Menerba
Encyclopedia
Menerba is a selective estrogen receptor modulator
(SERM) for the treatment of hot flashes associated with menopause
. Menerba, an estrogen receptor beta
agonist (ERBA) is part of a new class of receptor sub-type Selective Estrogen Receptor Modulator (SERM), which is selective in transcriptional regulation to one of the two known estrogen receptor
subtypes. Menerba consists of 22 herbs that have been used historically in traditional Chinese medicine
.
In mouse xenograft models, Menerba produced a different conformation in ER-alpha (ERα) from ER-beta (ERβ) when compared with the conformations produced by estradiol
. The specific conformational change induced by Menerba allows ERβ to bind to an estrogen response element and recruit coregulatory proteins that are required for gene activation. It has been shown that the increased risk of breast and uterine cancers is associated with ER alpha activation and that ER beta blocks the growth promoting effects on breast cancer
cells. 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 for hormone therapy
in comparison to estrogens that non-selectively activate both ER subtypes.
In 2007, Menerba completed a multi-center Phase 2, double-blind, placebo-controlled randomized clinical trial
evaluating its potential for the treatment of hot flashes in 217 healthy post-menopausal women in the U.S. The principal investigator
of the trial was Dr. Deborah Grady from the University of California, San Francisco
. Menerba showed a statistically significant reduction in the number of hot flashes after 12 weeks of treatment and had a statistically significant reduction in nighttime awakenings from hot flashes (-67%, p=0.05). There was no difference in uterine bleeding between treatment groups and placebo
, 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 the placebo group).
Further studies have shown that most active estrogenic compound in Menerba is liquiritigenin, derived from the root of Glycyrrhizae uralensis Fisch, one of the 22 botanically derived ingredients found in Menerba. In a mouse xenograph 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 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. In a further study, Menerba was shown to regulate calcium influx, which is related to temperature regulation.
Up to date status of clinical trials is available at the manufacturer's website Menerba trials
Menerba underwent Phase 1 safety trials evaluating its toxicity
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.
Selective estrogen receptor modulator
Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively...
(SERM) for the treatment of hot flashes associated with menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
. Menerba, an estrogen receptor beta
Estrogen receptor beta
Estrogen receptor beta , also known as NR3A2 , is a nuclear receptor which is activated by the sex hormone estrogen. In humans, ER-β is encoded by the ESR2 gene.- Function :...
agonist (ERBA) is part of a new class of receptor sub-type Selective Estrogen Receptor Modulator (SERM), which is selective in transcriptional regulation to one of the two known estrogen receptor
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
subtypes. Menerba consists of 22 herbs that have been used historically in traditional Chinese medicine
Traditional Chinese medicine
Traditional Chinese Medicine refers to a broad range of medicine practices sharing common theoretical concepts which have been developed in China and are based on a tradition of more than 2,000 years, including various forms of herbal medicine, acupuncture, massage , exercise , and dietary therapy...
.
Mode of Action
Menerba has been reported to alleviate menopausal symptoms such as hot flashes, while having no stimulative effects on endometrium or breast tissue.In mouse xenograft models, Menerba produced a different conformation in ER-alpha (ERα) from ER-beta (ERβ) when compared with the conformations produced by estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
. The specific conformational change induced by Menerba allows ERβ to bind to an estrogen response element and recruit coregulatory proteins that are required for gene activation. It has been shown that the increased risk of breast and uterine cancers is associated with ER alpha activation and that ER beta blocks the growth promoting effects on breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
cells. 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 for hormone therapy
Hormone therapy
Hormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...
in comparison to estrogens that non-selectively activate both ER subtypes.
In 2007, Menerba completed a multi-center Phase 2, double-blind, placebo-controlled randomized clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
evaluating its potential for the treatment of hot flashes in 217 healthy post-menopausal women in the U.S. The principal investigator
Principal investigator
A principal investigator is the lead scientist or engineer for a particular well-defined science project, such as a laboratory study or clinical trial....
of the trial was Dr. Deborah Grady from the University of California, San Francisco
University of California, San Francisco
The University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dentistry, nursing, and graduate schools are among the top health science professional schools in the world...
. Menerba showed a statistically significant reduction in the number of hot flashes after 12 weeks of treatment and had a statistically significant reduction in nighttime awakenings from hot flashes (-67%, p=0.05). There was no difference in uterine bleeding between treatment groups and placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
, 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 the placebo group).
Further studies have shown that most active estrogenic compound in Menerba is liquiritigenin, derived from the root of Glycyrrhizae uralensis Fisch, one of the 22 botanically derived ingredients found in Menerba. In a mouse xenograph 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 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. In a further study, Menerba was shown to regulate calcium influx, which is related to temperature regulation.
Up to date status of clinical trials is available at the manufacturer's website Menerba trials
Menerba underwent Phase 1 safety trials evaluating its toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
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.
External links
- Official Menerba (MF101) website: http://www.menerba.com
- Official Menerba manufacturer website: http://bionovo.com/pipeline/menerba