Cristina Fiore

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.

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.

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.

Treatment of polycystic ovary syndrome with spironolactone plus licorice

OBJECTIVE The aim of the study was to compare the effect of spironolactone (antagonist of mineralocorticoid and androgen receptors) versus spironolactone plus licorice (agonist of mineralocorticoid receptors and mild inhibitor of androgen synthesis) on plasma renin activity, aldosterone and androgen levels in women with polycystic ovary syndrome (PCOS). STUDY DESIGN Thirty-two women with PCOS were divided into two groups: 16 received 100 mg spironolactone and 16 spironolactone plus 3.5 g of licorice a day. Blood pressure, body mass index, serum electrolytes, plasma renin activity, plasma aldosterone and cortisol, serum testosterone, and urinary tetrahydrocortisol/tetrahydrocortisone ratio were measured before and during treatment. RESULTS Mean blood pressure was significantly reduced during spironolactone treatment, while it was unchanged in women receiving spironolactone plus licorice. Twenty percent of women treated with spironolactone and none treated with the addition of licorice complained of symptoms related to volume depletion. Consistently, the activation of the renin-aldosterone system was significantly lower during spironolactone plus licorice than with spironolactone alone. The prevalence of metrorrhagia was lower in the combined therapy. CONCLUSIONS In patients with PCOS the mineralocorticoid properties of licorice can reduce the prevalence of side effects related to the diuretic activity of spironolactone.

Alzheimer's disease: pathophysiological implications of measurement of plasma cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid receptors

Alzheimer’s disease is often characterized by an increase in plasma cortisol without clinical evidence of hypercorticism. Twenty-three consecutive patients with Alzheimer’s disease and 23 age- and sex-matched healthy controls were studied by measuring plasma cortisol and dehydroepiandrosterone sulfate (DHEAS) (by enzyme immunoassay), the number of type I and type II corticosteroid receptors in mononuclear leukocytes (by radioreceptorassay), and the lymphocyte subpopulations (by cytofluorimetry). Results are expressed in terms of median and range. In Alzheimer’s disease, plasma cortisol was higher than in controls (median 0.74, range 0.47–1.21 vs 0.47, 0.36–0.77 mmol/L; p<0.001). Plasma DHEAS, the DHEAS/cortisol ratio, and the number of type II corticosteroid receptors were significantly lower in AD than in controls (DHEAS: median 1.81, range 0.21–3.69 vs 3.51, 1.35–9.07 µmol/L; DHEAS/cortisol: 2.04, range 0.3–5.8 vs 6.8, range 2.7–24 and type II receptors: 1219, 1000–2700 vs 1950, 1035–2750 receptors per cell; p<0.001). No correlation was found between the hormonal parameters, age, and minimental test score. These data support the hypothesis of a dysregulation of the adrenal pituitary axis in Alzheimer’s disease, which is probably the consequence of damage to target tissues by corticosteroids.

Evaluation of correct endogenous reactive oxygen species content for human sperm capacitation and involvement of the NADPH oxidase system

BACKGROUND Generation of controlled amounts of reactive oxygen species (ROS) and phosphorylation of protein tyrosine residues (Tyr) are two closely related changes involved in sperm capacitation. This study investigated the effect of altered endogenous ROS production on Tyr-phosphorylation (Tyr-P), acrosome reaction (AR) and cell viability during sperm capacitation. The possible origin of the altered ROS production was also evaluated by apocynin (APO) or oligomycin (Oligo) addition. METHODS A total of 63 samples of purified sperm were analysed for ROS production by enhanced chemiluminescence, Tyr-P pattern by immunocytochemistry, and AR and viability by fluorochrome fluorescein isothiocyanate (FITC)-labelled peanut (Arachis hypogaea) agglutinin and propidium iodide positivity, respectively. RESULTS Samples were divided into four categories depending on the ability of sperm to produce ROS, expressed as Relative Luminescence Units (RLU), in capacitating conditions: low ROS production (LRP), range about 0.0-0.05 RLU; normal (NRP), 0.05-0.1 RLU; high (HRP), 0.1-0.4 RLU; very high (VHRP) 0.4-2.0 RLU. In NRP sperm heads, capacitation induced Tyr-P in 87.9 ± 4.3%, and the AR occurred in 62.5 ± 5.4% of cells; in LRP, HRP and VHRP Tyr-P labelling rarely spread over the head, acrosome-reacted cells only accounted for a small number of sperm, and the non-viable cells (NVC) were increased. The addition of APO, but not Oligo, drastically decreased ROS production in analysed samples. CONCLUSIONS This study proposes the optimal threshold for endogenous ROS production for correct sperm viability and functioning, and indicates the direct involvement of APO-sensitive NADPH oxidase in ROS production.

Aldosterone and the conquest of land

The sequence of the phylogenetic events that preceded the appearance of aldosterone in vertebrates is described, starting from the ancestral conversion of cytochrome P450s from oxygen detoxification to xenobiotic detoxification and synthesis of oxygenated endobiotics with useful functions in intercellular signalling, such as steroid hormones. At the end of the Silurian period [438–408 million yr ago, (Mya)], a complete set of cytochrome P450s for corticoid synthesis was presumably already available, except for mitochondrial cytochrome P450c18 or aldosterone synthase encoded by CYP11B2. This gene arose by duplication of the CYP11B gene in the sarcopterygian or lobe-finned fish/tetrapod line after its divergence from the actinopterygian or ray-finned fish line 420 Mya, but before the beginning of the colonization of land by tetrapodsin the late Devonian period, around 370 Mya. The fact that aldosterone is already present in Dipnoi, which occupy an evolutionary transition between water- and air-breathing but are fully aquatic, suggests that the role of this steroid was to potentiate the corticoid response to hypoxia, rather than to prevent dehydration out of the water. In terrestrial amphibians, there is no differentiation between the secretion rates and gluco- and mineralocorticoid effects of aldosterone and corticosterone. In sauropsids, plasma aldosterone concentrations are much lower than in amphibians, but regulation of salt/water balance is dependent upon both aldosterone and corticosterone, though sometimes with opposed actions. In terrestrial mammals, aldosterone acquires a specific mineralocorticoid function, because its interaction with the mineralocorticoid receptor is protected by the coexpression of the enzyme 11β-hydroxysteroid dehydrogenase type 2, which inactivates both cortisol and corticosterone. There is evidence that aldosterone can be also synthesized extra-adrenally in brain neurons and cardiac myocytes, which lack this protection and where the effects of aldosterone oppose those of glucocorticoids. In conclusion, the phylogenetic history of aldosterone documents the erratic progression of evolutionary changes in the course of the strenuous struggle for environmental resources and survival.

Anti-Helicobacter pylori antibodies in cervical mucus: a new cause of infertility

OBJECTIVE The aims of our study were to determine on the one hand a correlation between the presence of anti-Helicobacter pylori (anti-H. pylori) IgG antibodies in serum and cervical mucus of women with idiopathic infertility, and on the other hand the effect of these antibodies on cervical mucus quality, in particular related to the ability of spermatozoa to penetrate it. STUDY DESIGN We analysed anti-H. pylori IgG antibodies in the serum and cervical mucus of 67 patients diagnosed with idiopathic infertility using the Quanta Lite H. pylori IgG test. The penetration of normal sperm, in 15 cervical mucus samples positive for anti-H. pylori antibodies and in 15 negative samples, was assessed using the simplified slide test. RESULTS A significant positive correlation emerged between anti-H. pylori IgG antibody concentrations in the serum and in the cervical mucus (r=0.9275; p<0.00001). In the 15 anti-H. pylori IgG mucus-positive samples the slide test showed abnormal penetration by the spermatozoa. CONCLUSIONS Our study demonstrated that the presence of anti-H. pylori antibody in the cervical mucus can be involved in female infertility, interfering with sperm progression. Considering the close correlation found between serum and cervical mucus anti-H. pylori antibody titres, measuring serum antibodies could become an additional test, in particular in couples with unexplained infertility.