Article

Reduction of Serum Testosterone in Men by Licorice

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Abstract

To the Editor: Extracts of licorice root are widely used in many countries as flavoring agents, breath fresheners, or candy. The active component of licorice is glycyrrhizic acid, which is hydrolyzed in vivo to glycyrrhetinic acid. The well-known mineralocorticoid-like effect of licorice results from the inhibition of 11β-hydroxysteroid dehydrogenase, the enzyme that catalyzes the conversion of cortisol to cortisone, thereby minimizing the binding of cortisol to mineralocorticoid receptors.1 Licorice may also directly activate mineralocorticoid receptors.2 In vitro, licorice can block 17β-hydroxysteroid dehydrogenase, which catalyzes the conversion of androstenedione to testosterone.3 We evaluated the effect of licorice on gonadal function in . . .

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... In vitro (48) Ex vivo (48) Human (68,69) Total extract Animal (33) Human (32,34) In vitro (36)(37)(38)(39)(40)(41)(42) In vitro (51) In vitro (51,62,63) In vitro (71) ...
... Licorice is known as an anti-androgenic herb through different pharmacological mechanisms. Glycyrrhizin (28)(29)(30), licochalcone A (31), and total extract of licorice (32)(33)(34) have been identified with anti-androgenic activities. ...
... Licorice has reduced the production of testosterone by blocking 3β-HSD, 17β-HSD, and 17-20 lyase in humans (32,34). Administration of high amounts of pure licorice extract to male volunteers could significantly reduce total serum testosterone, however, the values of testosterone never dropped below the normal range (34). ...
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Clinical advantages of licorice (Glycyrrhiza spp.) have been investigated for several years. It has been traditionally used for a variety of disorders. Different constituents with various characteristics have been isolated from Glycyrrhiza spp. extracts. This review aimed to summarize the current knowledge on the pharmacological efficacy and safety of licorice extract constituents to treat the pathophysiology of acne vulgaris (AV) and the associated postinflammatory hyperpigmentation (PIH). Anti-androgenic, antimicrobial, anti-inflammatory, antioxidant, depigmenting, and skinturnover-accelerating properties have been identified for licorice extract which could be effective against AV and PIH through multiple pharmacological mechanisms. The active compounds responsible for these pharmacological activities, molecular mechanisms, safety profile, as well as the in vitro, in vivo, animal, and clinical studies are discussed. Licorice extract possesses broadspectrum activity and could be considered as an effective and safe option in the treatment of AV and its associated PIH. However, evidence-based clinical trials are required to prove its efficacy as well as safety. We hope this paper can provide new insights for further studies, particularly large controlled clinical trials.
... Breslow et al., 1977; R. Yatani et al., 1982).säure) zu sich nahmen, eine stark reduzierte Testosteronkonzentration im Serum gemessen werden (D. Armanini et al., 1999). Es wurde beobachtet, dass durch Lakritzkonsum die Aktivität der 11β-HSD-(B. ...
... Es wurde beobachtet, dass durch Lakritzkonsum die Aktivität der 11β-HSD-(B. R. Walker et al., 1995 ), 17, 20-Lyase-und der 17β-HSD- Aktivität inhibiert wird (D. Armanini et al., 1999) Für zahlreiche Phytoestrogene konnten bereits weitere, in die Krebsentstehung und -entwicklung eingreifende, nicht über den Hormonrezeptor vermittelte Eigenschaften bestimmt werden. Diese Effekte beinhalten antioxidative Eigenschaften (A. ...
Article
Epidemiological studies have shown differences in the incidence rates for hormone dependent types of cancer like prostate and breast cancer. These types of cancer are more common in Europe and North America than in Asia. The reason for these observations is seen in the different diets. Phytoestrogens especially are taken up by Asians due to soybean-rich food. Phytoestrogens are thought to interact in a protective way with the human hormone system. This work investigates the influence of phytoestrogens on the activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs). The catalytic functions of 17beta-HSD 4 and 5 were tested in the presence of different plant derived and synthetic compounds within an in vitro-assay. Both steroid metabolising enzymes were inhibited by phytoestrogens. The strongest inhibitory effects on estradiol dehydrogenase activity of 17beta-HSD 4 were observed with quercetin and biochanin A while most potent inhibitors for type 5 were zearalenone, coumestrol and biochanin A. Thus, it was shown, that each type of 17beta-HSD possesses a specific inhibitory compound within the phytoestrogens. The tested catalytic activities of 17beta-HSD 5 were the reduction of androstenedione to testosterone and the oxidation of androstanediol to androsterone. 18beta-Glycyrrhetinic acid, a compound found in licorice, specifically inhibited the reductive activity of the enzyme. This means that this substance inhibits testosterone synthesis catalysed by this enzyme within the prostate. Low serum testosterone levels were also found in men after licorice consumption due to the inhibition of the 17beta-HSD 3-activity within the testis. Thus, 18beta-Glycyrrhetinic acid affects both, endocrine (17beta-HSD 3) and intracrine (17beta-HSD 5) signalling of androgens and this compound could be defined as potential canditate for the therapy of androgen regulated types of cancer like prostate cancer. Furthermore a new human 17beta-HSD could be isolated, cloned and characterized: the type 7. The enzyme is an orthologue of m17beta-HSD 7 and rPRAP known in rodents. The HSD17B7-gene consisting of 9 exons was found to be localized on chromosome 10p11.2 in the vicinity of candidate genes for hyperlipidemia, adipositas and diabetes mellitus type 1. The estradiol synthesis activity which was shown for the murine enzyme could be confirmed for the human 17beta-HSD 7 using recombinant overexpressed and purified protein. RT-PCR used for the analysis of tissue distribution showed the expression in ovary, breast and testis but also in brain and liver and leads th the proposal of an additional function of the enzyme was proposed. This hypothesis was supported by a an in silico-Northern blot, a 3D-model of the enzyme and a phylogenetic analysis indicating that ERG27, a yeast protein involved in ergosterol synthesis is the next relative to the human enzyme. Consequently a potential role of the human enzyme within cholesterol biosynthesis was postulated.
... 34 Endokrin etkinin fitoöstrojenlerden başka zayıf bir antiandrojen olan steroid glisirizin ve glisiretik asit gibi maddelere bağlı olduğu düşünülmektedir. 35,36 Meyan kökü ayrıca testosteron seviyesini azaltır ve böylece kadınlarda hirsutizme katkıda bulunabilir. 19 Armanini ve ark. ...
... tarafından 2004 yılında bildirilen küçük bir klinik çalışmada günlük meyan kökü alan sağlıklı kadın gönüllülerde 1 ay sonra testosteron düzeylerinin belirgin ölçüde azaldığı, meyan kökü kesildikten sonra normale döndüğü ortaya koymuştur. 36 Bununla birlikte meyan kökünün serbest testosteron düzeylerine etkisinin olup olmadığı belirsizdir. 17 L La av va an nt ta a v ve e ç ça ay y a ağ ğa ac cı ı y ya ağ ğı ı: : Tirabassi ve ark.nın toplam 24 hafif idiyopatik hirsutizmli kadın hastanın 12 sinde Lavanta ve çay ağacı yağı spreyi ile 12 sine plasebo uyguladıkları bir araştırmada günde 2 kez 3 ay süre ile uygulanan bitkisel yağın hormonlarda bir değişiklik yapmaksızın kılların çapında ve total hirsutizm skorlarında istatistik olarak anlam ifade edecek derecede azalma sağladığı ve bu tedavinin hafif derece hirsutizmde ekonomik ve pratik bir tedavi aracı olabileceği gösterilmiştir. ...
... Women taking daily licorice root experienced a drop in total testosterone levels after 1 month and testosterone levels returned to normal after discontinuation. It is unclear as to whether licorice root affects free testosterone levels (4). The endocrine effect is thought to be due to phytoestrogens and other chemicals found in licorice root, including the steroid glycyrrhizin and glycyrrhetic acid, which also have a weak anti-androgen effect (5, 6). ...
... Reduction in total testosterone levels (effect on free testosterone levels not clear) (4)(5)(6) White Peony (Paeonia lactiflora) Paeoniflorin inhibits the production of testosterone and promotes the activity of aromatase -the enzyme that converts testosterone into estrogen (7) Green Tea (Camellia Sinensis) Contains chemicals epigallocatechins, which inhibit the enzyme 5-alpha-reductase, and thereby reduce the conversion of normal testosterone into the more potent DHT ...
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Anti-androgens are an assorted group of drugs and compounds that reduce the levels or activity of androgen hormones within the human body. Disease states in which this is relevant include polycystic ovarian syndrome, hirsutism, acne, benign prostatic hyperplasia, and endocrine related cancers such as carcinoma of the prostate. We provide an overview and discussion of the use of anti-androgen medications in clinical practice and explore the increasing recognition of the benefits of plant-derived anti-androgens, for example, spearmint tea in the management of PCOS, for which some evidence about efficacy is beginning to emerge. Other agents covered include red reishi, which has been shown to reduce levels 5-alpha reductase, the enzyme that facilitates conversion of testosterone to dihydrotestosterone (DHT); licorice, which has phytoestrogen effects and reduces testosterone levels; Chinese peony, which promotes the aromatization of testosterone into estrogen; green tea, which contains epigallocatechins and also inhibits 5-alpha reductase, thereby reducing the conversion of normal testosterone into the more potent DHT; black cohosh, which has been shown to kill both androgenresponsive and non-responsive human prostate cancer cells; chaste tree, which has a reduces prolactin from the anterior pituitary; and saw palmetto extract, which is used as an anti-androgen although it shown no difference in comparison to placebo in clinical trials.
... The days of estrous cycles was illustrated in figure (12), the orally administration of Glycyrhazia globra extract to animals caused a significant depletion (P<0.05) in days of estrous cycle four and cycle five as compared with other cycles (one, two and three), while in piogiltazone and Glycyrhazia globra extract with piogiltazone treated groups caused significant depletion (P<0.05) in days of estrous cycles two, three, four and five when compared with cycle one. The days of estrous in Glycyrhazia globra extract, piogiltazone, Glycyrhazia globra extract and piogiltazone groups revealed significant depletion (P<0.05) in all cycles in comparison with distilled water treated group, furthermore, in cycles four and five consequences there were no significant difference (P<0.05) in mean value when compared with baseline group. ...
... This altitude of androgen levels stamped on the hypothalamus result in a non-cyclic discharge of gonadotrophins and abnormality in all estrous phases, the same result mentioned by Kafali, et al., [7], in addition to testosterone is needed for usual folliculogenesis, mostly before time of follicular growth , and an intemperance of intra ovarian androgens lead to atresia follicles formation furthermore, the testosterone allowed the stimulation of the primary follicles by way of phosphatidylinositol-3-kinases-Akt-Foxo-3a and also depleted the growth differentiation factors 9 appearance in oocyte, leading to capture of preantral follicles growth, which can be clarified estrous cycle disturbances in PCOS, this outcomes supported by consequences [11]. The estrous cycles measurements, altered to the ordinary sequences following handled rats with Glycyrrhiza glabra roots extract is due to the extract has the capability to manipulate on metabolism of androgen [12], several studies established that the Glycerrhezia globra closed effect of 17-20lyase, 3-hydroxysteroid dehydrogenase, 17-hydroxysteroid dehydro-genase and activated the aromatase activity [13]. Estrogens androgens occupied in the metabolism and creation by these enzymes, in addition, the influence of the glycyrrhizic acid which establish in herbal product participated in ruling the hormones and activation the ovulation, Glycyrrhiza glabra roots extract in vitro produced endorsement the formation of estradiol and activate activity of aromatase by glycyrrhizic acid, therfore the estrous cycles after adminstered rats with Glycyrrhiza glabra roots extract it can be returned to the regular sequences, this result also agreed with Takeuchi , et al., [14]. ...
... Estrogen-like compounds such as flavonoids in this plant can be increased estrogen levels [Bonani, 1999]. However, excessive secretion of pituitary FSH producing estrogen reduces [Gayton, 2008]. ...
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Celery (Apium graveolens) has many therapeutic effects. This plant has many phytoestrogens that can affect on the reproductive endocrine system and can reduce fertility. In this study, Hydro alcoholic extracts of celery leaves on the pituitary -gonad axis in young male l mice of Balb/C was investigated. The samples were randomly divided into 5 groups (three treatment groups, placebo and control). Celery leaves hydroalcoholic extract in different doses (50, 100,150 mg/kg/2day) was injected (IP) for 20 days. The Placebo group was used for injection of normal saline. The samples were randomly divided into 5 groups (three treatment groups, placebo and control). Celery leaves hydroalcoholic extract in different doses (50, 100,150 mg/kg/2day) was injected (IP) for 20 days. The Placebo group was used for injection of normal saline. After 10 injections, samples bloods were analyzed for FSH, LH, and testosterone using RIA method and compared with control groups and compared with control groups. Concentrations of FSH in 100 and 150 mg/kg decreased significantly while LH and testosterone concentrations in all experimental groups decreased (P<0.05). This study showed dose-dependent negative effect of celery extracts in the pituitary - gonad axis in male mice. (C) 2012 Published by Elsevier B. V. Selection and/or peer review under responsibility of Asia-Pacific Chemical, Biological & Environmental Engineering Society
... The included ingredients might affect the specific parameters of PCOS via different mechanisms. While omega-3 fatty acids, selenium, vitamin E, and also co-enzyme Q10, known to scavenge free radicals and inhibit lipid and protein oxidation [25], might have acted as antioxidants and thereby likely influenced the proinflammatory PCOS state [9], licorice with its active component glycyrrhizin has been shown to affect androgen metabolism, probably via blocking the activity of 3-β-hydroxysteroid dehydrogenase (3HSD), 17-hydroxysteroid dehydrogenase (17HSD) and 17-20 lyase [26][27][28][29][30][31][32][33] and stimulation of the aromatase activity [31]. Notably, a lowering effect on ovarian androgens has already been reported for licorice [33], even in PCOS women [32]. ...
Article
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Purpose To evaluate whether a micronutrient supplementation preparation that includes a high amount of omega-3 unsaturated acids, other anti-oxidants and co-enzyme Q10 would have an impact on specific serum parameters in women with polycystic ovary syndrome (PCOS). Methods The study was designed as a monocentral, randomized, controlled, double-blinded trial, from June 2017 to March 2018 (Clinical Trials ID: NCT03306745). Sixty women with PCOS were assigned to either the “multinutrient supplementation group” (one unlabeled soft capsule containing omega-3 fatty acids and one unlabeled tablet containing folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, for 3 months) or the “control group” (two unlabeled soft capsules containing 200 μg folic acid each, for 3 months). The main outcome parameters were anti-Mullerian hormone (AMH), total testosterone, and androstenedione. In addition, the focus was on luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, sexual hormone-binding globulin (SHBG), and estradiol. Results In the multinutrient supplementation group, the LH:FSH ratio (2.5 ± 1.1 versus 1.9 ± 0.5, p = 0.001), testosterone (0.50 ± 0.19 versus 0.43 ± 0.15, p = 0.001), and AMH (8.2 ± 4.2 versus 7.3 ± 3.6, p < 0.001) declined significantly, whereas the other parameters, namely estradiol, LH, FSH, androstenedione, and SHBG remained stable. Conclusion A micronutrient supplementation that includes omega-3 fatty acids, folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, given for a minimum of 3 months, is beneficial for women with PCOS in terms of PCOS-specific parameters (LH:FSH ratio, serum testosterone and serum AMH).
... 며 [3][4][5][6] , 김 6 7) . 감초는 항안드로젠 활동 (antiandrogenic activity)에 효과가 있으나 장기간 섭취시 테스토스테론을 감 소시킬 뿐만 아니라 [7][8][9][10][11] , 에스트로젠 대사와 합성에 영향을 미친다고 보고하고 있다 10) . ...
Article
Objectives : The aim of this study was to investigate the effects of licorice supplementation on muscle injury, plasma cortisol, testosterone and insulin sensitivity after high intensity resistance exercise. Methods : The fourteen health college male students were voluntarily participated in this study and were randomly divided into 2 groups: Control group (CON, n
... Moreover, the metabolites of licorice, glabridin, and glabrene have an estrogen-like effect and have been used for the treatment of menopause [16]. In addition, Armanini et al. reported a significant reduction in serum testosterone in healthy women and men over 2 months of licorice intake [17,18]. The root of licorice plant is rich in triterpenes especially glycyrrhizin, which has a beneficial effect on estrogen receptors [4,19]. ...
Article
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Hirsutism is one of the most prevalent health problems in women. The aim of the study was to compare the effect of 755 nm alexandrite hair removal laser with that of alexandrite laser plus topical licorice on the improvement of idiopathic hirsutism. A double-blind, randomized placebo-controlled study was performed on 90 female subjects. The patients were divided into two groups: alexandrite laser plus 15% licorice gel (group A) and placebo (group B). Each subject received one of both products over one side of the face, twice daily for 24 weeks on the hirsute locations. Each group underwent five sessions of alexandrite laser at 6-week intervals. To minimize the effects of confounding variables, the test was performed on two separate zones of patients’ skin. The mean ± SD numbers of terminal hairs in group A were 7.05 ± 4.55 for zone 1 and 6.06 ± 3.70 for zone 2. In group B, they were 3.18 ± 1.75 for zone 1 and 2.49 ± 1.63 for zone 2. The difference in the mean number of terminal hairs was statistically significant between the two groups ( p < 0.001 ), and there were no serious adverse reactions. The treatment of idiopathic hirsutism with 755 nm alexandrite laser plus topical licorice is more effective than alexandrite laser only.
... Another study also found that high dose administration of glycyrrhizin for pregnant women will increase the premature birth rate [221]. For male patients, licorice extracts can lead to down-regulation of serum testosterone secretion and cause impotency [222]. Other studies have confirmed that high doses of glycyrrhizin can induce hypermineralocorticoid-like effects. ...
Article
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Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.
... ma-yuen (Roman.) Stapf (Armanini et al., 1999;Hsia et al., 2009;Hsia et al., 2007;Kim et al., 2014). This unique hormonal therapy and subsequent decrease in sebum secretion may be the reason why Coix lacryma-jobi L. var. ...
Article
Ethno-pharmacological relevance: Acne is a highly prevalent inflammatory skin disease which causes patients great psychological stress, especially teenagers. Chinese herbal medicine (CHM) is commonly used to treat acne with personalized but complicated prescriptions. The aim of this study is to determine a CHM network and core CHM treatments for acne by analyzing a nationwide database. Materials and methods: From January 1(st) to December 31(st), 2011, all CHM prescriptions made for acne (ICD-9-CM code: 706.0 or 706.1) were included in this study. Visits with acupuncture, manual therapy or other treatment modalities were excluded, and CHM visits with other diagnoses were also excluded in final analysis. Association rule mining (ARM) and social network analysis (SNA) were used to explore and demonstrate a CHM network. Results: A total of 91,129 patients used traditional Chinese medicine, and 99% of them chose CHM for acne treatment. Most CHM users were teenagers, and there were twice as many female patients as male patients. A total of 279,823 CHM prescriptions were made for acne in 2011. Qing-Shang-Fang-Feng-Tang was the most commonly used CHM (31.2% of all prescriptions), and Zhen-Ren-Huo-Ming-Yin combined with Forsythia suspensa (Thunb.) Vahl. (Lian Qiao) was the most commonly used CHM-CHM combination. Thirty-one important CHM-CHM combinations were identified, and the CHM network could be built. Extensive coverage of the known pathogenesis of acne could be found in the CHM network when incorporating CHM pharmacological mechanisms into the network. Anti-inflammatory and anti-bacterial effects were commonly found in the CHM network, and CHMs with anti-androgen, anti-depressive and skin whitening effects were frequently used in combination. Conclusions: The CHM combination patterns and core treatments for acne were disclosed in this study by applying network analysis to a CHM prescription database. These results may be beneficial for further bench or clinical studies when choosing target CHM.
... Furthermore, LRDs such as GL and 18βGA have also been reported to directly interact with mammalian corticosteroid receptors (CRs) in cortisol sensitive tissues (Ulmann et al., 1975;Armanini et al., 1983). Therefore, LR and LRDs have been widely investigated for their effects on the mammalian endocrine system (Armanini et al., 1983(Armanini et al., , 1999(Armanini et al., , 2004Latif et al., 1990;Räikkönen et al., 2010;Tamir et al., 2000;Ulmann et al., 1975;Van Uum et al., 2002). ...
Article
To consider the idea that a dietary botanical supplement could act as an adaptogen in a teleost fish, the effect of a liquorice root derivative (18β-glycyrrhetinic acid, 18βGA) on rainbow trout following an acute ionoregulatory stressor was examined. Freshwater (FW) trout were fed a control or 18βGA supplemented diet (0, 5, or 50 μg 18βGA/g diet) for 2 weeks, then abruptly exposed to ion-poor water (IPW) for 24 h. Following IPW exposure, muscle moisture content and serum cortisol levels elevated and serum [Na+] and/or [Cl−] reduced in control and 50 μg/g 18βGA-fed fish. However, these endpoints were unaltered in 5 μg/g 18βGA-fed fish. Gill tissue was investigated for potential mechanisms of 18βGA action by examining mRNA abundance of genes encoding corticosteroid receptors (CRs), 11β-hydroxysteroid dehydrogenase 2 (11β-hsd2), and tight junction (TJ) proteins, as well as Na+-K+-ATPase and H+-ATPase activity, and mitochondrion-rich cell (MRC) morphometrics. Following IPW exposure, CR and 11β-hsd2 mRNA, MRC fractional surface, Na+-K+-ATPase and H+-ATPase activity were unaltered or decreased in 50 μg 18βGA fish, as was mRNA encoding select TJ proteins. In contrast, 5 μg 18βGA-fed fish exhibited elevated 11β-hsd2 and CR mRNA abundance versus 50 μg 18βGA-fed, and reduced MRC apical area as well as some differences in TJ protein mRNA abundance versus control fish. Data suggest that 18βGA, at low levels, may be adaptogenic in trout and might help to ameliorate ionoregulatory perturbation following IPW exposure. This seems to occur, in part, through 18βGA-induced alterations in the biochemistry and physiology of the gill.
... 1238 -41. 85.Armanini D, Bonanini G and Palermo M. (1999). Reduction of serum tresto sterone in men by licorice. ...
Thesis
Background: Osteoporosis or silent disease is one of the most prevalent disease in elderly monopaused women in current century. Estrogen plays an important role in osteogenesis and prevention of bone Fractures. Hormone replacement therapy (HRT) can increase the risk of breast and ovary cancers and cardiovascular disease. Thus, the treatment by plant phytoestrogens is increasing. This study is focused on determining the effects of aqueous extracts of licorice root on proliferation and osteogenesis progress in human mesenchymal stem cells. Methods: Human umbilical cord wharton’s jelly mesenchymal Stem cells were isolated And treated with different amount of plant extracts (0.15- 10000). Extract cytotoxicity were measured by MTT assey and its differential effects measured by Alizarine Red S staining and by Alkaline phosphatase activity. Results: The results of MTT assay showed that the amount of extract concentration of 2500 μg/ml, within 72 hours, leading to the death of almost 50% of stem cells derived from human umbilical cord Wharton’s jelly (P<0.001). Staining results showed that the aqueous extract of licorice root a dose-dependent manner (the highest differentiation the concentration of 600 μg/ml) during 21 days leads to the differentiation of these cells into osteoblast. The alkaline phosphatase activity is higher in the treatment groups than control group that was observed at 7 days (P<0.001). Conclusion: The findings of this study showed that stem cells derived from the human umbilical cord Wharton’s jelly that treated with aqueous extract of licorice root are entered in the path of differentiation into osteoblasts. Keywords : licorice, osteogenesis, differentiation, MTT, alizarin Red S, alkaline phosphatase.
... Licorice containing 0.5 g GA decreases serum testosterone and increases 17-hydroxyprogesterone by inhibiting 17-20-lyase and 17-hydroxysteroid dehydrogenase activity after 4 and 7 days of administration in males (Faghihi et al., 2015). On the other hand, studies suggest that salivary testosterone and dehydroepiandrosterone increased after consuming licorice confectionery (3% licorice extract) for 7 days in male and female volunteers (Armanini et al., 1999). These findings lend support to the reasonable use of licorice as a promising strategy to treat hormone-dependent diseases. ...
Chapter
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Nitric oxide (NO) is a gaseous signaling molecule with a short half-life that's known to exert its biological functions through cyclic guanosine monophosphate. In our system, nitric oxide is produced by nitric oxide synthase enzymes, which use substrates l-arginine, reduced nicotinamide adenine dinucleotide phosphate (NADPH), and oxygen by producing citrulline, nicotinamide adenine dinucleotide phosphate (NADP⁺), and NO. Nitric oxide can react with superoxide to produce peroxynitrite (ONOO?), which can cause irreversible modification and inhibition of different biological molecules, including mitochondrial membrane complexes and antioxidant defense enzymes through oxidizing reactions. This chapter focuses on the direct and indirect role of NO in terms of energy metabolism. Nitric oxide in this context governs and regulates metabolism, heat production, and body composition, which overall change the tissue distribution of oxygen, adenosine triphosphate production, blood flow, glucose utilization, and supply of other nutrients by resulting in altered tissue functions and physical activities.
... Licorice root (Glycyrrhiza glabra) is also able to affect androgen metabolism in human [13]. Various studies have demonstrated that licorice blocks the activity of 3-β-hydroxysteroid dehydrogenase (3HSD), 17-hydroxysteroid dehydrogenase (17HSD) and 17-20 lyase [13,15] and stimulates the activity of aromatase [16][17][18]. All these enzymes are involved in the synthesis and/or metabolism of androgens and estrogens. ...
Article
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The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice is commonly present in menopausal botanical supplements in the United States. The estrogenic activities of different licorice species are variable and likely depend on the type and amounts of bioactive compounds. This study examined the effects of Licorice root extract on sex reversal in guppy, Poecilia reticulata. Newly born guppy fry (0.014 ± 0.001 mean weight), were randomly distributed into 30 L aquaria at a density of 80 fish per aquarium and subjected to a sex-reversal treatment by immersion application of licorise root extract for 30 days. The licorise root extract was incorporated into the aquarium water as follows: 0 (control), 0.25 and 0.5 g/ L licorice root extract. Each of the treatment group was randomly assigned to triplicate groups of fish. The treatment was repeated twice (in the beginning and half way through the experiment) during 30 days. At the end of experiment, the highest feminization (88%) was observed at 0.5 g\L licorise root extract group. Morphological and histological examinations of the gonads in all groups revealed no intersex fish. Histological examination of fish treated with licorise root revealed no damage to the testes or ovaries. This study demonstrated successful sex reversal with treatment of licorise root on new-born progenies of P. reticulate.
... However, these side effects were reversible (209). Cold or "flu-like" symptoms, thoracic distress, transient visual loss/aberrations, and reduction of serum testosterone may also be attributed to the licorice ingestion (210)(211)(212)(213). ...
Article
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Cancer is the second leading cause of death with profound socio-economic consequences worldwide. Growing evidence suggests the crucial role of diet on cancer prevention and treatment. In Traditional Persian Medicine (TPM) there is a major focus on contribution of special diet and foods to cancer management. In the present article, the cytotoxic and antitumor activities of several food items including plants and animal products recommended by TPM as anticancer agents are discussed. Strong evidence supports the anticancer effects of beetroot (Beta vulgris) and its major compound betanin, cinnamon and cinnamaldehyde, barley (H. vulgare) and its products, extra-virgin olive oil, black pepper (P. nigrum) and its piperine, grapes (V. vinifera) and its compound resveratrol, ginger and its compound 6-gingerol, whey protein, fish, and honey. However, additional pharmacological studies and clinical trials are needed to elucidate their molecular and cellular mechanisms of actions, frequency, and amount of consumption, possible adverse effects, and optimum preparation methods. Moreover, studying mechanisms of actions of the bioactive compounds present in the discussed food items can be helpful in identifying and development of new anticancer agents.
... A histopathological study showed that follicular microinflammation plays an integral role in the androgenetic alopecia that is widely recognized as male pattern baldness. In addition, GA inhibits the formation of DHT, which is clearly involved in baldness [40,41]. ...
Article
Recently, attention has been focused on identifying natural herbal compounds with high biological activity, especially antioxidative, anti-inflammatory and antimicrobial properties, for preventing and controlling various skin conditions, including inflammation-related diseases such as atopic dermatitis and UV-induced skin photoaging. One key active plant ingredient is 18β-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizin (GL), obtained from licorice root. The review examines the valuable biological properties of GA, particularly those playing key roles in the treatment of various dermatological disorders in humans. The review highlights the key anti-inflammatory, antioxidant and antimicrobial properties of GA and its toxicity towards normal cells lines. It also examines the physicochemical properties of GA and presents methods of increasing its penetration through the stratum corneum and bioaccumulation with the use of modern delivery systems such as liposomes and nanoemulsions. © 2019 Society of Cosmetic Scientists and the Société Française de Cosmétologie.
... Liquorice has been shown to have great antioxidant, free radical scavenging (Haraguchi et al., 1998; Di Mambro & Fonseca, 2005) and anticonvulsant activities (Nassiri-Asl et al., 2007). It has been shown to decrease circulating levels of testosterone in men (M.M. Rafi et al 2002, D. Armanini et al 1999, D. Armanini et al 2002). Moreover, it is reported that Licochalcone-A isolated from Glycyrrhiza root demonstrated potent antitumor properties when assayed using CaP, breast, and leukemia cells (DiPaola, et al, 1998) Isolation of various chemical constituent has been reported previously which include glycyrrhizin, glycyrrhizinic acid (Tang and Eisenbrand, 1992), glabridin, glabrene, glabrol, licoflavonol, glycyrol, licoricone, formononetin, phaseollinisoflavan, hispaglabridin A&B, 3-hydroxy glabrol, 3-methoxy glabridin (Kinoshita et al., 1976; Mitscher et al., 1978 Mitscher et al., , 1980 Saitoh et al., 1978; Fukai et al., 1996 Fukai et al., , 2002 Fukai et al., a,b, 2003), glabranin isomer, narigenin, lupiwightenone (Biondi et al., 2003 The present study was undertaken to evaluate the antioxidant, cytotoxic and antimicrobial activity of Glycyrrhiza glabra so that it could be a guide in the discovery of new molecule with antioxidant, cytotoxic and antimicrobial property. ...
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The present study was undertaken to explore the free radical scavenging, antimicrobial and cytotoxic activity of the methanolic extract of Glycyrrhiza glabra (Fabaceae) using DPPH, disc diffusion and brine shrimp lethality bioassay methods respectively. Different degrees of effect was noticed incase of different methods of study. In antimicrobial screening, G. glabra showed potent antimicrobial activity against almost all the test organisms except Pseudomonas aeruginosa. It exhibited highest sensitivity against Staphylococcus aureus with the zone of inhibition 22 mm. The extract possessed potent cytotoxic activity having LC 50 value of 0.771μg/ml. On the other hand, the free radical scavenging activity was found moderate having IC 50 value of 87.152 μg/ml
... In traditional Western medicine, the root rhizomes of Glycyrrhiza glabra (liquorice) are used to treat peptic ulcer and cough, but a number of studies indicate that liquorice also has antiviral, antimicrobial, anti-inflammatory, endocrinological and other properties [173,174]. The main phytochemicals involved are glycyrrhizin (a mixture of potassium and calcium salts of the triterpenoid saponin glycyrrhizic acid, glycoside of glycyrrhetinic acid), liquiritic acid, glycyrretol, glabrolide, flavonoids, chalcone, isoflavones, coumarins, stilbenoids, fatty acids, phenols and sterols [175]. ...
Article
Many herbal medications are used to treat diseases but while they are often efficacious, their safety is rarely considered by physicians or users. One particular safety concern is the risk of interactions with drugs, which often lead to toxicity or loss of therapeutic efficacy. In order to assess this risk, it is important to consider all potential mechanisms of pharmacokinetic interference. A large number of in vivo and invitro experiments and clinical studies have cast light on the possible effects of botanical products and phytochemicals on the many enzymes and transporters involved in gastrointestinal drug absorption. This review gives an overview and assessment of the most widely sold herbal medicinal products, including liquorice, garlic, ginger, ginkgo, green tea, St. John's wort, saw palmetto, turmeric, valerian, milk thistle and echinacea, on the basis of the available scientific evidence. Sound knowledge of the mechanisms of herb-drug interactions is essential for clinical risk assessment, in turn vital to healthcare practitioners in their efforts to reduce minimise risk and ensure that taking herbal medicinal products is as safe as possible.
... g of GZA per day, which is significantly below the amount generally believed to cause symptoms. [13][14][15] Of note, potassium sorbate is an ingredient in the involved candy, and may have contributed to the patient being normokalemic. Additional ingredients of these licorice candy cigars include wheat flour, cooking molasses, liquid sugar, corn starch, salt, mineral oil, soy lecithin, natural flavour, dextrin, artificial colour and potassium sorbate. ...
Article
A 49-year-old female physician presented with peripheral edema, weight gain and relative hypertension caused by the consumption of licorice candy cigars containing glycyrrhizic acid (GZA) found in natural licorice extract. Although the patient's response to GZA resolved spontaneously, emergency physician awareness of the toxic effects of natural licorice extract may avert symptom progression in early-identified cases. The benefits of natural licorice extract as a flavour enhancer and herbal medicine are recognized worldwide. The Canadian public is likely not generally aware of the toxic potential of GZA, or that it may be present in the following commonly consumed products: black licorice, chewing gum, herbal teas, soft drinks, tobaccos and herbal remedies for cough, stomach ailments and constipation. Emergency physicians should inquire about the consumption of products that may contain natural licorice extract when patients present with unexplained hypertension, hypokalemia, edema, rhabdomyolysis or myoglobinuria.
... In recent years, the most fascinating use of licorice has been in the treatment of PCOS. We previously demonstrated that licorice can decrease the secretion of testosterone both in men and in women (39,40). In healthy men this effect is not usually relevant, as the serum concentrations of testosterone are relatively high, while in women affected by hyperandrogenism, as in PCOS, the anti-androgen effect of licorice can be important, especially when associated with spironolactone. ...
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Licorice has been used as a medicinal plant from 2.500 years. It shows a wide range of biological and pharmacological activities, including anti-inflammatory and immune regulatory actions. One of its most known effects is the induction of hypertension, and it can induce what appears to be pseudohyperaldosteronism, due to glycyrrhetinic acid, the main active component of the root. Glycyrrhetinic acid and metabolites block the 11 beta-hydroxysteroid dehydrogenase type 2 and also bind mineralocorticoid receptors directly, acting as agonists. However, other interesting therapeutic uses of licorice are linked to its anti-androgen and estrogen-like activity, especially in the treatment of polycystic ovary syndrome (PCOS) in conjunction with spironolactone therapy. In this brief review, we report the main features and possible therapeutic uses of this ancient plant.
... The included ingredients might affect the specific parameters of PCOS via different mechanisms. While omega-3 fatty acids, selenium, vitamin E, and also co-enzyme Q10, known to scavenge free radicals and inhibit lipid and protein oxidation [25], might have acted as antioxidants and thereby likely influenced the proinflammatory PCOS state [9], licorice with its active component glycyrrhizin has been shown to affect androgen metabolism, probably via blocking the activity of 3-β-hydroxysteroid dehydrogenase (3HSD), 17-hydroxysteroid dehydrogenase (17HSD) and 17-20 lyase [26][27][28][29][30][31][32][33] and stimulation of the aromatase activity [31]. Notably, a lowering effect on ovarian androgens has already been reported for licorice [33], even in PCOS women [32]. ...
... The antiandrogenic effect of licorice, which may precipitate erectile dysfunction, has been reported. This was because licorice inhibits the enzymes catalysing the production of androstenedione [142][143][144]. This activity is attributed to glycyrrhetinic acid, the active metabolite of glycyrrhizin from licorice. ...
Article
Malaria, caused mainly by Plasmodium falciparum among other Plasmodium species, is one of the main causes of death from parasitic diseases. Malaria is still a health problem mainly because of the cost of effective antimalarial drugs and the growing parasite resistance to conventional antimalarial drugs, making a great proportion of the people in malaria endemic countries dependent on plants for its treatment. Corollary, a large number of the rural populations consume antimalarial herbal preparations in large or excessive quantities despite the fact that it has been reported that some of them could cause male-factor infertility, a growing global health concern. Few studies have compiled information on the scientifically validated male-factor antifertility effects of these antimalarial plant remedies. The aim of this review therefore is to compile information on commonly used antimalarial plant remedies that have been experimentally validated as having male-factor antifertility effects. Thus, antimalarial plant remedies with experimentally confirmed male-factor antifertility potentials and compounds isolated from them are identified and discussed. The male-factor antifertility effects of these plants include reduction of sperm quality, regulation of reproductive hormone levels and induction of lipid peroxidation. Indiscriminate use of such antimalarial plants is discouraged when male contraception is not desired.
... However, other studies have reported decreased serum testosterone levels by high levels of Licorice (Sakamoto and Wakabayashi 1988;Armanini et al. 1999). The probable mechanism is through glycyr-rhizic acid, one of the active components of Licorice, which impairs the conversion of androstenedione to testosterone through interference with 17β-hydroxysteroid dehydrogenase -catalyzer of the androstenedione-to-testosterone conversion (Fukui et al. 2003). ...
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Objectives. Adverse effects of obesity, which is caused by an imbalance between the energy intake and expenditure, on the male reproductive system have been reported. Considering the anti-obesity effect of Glycyrrhiza Glabra (GC), we conducted this study to elucidate whether it can ameliorate the sperm parameters. Methods. In this experimental study, male Wistar rats of 6–8 weeks old were divided into four groups: control, high fat diet (HFD), GC50 (HFD plus 50 mg/kg GC extract), and GC100 (HFD plus 100 mg/kg GC extract). During the 16 weeks of the study course, the rats consumed the extract through gavage, daily. Body mass index (BMI), body weight gain, serum lipid profile, leptin concentration, and sperm parameters were investigated. Data were analyzed by one-way analysis of variance (ANOVA) (post hoc Tukey) to express the significance of mean differences of variables between groups, and linear regression test was used to express the correlation model of variables. Both tests were performed by SPSS software; p≤0.05 was considered significant. Results. BMI was significantly decreased by the GC50 and GC100 groups compared to HFD group. GC50 group considerably decreased leptin level compared to HFD group. A significant positive correlation between leptin and triglyceride levels was evident. GC50 and GC100 extensively increased the total sperm motility and ameliorated the sperm abnormal morphology and count compared to HFD group. Conclusion.Glycyrrhiza Glabra extract may exert its ameliorating effects on the sperm parameters through its anti-obesity impact. Both doses of the extract were effective, however, the GC100 was more effective in improving the sperm parameters.
... In addition to effects on glucocorticoid metabolism GA is thought to have other endocrine effects. For example, there have been several reports (Armanini et al., 1999;Takahashi et al., 1988;Takeuchi et al., 1991) albeit disputed (Josephs et al., 2001) that GA and glycyrrhyzic acid (GZ) inhibit 17-20-lyase and 17-hydroxysteroid dehydrogenase activities thereby reducing testosterone synthesis in males and females by blocking the conversion of 17-hydroxyprogesterone (17-OHP) to androstenedione and then the conversion of androstenedione to testosterone. ...
Article
The mineralocorticoid effects of liquorice are mediated by the inhibitory effects of one of its active components glycyrrhetinic acid on 11β-hydroxysteroid dehydrogenase type 2. However, liquorice is reputed to have many medicinal properties and also contains a number of other potentially biologically active compounds. Here we have investigated the wider effects of oral liquorice on steroidogenesis focussing particularly on possible inhibitory effects of glycyrrhetinic acid on adrenal sulfotransferase activity.
... The same group found that total testosterone is reduced slightly in healthy males and females after 1 week of daily liquorice intake. 81,82 The maximum dose of GLA 1 recommended by the European Commission Scientific Committee on Food is 100 mg per day, although the committee acknowledged the limited amount of research on human toxicity of this compound. 83 A comprehensive review on the toxicology of liquorice, which acknowledged the difficulty of assessing safety due to the differences in the administered substances tested, estimated that, based on rodent studies, a no-observed-effects-level (NOEL) for purified GLA 1 would be in the range of 15-229 mg/kg/day and, by applying uncertainty factors for intraspecies and interspecies differences, an acceptable daily intake (ADI) for GLA 1 would be 0.015-0.229 ...
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Liquorice has a long history of use in traditional Chinese, Ayurvedic and herbal medicine. The liquorice plant contains numerous bioactive compounds, including triterpenes, flavonoids and secondary metabolites, with glycyrrhizin being the main active compound. Liquorice constituents have been found to have anti-inflammatory, antioxidant, antiviral, anticancer, hepatoprotective and neuroprotective properties. In addition, they appear to have antidepressant actions and effects on morphine tolerance. Glycyrrhizin, its metabolite glycyrrhetic (glycyrrhetinic) acid and other liquorice-derived compounds such as isoflavonoids and trans-chalcones, exert potent anti-inflammatory effects via a wide range of mechanisms including high mobility group box 1 protein (HMGB1) inhibition, gap junction blockade and α 2A -adrenoceptor antagonism. These properties, together with an increasing body of preclinical studies and a long history of use in herbal medicine, suggest that liquorice constituents may be useful for pain management. Glycyrrhizin is used widely in the confectionary, food and tobacco industries, but has documented adverse effects that may limit clinical use. Whether liquorice plant-derived compounds represent a novel class of analgesics is yet to be established. Having a host of bioactive compounds with a broad range of mechanisms of effect, liquorice is a plant that, in the future, may give rise to new therapies for pain.
Article
Abnormal levels of androgens cause many diseases like benign prostatic hyperplasia and hormone dependent cancers. Although the reduction in serum testosterone (T) by Glycyrrhiza glabra has been reported, its effects on seminal vesicle (SV) and prostate tissues have never been reported. This study was carried out to investigate different aspects of antiandrogenic properties of this plant. Immature male rats were divided into five groups (n = 7): castrated rats without any treatment received only vehicle; castrated rats plus T replacement; three castrated groups with T replacement plus various doses of G. glabra extract (75, 150 and 300 mg/kg). All of the injections were carried out once daily in subcutaneous manner for 7 days. On the eighth day, blood samples were collected for total T measurement. Ventral prostate (VP), SV and levator ani muscle were dissected and weighed. Slides prepared from prostate were assessed histologically. The variation in the relative and absolute volume of the prostate tissue compartments was determined. Those receiving the doses of 150 and 300 mg/kg showed a significant reduction (p < 0.05) in prostate weight, total T and VP epithelium/stroma ratio (V/V). These results in SV and levator ani were shown in response to 300 mg/kg of extract. Increasing in T metabolism, down-regulation of androgen receptors or activation of oestrogen receptors could be involved mechanisms. This study showed that alcoholic extract of G. glabra has antiandrogenic properties.
Article
A 57 yr old man presented to endocrinology clinic with a six year history of poorly controlled hypertension which was treated with Metoprolol 200 mg/day and Enalapril 20 mg/day. He was asymptomatic but incidentally hypokalaemia was detected while having cholecystectomy, two years prior to his clinic appointment. He had never been on diuretics or laxatives. He was started on potassium supplements (120 mmol/d) and advised to increase dietary potassium by the surgical team. A detailed personal history revealed ingestion of 300-500 g licorice per day. Physical examination was unremarkable apart from increased blood pressure of 180/105 mmHg. Following the initial visit, his serum electrolyes (K+3.7 mmol/l) were normal with potassium supplementation and as were morning cortisol, ACTH, 11-deoxycortisol and plasma metanephrines. 17 OH-P, DHEAS and androstenedione were normal but testosterone was low. Morning ambulant aldosterone was slightly increased at 801 pmol/L and renin activity was undetectable. Urinary 24 h aldosterone excretion was significantly increased at 162 ng/24 h with normal cortisol and catecholamine excretion. Four weeks following advice to stop licorice, serum potassium decreased to 3.4 mmol/L despite continuous supplementation. Morning plasma aldosterone increased to 1 449 pmol/ml, renin activity remained undetectable but 24 h urine aldosterone excretion increased to 434 ng/24 h with a reduction in urinary cortisol excretion. Interestingly 17 OH-P and androstenedione levels, although within the reference range, were slightly higher compared to the levels whilst on licorice. Testosterone level had significantly increased to be within normal range. Abdominal imaging with US and MRI showed a 2.7 cmx2.2 cmx1.7 cm left adrenal mass. He underwent laparoscopic left adrenalectomy and histology confirmed aldosterone producing adrenal adenoma. Post-operatively his aldosterone and serum potassium levels normalized and he became normotensive without any antihypertensive medication.
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There is a large interest in prostate cancer prevention and/or slowing the progression of this disease via dietary/lifestyle/supplement interventions. Numerous mechanisms have been suggested as to how these interventions may lower PSA levels. However, it is possible that the primary mechanism of action is partial androgen suppression and/or estrogen manipulation.
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Introduction The Licorice Plant Medicinal Preparation of Licorice Physiological Effects of Licorice Safety Precautions and Licorice–Disease and Licorice–Drug Interactions Conclusions References
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Chronic hepatitis C is a slowly progressive liver disease that may evolve into cirrhosis with its potential complications of liver failure or hepatocellular carcinoma. Current therapy with alpha-interferon is directed at viral clearance, but sustained response is only achieved in 20-40% of patients without cirrhosis, and less than 20% in patients with cirrhosis who need therapy most. Treatment for those who do not respond to antiviral therapy is highly desirable. In Japan, glycyrrhizin has been used for more than 20 years as treatment for chronic hepatitis. In randomized controlled trials, glycirrhizin induccd a significant reduction of serum uminotransferases and improvement in liver histology compared to placebo. Recently, these short-term effects have been amplified by a well-conducted retrospective study suggesting that long-term usage of glycirrhizin prevents development of hepatocellular carcinoma in chronic hepatitis C. The mechanism by which glycyrrhizin improves liver biochemistry and histology are undefined. Metabolism, phannacokilletics, side-effects, antiviral and hepatoprotective effects of glycyrrhizin are discussed.
Article
Background and Aims: Treatment with intravenous glycyrrhizin reduces the progression of liver disease caused by chronic hepatitis C (HCV) infection. Glycyrrhetinic acid, a metabolite of glycyrrhizin, inhibits the renal conversion of cortisol to cortisone by inhibiting the enzyme 11β-hydroxysteroiddehydrogenase in the kidney. The resulting excess of cortisol subsequently stimulates the mineralocorticoid receptor, leading to pseudo-aldosteronism with hypertension, hypokalemia and eventually renin and aldosterone suppression. The aim of this study was to evaluate the occurrence of pseudo-aldosteronism after treatment of chronic hepatitis C (HCV) patients with increasing doses of intravenous glycyrrhizin. Methods: Forty-four HCV patients with chronic hepatitis or compensated cirrhosis were treated with intravenous glycyrrhizin 6 × 200 mg/week, 3 × 240 mg/week or 3 × 0 mg/week (placebo) for 4 weeks. In all patients, bodyweight, blood pressure and plasma concentrations of sodium, potassium, cortisol, DHEA-S (dehydroepiandrosterone sulfate), renin and aldosterone were measured before, and at 0 and 4 weeks after treatment. Results: Within the placebo group, no significant changes were observed. Within the 1200 mg group systolic blood pressure was significantly higher at the end of treatment, while aldosterone was significantly lower; at the end of the follow-up period these values had returned to baseline. The changes from baseline in systolic and diastolic blood pressure at the end of treatment were significantly higher in the 1200 mg group compared to the placebo group. The changes in aldosterone and potassium concentrations at the end of treatment increased with increasing dosage, although not significantly. Conclusion: Hepatitis C virus patients with chronic hepatitis or compensated cirrhosis show minor reversible symptoms of pseudo-aldosteronism after treatment with 1200 mg glycyrrhizin weekly for 4 weeks.
Article
In two randomized double-blind placebo-controlled experiments, 63 normal nonclinical men and women received treatments designed to raise or lower their testosterone levels. Sixteen men and 17 women applied testosterone or placebo gel to their skin for five-day periods, and 13 men and 17 women ingested capsules of licorice extract (which lowers testosterone) or placebo for four-day periods. Subjects described their feelings on daily check lists, wrote paragraphs summarizing their experience, and completed implicit-attitude measures. Testosterone increased arousal and hostility, and licorice decreased energy and positive affect. Reactions were stronger among women than among men.
Article
Background : The potential clinical effects of licorice (Glycyrrhiza spp.) and its extracts have been investigated since ancient times. It is uncertain if pseudohyperaldosteronism, with consequent arterial hypertension, is the only endocrine effect produced by licorice, and a role in the reproductive system has been proposed. This review aimed to summarize the current knowledge on the pharmacological effects of licorice on the male and female reproductive systems. Method : Overall, 1462 records were extracted from electronic databases and systematically examined. 28 studies were included in the final analysis. Results : Preclinical and clinical studies revealed an estrogen-like activity of licorice components, especially flavonoids, isoflavonoids and chalcones, showing a potential role of licorice in ameliorating symptoms associated with estrogen insufficiency. Preclinical studies also displayed weak antiandrogen properties and beneficial effects of licorice on gonadal function in both sexes, while clinical studies yield to poor and conflicting results, depending on the type and dose of licorice. Conclusions : Licorice consumption can affect the reproductive system. However, its role needs to be further explored, especially due to the great variability of bioactive compounds used in existing studies.
Chapter
Bei onkologischen Erkrankungen der Urogenitalorgane erfolgt die tumorspezifische Behandlung durch Operation, Bestrahlung, Chemotherapie sowie bei einigen Tumoren durch Hormonabsenkung und/oder Immuntherapie.
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The specific conversion of androstenedione to testosterone is catalyzed by 17-β-hydroxysteroid dehydrogenase type 3 (17-β-HSD 3), an enzyme which has been shown to be localized in the microsomal fraction of the Leydig cells of the testis. As such, this enzyme has become a major target in the treatment of hormone-dependent prostate diseases, since the biosynthesis of testosterone allows the formation of the more potent androgen dihydrotestosterone. Here we report some of the steroidal and nonsteroidal inhibitors that have been considered for development as potent and specific inhibitors of 17-β-HSD 3. Copyright © 2009 Prous Science, S.A.U. or its licensors. All rights reserved.
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Glycyrrhiza glabra L (Licorice) as native and pasture medicinal plant has most important export rule. Glycyrrhizic acid (GA) or Glycyrrhizin as a main active component of licorice root and rhizomes, is a triterpenoid saponin claimed to be up to 30-50 times sweeter than sucrose and to be used in pharmaceuticals, food and tobacco industry. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. Understanding of the limitations and challenges in the medicinal plant are need for planning principles for development activities and conservation in this field.In this review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical as one of the most important herbs in exports and adverse effects of licorice.
Article
Dietary habits reflect both the recent economic possibilities and the cultural history of individual human populations. They may influence endocrine systems and thus affect the health of the respective populations in several manners: (1) People consuming exclusively local products may lack certain micronutrients. This is important especially in areas with low levels of iodine and/or selenium in the environment. Thyroid gland insufficiency resulting from the iodine deficiency was widespread in many areas of Central Europe until the introduction of iodine supplementation in the second half of 20(th) century. Iodine deficiency is still a serious problem in many areas of Africa and Asia. (2) Numerous cultural plants contain compounds able to influence important metabolic pathways. Iodine deficiency is usually worsened by thyroidal peroxidase inhibitors, so-called goitrogens. Phenolic and terpenoid compounds may interfere in the metabolism of steroid hormones. Glycyrrhetinic acid from licorice is a potent inhibitor of 11-beta-hydroxysteroid dehydrogenase. Isoflavonoids from legumes (e.g. genistein and daidzein) and their metabolites (e.g. equol) were found to inhibit the following enzymes: aromatase, 5alpha-reductase, 7alpha-hydroxylase, 3beta-hydroxysteroid and 17beta-hydroxysteroid dehydrogenases, etc. Isoflavonoid sulphates influence local availability of steroids by inhibiting sterol sulphatases. (3) Plant-derived compounds are able to interact with nuclear receptors and act either as hormone agonists or as antagonists. Recently, the attention has been paid namely to the phenolic substances interacting with oestrogen receptors so-called phyto-oestrogens.
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Chinesische Arzneidrogen wurden in der Chinesischen Medizin von früh an für Funktionsstörungen und Krankheiten des reproduktiven Systems eingesetzt. Daher verwundert es nicht, dass sich unter diesen viele mit hormonartigen Effekten finden lassen. Diese wurden von der westlichen TCM-Welt bisher so gut wie gar nicht zur Kenntnis genommen. Am meisten untersucht und nachgewiesen sind die Phytoöstrogeneffekte, dazu kommen progesteronartige, androgenartige, ihre jeweiligen antagonistischen Wirkungen sowie weitere. Bei den östrogenartig wirkenden Drogen stellt sich die Frage eines potenziellen Proliferationseffektes bei Mammakarzinomen, zumal viele von ihnen in vitro das Wachstum humaner Mammakarzinomzellen stimulieren. Soja und Sojaisoflavone können in dieser Hinsicht als sicher gelten, jedoch kann man diese Aussage nicht einfach auf andere Drogen mit Phytoöstrogencharakter extrapolieren. Vielmehr bedarf jede Arzneidroge einer gesonderten Betrachtung. Epidemiologische Studien zur Auswirkung einer chinesischen Arzneitherapie auf die Inzidenz oder — bei Einnahme nach Diagnosestellung — auf den Verlauf östrogenabhängiger Tumore liegen nur ganz vereinzelt vor. Diese sprechen nicht für eine erhöhte Inzidenz eines Mammakarzinoms, eines Endometriumkarzinoms oder den ungünstigen Verlauf eines Mammakarzinoms, sondern eher für das Gegenteil. Angesichts der In-vitro- und In-vivo-Ergebnisse und des nicht beweisenden Charakters epidemiologischer Studien ist der Einsatz der in Frage stehenden Arzneidrogen sehr sorgsam gegenüber den Risiken abzuwägen und im Zweifelsfall Zurückhaltung zu üben.
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Background and objectives:Today, due to the increasing antibiotic resistance of bacteria, the use of medicinal plants as a suitable alternative to antibiotics has increased significantly; therefore, in this study, the antibacterial effects of methanolic extracts of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa and Escherichia coli were evaluated.Methods:In this laboratory research, after collecting plants and confirming its scientific name, extract of Glycyrrhiza glabra L. Root was prepared by Soxhlet extractor method at concentrationsof 20 mg / ml to 400 mg / ml. Then the antimicrobial effects of this extract were investigated using Agar well diffusion and Dilution test methods.Results:The results showed that the methanolic extracts of G.glabra L. in both Agar well diffusion and Dilution test methods had antibacterial effects on the tested bacteria. The highest effect was observed on S.aureus and the lowest effect was observed in P.aeruginosa.Conclusion:According to the above results, it can be expected that the G.glabra L. extract can be used to treat bacterial infections and is a suitable alternative to commonly used chemical treatments for the treatment of infections
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Background & Aims: Polycystic ovary syndrome is a complex endocrine and metabolic disorder characterized by chronic anovulation, polycystic ovaries and pathological conditions such as hyperandrogenism. Increase in the level of estrogen is an important symptom of polycystic ovary syndrome. This study aimed to investigate how hyperandrogenism-induced polycystic ovary syndrome (PCOS) affects the histological structure of ovaries. Materials & Methods: Sixty adult female mice were divided into six groups: Control group, Experimental group that Hyperandrogenism (HA) was induced by oral administration of 2mg/kg letrozole and protective effect of licorice root was studied in three doses: 150, 300, 450 mg/kg by gavage for 21 consecutive days. About 450mg/kg licorice extract was administered to the sixth group. Each group had 14mice and only 8 of them were used for histological studies. Ovaries were separated and samples were analyzed in Bouinchr('39')s solution. Histological and histomorphometrical studies were done by Hematoxylin and Eosin staining. Results: Results showed that histological parameters in hyperandrogen ovaries were greatly reduced and Licorice root extract had a protective effect. Conclusion: Finally, it can be concluded that administration of appropriate doses of licorice root extract improved antioxidant ingredients and affected the histological structure of reproductive system in females with hyperandrogenism.
Chapter
Licorice (Glycyrrhiza glabra) has many of the benefits and risks of corticosteroid drugs. The physiological effects of licorice include anti-inflammatory, antioxidant, antiallergic, antimicrobial, laxative, and ulcer-healing properties. It has many applications in traditional herbalism including bronchitis, chest congestion, hepatitis, peptic ulcer disease, constipation, menopause, Addison’s disease, general inflammation, infections, and prostate cancer. Licorice may be beneficial for mucositis, pharyngitis, asthma, dyslipidemia, hepatoprotection, peptic ulcer disease (non-DGL only), functional dyspepsia, polycystic ovary syndrome, menopause, Parkinson’s disease, hyperpigmentation, and eczema. This chapter examines some of the scientific research conducted on licorice, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of licorice’s use in treating ENT, pulmonary, cardiometabolic, gastrointestinal, genitourinary, neurologic, dermatologic, adrenal, and inflammation disorders. Finally, the chapter presents a list of licorice’s active constituents, different Commonly Used Preparations and Dosage, and a section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
Article
Application of a sensitive UHPLC-MS/MSMRM method enabled the simultaneous quantitation of 23 sweet-, licorice-, and bitter-tasting saponins in Glycyrrhiza glabra L., Glycyrrhiza uralensis Fisch., different licorice plants and root compartments, processed licorice, as well as different Glycyrrhiza spp. The combination of quantitative data with sweet, licorice, and bitter taste thresholds led to the determination of dose-over-threshold factors to elucidate the sweet, licorice, and bitter impact of the individual saponins with and without mycorrhiza symbiosis to evaluate the licorice root quality. Aside from glycyrrhizin (1), which is the predominant sweet- and licorice-tasting saponin in all licorice samples, 20 out of 22 quantitated saponins contributed to the taste profile of licorice roots. Next to sweet-/licorice-tasting glycyrrhizin (1), 24-hydroxy-glycyrrhizin (9), 30-hydroxy-glycyrrhizin (11), and 11-deoxo-24-hydroxy-glycyrrhizin (14) as well as licorice tasting saponins 20α-galacturonic acid glycyrrhizin (17), 24-hydroxy-20α-glycyrrhizin (21), and 11-deoxo-glycyrrhizin (12) were determined as key contributors to licorice root's unique taste profile. A quantitative comparison of 23 saponins as well as 28 polyphenols between licorice roots inoculated with arbuscular mycorrhiza fungi and controls showed that important taste-mediating saponins were increased in mycorrhizal roots, and these alterations depended on the growth substrate and the level of phosphate fertilization.
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Despite the shortage of adequate evidence on the safety of herbal products, their practice as an alternative or complementary medicine is gaining popularity worldwide among health practitioners. Evidence shows increasing attention toward the medical herbs as a forerunner for a pharmacological activity to treat different ill patients. One of the severe associations is the coadministration of herbal medicine along with traditional/conventional drugs. Herb–drug interaction becomes the single most essential clinical consequence of the practice. It can impact health and the effectiveness of treatments. Using the structural evaluation process, the confirmation of herb–drug interaction presents a different degree of clinical importance. Various pharmacokinetic and pharmacodynamic mechanisms were proposed for herb–drug interactions, including the alteration/modification in the gastrointestinal function with the subsequent effects on the absorption, distribution, inhibition, and induction of the metabolic enzymes and transporters, and altercation of renal elimination of the drugs and their respective metabolites. This chapter expounds on the risk associated with herb–drug interactions with some classical examples supported with clinical evidence and mechanisms involved. A cross-talk on the regulatory aspects and methods followed for the prediction of herb–drug interactions is also provided.
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Glycyrrhiza glabra is a perennial herb, belonging to family fabaceae. It is also known as Licorice, sweet wood, Liquorice. It is a popular ingredient and well known remedy for coughs, syrups and various medicines with its relieving properties. Glycyrrhiza glabra Linn. Is one of the most important herb which is used in Ayurvedic medication since thousands of years. Medicinal plants are often used for treating various diseases. Now a days, the demand various herbal medicines, pharmaceuticals & health related products is increasing widely. Herbal medicine, include fruit, vegetables, as dry material on the extract of Glycyrrhiza to cure different diseases and maintenance of health. Glycyrrhiza is used in herbal preparation which is obtained from licorice roots for the treatment of liver related diseases. The root can help to heal gastric ulceration. It is also used in traditional medicine for its ethnobotanical and pharmacological value. It possesses anti-oxidant, antibacterial, antifungal, anti-viral, anti-inflammatory, skin whitening, anti-diuretic agent. The present article on Glycyrrhiza glabra is an effort to compile with the medicinal uses, ethnobotanical, pharmaceuticals and therapeutic effects.
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Over 2 million Americans are currently living with prostate cancer. Current chemotherapeutic strategies are only partially effective in controlling the disease. There is always a need for an effective newer drug for treating prostate cancer. Use of active principles from medically important herbs has proven to be effective in treating various forms of cancers. Glycyrrhizin, a triterpene compound isolated from roots of licorice has been found to exhibit potent in vitro cytotoxic activity against several human cancer cell lines. In this study, we evaluated the effects of glycyrrhizin on the viability of two human prostate cancer cells LNCaP (hormone-dependent) and DU-145 (hormone-independent) in vitro. Cell viability assay showed that glycyrrhizin inhibited the cell proliferation of prostate cancer cells in a time- and dose-dependent manner. The decreased viability of prostate cancer cells was due to apoptosis as confirmed by Annexin-V FITC flow cytometric analyses. Glycyrrhizin also caused DNA damage in DU-145 and LNCaP cells in a time-dependent manner. Caspase-3 and -8 activities were not detected in glycyrrhizin-treated prostate cancer cells suggesting that caspase-independent pathways may be involved in the apoptotic mechanism. Collectively, these studies suggest that glycyrrhizin has therapeutic potential against prostate cancer.
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EXCESSIVE ingestion of licorice may result in sodium and water retention, hypertension, hypokalemia, and suppression of the renin-aldosterone system.1 , 2 It was thought for years that licorice produced these effects through the binding of its active components, glycyrrhizic acid and its hydrolytic metabolite glycyrrhetinic acid, to mineralocorticoid receptors. Two findings, however, argue against this proposed mechanism. First, the affinity of glycyrrhetinic acid, the most active component of licorice, for mineralocorticoid receptors is 0.01 percent of that of aldosterone.3 Second, licorice, or glycyrrhetinic acid, does not have mineralocorticoid effects in patients with Addison's disease2 or adrenalectomized rats1 unless cortisone or hydrocortisone is . . .
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Transdermal nicotine therapy is widely used to aid smoking cessation, but there is uncertainty about its safety in patients with cardiac disease. In a randomized, double-blind, placebo-controlled trial at 10 Veterans Affairs medical centers, we randomly assigned 584 outpatients (of whom 576 were men) with at least one diagnosis of cardiovascular disease to a 10-week course of transdermal nicotine or placebo as an aid to smoking cessation. The subjects were monitored for a total of 14 weeks for the primary end points of the study (death, myocardial infarction, cardiac arrest, and admission to the hospital due to increased severity of angina, arrhythmia, or congestive heart failure); the secondary end points (admission to the hospital for other reasons and outpatient visits necessitated by increased severity of heart disease); any side effects of therapy; and abstinence from smoking. There were 48 primary and 78 secondary end points noted in a total of 95 subjects. At least one of the primary end points was reached by 5.4 percent of the subjects in the nicotine group and 7.9 percent of the subjects in the placebo group (difference, 2.5 percent; 95 percent confidence interval, -1.6 to 6.5 percent; P=0.23). In the nicotine group, 11.9 percent of the subjects had at least one of the secondary end points, as compared with 9.7 percent in the placebo group (difference, 2.2 percent; 95 percent confidence interval, -2.2 to 7.4 percent; P= 0.37). After 14 weeks the rate of abstinence from smoking was 21 percent in the nicotine group, as compared with 9 percent in the placebo group (P=0.001), but after 24 weeks the abstinence rates were not significantly different (14 percent vs. 11 percent, P= 0.67). Transdermal nicotine does not cause a significant increase in cardiovascular events in high-risk outpatients with cardiac disease. However, the efficacy of transdermal nicotine as an aid to smoking cessation in such patients is limited and may not be sustained over time.
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Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.
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We studied the effects of shakuyaku-kanzo-toh (a Chinese herbal medicine) and its components on testosterone production by rat gonads. We used paeoniflorin as a main component of shakuyaku (paeoniae radix), glycyrrhizin as a main component of kanzo (glycyrrhizae radix) and glycyrrhetinic acid as a main metabolite of glycyrrhizin. Oral administration of shakuyaku-kanzo-toh, glycyrrhizin, and glycyrrhetinic acid decreased in vitro basal testosterone production in Leydig cells by LH stimulation. Glycyrrhizin and glycyrrhetinic acid caused a significant decrease in testosterone production with an accumulation of 17 alpha-hydroxyprogesterone when incubated with isolated Leydig cells, while paeoniflorin showed no such effect. The inhibitory effect of glycyrrhetinic acid was far more potent than that of glycyrrhizin, causing about 90% inhibition at 10 micrograms/ml. Glycyrrhizin and glycyrrhetinic acid did not change the cyclic AMP or progesterone level in the Leydig cells. When 14C-labeled androstenedione was incubated with microsomal fraction of testicular or ovarian tissue, glycyrrhizin and glycyrrhetinic acid inhibited the conversion of androstenedione to testosterone, indicating that these compounds inhibit the activity of 17 beta-hydroxysteroid dehydrogenase (EC. 1.1.1.64). The ED50 of glycyrrhetinic acid was about 4 microM.
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A major limitation in the use of amphotericin B is its potential to cause nephrotoxicity. In animals, increased dietary sodium reduces renal toxicity. Experience with five patients in whom impaired renal function developed early during amphotericin B therapy is reported. In four of the patients, there was evidence of sodium depletion due to low sodium intake, diuretic administration, or vomiting. In all five patients, sodium loading was associated with improved renal function, which permitted amphotericin B therapy to be continued in fully effective doses to the completion of elective courses of treatment without evidence of residual impaired renal function. These observations are consistent with the hypothesis that intrarenal regulatory mechanisms contribute to changes in renal function due to amphotericin B therapy.
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Amphotericin B is an effective therapeutic agent for most systemic or invasive mycoses, but its usefulness is limited by the frequent occurrence of nephrotoxicity. Given the high and increasing frequency of serious fungal infections, especially in immunocompromised patients, the importance of the morbidity caused by this toxicity is substantial. Salt loading may prevent and even reverse amphotericin B-induced azotemia by an unknown mechanism. A prospective, randomized, placebo-controlled trial in a relevant patient group would strengthen the support for this simple, safe therapy, but will not likely be carried out because of practical and ethical considerations. Thus, a few prospective and limited controlled human studies may be the only supportive evidence for using this therapy. Supplementing dietary sodium chloride intake with 150 mEq of sodium chloride daily intravenously or orally beginning when or before amphotericin B therapy is initiated will likely prevent much of the observed nephrotoxicity and should be carried out routinely.
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The pathogenesis of pseudohyperaldosteronism from licorice has been evaluated in 6 male volunteers taking daily 7 g of a commercial preparation of licorice for 7 days, corresponding to an intake of 500 mg/day of glycyrrhizic acid. Pseudohyperaldosteronism was evident during the treatment (increase of body weight, suppression of plasma renin activity and plasma aldosterone, reduction of serum potassium). The ratio (tetrahydrocortisol + allo tetrahydrocortisol)/tetrahydrocortisone in urine increased in 5 cases after 3 days of treatment, without an increase of plasma mineralocorticoid activity (PMA). In the 6th case the urinary ratio was unchanged and PMA increased from the pretreatment value. After 7 days of therapy the ratio remained high and PMA was not measurable in 3 cases, while in the other 3 cases the ratio returned to pretreatment and PMA was higher than pretreatment value. We conclude that the pseudohyperaldosteronism from licorice is initially related to decreased activity of 11 beta-hydroxysteroid-dehydrogenase and afterwards also a direct effect of licorice derivatives on mineralocorticoid receptors becomes evident in some cases. In other cases however the effect on the enzyme is prevailing probably due to individual factors.
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Medical evidence may be biased over time if completion and publication of randomized efficacy trials are delayed when results are not statistically significant. To evaluate whether the time to completion and the time to publication of randomized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials. Prospective cohort of randomized efficacy trials conducted by 2 trialist groups from 1986 to 1996. Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health. A total of 109 efficacy trials (total enrollment, 43708 patients). Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer-reviewed publication assessed with survival analysis. The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm (6.5 vs 4.3 years, respectively; P<.001; hazard ratio for time to publication for positive vs negative trials, 3.7; 95% confidence interval [CI], 1.8-7.7). This difference was mostly attributable to differences in the time from completion to publication (median, 3.0 vs 1.7 years for negative vs positive trials; P<.001). On average, trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results (median, 2.3 vs 2.5 years; P=.045), but long-protracted trials often had low event rates and failed to reach statistical significance, while trials that were terminated early had significant results. Positive trials were submitted for publication significantly more rapidly after completion than were negative trials (median, 1.0 vs 1.6 years; P=.001) and were published more rapidly after submission (median, 0.8 vs 1.1 years; P=.04). Among randomized efficacy trials, there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up.
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It has been suggested that a consequence of the declining prevalence of smoking in the United States over the past 25 years is that the population of remaining smokers is becoming more difficult to treat. That is, compared to smokers of years past, today's smokers are more likely to be highly nicotine dependent, have comorbid psychiatric and substance abuse disorders, have less education, and be of lower economic status. If this is indeed the case, there should be found declining abstinence rates in published clinical trials, when the type of treatment is held constant. To test this hypothesis, a literature search was conducted for group-administered multicomponent smoking cessation trials that emphasized coping skills training. Twenty-three studies published between 1977 and 1996 were identified. As predicted, robust negative correlations were found between year of publication and end-of-treatment abstinence rates. Using point-prevalence abstinence rates from later follow-up points produced somewhat weaker associations. Controlling for the use of biochemical verification or nicotine replacement therapies did not alter the findings. In summary, the efficacy of clinical trials--with treatment held constant--appears to be declining. One possible cause is the increasing recalcitrance of those individuals who continue to smoke despite social, regulatory, and medical pressures to quit.
Smoking cessation. Clinical practice guideline no. 18. Washington, D.C.: Government Printing Office
  • Mc Fiore
  • Wc Bailey
  • Sj Cohen
Fiore MC, Bailey WC, Cohen SJ, et al. Smoking cessation. Clinical practice guideline no. 18. Washington, D.C.: Government Printing Office, 1996. (AHCPR publication no. 96-0692.)