Menerba has been reported to alleviate menopausal symptoms such ashot flashes, while having no stimulative effects onendometrium orbreast tissue.[1]
In mouse xenograft models, Menerba produced a different conformation inestrogen receptor alpha (ERα) from ERβ when compared with the conformations produced byestradiol. The specific conformational change induced by Menerba allows ERβ to bind to an estrogen response element and recruit coregulatory proteins that are required forgene activation.[6] It has been shown that the increased risk of breast and uterine cancers is associated with ERα activation and that ERβ blocks the growth promoting effects onbreast cancer cells.[7] Menerba does not activate the ERα-regulated proliferative genes, c-myc and cyclin D1, or stimulate MCF-7 breast cancer cell proliferation or tumor formation, demonstrating that it may be a viable alternative forhormone therapy in comparison toestrogens that non-selectively activate bothER subtypes.[1]
In 2007, Menerba completed a multi-center Phase 2, double-blind, placebo-controlled randomizedclinical trial evaluating its potential for the treatment of hot flashes in 217 healthy post-menopausal women in the U.S. Theprincipal investigator of the trial was Dr. Deborah Grady from theUniversity of California, San Francisco. Menerba showed a statistically significant reduction in the number of hot flashes after 12 weeks of treatment and had astatistically significant reduction in nighttime awakenings fromhot flashes (-67%, p=0.05). There was no difference inuterine bleeding between treatment groups andplacebo, and no uterine abnormalities were observed during the study. The only side effect observed was mild loose stools (12% in treatment group vs. 3% in theplacebo group).[1]
Further studies have shown that most active estrogenic compound in Menerba isliquiritigenin, derived from the root ofGlycyrrhizae uralensis Fisch, one of the 22botanically derived ingredients found in Menerba. In a mouse xenograft model, liquiritigenin activated multiple ER regulatory elements and native target genes with ERβ but not ERα. The ERβ-selectivity of liquiritigenin was due to the selective recruitment of the coactivator steroid receptor coactivator-2 to target genes. Liquiritigenin did not stimulate uterine size or tumorigenesis of MCF-7 breast cancer cells. The results demonstrate that some plants contain highly selective estrogens for ERβ[8] and are as selective as synthetic compounds, but regulate different genes. (PLOs 1 – July 17) and suggests that plant-derived ERb-selective compounds could lead to safer, more attractive alternative therapies for menopausal symptoms.[2][9] In a further study, Menerba was shown to regulatecalcium influx, which is related totemperature regulation.[10]
Menerba underwent Phase 1 safety trials evaluating itstoxicity at 10 g/day and 15 g/day doses. No significant toxicities have been observed in any of the animal studies with doses ranging from 2000 mg/kg/day in dogs to 16,000 mg/kg/day in rodents. Due to acceptable toxicity results on the Phase 1 trial, the FDA approved Menerba to initiate a Phase 3 trial with 1200 women reporting seven or more menopausal hot flashes per day.
^Stovall, DW; Pinkerton, JV (2009). "MF-101, an estrogen receptor beta agonist for the treatment of vasomotor symptoms in peri- and postmenopausal women".Current Opinion in Investigational Drugs.10 (4):365–71.PMID19337958.
