Herbal Science Research Abstracts

Plant-based vaccines against diarrheal diseases.

Trans Am Clin Climatol Assoc. 2007;118:79-87

Authors: Tacket CO

Every year 1.6 million deaths occur due to diarrhea related to unsafe water and inadequate sanitation-the vast majority in children under 5 years old. Safe and effective vaccines against enteric infections could contribute to control of these diseases. However, purification of protective antigens for inclusion in vaccines using traditional expression systems is expensive and unattractive to vaccine manufacturers who see the vaccine market as economically uninviting. Cost is one of the persistent barriers to deployment of new vaccines to populations that need them most urgently.Transgenic plant-derived vaccines offer a new strategy for development of safe, inexpensive vaccines against diarrheal diseases. In phase 1 clinical studies, these vaccines have been safe and immunogenic without the need for a buffer or vehicle other than the plant cell. This paper describes early clinical studies evaluating oral transgenic plant vaccines against enteric infections such as enterotoxigenic E. coli infection and norovirus.

PMID: 18528491 [PubMed - indexed for MEDLINE]

The immunopharmaceutical effects and mechanisms of herb medicine.

Cell Mol Immunol. 2008 Feb;5(1):23-31

Authors: Huang CF, Lin SS, Liao PH, Young SC, Yang CC

In recent years, studies on evaluation of the therapeutic and toxic activity of herbal medicinal products became available and popular. The advances in modern biotechnology have led to discovery of many new active constituents. However, it is a constant challenge to establish the pharmacological basis for efficacy and safety of herbal medicinal products. A better understanding of the effects and bioavailability of phytopharmaceuticals can help in discovering suitable and rational therapies. In this review, we present the bioavailability studies in immune system that has been conducted for some of the more important or widely used phytopharmaceuticals. Furthermore, various new drug targets worthy of using for drug development in immunomodulating herbal medicine area and their regulatory mechanisms are also discussed. Adverse effects, drug interactions, and contraindications are also discussed which show that caution should be exercised when combining phytopharmaceuticals with chemically derived pharmaceutical components.

PMID: 18318991 [PubMed - indexed for MEDLINE]

Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium.

BMC Genomics. 2008;9:259

Authors: Sridhar S, Schembri F, Zeskind J, Shah V, Gustafson AM, Steiling K, Liu G, Dumas YM, Zhang X, Brody JS, Lenburg ME, Spira A

BACKGROUND: Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers. RESULTS: Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure. CONCLUSION: Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a non-invasive screening or diagnostic tool providing information about individual susceptibility to smoking-induced lung diseases.

PMID: 18513428 [PubMed - indexed for MEDLINE]

Effects of alcohol and cigarette smoking on change in serum estrone levels in postmenopausal women randomly assigned to fixed doses of conjugated equine estrogens with or without a progestin.

Menopause. 2008 Mar-Apr;15(2):382-5

Authors: McDivit AM, Greendale GA, Stanczyk FZ, Huang MH

OBJECTIVE: To determine the effects of alcohol and smoking on serum estrone levels among women assigned to hormone therapy. DESIGN: We analyzed the data from 676 participants in the Postmenopausal Estrogen/Progestin Interventions study. RESULTS: Those who consumed more than 5.5 g of alcohol daily demonstrated greater rises in serum estrone than those who drank less (>0 to < or =5.5 g/d) (P = 0.07) and those who were abstinent (P = 0.09). Current smokers had lesser gains in serum estrone compared with former smokers (P < 0.0001) and never smokers (P < 0.0001). CONCLUSIONS: Alcohol consumption augmented and smoking diminished serum estrone levels achieved while women were taking hormone therapy.

PMID: 18000469 [PubMed - indexed for MEDLINE]

An evolutionary model of premenstrual syndrome.

Med Hypotheses. 2008;70(5):1058-65

Authors: Reiber C

PMS has existed at least since the beginning of medical writing, and is estimated to affect large proportions of women worldwide. But the etiology remains unknown, diagnostic definition and methods vary tremendously, and treatment is wholly symptom-oriented. This poor state of understanding has been attributed to a lack of theoretical perspective. The current work provides such a theoretical perspective from an evolutionary paradigm. PMS is not evolutionarily adaptive in and of itself. Rather, it is part of a cyclic pattern that results from the cessation of heightened, positive physical and sociobehavioral states that are evolutionarily favored during the fertile phase of the menstrual cycle for some women. When the advantage of these positive states diminishes, they cease, causing relatively lower states that are subjectively experienced as symptoms. In its clinical extreme, this is PMS. However, eons of evolution would result in modern women who are choosy about the conditions under which they reproduce. Thus, women whose conditions suggest a high probability of successful immediate reproduction are expected to experience the heightened, positive states during the fertile phase of the menstrual cycle to attract mates and fertilizations; these women will experience symptoms premenstrually. But women whose conditions suggest a low probability of successful immediate reproduction are expected to experience the heightened, positive states during the premenstruum to retain mates, accrue or maintain resources, and/or otherwise improve their conditions; these women will experience symptoms during the fertile phase of the menstrual cycle ("pseudo-PMS"). In addition, the heightened states are expected to shift in response to changes in conditions throughout women's lives, being expressed at whatever point is most evolutionarily beneficial given current conditions. This suggests that our conceptualization of PMS should be reframed within a facultative (condition-sensitive), evolutionary model. It also generates predictions both within- and between women that should elucidate the syndrome.

PMID: 18053655 [PubMed - indexed for MEDLINE]

Adding phytoestrogens to clomiphene induction in unexplained infertility patients--a randomized trial.

Reprod Biomed Online. 2008 Apr;16(4):580-8

Authors: Shahin AY, Ismail AM, Zahran KM, Makhlouf AM

This study investigated the role of oral phytoestrogens in improving pregnancy rate and cycle outcomes with clomiphene citrate. Patients with unexplained infertility and recurrent clomiphene citrate induction failure, were randomly divided into two groups: group I (n = 60) and group II (n = 59). Both groups received clomiphene citrate 150 mg per day (days 3 to 7). Group I received additional oral phytoestrogen (Cimicifuga racemosa) 120 mg/day from days 1 to 12. Human chorionic gonadotrophin (HCG) injection (10,000 IU i.m.) was given and timed intercourse was recommended when a leading follicle reached >17 mm and serum oestradiol exceeded 200 (pg/ml). There was a non-significant shortening of induction cycles in group I. Oestradiol and LH concentrations were higher in group I compared with group II. Endometrial thickness, serum progesterone and clinical pregnancy rate were significantly higher in group I (8.9 +/- 1.4 mm versus 7.5 +/- 1.3 mm, P < 0.001; 13.3 +/- 3.1 ng/ml versus 9.3 +/- 2.0 ng/ml, P < 0.01; 36.7% versus 13.6%, P < 0.01, respectively). It is concluded that adding C. racemosa rhizome dry extract to clomiphene citrate induction can improve the pregnancy rate and cycle outcomes in these couples.

PMID: 18413068 [PubMed - indexed for MEDLINE]

Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women.

J Womens Health (Larchmt). 2008 Apr;17(3):355-66

Authors: Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi BH

OBJECTIVE: The objective of the study was to investigate the extent to which the daily incorporation of approximately 30 g of flaxseed, a rich source of lignans, omega-3 fatty acids, and fiber, for a period of 3 months into the diet of Native American postmenopausal women positively affects their lipid profiles. METHODS: Fifty-five mild to moderately hypercholesterolemic (> or =5.1 to < or =9.8 mmol/L) Native American postmenopausal women were randomly assigned to control (A), flaxseed (B) or flaxseed + additional oat bran fiber (C) groups. Overnight fasting venous blood was collected at baseline and at the end of the treatment period to analyze lipid parameters. RESULTS: Dietary flaxseed supplementation lowered total cholesterol and low-density lipoprotein cholesterol (LDL-C) by approximately 7% and 10%, respectively. However, the levels of high-density lipoprotein (HDL) and triglyceride remained unaltered. No changes were observed in other clinical and hematological parameters. CONCLUSIONS: The results of the present study indicate that Native American postmenopausal women benefit from regular consumption of flaxseed by reducing their risk of cardiovascular disease as seen from lowered LDL-C and total cholesterol levels.

PMID: 18328014 [PubMed - indexed for MEDLINE]

Habitual Tea Drinking and Bone Mineral Density in Postmenopausal Turkish Women: Investigation of Prevalence of Postmenopausal Osteoporosis in Turkey (IPPOT Study).

Int J Vitam Nutr Res. 2007 Nov;77(6):389-397

Authors: Hamdi Kara I, Aydin S, Gemalmaz A, Aktürk Z, Yaman H, Bozdemir N, Kurdak H, Sitmapinar K, Devran Sencar I, Basak O, Akdeniz M, Is?ldar H, Burgut E, Ozcan S, Akça U, Dagdeviren N, Ungan M

Aim: In this epidemiological report, we assessed the prevalence of osteopenia and osteoporosis (OP) in postmenopausal Turkish women and the relationship between body mass index (BMI), and some nutritional factors (habitual tea, coffee, tobacco, and milk product consumption) with OP. Methods: This multicenter study was done in postmenopausal women residing in five big cities, in four different regions of Turkey between August and November 2005. An inclusion criterion was being in the postmenopausal period for at least 12 months. A semi-structured questionnaire was completed by face-to-face interview, consisting of closed- and open-ended questions about demographic characteristics, nutritional status, and habits with two or more choices as possible responses. Bone mineral density (BMD) measurements were performed with a MetriScan(R) Densitometer (Alara Inc., Ca, USA). Results: Seven hundred twenty-four women were included in the study. The mean age was 57.6 +/- 9.6 years, and mean age at natural menopause was 46.4 +/- 5.6 years. Of the participants, 51% were illiterate. According to WHO classification; 42.5% were normal in terms of BMD, 27.2% had osteopenia, and 30.2% had OP. Women with high education levels had better T-scores (p = 0.019). Increase in BMI also had a positive effect on T-scores (p < 0.0001). A linear correlation was found between age (r= -0.386, p < 0.0001), BMI (r = -0.175, p < 0.0001), and education (r = -0.317, p < 0.0001), with T-scores. The T-scores of women who consumed tea on a regular basis were found to be higher than non-consumers (-1.51 +/- 1.68 vs. -1.09 +/- 1.66; p = 0.070) [when smokers, those who received hormonal therapy (HT), and those > 65 years were excluded]. Conclusion: OP was determined in 1/3 of the women. Advanced age (> 65) and being illiterate were negative factors, while high education levels, being overweight, and being treated with HT had a positive effects on BMD. Habitual tea drinking also may have a positive effect on BMD. However, tea drinking was not found to be a statistically significant factor in the present study.

PMID: 18622949 [PubMed - as supplied by publisher]

Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer.

Menopause Int. 2008 Mar;14(1):6-12

Authors: Powles TJ, Howell A, Evans DG, McCloskey EV, Ashley S, Greenhalgh R, Affen J, Flook LA, Tidy A

OBJECTIVE: To assess the safety and tolerability of a standardized 40 mg red clover isoflavone dietary supplement (Promensil, Novogen) in women with a family history of breast cancer to evaluate the feasibility of using the supplement for prevention of breast cancer in healthy women. STUDY DESIGN: Healthy women aged 35-70 years (n = 401) with at least one first-degree relative with breast cancer received red clover isoflavones or placebo for three years in a randomized, double-blind, placebo-controlled pilot trial. Participants were assessed clinically and blood samples taken for biochemical analysis every six months. In addition, study participants underwent mammography, bone density and transvaginal ultrasound (postmenopausal women only) once per year. RESULTS: No significant differences in breast density, endometrial thickness, serum cholesterol, follicle stimulating hormone levels and bone mineral density were detected between those taking red clover isoflavones and placebo. In postmenopausal women, some significant differences in bone marker levels were seen between active and placebo groups, at six months and at 12 months. The adverse event profile was similar across all red clover isoflavone and placebo groups. CONCLUSION: This three-year study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women. Supplements containing red clover isoflavones did not adversely affect breast density, skeletal strength or cardiovascular status. In postmenopausal women, endometrial status was not adversely affected. The adverse event profile was similar between red clover isoflavones, and placebo and endocrine status did not differ.

PMID: 18380954 [PubMed - indexed for MEDLINE]

High-content screening and mechanism-based evaluation of estrogenic botanical extracts.

Comb Chem High Throughput Screen. 2008 May;11(4):283-93

Authors: Overk CR, Yao P, Chen S, Deng S, Imai A, Main M, Schinkovitz A, Farnsworth NR, Pauli GF, Bolton JL

Symptoms associated with menopause can greatly affect the quality of life for women. Botanical dietary supplements have been viewed by the public as safe and effective despite a lack of evidence indicating a urgent necessity to standardize these supplements chemically and biologically. Seventeen plants were evaluated for estrogenic biological activity using standard assays: competitive estrogen receptor (ER) binding assay for both alpha and beta subtypes, transient transfection of the estrogen response element luciferase plasmid into MCF-7 cells expressing either ER alpha or ER beta, and the Ishikawa alkaline phosphatase induction assay for both estrogenic and antiestrogenic activities. Based on the combination of data pooled from these assays, the following was determined: a) a high rate of false positive activity for the competitive binding assays, b) some extracts had estrogenic activity despite a lack of ability to bind the ER, c) one extract exhibited selective estrogen receptor modulator (SERM) activity, and d) several extracts show additive/synergistic activity. Taken together, these data indicate a need to reprioritize the order in which the bioassays are performed for maximal efficiency of programs involving bioassay-guided fractionation. In addition, possible explanations for the conflicts in the literature over the estrogenicity of Cimicifuga racemosa (black cohosh) are suggested.

PMID: 18473738 [PubMed - indexed for MEDLINE]

A critical evaluation of drug interactions with Echinacea spp.

Mol Nutr Food Res. 2008 Jul 10;52(7):789-798

Authors: Freeman C, Spelman K

Accurate information concerning drug-herb interactions is vital for both healthcare providers and patients. Unfortunately, many of the reviews on drug-herb interactions contain overstated or inaccurate information. To provide accurate information on drug-herb interactions healthcare providers must account for product verification, dosage, medicinal plant species, and plant part used. This critical review assessed the occurrence of drug interactions with one of the top selling botanical remedies, echinacea including Echinacea angustifolia, E. pallida, and E. purpurea. Only eight papers containing primary data relating to drug interactions were identified. Herbal remedies made from E. purpurea appear to have a low potential to generate cytochrome P450 (CYP 450) drug-herb interactions including CYP 450 1A2 (CYP1A2) and CYP 450 3A4 (CYP3A4). Currently there are no verifiable reports of drug-herb interactions with any echinacea product. However, further pharmacokinetic testing is necessary before conclusive statements can be made about echinacea drug-herb interactions. Given our findings, the estimated risk of taking echinacea products (1 in 100 000), the number of echinacea doses consumed yearly (> 10 million), the number of adverse events (< 100) and that the majority of use is short term, E. purpurea products (roots and/or aerial parts) do not appear to be a risk to consumers.

PMID: 18618481 [PubMed - as supplied by publisher]

Does the Evidence Make a Difference in Consumer Behavior? Sales of Supplements Before and After Publication of Negative Research Results.

J Gen Intern Med. 2008 Jul 10;

Authors: Tilburt JC, Emanuel EJ, Miller FG

OBJECTIVE: To determine if the public consumption of herbs, vitamins, and supplements changes in light of emerging negative evidence. METHODS: We describe trends in annual US sales of five major supplements in temporal relationship with publication of research from three top US general medical journals published from 2001 through early 2006 and the number of news citations associated with each publication using the Lexus-Nexis database. RESULTS: In four of five supplements (St. John's wort, echinacea, saw palmetto, and glucosamine), there was little or no change in sales trends after publication of research results. In one instance, however, dramatic changes in sales occurred following publication of data suggesting harm from high doses of vitamin E. CONCLUSION: Results reporting harm may have a greater impact on supplement consumption than those demonstrating lack of efficacy. In order for clinical trial evidence to influence public behavior, there needs to be a better understanding of the factors that influence the translation of evidence in the public.

PMID: 18618194 [PubMed - as supplied by publisher]

Evaluation of widely consumed botanicals as immunological adjuvants.

Vaccine. 2008 Jul 17;

Authors: Ragupathi G, Yeung KS, Vickers A, Hood C, Deng G, Cheung NK, Cassileth B, Livingston P

BACKGROUND: Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with seven botanicals purported to have immune stimulant effects. METHODS: Groups of 5-10 mice were immunized with globo H-KLH or GD3-KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. three times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus versicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co. Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast beta-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semisynthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH. RESULTS: Consistent significant adjuvant activity was observed after s.c. vaccination with the Coriolus extracts (especially PSK), a 95% ethanol extract of Astragalus and yeast beta-glucan, and (to a lesser extent) Maitake. Antibodies against KLH in all cases and against globo H in most cases were induced by these botanicals. Little or no adjuvant activity was demonstrated with H-48 or Echinacea extracts or the Astragalus water extract. Experiments with GD3-KLH as immunogen confirmed the adjuvant activity of the Coriolus, yeast beta-glucan and Astragalus extracts. While extraction with ethanol concentrated the active ingredients in Astragalus, it had no impact on Coriolus where the 90% ethanol precipitate and solute were equally active. CONCLUSIONS: Some, but not all, botanicals purported to be immune stimulants had adjuvant activity in our model. PSK and Astragalus were surprisingly active and are being further fractionated to identify the most active adjuvant components.

PMID: 18640165 [PubMed - as supplied by publisher]

Deconstructing an Adaptogen: Eleutherococcus senticosus.

Holist Nurs Pract. 2008 Jul-Aug;22(4):220-4

Authors: Bleakney TL

The dried roots and rhizomes of Eleutherococcus senticosus (Araliacaea) plant are used in various preparations, primarily for its "adaptogenic" properties. An adaptogen supports health and prevents disease in both sick and healthy individuals through nonspecific effects, which neutralize various environmental and physical stressors while remaining relatively safe and free of side effects. The term "adaptogen," which has not been well defined scientifically, undermines the need for increased inquiry and research into the many promising effects of this herb. The primary clinical applications, pharmacology, evidence of efficacy, contraindications, drug interactions, and current clinical and scientific research are also reported.

PMID: 18607235 [PubMed - in process]

Inhibitory Effects of Eleutherococcus senticosus Extracts on Amyloid beta(25-35)-Induced Neuritic Atrophy and Synaptic Loss.

J Pharmacol Sci. 2008 Jul 8;

Authors: Tohda C, Ichimura M, Bai Y, Tanaka K, Zhu S, Komatsu K

Neurons with atrophic neurites may remain alive and therefore may have the potential to regenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons. We investigated the effects of Eleutherococcus senticosus extracts on the regeneration of neurites and the reconstruction of synapses in rat cultured cortical neurons damaged by amyloid beta (Abeta)(25-35). Treatment with Abeta(25-35) (10 muM) induced axonal and dendritic atrophies and synaptic loss in cortical neurons. Subsequent treatment with the methanol extract and the water extract of E. senticosus (10 - 1000 ng/ml) resulted in significant axonal and dendritic regenerations and reconstruction of neuronal synapses. Co-application of the extract and Abeta(25-35) attenuated Abeta(25-35)-induced neuronal death. We investigated neurite outgrowth activities of eleutherosides B and E and isoflaxidin, which are known as major compounds in E. senticosus. Although eleutheroside B protected against Abeta(25-35)-induced dendritic and axonal atrophies, the activities of eleutheroside E and isofraxidin were less than that of eleutheroside B. Although the contents of these three compounds in the water extract were less than in the methanol extract, restoring activities against neuronal damages were not different between the two extracts. In conclusion, extracts of E. senticosus protect against neuritic atrophy and cell death under Abeta treatment, and one of active constituents may be eleutheroside B.

PMID: 18612196 [PubMed - as supplied by publisher]

Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin immunoassay.

J Clin Lab Anal. 2008;22(4):295-301

Authors: Dasgupta A, Tso G, Wells A

Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha demonstrated modest interference with serum digoxin measurements by the fluorescent polarization immunoassay (FPIA). Recently, Abbott Laboratories marketed a new digoxin immunoassay, Digoxin III for application on the AxSYM analyzer. We studied potential interference of these herbal supplements on serum digoxin measurement by Digoxin III assay in vitro and compared our results with the values obtained by Tina-quant assay. Aliquots of drug-free serum pool were supplemented with various amounts of Asian ginseng, Siberian ginseng, or Ashwagandha approximating expected concentrations after recommended doses and overdoses of these herbal supplements in serum. Then digoxin concentrations were measured by the Digoxin III and Tina-quant (Roche Diagnostics) assay. We also supplemented aliquots of a digoxin pool prepared from patients receiving digoxin with various amounts of these herbal supplements and then measured digoxin concentrations again using both digoxin immunoassays. We observed modest apparent digoxin concentrations when aliquots of drug-free serum pool were supplemented with all three herbal supplements using Digoxin III assay (apparent digoxin in the range of 0.31-0.57 ng/ml), but no apparent digoxin concentration (except with the highest concentration of Ashwagandha supplement for both brands) was observed using the Tina-quant assay. When aliquots of digoxin pool were further supplemented with these herbal supplements, digoxin concentrations were falsely elevated when measured by the new Digoxin III assay. For example, we observed 48.2% (1.63 ng/ml digoxin) increase in digoxin concentration when an aliquot of Digoxin pool 1 (1.10 ng/ml digoxin) was supplemented with 50 microl of Asian ginseng extract (Brand 2). Measuring free digoxin does not eliminate the modest interferences of these herbal supplements in serum digoxin measurement by the Digoxin III assay.

PMID: 18623124 [PubMed - in process]

Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials.

Am J Clin Nutr. 2008 Jul;88(1):38-50

Authors: Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, Ryder JJ, Hall WL, Cassidy A

BACKGROUND: The beneficial effects of flavonoid consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence. OBJECTIVE: We aimed to systematically review the effectiveness of different flavonoid subclasses and flavonoid-rich food sources on cardiovascular disease (CVD) and risk factors--ie, lipoproteins, blood pressure, and flow-mediated dilatation (FMD). DESIGN: Methods included a structured search strategy on MEDLINE, EMBASE, and Cochrane databases; formal inclusion or exclusion, data extraction, and validity assessment; and meta-analysis. RESULTS: One hundred thirty-three trials were included. No randomized controlled trial studied effects on CVD morbidity or mortality. Significant heterogeneity confirmed differential effects between flavonoid subclasses and foods. Chocolate increased FMD after acute (3.99%; 95% CI: 2.86, 5.12; 6 studies) and chronic (1.45%; 0.62, 2.28; 2 studies) intake and reduced systolic (-5.88 mm Hg; -9.55, -2.21; 5 studies) and diastolic (-3.30 mm Hg; -5.77, -0.83; 4 studies) blood pressure. Soy protein isolate (but not other soy products or components) significantly reduced diastolic blood pressure (-1.99 mm Hg; -2.86, -1.12; 9 studies) and LDL cholesterol (-0.19 mmol/L; -0.24, -0.14; 39 studies). Acute black tea consumption increased systolic (5.69 mm Hg; 1.52, 9.86; 4 studies) and diastolic (2.56 mm Hg; 1.03, 4.10; 4 studies) blood pressure. Green tea reduced LDL (-0.23 mmol/L; -0.34, -0.12; 4 studies). For many of the other flavonoids, there was insufficient evidence to draw conclusions about efficacy. CONCLUSIONS: To date, the effects of flavonoids from soy and cocoa have been the main focus of attention. Future studies should focus on other commonly consumed subclasses (eg, anthocyanins and flavanones), examine dose-response effects, and be of long enough duration to allow assessment of clinically relevant endpoints.

PMID: 18614722 [PubMed - in process]

Epigallocatechin gallate inhibits endothelial exocytosis.

Biol Chem. 2008 Jun 6;

Authors: Yamakuchi M, Bao C, Ferlito M, Lowenstein CJ

Abstract Consumption of green tea is associated with a decrease in cardiovascular mortality. The beneficial health effects of green tea are attributed in part to polyphenols, organic compounds found in tea which lower blood pressure, reduce body fat, decrease LDL cholesterol, and inhibit inflammation. We hypothesized that epigallocatechin gallate (EGCG), the most abundant polyphenol in tea, inhibits endothelial exocytosis, the initial step in leukocyte trafficking and vascular inflammation. To test this hypothesis, we treated human umbilical vein endothelial cells (HUVEC) with EGCG and other polyphenols, and then measured endothelial exocytosis. We found that EGCG decreases endothelial exocytosis in a concentration-dependent manner, with the effects becoming most prominent after 4 h of treatment. Other catechin polyphenols had no effect on endothelial cells. By inhibiting endothelial exocytosis, EGCG decreases leukocyte adherence to endothelial cells. Searching for a mechanism by which EGCG affects endothelial cells, we found that EGCG increases Akt phosphorylation, eNOS phosphorylation, and nitric oxide (NO) production. NOS inhibition revealed that NO mediates the anti-inflammatory effects of EGCG. Our data suggest that polyphenols can decrease vascular inflammation by increasing synthesis of NO which blocks endothelial exocytosis.

PMID: 18627310 [PubMed - as supplied by publisher]

Relationship between the methylation status of dietary flavonoids and their growth-inhibitory and apoptosis-inducing activities in human cancer cells.

J Cell Biochem. 2008 Jul 17;

Authors: Landis-Piwowar KR, Milacic V, Dou QP

Flavonoids are polyphenolic compounds widely distributed in the plant kingdom. Compelling research indicates that flavonoids have important roles in cancer chemoprevention and chemotherapy possibly due to biological activities that include action through anti-inflammation, free radical scavenging, modulation of survival/proliferation pathways, and inhibition of the ubiquitin-proteasome pathway. Plant polyphenols including the green tea polyphenol (-)-epigallocatechin gallate or (-)-EGCG, and the flavonoids apigenin, luteolin, quercetin, and chrysin have been shown to inhibit proteasome activity and induce apoptosis in human leukemia cells. However, biotransformation reactions to the reactive hydroxyl groups on polyphenols could reduce their biological activities. Although methylated polyphenols have been suggested to be metabolically more stable than unmethylated polyphenols, the practical use of methylated polyphenols as cancer preventative agents warrants further investigation. In the current study, methylated and unmethylated flavonoids were studied for their proteasome-inhibitory and apoptosis-inducing abilities in human leukemia HL60 cells. Methylated flavonoids displayed sustained bioavailability and inhibited cellular proliferation by arresting cells in the G(1) phase. However, they did not act as proteasome inhibitors in either an in vitro system or an in silico model and only weakly induced apoptosis. In contrast, unmethylated flavonoids exhibited inhibition of the proteasomal activity in intact HL60 cells, accumulating proteasome target proteins and inducing caspase activation and poly(ADP-ribose) polymerase cleavage. We conclude that methylated flavonoids lack potent cytotoxicity against human leukemia cells and most likely have limited ability as chemopreventive agents. J. Cell. Biochem. (c) 2008 Wiley-Liss, Inc.

PMID: 18636546 [PubMed - as supplied by publisher]

Nongallated compared with gallated flavan-3-ols in green and black tea are more bioavailable.

J Nutr. 2008 Aug;138(8):1529S-1534S

Authors: Henning SM, Choo JJ, Heber D

Green tea and black tea (BT) contain gallated [(-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate] and nongallated [(-)-epicatechin, (-)-epigallocatechin (EGC)] tea polyphenols (PP). During BT production, PP undergo oxidation and form larger polymers such as theaflavins (THE) and thearubigins, which contribute to the health benefit of BT. This article gives an overview of the role of chemical characteristics and endogenous metabolism of tea PP and their bioavailability in humans and describes attempts to increase their bioavailability. At pH close to neutral, EGCG and EGC form homo- and heterodimers generating hydrogen peroxide. To confirm the pH instability of EGCG, EGC, and THE in cell culture medium, their antiproliferative activity was determined in the presence and absence of catalase. The antiproliferative activity in LNCaP prostate cancer cells was decreased when incubated with catalase prior to EGCG, EGC, and THE treatment. In addition, new findings demonstrated that the formation of methyl-EGC increased the stability at neutral pH compared with EGC. Approaches to increase the bioavailability of flavan-3-ols are reviewed, which include the administration of tea in combination with fruit juices, coadministration with piperine, and peracetylation of EGCG. Future intervention studies will need to focus on the bioactivity not only of green tea and BT PP but also of their metabolites and biotransformation products.

PMID: 18641202 [PubMed - in process]