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

• Published in: Scientific reports 2015-07, Vol.5 (1), p.10179-10179, Article 10179
• Main Authors: Lok Wong, Kam, Ming Lai, Yau, Li, Ka Wan, Fai Lee, Kai, Ng, Tzi Bun, Pan Cheung, Ho, Bo Zhang, Yan, Lao, Lixing, Ngok-Shun Wong, Ricky, Chui Shaw, Pang, Ho Wong, Jack, Zhang, Zhang-Jin, Lam, Jenny Ka Wing, Ye, Wen-cai, Wing Sze, Stephen Cho
• Format: Article
• Language: English
• Subjects: 13; 17β-Estradiol; 38/88; 64/86; 692/308/153; 692/308/2778; 82/16; 82/29; 82/58; 82/81; 82/83; Amino Acid Sequence; Animals; Aromatase; Aromatase - genetics; Aromatase - metabolism; Biosynthesis; Bone and Bones - diagnostic imaging; Bone Density; Bone mineral density; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Breast cancer; Cell Line; Cell proliferation; Cell Survival - drug effects; Cognitive ability; Dioscorea - metabolism; Estradiol - biosynthesis; Female; Follicle-stimulating hormone; Granulosa cells; Hormone replacement therapy; Humanities and Social Sciences; Menopause; Molecular Sequence Data; multidisciplinary; Osteoporosis; Osteoporosis - prevention & control; Ovarian cancer; Ovary - cytology; Peptides - chemistry; Peptides - therapeutic use; Plant Proteins - chemistry; Plant Proteins - metabolism; Prefrontal cortex; Prefrontal Cortex - metabolism; Progesterone; Proteins; Rats; Rats, Sprague-Dawley; Receptor, trkB - metabolism; Receptors, FSH - genetics; Receptors, FSH - metabolism; Rhizome - metabolism; RNA, Messenger - metabolism; Science; Side effects; TrkB receptors; X-Ray Microtomography
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep10179

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.