (BPA) in human mast cells (HMC-1). Thus, we investigated that CTB glycoprotein inhibits the degranulation of histamine, expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), as a mitogen activated protein (MAP) kinase, nuclear transcription factors involving nuclear factor (NF)-kappaB and Activator protein (AP)-1, cyclooxygenase (COX)-2. The results indicated that CTB glycoprotein decreased gene expression of cytokines of IL-4, IFN-gamma, interleukin (IL)-1beta and cyclooxygenase (COX)-2 in BPA-stimulated HMC-1 cells. Hence, we speculate that CTB glycoprotein can use as a potent anti-inflammatory agent for inflammatory allergic diseases.

[Analysis of phytosterol contents in food plant materials and Chinese traditional medicines]

Wei Sheng Yan Jiu. 2009 Mar; 38(2): 188-91Han J, He M, Zhou S, Wang GOBJECTIVE: To analyze the phytosterol content in food plant materials and Chinese traditional herbal medicines commonly used in China. METHODS: 18 kinds of food plant materials and 32 kinds of Chinese traditional herbal medicines, which were commonly used in functional food, were chosen as samples. The contents of beta-sitosterol, campesterol, stigmasterol, beta-sitostanol were analyzed by GC methods and the percent of each ingredient were calculated. RESULTS: The contents of phytosterols in 18 kinds of food plant materials were from 14.8 mg/100 g to 208.3 mg/100 g, while the content of phytosterols in 32 Chinese traditional herbal medicines were from 9.4 mg/100 g to 280.3 mg/100 g. In most samples, beta-sitosterol is the largest part of total phytosterol. CONCLUSION: Phytosterols were existed in 50 kinds of food plant materials and Chinese traditional herbal medicines commonly used in functional food, maybe phytosterol is an important functional ingredient in some plant materials.

Safety and pharmacokinetic trial of docetaxel plus an Astragalus-based herbal formula for non-small cell lung cancer patients.

Cancer Chemother Pharmacol. 2009 May 7; Cassileth BR, Rizvi N, Deng G, Yeung KS, Vickers A, Guillen S, Woo D, Coleton M, Kris MGPURPOSE: To study a commonly used Astragalus-based herbal formula previously found effective in non-small cell lung cancer (NSCLC) on the pharmacokinetics of docetaxel in patients with NSCLC. METHODS: Patients with advanced NSCLC who progressed after prior platinum-containing chemotherapy were accrued and received docetaxel at 35 mg/m(2) for 3 weeks followed by 1 week of rest. At 4 days prior to the second dosing, Jinfukang was given orally. Pharmacokinetic studies of initial-dose docetaxel (in the absence of Jinfukang) and the third dose (in the presence of Jinfukang) were compared. RESULTS: Of the 24 patients enrolled, 21 started Jinfukang and docetaxel. Jinfukang had no significant impact on the pharmacokinetics of docetaxel. Median time to progression or withdrawal from treatment was 7 weeks. Twelve patients were removed from study for progression of disease; nine patients withdrew. CONCLUSIONS: Jinfukang did not alter the pharmacokinetics of docetaxel nor appear to affect survival in this study.

Inhibitory effects of atractylodis lanceae rhizoma and poria on collagen- or thromboxane A2-induced aggregation in rabbit platelets.

Biol Pharm Bull. 2009 May; 32(5): 856-60Nasu Y, Iwashita M, Saito M, Fushiya S, Nakahata NKami-shoyo-san (Jia-Wei-Xiao-Yao-San), Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) and Toki-shigyaku-ka-goshuyu-shokyo-to (Dang-Gui-Si-Ni-Jia-Wu-Zhu-Yu-Sheng-Jiang-Tang) are Kampo (traditional Chinese) medicines which are traditionally and effectively used for the treatment of chilly sensation (Hiesho) in Japan, but the active components and their detailed mechanisms have not yet been clarified. Etiologies of Hiesho include poor peripheral blood circulation and platelet aggregability contributes to peripheral blood circulation; therefore, we investigated the effect of Kampo medicines on platelet aggregation using rabbit platelets in vitro. Collagen and U46619, a thromboxane A(2) receptor agonist, caused rabbit platelet aggregation, which was potently inhibited by pretreatment of platelets with Kami-shoyo-san and Toki-shakuyaku-san in vitro. Toki-shigyaku-ka-goshuyu-shokyo-to, however, did not significantly inhibit collagen- or U46619-induced platelet aggregation. Therefore, we examined the effect on platelet aggregation of two herbal medicines, Atractylodis Lanceae Rhizoma and Poria, both of which are contained in Kami-shoyo-san and Toki-shakuyaku-san but not in Toki-shigyaku-ka-goshuyu-shokyo-to. As the results indicate, Atractylodis Lanceae Rhizoma inhibited platelet aggregation induced by collagen but not by U46619. Poria effectively inhibited U46619-induced platelet aggregation and it partially inhibited collagen-induced platelet aggregation. On the other hand, Atractylodis Lanceae Rhizoma and Poria did not inhibit adrenaline/adenosine diphosphate- or adrenaline/serotonin-induced platelet aggregation. These results suggest the possibility that the inhibition of platelet aggregation by two Kampo medicines, Kami-shoyo-san and Toki-shakuyaku-san, is one of the mechanisms underlying the improvement of Hiesho. Furthermore, Atractylodis Lanceae Rhizoma and Poria are possible herbal medicines for the inhibition of platelet aggregation.

Isolation of a chemical inhibitor against K-Ras-induced p53 suppression through natural compound screening.

Int J Oncol. 2009 Jun; 34(6): 1637-43Lee SJ, Jung YS, Lee SH, Chung HY, Park BJThe strong tumor suppressor p53 shows loss of function in large portion of human cancer. In addition to genetic mutation, biological function of p53 is suppressed by signaling distortion or elevated expression of p53 inhibitors (such as overexpression of MDM2 or deletion of p14/ARF). In this study, we demonstrate that K-Ras, a frequently altered oncogene in human cancers including pancreatic cancer (about 80%), colon cancer (45%) and lung cancer (45%), suppresses p53. Based on this fact, we perform Western blot analysis-based chemical screening to isolate a K-Ras-specific activator of p53. From 117 kinds of chemicals (34 kinds of natural compounds that are obtained from herbal plants, 53 kinds of flavonoid, and 31 kinds of phenolic compounds), we find that quercetin works as an activator of p53 in K-Ras mutated cells but not in wild-type cells. Treatment with quercetin can induce p53 target genes such as PUMA and p21. These results suggest that although quercetin has limitations for use as a therapeutic drug due to its broad effects, specific function of it on K-Ras-p53 may be useful for K-Ras-induced cancer prevention and therapy through further development.

Immunosuppressive Effects of Demethylzeylasteral in a Rat Kidney Transplantation Model.

Int Immunopharmacol. 2009 Apr 18; Xu W, Lin Z, Yang C, Zhang Y, Wang G, Xu X, Lv Q, Ren Y, Dong YIn this study, we examined the immunosuppressive activity of demethylzeylasteral (T-96), isolated from the traditional Chinese herbal medicine, Tripterygium wilfordii Hook f. Its immunosuppressive effect was investigated using mouse splenocytes in vitro, and in an in vivo rat kidney transplant model. T-96 inhibited mouse splenocyte proliferation in a dose dependent manner. In the rat kidney transplant study, rats were randomly divided into eight groups following kidney transplantation, and different doses of T-96 or cyclosporin A (CsA) were administered to each group. T-96 alone at doses of 10 or 20 mg/kg/day significantly prolonged the survival of kidney-transplanted rats, compared with transplanted but untreated control rats. A combination of T-96 and prednisone also significantly prolonged survival: 10 mg/kg/day T-96 with 10 mg/kg/day prednisone increased the survival time to 31.8+/-6.5 days. Moreover, the combination of T-96 and prednisone was also effective in suppressing rejection of rat transplanted kidneys. These results demonstrate the strong immunosuppressive activity of T-96 and suggest a possible clinical use for T-96 as an immunosuppressive agent in the fields of organ transplantation and autoimmune disorders.

Induction of multiple pro-inflammatory cytokines by respiratory viruses and reversal by standardized Echinacea, a potent antiviral herbal extract.

Antiviral Res. 2009 Apr 29; Sharma M, Anderson SA, Schoop R, Hudson JBSeveral viruses associated with upper respiratory diseases have been shown to stimulate the secretion of pro-inflammatory cytokines, including chemokines, sometimes in the absence of viral cytopathology. We evaluated the ability of a standardized preparation of the popular herbal medicine Echinacea (Echinaforce((R)), an ethanol extract of herb and roots of E. purpurea, and containing known concentrations of marker compounds) to inhibit the viral induction of various cytokines in a line of human bronchial epithelial cells (BEAS-2B), and in two other human cell lines. All of the viruses tested, rhinoviruses 1A and 14, influenza virus, respiratory syncytial virus, adenovirus types 3 and 11, and herpes simplex virus type 1, induced substantial secretion of IL6 and IL8 (CXCL8), in addition to several other chemokines, depending on the virus, although only viable viruses were able to do this. In every case however Echinacea inhibited this induction. The Echinacea preparation also showed potent virucidal activity against viruses with membranes, indicating the multifunctional potential of the herb. These results support the concept that certain Echinacea preparations can alleviate "cold and flu" symptoms, and possibly other respiratory disorders, by inhibiting viral growth and the secretion of pro-inflammatory cytokines.

[Pathological study on autopsy died of tripterygium intoxication--report of 4 cases]

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009 Feb; 29(2): 165-8Huang GZ, Li L, Liu LThe Tripterygium preparation, a Chinese herbal medicine, has been widely used to treat various autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Its significant clinical effects have received a great praise and attention by the public health in China, but its toxicity also definitely exists, with the therapeutic dosage approaching the minimal toxic dosage. In order to provide reference for the safe use of Tripterygium preparation in clinical practice, the pathological changes of 4 autopsy cases by Tripterygium poisoning were reported in this paper. In them, 2 cases died of acute cardiogenic shock caused by myocardial damage, showing hydropic degeneration of the myocardial cells, even with obvious contraction band necrosis in the papillary muscles; the other 2 died of severe acute renal failure due to severe acute toxic nephrosis; cerebral edema and gastrointestinal inflammatory changes were found in all cases. The authors suggested that careful dosage control is the key step to prevent Tripterygium intoxication during the medical treatments; directly using the crude Tripterygium in clinics should be prohibited; and the Tripterygium preparation used should be produced by the pharmaceutical companies regulated by the government.

Study of the characteristic fragmentation behavior of hydroquinone glycosides by electrospray ionization tandem mass spectrometry with optimization of collision energy.

J Mass Spectrom. 2009 May 7; Liu Y, He J, Zhang R, Shi J, Abliz ZThe fragmentation behavior of hydroquinone glycosides involving one or two sugar groups from Fraxinus sieboldiana and their analogue arbutin was investigated systematically by electrospray ionization tandem mass spectrometry in negative ion mode. The characteristic fragmentation reaction of these compounds was through the homolytic and heterolytic cleavage of the O-glycosidic bond to produce radical aglycone ion ([Y(0) - H](-*)) and aglycone ion (Y(0) (-)), respectively. Unambiguous differentiation between the mono-O-glycoside isomers which differ in glycosylation position was achieved by comparing the relative abundance of [Y(0) - H](-*) and Y(0) (-) ions with the optimized collision energy. In the fragmentation of 1, 4-di-O-glycosides, only the Y(0) (-) ion was produced when the first glucosyl residue was expelled. However, both the [Y(0) - H](-*) and Y(0) (-) ions were present when the second glucosyl residue was eliminated. In addition, an interesting [Y(0)-2H](-) ion was present in the product ion spectra of hydroquinone glycosides with methoxy group(s) substituted at C-3 or/and C-5 positions of the benzene ring. The results of this study can facilitate the rapid determination of hydroquinone glycosides in crude plant extracts and also reveal that the systematic investigation and optimization of collision energy play an important role in the differentiation of isomers which have subtle differences in structures. Copyright (c) 2009 John Wiley & Sons, Ltd.

Discrimination of three medicinal materials from the Citrus genus by HPLC fingerprint coupled with two complementary software.

Phytochem Anal. 2009 May 8; Qin XM, Dai YT, Zhang LZ, Guo XQ, Shao HXINTRODUCTION: Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride and Fructus Aurantii come from the fruit of Citrus genus and possess analogous pharmacological activities. Either two or three of them are often present in one preparation. However, there is no standard method to differentiate the three herbal medicines for quality control. OBJECTIVE: To develop a fingerprint method for authentication of these three herbal medicines by HPLC. METHODOLOGY: Methanol extracts were analysed by HPLC, with a mobile phase of 0.1% phosphoric acid in water (A) and acetonitrile (B) in a gradient programme. The flow rate was set at 0.8 mL/min and UV detection at 320 nm. Principal component analysis and similarity evaluation were employed to analyse the chromatographic dataset. RESULTS: The chromatograms of 20 Pericarpium Citri Reticulatae, 13 Pericarpium Citri Reticulatae Viride and 15 Fructus Aurantii samples from diverse habitats had 13 peaks in common, and showed one peak characteristic for Pericarpium Citri Reticulatae Viride and two peaks characteristic for Fructus Aurantii. Furthermore, it was possible to differentiate the three medicines by a 'fingerprint region'. The difference between Pericarpium Citri Reticulatae and Fructus Aurantii was much bigger than that between Pericarpium Citri Reticulatae and Pericarpium Citri Reticulatae Viride, as could be shown by calculation of common peak ratio and variation peak ratio. CONCLUSION: A reliable HPLC fingerprint method coupled with principal component analysis and similarity evaluation was developed and showed substantial differentiation power for the three medicines. Copyright (c) 2009 John Wiley & Sons, Ltd.

Inhibitory effects of atractylodis lanceae rhizoma and poria on collagen- or thromboxane a(2)-induced aggregation in rabbit platelets.

Biol Pharm Bull. 2009 May; 32(5): 856-60Nasu Y, Iwashita M, Saito M, Fushiya S, Nakahata NKami-shoyo-san (Jia-Wei-Xiao-Yao-San), Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) and Toki-shigyaku-ka-goshuyu-shokyo-to (Dang-Gui-Si-Ni-Jia-Wu-Zhu-Yu-Sheng-Jiang-Tang) are Kampo (traditional Chinese) medicines which are traditionally and effectively used for the treatment of chilly sensation (Hiesho) in Japan, but the active components and their detailed mechanisms have not yet been clarified. Etiologies of Hiesho include poor peripheral blood circulation and platelet aggregability contributes to peripheral blood circulation; therefore, we investigated the effect of Kampo medicines on platelet aggregation using rabbit platelets in vitro. Collagen and U46619, a thromboxane A(2) receptor agonist, caused rabbit platelet aggregation, which was potently inhibited by pretreatment of platelets with Kami-shoyo-san and Toki-shakuyaku-san in vitro. Toki-shigyaku-ka-goshuyu-shokyo-to, however, did not significantly inhibit collagen- or U46619-induced platelet aggregation. Therefore, we examined the effect on platelet aggregation of two herbal medicines, Atractylodis Lanceae Rhizoma and Poria, both of which are contained in Kami-shoyo-san and Toki-shakuyaku-san but not in Toki-shigyaku-ka-goshuyu-shokyo-to. As the results indicate, Atractylodis Lanceae Rhizoma inhibited platelet aggregation induced by collagen but not by U46619. Poria effectively inhibited U46619-induced platelet aggregation and it partially inhibited collagen-induced platelet aggregation. On the other hand, Atractylodis Lanceae Rhizoma and Poria did not inhibit adrenaline/adenosine diphosphate- or adrenaline/serotonin-induced platelet aggregation. These results suggest the possibility that the inhibition of platelet aggregation by two Kampo medicines, Kami-shoyo-san and Toki-shakuyaku-san, is one of the mechanisms underlying the improvement of Hiesho. Furthermore, Atractylodis Lanceae Rhizoma and Poria are possible herbal medicines for the inhibition of platelet aggregation.

Associations of Herbal and Specialty Supplements with Lung and Colorectal Cancer Risk in the VITamins And Lifestyle Study.

Cancer Epidemiol Biomarkers Prev. 2009 May; 18(5): 1419-28Satia JA, Littman A, Slatore CG, Galanko JA, White EMillions of Americans use dietary supplements with little knowledge about their benefits or risks. We examined associations of various herbal/specialty supplements with lung and colorectal cancer risk. Men and women, 50 to 76 years, in the VITamins And Lifestyle cohort completed a 24-page baseline questionnaire that captured duration (years) and frequency (days per week) of use of commonly used herbal/specialty supplements. Dose was not assessed due to the lack of accurate potency information. Supplement exposure was categorized as "no use" or "any use" over the previous 10 years. Hazard ratios (HR) were estimated by multivariate Cox regression models. Incident lung (n = 665) and colorectal cancers (n = 428) were obtained from the Surveillance, Epidemiology, and End Results cancer registry. Any use of glucosamine and chondroitin, which have anti-inflammatory properties, over the previous 10 years, was associated with significantly lower lung cancer risk: HR 0.74 [95% confidence interval (95% CI), 0.58-0.94] and HR 0.72 (95% CI, 0.54-0.96) and colorectal cancer risk: HR 0.73 (95% CI, 0.54-0.98) and HR 0.65 (95% CI, 0.45-0.93), respectively. There were also statistically significantly inverse associations of fish oil: HR 0.65 (95% CI, 0.42-0.99), methylsulfonylmethane: HR 0.46 (95% CI, 0.23-0.93), and St. John's wort: HR 0.35 (95% CI, 0.14-0.85) with colorectal cancer risk. In contrast, garlic pills were associated with a statistically significant 35% elevated colorectal cancer risk. These results suggest that some herbal/specialty supplements may be associated with lung and colorectal cancer risk; however, these products should be used with caution. Additional studies examining the effects of herbal/specialty supplements on risk for cancer and other diseases are needed. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1419-28).