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Comparative Analysis of Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro Using Both Phenotypic and Target-based Approaches: Implication for Treating Menopause

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Abstract

Rhizomes of Dioscorea species are traditionally used for relieving menopausal syndromes in Chinese medicine. The estrogen-stimulating bioactive principles have been demonstrated in our previous study. In this study, the estrogen-stimulating effects of proteins isolated from four Dioscorea species [D. alata L. (DA), D. zingiberensis C.H. Wright (DH), D. collettii var. hypoglauca (Palib.) S.J. Pei & C.T. Ting (DH), and D. oppositifolia L. (DO)] have been investigated and compared. Microscopic authentication of four Dioscorea species was performed by using paraffin and powder sections of the rhizomes. The potential bioactive proteins of four Dioscorea species have been rapidly isolated by using a DOI-antibody affinity column chromatography on immobilized antibodies against on estradiol-stimulating protein from DO (DOI), and their bioactivity has been rapidly confirmed and compared by phenotypic (i.e., estradiol-stimulating effect) and target-based (i.e., STAR, aromatase, estrogen receptors) screening approaches. The estrogen-stimulating activity of bioactive proteins from DO is the highest. In addition, bioactive proteins from DO upregulated the estradiol-metabolizing enzymes (aromatase and steroidogenic acute regulatory protein). Meanwhile, bioactive proteins from DA, DH and DO upregulated estrogen receptor β (ERβ). All bioactive proteins did not change the expression of estrogen receptor β (ERα). The estrogen-stimulating bioactive proteins isolated from DO increased biosynthesis of estradiol and upregulated the protein expression of aromatase, steroidogenic acute regulatory protein, and ERβ. The results scientifically support the traditional use of DO in Chinese medicine for relieving menopausal syndrome. Besides, proteins from DA and DZ could also upregulate the translational levels of ERβ, and potentially reducing the risk of ovarian cancer, which also support the clinical use of them for treating female aging disorder.

Comparative Analysis of DOI-like Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro

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Abbreviations

DA:

D. alata L.

DZ:

D. zingiberensis C.H. Wright

DH:

D. collettii var. hypoglauca (Palib.) S.J. Pei & C.T. Ting

DO:

D. oppositifolia L

E2 :

17β-estradiol

CYP19:

aromatase

StAR:

steroidogenic acute regulatory protein

ERα:

estrogen receptor alpha

ERβ:

estrogen receptor beta

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Authors and Affiliations

  1. School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong SAR, People’s Republic of China

    J. Lu, L. Zhang, R. Y. L. Wong, K. F. Lee, Y. B. Zhang, L. X. Lao, J. Y. Liu & S. C. W. Sze

  2. Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, People’s Republic of China

    R. N. S. Wong

  3. School of Biomedical Science, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of China

    T. B. Ng

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  1. J. Lu
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Correspondence to S. C. W. Sze.

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The authors declare that they have no conflicts of interest.

Funding

We thank the Innovation and Technology Support Programme of the government of Hong Kong Special Administrative Region for the generous support of this project (Project code: ITS/262/09FP) and Seed Funding for Basic Research of the University of Hong Kong (Project code: 201211159146; 201011159213).

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Lu, J., Wong, R.N.S., Zhang, L. et al. Comparative Analysis of Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro Using Both Phenotypic and Target-based Approaches: Implication for Treating Menopause. Appl Biochem Biotechnol 180, 79–93 (2016). https://doi.org/10.1007/s12010-016-2084-x

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