The following information is directly pulled from the National Institutes of Health database. The National Institutes of Health (NIH) is a biomedical research facility primarily located in Bethesda, Maryland. An agency of the United States Department of Health and Human Services, it is the primary agency of the United States government responsible for biomedical and health-related research.
Effects of Licorice on Relief and Recurrence of Menopausal Hot Flashes
Vasomotor hot flash is the most common and distressful complication of menopausal women. Its treatment is the most frequent clinical challenge. As a result, an effective and harmless therapy is needed. This double-blind controlled clinical trial was conducted to determine the effects of licorice roots on the relief and recurrence of hot flash in menopausal women referring to the healthcare centers affiliated to Shahid Beheshti Medical University in 2010.
Ninety menopausal women complaining of hot flash were selected by reviewing their records in healthcare centers and randomly divided into 2 licorices (3 capsules daily containing 330 mg licorice abstract) and placebo (3 capsules daily containing 330 mg starch) groups over the 8 weeks of intervention and 4 weeks of follow-up. Two weeks prior to the intervention, the severity as well as frequency of hot flashes and the foods taken were asked and documented with questionnaires and data sheets. Data within and between the groups were analyzed by ANOVA with repeated measurements and t-test respectively.
Means of age and body mass index (BMI) of the subjects in licorice and placebo groups were 53 ± 3.2, 52.69 ± 2.8, 24.71 ± 3.2 and 23.61 ± 3.3, respectively. The groups were similar in terms of intervening variables. The frequency of hot flash decreased significantly in the experimental (than the placebo group) and this lasted for 2 weeks after the administration of the capsules. The severity of hot flash decreased in the licorice group as well. This decrease was also seen in the placebo group in the first week of the intervention. Decreased hot flash in the placebo group was only significant after the 1st week of intervention compared to the previous period. Recurrence of frequency and severity of hot flashes occurred 2 weeks after the termination of therapy.
The significant decrease in the placebo group after the 1st week of the intervention may be attributed to the psychological effects of placebo. Licorice roots decreased the frequency and severity of hot flashes. The administration of this harmless, inexpensive herb well accepted by the menopausal women together with the appropriate and continuous physical activities and consumption of dairy products are recommended for relieving this complication. Read More.
Key Words: Menopause, Menopausal women, Vasomotor hot flash, Post menopausal hot flash, Herbal medicine, Licorice
Differential effects of Glycyrrhiza species on genotoxic estrogen metabolism: licochalcone A downregulates P450 1B1 whereas isoliquiritigenin stimulates
Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by up-regulating P450 1B1. The present study tested the three authenticated medicinal species of licorice, [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)], used by women as dietary supplements, for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI > GG > GU and LigC ≅ LicA > LigF. The Michael acceptor chalcone LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as non-toxic and 4-MeOE1 as genotoxic biomarkers in the non-tumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1 μM, 10 μM) decreased cytokine- and TCDD-induced, P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50=12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women’s health. Additionally, the differential effects of the Glycyrrhizaspecies on estrogen metabolism emphasize the importance of standardization of botanical supplements to species-specific bioactive compounds.
Keywords: Aryl hydrocarbon receptor, cytochrome P450 1B1, estrogen carcinogenesis, estrogen metabolism, Glycyrrhiza glabra, inflata, uralensis, inflammation, iNOS, nuclear factor-kappaB, quinone, xenobiotic response element, licochalcone A, isoliquiritigenin
Breast cancer is the second leading cause of cancer-related deaths among women in the United States,1 and the risk of developing the disease increases with cumulative exposure to estrogens including hormone therapy (HT).1,2 The chemical mechanism of estrogen carcinogenesis involves metabolism of estrone/estradiol (E1/E2) to 2-hydroxy (non-toxic) and 4-hydroxy estrogen (genotoxic) metabolites by P450 1A1 and P450 1B1 enzymes, respectively (Figure 1).2 These estrogen metabolizing enzymes are typically up-regulated through activation of the aryl hydrocarbon receptor (AhR), which also controls polycyclic aromatic hydrocarbon (PAH) metabolism.3 The genotoxic estrogen o-quinone formed from 4-hydroxy estrogen produces reactive oxygen species (ROS) and DNA adducts that induce malignant transformation of normal breast cells.4–9 Alternatively, the estrogen o-quinones are reduced by NAD(P)H:quinone oxidoreductase 1 (NQO1), which are up-regulated by antioxidant response element (ARE) activation (Figure 1).10
Licorice extracts/compounds differentially modulated iNOS activity in macrophage cells
Since inflammation can increase oxidative estrogen metabolism (Figure 1),17 the anti-inflammatory activity of the licorice species and their major bioactive compounds was determined. Previous studies have measured the anti-inflammatory activities of some licorice species;28,48–50 however, the current studies represent the first direct comparison of authenticated extracts and pure compounds. Among the three Glycyrrhiza species, GI was the most anti-inflammatory extract in RAW 264.7 macrophage cells, reducing iNOS activity to 35% of the LPS control versus 67% of control for GG at 20 μg/mL (Figure 3A). No anti-inflammatory effect was detected up to 20 μg/mL for GU. To determine the effect of the compounds on iNOS activity, LigF, LigC, and LicA were tested in the Griess assay (Figure 3B). The chalcones, LicA and LigC, reduced iNOS activity in macrophage cells to 50% at 10 μM and to 25% and 20% (20 μM) of the LPS control, respectively. LigF did not reduce iNOS activity. These data showed that GI’s anti-inflammatory activity is mainly due to LicA, which is only present in GI.