Decio Armanini

Antiviral effects of Glycyrrhiza species

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus‐induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV‐1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus.

A history of the therapeutic use of liquorice in Europe

Abstract Liquorice root has been used in Europe since prehistoric times, and is well documented in written form starting with the ancient Greeks. In this review we compare the independent development of medical uses of this botanical drug in several ancient cultures, attempting to show the rationality of specific indications across different ethnic groups with different cultural backgrounds. Identical specific indications in different cultures highlight universally reproducible therapeutic effects that are beyond those of a mere placebo. In the first part of the review, historical sources dealing with liquorice (Scythian, Greek, Roman, and from the Middle Ages in Germany, Italy, Spain, England) have been considered. In the second part, the historical records of diseases treated with liquorice have been presented. Finally, a comparison between traditional use in and outside Europe, with the most important recent scientific studies concerning its use, is presented.

Genital tract infections and infertility.

Infectious agents can impair various important human functions, including reproduction. Bacteria, fungi, viruses and parasites are able to interfere with the reproductive function in both sexes. Infections of male genito-urinary tract account for about 15% of the case of male infertility. Infections can affect different sites of the male reproductive tract, such as the testis, epididymis and male accessory sex glands. Spermatozoa themselves subsequently can be affected by urogenital infections at different levels of their development, maturation and transport. Among the most common microorganisms involved in sexually transmitted infections, interfering with male fertility, there are the Chlamydia trachomatis and Neisseria gonorrhoeae. Less frequently male infertility is due to non-sexually transmitted epididymo-orchitis, mostly caused by Escherichia coli. In female, the first two microorganisms are certainly involved in cervical, tubal, and peritoneal damage, while Herpes simplex cervicitis is less dangerous. The overall importance of cervical involvement is still under discussion. Tubo-peritoneal damage seems to be the foremost manner in which microorganisms interfere with human fertility. C. trachomatis is considered the most important cause of tubal lacerations and obstruction, pelvic inflammatory disease (PID) and adhesions. N. gonorrhoeae, even though its overall incidence seems to decline, is still to be considered in the same sense, while bacterial vaginosis should not be ignored, as causative agents can produce ascending infections of the female genital tract. The role of infections, particularly co-infections, as causes of the impairment of sperm quality, motility and function needs further investigation. Tropical diseases necessitate monitoring as for their diffusion or re-diffusion in the western world.

AFFINITY OF LIQUORICE DERIVATIVES FOR MINERALOCORTICOID AND GLUCOCORTICOID RECEPTORS

Liquorice abuse causes a syndrome of pseudohyperaldosteronism. Much less commonly, glucocorticoid‐like effects have been reported. The electrolyte‐active principle of liquorice is glycyrrhizic acid (GI), which can be hydrolyzed to glycyrrhetinic acid (GE). Previous studies have reported that GE, but not GI, may occupy mineralocorticoid and glucocorticoid receptors. We here report that both GE and GI can bind to both mineralocorticoid and glucocorticoid receptors. The affinity of GI for mineralocorticoid receptors is four orders of magnitude lower than aldosterone and for glucocorticoid receptors five orders of magnitude lower than dexamethasone. The affinity, though low, is sufficient to explain the mineralocorticoid‐like side effects, given the large amount of liquorice required to produce such a syndrome.

Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior *

OBJECTIVE To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women. DESIGN Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment. RESULTS Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug. CONCLUSIONS Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.

Spironolactone in the treatment of polycystic ovary syndrome: Effects on clinical features, insulin sensitivity and lipid profile

This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16–32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all overweight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women.

Licorice reduces serum testosterone in healthy women

UNLABELLED Licorice has been considered a medicinal plant for thousands of years. The most common side effect is hypokalemic hypertension, which is secondary to a block of 11beta-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid effect of cortisol. We have investigated the effect of licorice on androgen metabolism in nine healthy women 22-26 years old, in the luteal phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6% W.W. of glycyrrhizic acid) daily for two cycles. They were not on any other treatment. Plasma renin activity, serum adrenal and gonadal androgens, aldosterone, and cortisol were measured by radioimmunoassay. Total serum testosterone decreased from 27.8+/-8.2 to 19.0+/-9.4 in the first month and to 17.5+/-6.4 ng/dL in the second month of therapy (p<0.05). It returned to pre-treatment levels after discontinuation. Androstenedione, 17OH-progesterone, and LH levels did not change significantly during treatment. Plasma renin activity and aldosterone were depressed during therapy, while blood pressure and cortisol remained unchanged. CONCLUSIONS Licorice can reduce serum testosterone probably due to the block of 17-hydroxysteroid dehydrogenase and 17-20 lyase. Licorice could be considered an adjuvant therapy of hirsutism and polycystic ovary syndrome.

Reduction of serum testosterone in men by licorice

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 hydrolyz...

Inactivating mutations of the mineralocorticoid receptor in Type I pseudohypoaldosteronism.

Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive. Typical biochemical features include high levels of plasma aldosterone and renin, hyponatremia and hyperkalemia. Different mutations of the human mineralocorticoid receptor (hMR) gene have been identified in subjects affected by the autosomal dominant or sporadic form of the disease. Our laboratory has investigated a large number of subjects with familial and sporadic PHA1. Several different mutations have been detected, which are localized in different coding exons of the hMR gene. These mutations either create truncated proteins, either affect specific amino acids involved in receptor function. In this paper, we review hMR mutations described to date in PHA1 and their functional characterization. We discuss the absence of mutations in some kindreds and the role of precise phenotypic and biological examination of patients to allow for identification of other genes potentially involved in the disease.

Effect of licorice on the reduction of body fat mass in healthy subjects

The history of licorice, as a medicinal plant, is very old and has been used in many societies throughout the millennia. The active principle, glycyrrhetinic acid, is responsible for sodium retention and hypertension, which is the most common side-effect. We show an effect of licorice in reducing body fat mass. We studied 15 normalweight subjects (7 males, age 22–26 yr, and 8 females, age 21–26 yr), who consumed for 2 months 3.5 g a day of a commercial preparation of licorice. Body fat mass (BFM, expressed as percentage of total body weight, by skinfold thickness and by bioelectrical impedance analysis, BIA) and extracellular water (ECW, percentage of total body water, by BIA) were measured. Body mass index (BMI) did not change. ECW increased (males: 41.8±2.0 before vs 47.0±2.3 after, p<0.001; females: 48.2±1.4 before vs 49.4±2.1 after, p<0.05). BFM was reduced by licorice: (male: before 12.0±2.1 vs after 10.8±2.9%, p<0.02; female: before 24.9±5.1 vs after 22.1±5.4, p<0.02); plasma renin activity (PRA) and aldosterone were suppressed. Licorice was able to reduce body fat mass and to suppress aldosterone, without any change in BMI. Since the subjects were consuming the same amount of calories during the study, we suggest that licorice can reduce fat by inhibiting 11β-hydroxysteroid dehydrogenase Type 1 at the level of fat cells.