A Novel, Stable, Estradiol-Stimulating, Osteogenic Yam Protein with Potential for the Treatment of Menopausal Syndrome

Abstract

A novel protein, designated as DOI, isolated from the Chinese yam (Dioscorea opposita Thunb.) could be the first protein drug for the treatment of menopausal syndrome and an alternative to hormone replacement therapy (HRT), which is known to have undesirable side effects. DOI is an acid- and thermo-stable protein with a distinctive N-terminal sequence Gly-Ile-Gly-Lys-Ile-Thr-Thr-Tyr-Trp-Gly-Gln-Tyr-Ser-Asp-Glu-Pro-Ser-Leu-Thr-Glu. DOI was found to stimulate estradiol biosynthesis in rat ovarian granulosa cells; induce estradiol and progesterone secretion in 16- to 18-month-old female Sprague Dawley rats by upregulating expressions of follicle-stimulating hormone receptor and ovarian aromatase; counteract the progression of osteoporosis and augment bone mineral density; and improve cognitive functioning by upregulating protein expressions of brain-derived neurotrophic factor and TrkB receptors in the prefrontal cortex. Furthermore, DOI did not stimulate the proliferation of breast cancer and ovarian cancer cells, which suggest it could be a more efficacious and safer alternative to HRT.

Calycosin stimulates the proliferation of endothelial cells, but not breast cancer cells, via a feedback loop involving RP11-65M17.3, BRIP1 and ERα

“…According to the World Bank, the total population of postmenopausal women worldwide is predicted to reach 1200 million by 2030, and the proportion of these women living in the developing world will increase to 76% [ 1 , 2 ]. Decreased levels of sex hormones in the blood are thought to be responsible for postmenopausal syndrome, which is mainly caused by cessation of ovarian function and decline in steroid and peptide hormone secretion.…”

Identification of Steroidogenic Components Derived From Gardenia jasminoides Ellis Potentially Useful for Treating Postmenopausal Syndrome

“…The granulosa cells in serum-free DME/F12 1:1 medium (Thermo Scientific, USA) supplemented with 0.1% bovine serum albumin (Sigma-Aldrich, USA), 1% penicillin-streptomycin (Sigma-Aldrich, USA), and 1 μg/mL insulin (Sigma-Aldrich, USA) were seeded at a density of 2 × 10 4 cells/well in a 48-well plate and were incubated at 37°C in 5% CO 2 in an atmosphere for 2 h. Afterwards, the vehicle or different concentrations of GJE fractions (0.001%, 0.01%, 0.1%, 1%) or GJE components (10, 100 μM) were added to granulosa cells for 12 h. After that, the 17β-estradiol concentration in the cell culture medium was measured using an electro-chemiluminescence immunoassay (Elecsys, 2010, Roche Diagnostics, Basel, Switzerland) with a 17β- estradiol II kit (Roche Diagnostics, Switzerland) in a single batch. In order to explore whether GJE active components could bind to FSHR on FSHR-attenuated ovarian granulosa cells, ovarian granulosa cells were pretreated with FSHR (2 μg/mL, #sc13935; Santa Cruz, CA) for 0.5 h. After incubation with FSHR, granulosa cells were treated with GJE active compounds (100 μM) for 12 h (Wong et al, 2015 ).…”

Physicochemical, enzymatic and molecular characterisation of the storage protein of aerial tuber, Dioscorea bulbifera Linn.

“…Yam, a dioecious plant belonging to the Dioscorea genus, is an important staple crop in many areas of the tropics and sub-tropics [ 1 ]. There are 8 genera and 880 species of yam plant.…”