title: 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.
authors.affiliation: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Kam Lok
authors.initials: KL
authors.lastname: Wong
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
authors.forename: Yau Ming
authors.initials: YM
authors.lastname: Lai
authors.affiliation: Department of Molecular and Cellular Neurobiology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ka Wan
authors.initials: KW
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Kai Fai
authors.initials: KF
authors.lastname: Lee
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Tzi Bun
authors.initials: TB
authors.lastname: Ng
authors.affiliation: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Ho Pan
authors.initials: HP
authors.lastname: Cheung
authors.affiliation: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Yan Bo
authors.initials: YB
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Lixing
authors.initials: L
authors.lastname: Lao
authors.affiliation: Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Ricky Ngok-Shun
authors.initials: RN
authors.lastname: Wong
authors.affiliation: School of Life Sciences and Centre for Protein Science and Crystallography, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Pang Chui
authors.initials: PC
authors.lastname: Shaw
authors.affiliation: 1] School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China [2] School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Jack Ho
authors.initials: JH
authors.lastname: Wong
authors.affiliation: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Zhang-Jin
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology &Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Jenny Ka Wing
authors.initials: JK
authors.lastname: Lam
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, Guangdong Province, China.
authors.forename: Wen-cai
authors.initials: WC
authors.lastname: Ye
authors.forename: Y E
authors.initials: YE
authors.lastname: Wencai
authors.affiliation: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Stephen Cho Wing
authors.initials: SC
authors.lastname: Sze
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D027742:Dioscorea / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D008593:Menopause; D008969:Molecular Sequence Data; D010024:Osteoporosis / Q000517:prevention & control; D010053:Ovary / Q000166:cytology; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D027343:Rhizome / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D010455:Peptides; D010940:Plant Proteins; D012333:RNA, Messenger; D011962:Receptors, FSH; D004958:Estradiol; D001141:Aromatase; D020813:Receptor, trkB