Herbal Science Research - endocrine

Antidiabetic drugs used in Europe prior to the discovery of insulin.

Site Editor — Mon, 22 Oct 2007 18:11:56 -0700

Antidiabetic drugs used in Europe prior to the discovery of insulin.: Pharmazie. 2007 Sep;62(9):717-20 Authors: Helmstädter A

Many therapeutic agents had been used for the treatment of diabetes mellitus before insulin was discovered and several hundred plants have shown some extent of antidiabetic activity. This study tries to explore which agents were most widely used in Europe in the pre-insulin era. According to the scientific literature and the proprietary drug industry around 1900, more than 100 agents were considered to have hypoglycemic activity. Most of them seem to have been used only occasionally while some others were recommended and marketed to a large extent. Among the medicinal plants, Syzygium cumini (syn. S. jambolanum, Eugenia jambolana), Vaccinum myrtillus and Phaseolus sp. were most common, and other frequently used agents were opium, opium alkaloids, other alkaloids like quinine or Belladonna alkaloids, salicylates, alkaline substances like sodium (bi)carbonate and even strong poisons like arsenic or uranium salts. Syzygium jambolanum seed powder seems to be one of the most intensively studied antidiabetic agents of plant origin.

PMID: 17944329 [PubMed - in process]

[...] the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.

Site Editor — Sun, 14 Oct 2007 01:17:38 -0700

A pilot and feasibility study on the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.: Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1601-9 Authors: Greenlee H, Atkinson C, Stanczyk FZ, Lampe JW

Naturopathic physicians commonly make dietary and/or dietary supplement recommendations for breast cancer prevention. This placebo-controlled, parallel-arm, pilot study tested the effects of two naturopathic interventions over five menstrual cycles on sex steroid hormones and metabolic markers in 40 healthy premenopausal women. The intervention arms were as follows: combination botanical supplement (Curcuma longa, Cynara scolymus, Rosmarinus officinalis, Schisandra chinensis, Silybum marinum, and Taraxacum officinalis; n = 15), dietary changes (3 servings/d crucifers or dark leafy greens, 30 g/d fiber, 1-2 liters/d water, and limiting caffeine and alcohol consumption to 1 serving each/wk; n = 10), and placebo (n = 15). Early-and late-follicular phase serum samples from cycles 1 and 5 were analyzed for estrogens (estrone, estrone-sulfate, total estradiol, and free estradiol), androgens (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and free testosterone), sex hormone-binding globulin, and metabolic markers (insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and leptin). Serum samples collected during the mid-luteal phase of cycles 1 and 5 were analyzed for total estradiol, free estradiol, and sex hormone-binding globulin. Urine samples collected during the late follicular phase of cycles 1 and 5 were analyzed for 2-hydroxyestrone and 16alpha-hydroxyestrone. During the early follicular phase, compared with placebo, the botanical supplement decreased dehydroepiandrosterone (-13.2%; P = 0.02), dehydroepiandrosterone-sulfate (-14.6%; P = 0.07), androstenedione (-8.6%; P = 0.05), and estrone-sulfate (-12.0%; P = 0.08). No other trends or statistically significant changes were observed. When comparing dietary changes with placebo, no statistically significant differences were observed. Overall, in this pilot study, the naturopathic interventions had no substantial effects on estrogen measures. Early-follicular phase androgens decreased with the botanical supplement.

PMID: 17684134 [PubMed - indexed for MEDLINE]

Changes in components, glycyrrhizin and glycyrrhetinic acid, [...] modify insulin sensitizing and insulinotropic actions.

Site Editor — Thu, 27 Sep 2007 19:09:32 -0700

Changes in components, glycyrrhizin and glycyrrhetinic acid, in raw Glycyrrhiza uralensis Fisch, modify insulin sensitizing and insulinotropic actions.: Biosci Biotechnol Biochem. 2007 Jun;71(6):1452-61 Authors: Ko BS, Jang JS, Hong SM, Sung SR, Lee JE, Lee MY, Jeon WK, Park S

We hypothesized that roasted Glycyrrhizae Radix (Glycyrrhizin Radix Praeparata, GRP) might modify anti-diabetic action due to compositional changes. Then we examined the anti-diabetic effect and mechanism of raw Glycyrrhizae Radix (GR) and GRP extracts and their major respective components, glycyrrhizin and glycyrrhetinic acid. In partial pancreatectomized (Px) diabetic mice, both GR and GRP improved glucose tolerance, but only GRP enhanced glucose-stimulated insulin secretion as much as exendin-4. Both GR and GRP extracts enhanced insulin-stimulated glucose uptake through peroxisome proliferation-activated receptor (PPAR)-gamma activation in 3T3-L1 adipocytes. Consistently with the results of the mice study, only GRP and glycyrrhetinic acid enhanced glucose-stimulated insulin secretion in isolated islets. In addition, they induced mRNA levels of insulin receptor substrate-2, pancreas duodenum homeobox-1, and glucokinase in the islets, which contributed to improving beta-cell viability. In conclusion, GRP extract containing glycyrrhetinic acid improved glucose tolerance better than GR extract by enhancing insulinotropic action. Thus, GRP had better anti-diabetic action than GR.

PMID: 17587675 [PubMed - indexed for MEDLINE]

A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix.

Site Editor — Wed, 26 Sep 2007 19:14:37 -0700

A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix.: Phytomedicine. 2007 Aug;14(7-8):568-79 Authors: Chrubasik JE, Roufogalis BD, Wagner H, Chrubasik S

Nettle root is recommended for complaints associated with benign prostatic hyperplasia (BPH). We therefore conducted a comprehensive review of the literature to summarise the pharmacological and clinical effects of this plant material. Only a few components of the active principle have been identified and the mechanism of action is still unclear. It seems likely that sex hormone binding globulin (SHBG), aromatase, epidermal growth factor and prostate steroid membrane receptors are involved in the anti-prostatic effect, but less likely that 5alpha-reductase or androgen receptors are involved. Extract and a polysaccharide fraction were shown to exert anti-inflammatory activity. A proprietary methanolic nettle root extract and particular fractions inhibited cell proliferation. Isolated lectins (UDA) were shown to be promising immunomodulatory agents, having also anti-viral and fungistatic effects. However, despite these in vitro studies it is unclear whether the in-vitro or animal data are a surrogate for clinical effects. The clinical evidence of effectiveness for nettle root in the treatment of BPH is based on many open studies. A small number of randomised controlled studies indicate that a proprietary methanolic extract is effective in improving BPH complaints. However, the significance and magnitude of the effect remains to be established in further confirmatory studies before nettle root treatment may be accepted in the guidelines for BPH treatment. The risk for adverse events during nettle root treatment is very low, as is its toxicity. Pre-clinical safety data remain to be completed.

PMID: 17509841 [PubMed - indexed for MEDLINE]

Reduction of PSA values by combination pharmacological therapy in patients with chronic prostatitis [...].

Site Editor — Wed, 26 Sep 2007 19:05:40 -0700

Reduction of PSA values by combination pharmacological therapy in patients with chronic prostatitis: implications for prostate cancer detection.: Arch Ital Urol Androl. 2007 Jun;79(2):84-92 Authors: Magri V, Trinchieri A, Montanari E, Del Nero A, Mangiarotti B, Zirpoli P, de Eguileor M, Marras E, Ceriani I, Vral A, Perletti G

We identified from our clinical database a total of 471 patients affected by cat. II chronic bacterial prostatitis (CBP), cat. III (IIIa and IIIb) chronic pelvic pain syndrome (CP/CPPS), or cat. IV asymptomatic inflammatory prostatitis (AIP), according to NIH criteria. 132 intent-to-treat patients, showing levels of PSA > or =4 ng/mL, were subjected to a 6-week course of combination pharmacological therapy with 500 mg/day ciprofloxacin, 500 mg/day azithromycin (3 days/week), 10 mg/day alfuzosin and 320 mg b.i.d. Serenoa repens extract. At the end of treatment, 111 per-protocol patients belonging to all categories of prostatitis showed a total 32.5% reduction of PSA levels. In the same group, 66 patients (59.4%) showed "normalization" of PSA values under the 4 ng/mL limit. Patients affected by cat. IIIb CP/CPPS showed the highest PSA reduction and normalization rates (40% and 68.4%, respectively). Follow-up data show that, after a marked, significant reduction at completion of therapy, PSA levels, urine peak flow rates and NIH-CPSI symptom scores remained constant or decreased throughout a period of 18 months in patients showing normalization of PSA values. Prostatic biopsy was proposed to 45 patients showing persistently high PSA values (> or = 4 ng/mL) at the end of treatment. Fourteen patients rejected biopsy; of the remaining 31, 10 were diagnosed with prostate cancer. Four months after a first biopsy, a second biopsy was proposed to the 21 patients with a negative first diagnosis and persistently elevated PSA levels. Three patients rejected the procedure; of the remaining 18, four were diagnosed with prostatic carcinoma. In summary, combination pharmacological therapy decreased the number of patients undergoing prostatic biopsy from 111 to 45. Normalization of PSA values in 59.4% of patients--not subjected to biopsy--increased the prostate cancer detection rate from 12.6% (14/111) to 31.1% (14/45). The reduction of PSA after a 6-week course of therapy was calculated in patients affected by cat. II, IIIa, IIIb and IV prostatitis after stratification with respect to the concomitant presence or absence of benign prostatic hyperplasia (BPH). PSA was reduced by 41% in cat. II CBP patients without BPH, compared to a 12.7% reduction in patients affected by BPH. Cat. IIIa CP/CPPS patients without BPH showed a 58.3% reduction of PSA levels, compared to a 20.7% reduction observed in CPPS/BPH patients. These data show that the presence of BPH may prevent the reduction of PSA induced by combination pharmacological therapy, and suggest that care has to be taken in the adoption of PSA as a marker of therapeutic efficacy in the presence of confounding factors like BPH. PSA should in our opinion be used as a significant component of a strategy integrating multiple diagnostic approaches.

PMID: 17695414 [PubMed - indexed for MEDLINE]

Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.

Site Editor — Wed, 26 Sep 2007 18:51:16 -0700

Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.: Phytomedicine. 2007 Aug;14(7-8):460-4 Authors: Gasco M, Villegas L, Yucra S, Rubio J, Gonzales GF

The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.

PMID: 17289361 [PubMed - indexed for MEDLINE]

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.

Site Editor — Fri, 13 Jul 2007 18:25:27 -0700

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.: Phytother Res. 2007 May;21(5):444-7 Authors: Akdoğan M, Tamer MN, Cüre E, Cüre MC, Köroğlu BK, Delibaş N

Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism.

PMID: 17310494 [PubMed - indexed for MEDLINE]

[...] Tribulus terrestris [...] on Muscle Strength and Body Composition During Preseason Training in Elite Rugby League Players.

Site Editor — Wed, 30 May 2007 01:14:05 -0700

The Effect of Five Weeks of Tribulus terrestris Supplementation on Muscle Strength and Body Composition During Preseason Training in Elite Rugby League Players.: J Strength Cond Res. 2007 May 1;21(2):348-353 Authors: Rogerson S, Riches CJ, Jennings C, Weatherby RP, Meir RA, Marshall-Gradisnik SM

Rogerson, S., C.J. Riches, C. Jennings, R.P. Weatherby, R.A. Meir, and S.M. Marshall-Gradisnik. The effect of five weeks of Tribulus terrestris supplementation on muscle strength and body composition during preseason training in elite rugby league players. J. Strength Cond. Res. 21(2):348-353. 2007.- Tribulus terrestris is an herbal nutritional supplement that is promoted to produce large gains in strength and lean muscle mass in 5-28 days (15, 18). Although some manufacturers claim T. terrestris will not lead to a positive drug test, others have suggested that T. terrestris may increase the urinary testosterone/epitestosterone (T/E) ratio, which may place athletes at risk of a positive drug test. The purpose of the study was to determine the effect of T. terrestris on strength, fat free mass, and the urinary T/E ratio during 5 weeks of preseason training in elite rugby league players. Twenty-two Australian elite male rugby league players (mean +/- SD; age = 19.8 +/- 2.9 years; weight = 88.0 +/- 9.5 kg) were match-paired and randomly assigned in a double-blind manner to either a T. terrestris (n = 11) or placebo (n = 11) group. All subjects performed structured heavy resistance training as part of the club's preseason preparations. A T. terrestris extract (450 mg.d(-1)) or placebo capsules were consumed once daily for 5 weeks. Muscular strength, body composition, and the urinary T/E ratio were monitored prior to and after supplementation. After 5 weeks of training, strength and fat free mass increased significantly without any between-group differences. No between-group differences were noted in the urinary T/E ratio. It was concluded that T. terrestris did not produce the large gains in strength or lean muscle mass that many manufacturers claim can be experienced within 5-28 days. Furthermore, T. terrestris did not alter the urinary T/E ratio and would not place an athlete at risk of testing positive based on the World Anti-Doping Agency's urinary T/E ratio limit of 4:1.

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.

Site Editor — Wed, 21 Feb 2007 18:03:54 -0800

Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.: Phytother Res. 2007 Feb 20; Authors: Akdoğan M, Tamer MN, Cüre E, Cüre MC, Köroğlu BK, Delibaş N

Novel phytoandrogens and lipidic augmenters from Eucommia ulmoides.

Site Editor — Thu, 01 Feb 2007 16:38:19 -0800

Novel phytoandrogens and lipidic augmenters from Eucommia ulmoides.: BMC Complement Altern Med. 2007 Jan 29;7(1):3 Authors: Ong VY, Tan BK

ABSTRACT: BACKGROUND: Plants containing compounds such as the isoflavonoids, with female hormone-like effects that bind to human estrogen receptors, are known. But none has been previously shown to have corresponding male hormone-like effects that interact with the human androgen receptor. Here, we report that the tree bark (cortex) of the Gutta-Percha tree, Eucommia ulmoides, possesses bimodal phytoandrogenic and hormone-potentiating effects by lipidic components. METHODS: The extracts of E. ulmoides were tested using in-vitro reporter gene bioassays and in-vivo animal studies. Key compounds responsible for the steroidogenic effects were isolated and identified using solid phase extraction (SPE), high performance liquid chromatography (HPLC), thin layer chromatography (TLC), gas chromatography-mass spectroscopy (GC-MS), electron spray ionisation-mass spectroscopy (ESI-MS) and nuclear magnetic resonance (NMR). RESULTS: The following bioactivities of E. ulmoides were found: (1) a phenomenal tripartite synergism between the sex steroid androgen and estrogen receptors, their cognate steroidal ligands and lipidic augmenters isolated from E. ulmoides, (2) androgenic activity mediated by plant triterpenoids binding cognately to the androgen receptor (AR). CONCLUSION: In addition to well-known phytoestrogens, the existence of phytoandrogens is reported in this study. Furthermore, a form of tripartite synergism between sex steroid receptors, sex hormones and phytolipids is described for the first time. This could have contrasting clinical applications for hypogonadal- and hyperlipidaemic-related disorders.

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.

Site Editor — Sat, 06 Jan 2007 19:01:39 -0800

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.: Int J Cancer. 2007 Jan 4; Authors: Rebbeck TR, Troxel AB, Norman S, Bunin GR, Demichele A, Baumgarten M, Berlin M, Schinnar R, Strom BL

Hormone-related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population-based case-control study in 3 counties of the Philadelphia metropolitan area consisting of 949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p = 0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p = 0.003), ginseng (12.5% vs. 7.9%, p < 0.001) and red clover (4.7% vs. 0.6%, p < 0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22-0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer. (c) 2006 Wiley-Liss, Inc.

Augmentation and proliferation of T lymphocytes and Th-1 cytokines by Withania somnifera in stressed mice.

Site Editor — Sat, 06 Jan 2007 18:57:42 -0800

Augmentation and proliferation of T lymphocytes and Th-1 cytokines by Withania somnifera in stressed mice.: Int Immunopharmacol. 2006 Sep;6(9):1394-403 Authors: Khan B, Ahmad SF, Bani S, Kaul A, Suri KA, Satti NK, Athar M, Qazi GN

Stress has been associated with reports of both greater severity and prolongation of diseases in patients with the infectious origin as well as other immune-mediated diseases. Withania somnifera, an Indian medicinal plant used widely in the treatment of many clinical conditions in India, was investigated for its anti-stress properties using BALB/c mice subjected to chronic stress. The study aimed to investigate chronic stress-induced alterations on Th1 lymphocyte subset distribution and corresponding cytokine secretion patterns. Oral administration of chemically standardized and identified aqueous fraction of W. somnifera root (WS) at the graded doses of 25, 50, 100 and 200 mg/kg p.o. caused significant increase in the stress-induced depleted T-cell population and increased the expression of Th1 cytokines in chronically stressed mice.

Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses.

Site Editor — Sat, 06 Jan 2007 00:03:36 -0800

Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses.: Trends Neurosci. 2006 Nov;29(11):632-9 Authors: Mattson MP, Cheng A

Diets rich in vegetables and fruits are associated with reduced risk of several major diseases, including neurodegenerative disorders. Although some beneficial phytochemicals might function solely as antioxidants, it is becoming clear that many of the beneficial chemicals in vegetables and fruits evolved as toxins (to dissuade insects and other predators) that, at subtoxic doses, activate adaptive cellular stress-response pathways in a variety of cells including neurons. Examples of such 'preconditioning' or 'neurohormesis' pathways include those involving cell-survival signaling kinases, the transcription factors NRF2 and CREB, and histone deacetylases of the sirtuin family. In these ways, neurohormetic phytochemicals such as resveratrol, sulforaphanes and curcumin might protect neurons against injury and disease by stimulating the production of antioxidant enzymes, neurotrophic factors, protein chaperones and other proteins that help cells to withstand stress. Thus, as we discuss in this review, highly conserved longevity and survival pathways in neurons are the targets of many phytochemicals.

Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo...

Site Editor — Wed, 03 Jan 2007 19:07:14 -0800

Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.: Ann Intern Med. 2006 Dec 19;145(12):869-79 Authors: Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J

BACKGROUND: Herbal supplements are widely used for vasomotor symptoms. OBJECTIVE: To test the efficacy of 3 herbal regimens and hormone therapy for relief of vasomotor symptoms compared with placebo. DESIGN: 1-year randomized, double-blind, placebo-controlled trial conducted from May 2001 to September 2004. SETTING: Group Health, Washington State. PARTICIPANTS: 351 women age 45 to 55 years with 2 or more vasomotor symptoms per day; 52% of the women were in menopausal transition and 48% were postmenopausal. MEASUREMENTS: Rate and intensity of vasomotor symptoms (1 = mild to 3 = severe), and Wiklund Vasomotor Symptom Subscale. INTERVENTIONS: 1) Black cohosh, 160 mg daily; 2) multibotanical with black cohosh, 200 mg daily, and 9 other ingredients; 3) multibotanical plus dietary soy counseling; 4) conjugated equine estrogen, 0.625 mg daily, with or without medroxyprogesterone acetate, 2.5 mg daily; or 5) placebo. RESULTS: Vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale score did not differ between the herbal interventions and placebo at 3, 6, or 12 months or for the average over all the follow-up time points (P > 0.05 for all comparisons) with 1 exception: At 12 months, symptom intensity was significantly worse with the multibotanical plus soy intervention than with placebo (P = 0.016). The difference in vasomotor symptoms per day between placebo and any of the herbal treatments at any time point was less than 1 symptom per day; for the average over all the follow-up time points, the difference was less than 0.55 symptom per day. The difference for hormone therapy versus placebo was -4.06 vasomotor symptoms per day for the average over all the follow-up time points (95% CI, -5.93 to -2.19 symptoms per day; P < 0.001). LIMITATIONS: The trial did not simulate the whole-person approach used by naturopathic physicians. Differences between treatment groups smaller than 1.5 Vasomotor symptoms per day cannot be ruled out. CONCLUSION: Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms. Clinical Trials Registration number: NCT00169299.

Genistein, estrogen receptors, and the acquired immune response.

Site Editor — Fri, 09 Jun 2006 07:22:21 -0700

Genistein, estrogen receptors, and the acquired immune response.: J Nutr. 2006 Mar;136(3):704-8 Authors: Cooke PS, Selvaraj V, Yellayi S

Estrogen regulates thymic development and immune function. Despite the critical role of estrogens in inducing thymic involution and modulating immune responses, the mechanism of this effect is unclear. Similarly, humans and animals are exposed to increasing amounts of the estrogenic soy isoflavone genistein in the diet, but whether genistein can induce immune changes has not been definitively established. We reported previously that genistein induces thymic atrophy in mice, and decreases both humoral and cell-mediated immunity. These thymic effects of genistein occur via estrogen receptor (ER)-mediated and non-ER-mediated pathways. Genistein injections produced the most pronounced effects, but dietary administration to mice that produced serum genistein concentrations similar to those reported in human infants consuming soy formula also had demonstrable effects. Microarray analysis of the effects of estradiol and genistein on neonatal thymus indicated that estradiol affected genes involved in transcription, apoptosis, cell cycle, and thymic development and function; genistein had similar effects on many estradiol target genes, but also had unique actions not replicated by estradiol. Despite extensive work showing inhibitory effects of genistein on immunity, other rodent studies reported that genistein or other phytoestrogens stimulate various aspects of immune function. Although the present data strongly indicate that genistein can regulate immune function, possibly at physiologic concentrations, further work is required to definitively establish overall thymic and immune effects of genistein and soy, which may vary with age, species, and specific end point.

Femal, a herbal remedy made from pollen extracts, reduces hot flushes and improves quality of life in menopausal women...

Site Editor — Fri, 09 Jun 2006 07:21:12 -0700

Femal, a herbal remedy made from pollen extracts, reduces hot flushes and improves quality of life in menopausal women: a randomized, placebo-controlled, parallel study.: Climacteric. 2005 Jun;8(2):162-70 Authors: Winther K, Rein E, Hedman C

BACKGROUND: The fact that hormone replacement therapy has been claimed to increase the risk of breast cancer has made it relevant to search for new non-hormonal treatments of menopausal symptoms. OBJECTIVES: This study aimed to evaluate whether Femal, a herbal remedy made from pollen extracts, alleviates the symptoms of the menopause, especially hot flushes. DESIGN: A randomized, double-blind, placebo-controlled, parallel trial of 64 menopausal women, of whom 54 completed the trial. After an initial run-in phase of 1 month, the women were randomly given either two Femal tablets each morning, or two identical placebo tablets, for 3 months of treatment. On inclusion, and then at 4-week intervals, the patients were asked to evaluate 16 symptoms of the menopause using Menopause Rating Scales (MRS). In addition, every day throughout the study, certain menopausal symptoms were recorded in a diary. RESULTS: The two treatment groups were identical regarding demographic data and the initial symptom scores. In the active-treatment group, 65% responded with a reduction in hot flushes compared with 38% in the placebo group (p<0.006) and, in this group, the number of hot flushes registered in diaries declined after 3 months by 27% as compared to the placebo group (p<0.026). MRS evaluation of hot flushes yielded similar results (p<0.031). There were 23% and 22% decreases in hot flushes after 2 and 3 months of treatment, respectively, and after both intervals of time the inter-group comparisons were significantly affected. An overall evaluation of the trend in 15 other 'quality-of-life' parameters showed likewise in favor of the pollen extract (p<0.031). CONCLUSION: The pollen extract Femal significantly reduces hot flushes and certain other menopausal symptoms when compared to placebo.

Clinical effect of treatment for clearing heat, detoxicating and nourishing Yin on patients with glucocorticosteroid induced...

Site Editor — Fri, 09 Jun 2006 07:19:17 -0700

[Clinical effect of treatment for clearing heat, detoxicating and nourishing Yin on patients with glucocorticosteroid induced facial dermatitis and its effect on skin barrier function]: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006 Jan;26(1):46-8 Authors: Du XH, Song WM, Xu AE

OBJECTIVE: To observe the clinical efficacy of treatment for clearing heat, detoxicating and nourishing Yin (abbr. as CHM) on glucocorticosteroid (GCS) induced facial dermatitis, and its effect in repairing skin barrier function. METHODS: One hundred and fifteen patients were randomly assigned into two groups, 68 in the treated group treated with CHM and 47 in the control group treated by oral administration of loratadine 10 mg once a day and ketotifen 1 mg once every night. The volume of transepidermal water loss (TEWL) of patients was measured before and after treatment. RESULTS: The effective rate was 77.9% (53/68) and 14.9% (7/47) in the treated group and the control group respectively, showing significant difference between the two groups, and it was better in the treated group than that in the control group (P < 0.01). The decrease of TEWL in the treated group was also superior to that in the control group (P < 0.01). CONCLUSION: Chinese herbal treatment for clearing heat, detoxicating and nourishing Yin has significant clinical efficiency on GCS induced facial dermatitis and in repairing the skin barrier function.

17beta-Hydroxysteroid dehydrogenase (17beta-HSD) in scleractinian corals and zooxanthellae.

Site Editor — Fri, 09 Jun 2006 07:17:40 -0700

17beta-Hydroxysteroid dehydrogenase (17beta-HSD) in scleractinian corals and zooxanthellae.: Comp Biochem Physiol B Biochem Mol Biol. 2006 Feb 1; Authors: Blomquist CH, Lima PH, Tarrant AM, Atkinson MJ, Atkinson S

Steroid metabolism studies have yielded evidence of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity in corals. This project was undertaken to clarify whether there are multiple isoforms of 17beta-HSD, whether activity levels vary seasonally, and if zooxanthellae contribute to activity. 17beta-HSD activity was characterized in zooxanthellate and azooxanthellate coral fragments collected in summer and winter and in zooxanthellae cultured from Montipora capitata. More specifically, 17beta-HSD activity was characterized with regard to steroid substrate and inhibitor specificity, coenzyme specificity, and Michaelis constants for estradiol (E(2)) and NADP(+). Six samples each of M. capitata and Tubastrea coccinea (three summers, three winters) were assayed with E(2) and NADP(+). Specific activity levels (pmol/mg protein) varied 10-fold among M. capitata samples and 6-fold among T. coccinea samples. There was overlap of activity levels between summer and winter samples. NADP(+)/NAD(+) activity ratios varied from 1.6 to 22.2 for M. capatita, 2.3 to 3.8 for T. coccinea and 0.7 to 1.1 for zooxanthellae. Coumestrol was the most inhibitory of the steroids and phytoestrogens tested. Our data confirm that corals and zooxanthellae contain 17beta-HSD and are consistent with the presence of more than one isoform of the enzyme.

Inhibition of sulfotransferases by xenobiotics.

Site Editor — Fri, 09 Jun 2006 07:15:00 -0700

Inhibition of sulfotransferases by xenobiotics.: Curr Drug Metab. 2006 Jan;7(1):83-104 Authors: Wang LQ, James MO

The sulfotransferase (SULT) family comprises important phase II conjugation enzymes for the detoxification of xenobiotics and modulation of the activity of physiologically important endobiotics such as thyroid hormones, steroids, and neurotransmitters. SULT enzymes catalyze the transfer of a sulfuryl group, donated by 3'-phosphoadenosine-5'-phosphosulfate (PAPS), to an acceptor substrate that may be a hydroxy group or an amine group in a process originally called sulfation, but more correctly referred to as sulfonation or sulfurylation. SULT activity may be inhibited when humans are exposed to certain xenobiotics including drugs (mefenamic acid, salicylic acid, clomiphene, danazol etc.), dietary chemicals (catechins, food colorants, flavonoids and phytoestrogens etc.), and environmental chemicals (hydroxylated polychlorinated biphenyls, hydroxylated polyhalogenated aromatic hydrocarbons, pentachlorophenol, triclosan and bisphenol A, etc.). Inhibition of individual SULT isoforms may cause adverse effects on human health. For example, hydroxylated polychlorinated biphenyls have been shown to interfere with the transport of thyroid hormones, inhibit estradiol sulfonation, and inhibit thyroid hormone sulfonation, thereby potentially disrupting the thyroid hormone system. Formation of sulfate conjugates of toxic xenobiotics usually decreases their toxicity, so inhibition of this pathway may lead to prolonged exposure to the compounds. Conversely, some sulfate conjugates are chemically reactive, inhibition of their formation may protect from toxicity. This manuscript will review the literature concerning the inhibition of SULTs by xenobiotics including isoform-selective effects, inhibition kinetics and health effects resulting from the inhibition.

17beta-estradiol suppresses TLR3-induced cytokine and chemokine production in endometrial epithelial cells

Site Editor — Fri, 09 Jun 2006 04:22:26 -0700

17beta-estradiol suppresses TLR3-induced cytokine and chemokine production in endometrial epithelial cells:

Background: The human endometrium is an important site for contact between the host and pathogens ascending the reproductive tract, and thus plays an important role in female reproductive tract immunity. Previous work in our laboratory has suggested that Toll-like receptors (TLRs) are involved in endometrial epithelial recognition of pathogens and that ligation of endometrial TLRs results in the production of cytokines and chemokines important for both immune and reproductive functions of the endometrium. We have also demonstrated cyclic regulation of TLR3 mRNA and protein expression in human endometrium, suggesting that steroid hormones might play a role in the expression and function of TLR3. In this study, the effects of 17beta-estradiol (E2) and progesterone (P) on TLR3 expression and function in endometrial cell lines were investigated. Methods: Endometrial epithelial cell lines were cultured and examined for the presence of TLR3 and hormone receptors by endpoint RT-PCR. For hormonal studies, cells were pre-treated with ethanol vehicle, 10^(-8) M E2, and/or 10^(-7) M P. For antagonist assays, cells were treated with the ER antagonist, ICI 182, 780, or the PR antagonist, RU486, for two hours prior to treatment with hormones. Following hormone or hormone/antagonist pre-treatment, cells were stimulated with vehicle, the synthetic TLR3 ligand, polyinosinic-polycytidylic acid (Poly I:C), a negative dsDNA control, or a positive control. Cytokine and chemokine production post-stimulation was measured by ELISA. The effects of E2 and P on TLR3 mRNA and protein expression were measured using Real Time RT-PCR and FACS analysis, respectively. Results: Stimulation of TLR3-expressing cells with the synthetic TLR3 ligand, Poly I:C, resulted in the production of cytokines and chemokines important for endometrial function and regulation. Suppression of Poly I:C-induced cytokine and chemokine production by cells treated with 10^(-8) M E2, but not cells treated with 10^(-7) M P, was observed in endometrial epithelial cell lines expressing TLR3 and estrogen receptor alpha (ERalpha). The effects of E2 were not observed on cells which did not express ERalpha or in cells pre-treated with the ER antagonist, ICI 182, 780. Treatment with E2 did not affect TLR3 mRNA or protein expression. However, treatment with E2 did suppress cytokine and chemokine production resulting from TLR3 stimulation with Poly I:C, suggesting that E2 modulates TLR3 function. Conclusion: The data presented in this study are the first indication that E2 can markedly alter the innate immune response to dsRNA, providing a previously unreported process by which E2 can alter immune responses.

Potent Antiandrogen and Androgen Receptor Activities of an Angelica gigas-Containing Herbal Formulation...

Site Editor — Fri, 09 Jun 2006 04:06:15 -0700

Potent Antiandrogen and Androgen Receptor Activities of an Angelica gigas-Containing Herbal Formulation for Prevention and Treatment of Prostate Cancer.: Cancer Res. 2006 Jan 1;66(1):453-63 Authors: Jiang C, Lee HJ, Li GX, Guo J, Malewicz B, Zhao Y, Lee EO, Lee HJ, Lee JH, Kim MS, Kim SH, Lu J

Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC(50), approximately 7 mug/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G(1) arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC(50) of approximately 0.4 mug/mL (1.3 mumol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G(1) arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases. (Cancer Res 2006; 66(1): 453-63).

Isoflavones modulate the glucuronidation of estradiol in human liver microsomes.

Site Editor — Fri, 09 Jun 2006 04:03:59 -0700

Isoflavones modulate the glucuronidation of estradiol in human liver microsomes.: Carcinogenesis. 2005 Dec;26(12):2172-8 Authors: Pfeiffer E, Treiling CR, Hoehle SI, Metzler M

Soy food has been associated with a reduced incidence of hormonal cancer in Asian countries, and the soy isoflavones daidzein and genistein are believed to protect against tumors induced by the endogenous hormone 17beta-estradiol (E2). In the present study, we have examined if daidzein and genistein as well as several structurally related isoflavones are able to modulate the in vitro glucuronidation of E2 in human hepatic microsomes. It is known that different isoforms of UDP-glucuronosyltransferase (UGT) are involved in E2 glucuronidation: UGT1A1 leads exclusively to the 3-glucuronide and is stimulated by E2 via homotropic kinetics, whereas UGT2B7 gives rise to the 17-glucuronide of E2 following Michaelis-Menten kinetics. In our study, daidzein markedly stimulated the 3-glucuronidation, thereby enhancing the metabolic clearance of E2. In contrast, genistein inhibited the 3-glucuronidation. The 17-glucuronidation of E2 was not affected by either compound. Formononetin and the daidzein metabolites equol, 3'-hydroxy-daidzein, 6-hydroxy-daidzein and glycitein behaved similar to daidzein, whereas biochanin A resembled genistein. The effect of daidzein on the 3-glucuronidation of E2 in human hepatic microsomes was also obtained with human recombinant UGT1A1. Since the only other compound known to stimulate E2 glucuronidation via allosteric kinetics is 17alpha-ethynylestradiol, our study is the first report of the heterotropic stimulation of a UGT by a non-steroidal and naturally occurring compound. An enhanced rate of glucuronidation of E2 by daidzein and its metabolites may contribute to the putative protection of soy against hormonal cancer.

[Primary and secondary prevention of cardiovascular events through hormone replacement therapy (HRT)]

Site Editor — Fri, 09 Jun 2006 04:02:47 -0700

[Primary and secondary prevention of cardiovascular events through hormone replacement therapy (HRT)]: Wien Med Wochenschr. 2005 Sep;155(17-18):397-403 Authors: Pilz H

A recently (2002) published, randomised, double blind placebo controlled trial of hormone replace ment therapy (HRT), the Women's Health Initiative (WHI), is not consistent with the decrease in cardiovascular disease under CEE/HPA seen in observational primary prevention studies like the Nurses' Health Study. Baseline characteristics of participants like age, body mass index, years since menopause and preexistent cardiovascular diseases may be responsible for the lack of benefit seen in this trial. Clinical outcome data of HRT from randomised trials in secondary prevention of cardiovasular diseases are limited. The first prospective, randomised placebo controlled trial, the Heart and Estrogen/Progestin Replacement Study (HERS) in secondary prevention did not show any difference in CHD events between treatment groups and placebo during a follow up of 4.1 years. However, an increased risk of CHD was seen especially during the first year on HRT, subsequent years showed a decrease in event rate compared with never-users. One explanation for this lack of benefit may be a bi-directional effect of estrogen - early risk and late benefit - especially in an elderly study population with established atherosclerotic lesions. In postmenopausal women, estrogen replacement therapy affects LDL- and HDL-cholesterol levels favorably, causes vasodilatation by activating NOS, inhibits platelet aggregation and proinflammatory cell adhesion on endothelial cells of vascular wall. Estrogen can affect the cardiovascular system adversely by increasing triglycerid levels, CPR and proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha). Alternatives to HRT like phytoestrogens act via estrogen alpha and beta receptor modulation. Phytoestrogens may lower LDL-cholesterol levels without increasing triglyceride levels, they have shown antioxidannt properties as well as favorable effects on vascular reactivity. The importance of HRT and phytoestrogens in primary and secondary prevention of cardiovascular disease remains to be established.

Effect of Ginkgo biloba extract on plasma steroid concentrations in healthy volunteers: a pilot study.

Site Editor — Fri, 09 Jun 2006 04:00:40 -0700

Effect of Ginkgo biloba extract on plasma steroid concentrations in healthy volunteers: a pilot study.: Pharmacotherapy. 2005 Oct;25(10):1337-40 Authors: Markowitz JS, DeVane CL, Lewis JG, Chavin KD, Wang JS, Donovan JL

STUDY OBJECTIVE: To determine if a standardized ginkgo supplement significantly alters concentrations of circulating androgenic steroids in humans. DESIGN: Open-label, fixed-treatment order, crossover study. SETTING: University general clinical research center. SUBJECTS: Eleven healthy volunteers (six men, five women). INTERVENTION: Volunteers received ginkgo biloba 240 mg/day for 14 days. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of cortisol, 11-deoxycortisol, 17alpha-hydroxyprogesterone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, androstenedione, and free testosterone, as well as free androgen index and combined concentrations of androsterone sulfate and epiandrosterone sulfate, were analyzed in all subjects before and after their 14-day course of ginkgo biloba. Ginkgo biloba did not significantly alter endogenous steroid levels compared with baseline values (p < 0.05). CONCLUSION: A 14-day oral administration of a widely used, standardized ginkgo extract at a generally advocated dosage of 240 mg/day did not significantly alter concentrations of major circulating steroids in men and women.

The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men.

Site Editor — Fri, 09 Jun 2006 03:56:45 -0700

The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men.: J Ethnopharmacol. 2005 Oct 3;101(1-3):319-23 Authors: Neychev VK, Mitev VI

OBJECTIVE: The aim of the current study is to investigate the influence of Tribulus terrestris extract on androgen metabolism in young males. DESIGN AND METHODS: Twenty-one healthy young 20-36 years old men with body weight ranging from 60 to 125 kg were randomly separated into three groups-two experimental (each n=7) and a control (placebo) one (n=7). The experimental groups were named TT1 and TT2 and the subjects were assigned to consume 20 and 10 mg/kg body weight per day of Tribulus terrestris extract, respectively, separated into three daily intakes for 4 weeks. Testosterone, androstenedione and luteinizing hormone levels in the serum were measured 24 h before supplementation (clear probe), and at 24, 72, 240, 408 and 576 h from the beginning of the supplementation. RESULTS: There was no significant difference between Tribulus terrestris supplemented groups and controls in the serum testosterone (TT1 (mean+/-S.D.: 15.75+/-1.75 nmol/l); TT2 (mean+/-S.D.: 16.32+/-1.57 nmol/l); controls (mean+/-S.D.: 17.74+/-1.09 nmol/l) (p>0.05)), androstenedione (TT1 (mean+/-S.D.: 1.927+/-0.126 ng/ml); TT2 (mean+/-S.D.: 2.026+/-0.256 ng/ml); controls (mean+/-S.D.: 1.952+/-0.236 ng/ml) (p>0.05)) or luteinizing hormone (TT1 (mean+/-S.D.: 4.662+/-0.274U/l); TT2 (mean+/-S.D.: 4.103+/-0.869U/l); controls (mean+/-S.D.: 4.170+/-0.406U/l) (p>0.05)) levels. All results were within the normal range. The findings in the current study anticipate that Tribulus terrestris steroid saponins possess neither direct nor indirect androgen-increasing properties. The study will be extended in the clarifying the probable mode of action of Tribulus terrestris steroid saponins.

Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women...

Site Editor — Fri, 09 Jun 2006 03:46:46 -0700

Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study.: Phytother Res. 2005 Oct;19(10):901-6 Authors: Donovan JL, DeVane CL, Lewis JG, Wang JS, Ruan Y, Chavin KD, Markowitz JS

St John's wort extract (SJW; Hypericum perforatum L.) is taken extensively as a putative herbal antidepressant. It has been shown to induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the clearance of numerous drugs and steroids such as cortisol and ethinyl estradiol. This study was conducted to determine if SJW exposure also alters the concentrations of circulating androgenic steroid hormones. The study was conducted using healthy volunteers (6M, 6F) studied before and after a 14-day treatment period with a SJW preparation previously demonstrated to induce the activity of CYP3A4. Plasma concentrations of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and the combined concentrations of androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were measured by immunoassay methods. The results of analysis demonstrated that SJW did not significantly alter the majority of the androgens studied (p > 0.05) although the combined concentrations of the 5alpha-reduced steroids, AoS and epiAoS, significantly declined following treatment in all subjects (p = 0.02), and in males (p = 0.04). Furthermore, the testosterone to DHT ratio was increased in both men and women. Although the latter increase did not reach statistical significance, it is also consistent with the possible inhibition of 5alpha-reductase by SJW. It is concluded that despite significant induction of CYP3A4, short term administration of SJW does not significantly alter the concentrations of most circulating androgens in men and women but may produce a dimunition in some of the circulating 5alpha-reduced androgens.

Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration.

Site Editor — Fri, 09 Jun 2006 03:44:59 -0700

Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration.: Phytother Res. 2005 Oct;19(10):819-38 Authors: Panossian A, Wagner H

Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors. The beneficial effects of multi-dose administration of adaptogens are mainly associated with the hypothalamic-pituitary-adrenal (HPA) axis, a part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation. In contrast, the single dose application of adaptogens is important in situations that require a rapid response to tension or to a stressful situation. In this case, the effects of the adaptogens are associated with another part of the stress-system, namely, the sympatho-adrenal-system (SAS), that provides a rapid response mechanism mainly to control the acute reaction of the organism to a stressor. This review focuses primarily on the SAS-mediated stimulating effects of single doses of adaptogens derived from Rhodiola rosea, Schizandra chinensis and Eleutherococcus senticosus. The use of these drugs typically generates no side effects, unlike traditional stimulants that possess addiction, tolerance and abuse potential, produce a negative effect on sleep structure, and cause rebound hypersomnolence or 'come down' effects. Furthermore, single administration of these adaptogens effectively increases mental performance and physical working capacity in humans. R. rosea is the most active of the three plant adaptogens producing, within 30 min of administration, a stimulating effect that continues for at least 4-6 h. The active principles of the three plants that exhibit single dose stimulating effects are glycosides of phenylpropane- and phenylethane-based phenolic compounds such as salidroside, rosavin, syringin and triandrin, the latter being the most active.

Cancer vaccine has strong response in young girls.

Site Editor — Fri, 09 Jun 2006 03:43:39 -0700

Cancer vaccine has strong response in young girls - NEW YORK (Reuters)

Girls aged 10 to 14 who received GlaxoSmithKline Plc's vaccine to prevent infection with the virus that causes cervical cancer had immune responses twice as strong as women 15-25 years old given the vaccine, the company said on Saturday, describing results of a late-stage trial.

Sex hormones as potential modulators of vascular function in hypertension.

Site Editor — Fri, 09 Jun 2006 03:43:28 -0700

Sex hormones as potential modulators of vascular function in hypertension.: Hypertension. 2005 Aug;46(2):249-54 Authors: Khalil RA

The greater incidence of hypertension in men and postmenopausal women compared with premenopausal women has suggested gender differences in vascular function. Vascular effects of the female sex hormones estrogen and progesterone and the male hormone testosterone have been described. Sex steroid receptors have been identified in vascular endothelium and smooth muscle. Interaction of sex hormones with cytosolic/nuclear receptors initiates long-term genomic effects that stimulate endothelial cell growth but inhibit smooth muscle proliferation. Activation of sex hormone receptors on the plasma membrane triggers nongenomic effects that stimulate endothelium-dependent vascular relaxation via NO-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Sex hormones also cause endothelium-independent inhibition of vascular smooth muscle contraction, [Ca2+]i, and protein kinase C. These vasorelaxant/vasodilator effects suggested vascular benefits of hormone replacement therapy (HRT) during natural and surgically induced deficiencies of gonadal hormones. Although some clinical trials showed minimal benefits of HRT in postmenopausal hypertension, the lack of effect should not be generalized because it could be related to the type/dose of sex hormone, subjects' age, and other cardiovascular conditions. The prospect of HRT relies on continued investigation of the molecular mechanisms underlying the vascular effects of sex hormones and identification of compounds that specifically target the vascular sex hormone receptors. Naturally occurring hormones and phytoestrogens may be more beneficial HRT than synthesized compounds. Also, the type/dose, time of initiation, and duration of HRT should be customized depending on the subject's age and preexisting cardiovascular condition, and thereby enhance the outlook of sex hormones as potential modulators of vascular function in hypertension.

3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease.

Site Editor — Fri, 09 Jun 2006 03:42:43 -0700

3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease.: Biochem Biophys Res Commun. 2005 Nov 25;337(3):1019-25 Authors: Tadi K, Chang Y, Ashok BT, Chen Y, Moscatello A, Schaefer SD, Schantz SP, Policastro AJ, Geliebter J, Tiwari RK

Considerable epidemiological evidence exists to link thyroid disease with differing patterns of dietary consumption, in particular, cruciferous vegetables. We have been studying the anti-thyroid cancer (TCa) activity of indole-3-carbinol (I3C) found in cruciferous vegetables and its acid catalyzed dimer, 3,3'-diindolylmethane (DIM). There are no studies as yet to elucidate the effect of these compounds on the altered proliferative patterns in goiter or thyroid neoplasia. In this study, we tested the anti-proliferative effects of I3C and DIM on four different thyroid cancer cell lines representative of papillary (B-CPAP and 8505-C) and follicular carcinoma of the thyroid (CGTH-W-1 and ML-1), and primary human goiter cells. Cell survival and IC50 values for I3C and DIM were calculated by the XTT assay and cell cycle distribution analysis was done by flow cytometry. DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C. The anti-proliferative activity of DIM in follicular TCa was mediated by a G1 arrest followed by induction of apoptosis. DIM also inhibited the growth of primary goiter cells by 70% compared to untreated controls. Contrary to traditional belief that cruciferous vegetables are "goitrogenic", DIM has anti-proliferative effects in glandular thyroid proliferative disease. Our preclinical studies provide a strong rationale for the clinical exploration of DIM as an adjuvant to surgery in thyroid proliferative disease.