Research and Development of Proteins and Peptides with Therapeutic Potential from Yam Tubers.

We discuss the diverse biological activities, therapeutic potential, and clinical applications of peptides and proteins isolated from various yams species including Dioscorea opposita Thunb (Chinese yam), D alata, D japonica (Japanese yam), D pseudojaponica, D batatas (Korea yam), and D cayenensis. Yam peptides and proteins have many pharmacological activities including immunomodulatory, antioxidant, estrogen-stimulating, osteogenic, angiotensin I-converting enzyme inhibiting, carbonic anhydrase and trypsin inhibiting, chitinase, anti-insect, anti-dust mite, lectin, and anti-proliferative activities. Yam peptides and proteins have therapeutic potential for treating cardiovascular diseases, inflammatory diseases, cancers, aging disorders, menopause, and osteoporosis.

Steroidogenic effect of Erxian decoction for relieving menopause via the p-Akt/PKB pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Erxian decoction (EXD), an empirical Chinese medicine formula, is effectively used in the clinical treatment of menopause-related symptoms in China. Previous data from our group show that EXD has steroidogenic effect on natural menopausal Sprague-Dawley-rats (SD-rats) as an animal model of menopause. However, the mechanistic studies on steroidogenic effects of EXD are still inadequate. Hence, the mechanisms of steroidogenic effects of EXD were studied in vitro and in vivo in this study. MATERIALS AND METHODS: Menopause causes a decline of endocrine function and a series of symptoms. In this study, 16-20-month-old female SD rats with a low serum estradiol level were employed. Their endocrine functions after treatment with EXD (4.1g/kg) were assessed by determination of their serum estradiol level. Proteins involved in the steroidogenic pathway including StAR, 17ßHSD, 3ßHSD, aromatase, and activation of phosphorylated Protein Kinase B (p-Akt/PKB), as well as estradiol receptor proteins (ERα & ERß) after EXD treatment were analyzed. Kinase inhibition assay was conducted to confirm the mechanism of steroidogenic effects of EXD in vitro. MCF-7 and BT-483 cells were used to investigate whether EXD stimulated breast cancer cell proliferation. RESULTS: Results revealed a significantly ameliorated serum estradiol level, and a significantly increased expression of ovarian aromatase and PKB in the EXD-treated rats. EXD attenuated 17ß-estradiol stimulated proliferation of breast cancer cells. CONCLUSIONS: The results obtained from immunoblotting and measurements of serum estradiol level of the present investigation revealed that EXD may relieve the menopausal syndrome through an upregulation of ovarian aromatase and p-PKB expression without stimulating the growth of breast cancer cells.

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

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.

Network pharmacological identification of active compounds and potential actions of Erxian decoction in alleviating menopause-related symptoms.

BACKGROUND: Erxian decoction (EXD) is used to treat menopause-related symptoms in Chinese medicine. This study aims to identify the bioactive compounds and potential actions of EXD by network pharmacological analysis. METHODS: Two databases, the Traditional Chinese Medicine Systems Pharmacology database and TCM Database@Taiwan, were used to retrieve literature of phytochemicals of EXD. STITCH 4.0 and the Comparative Toxicogenomics Database were used to search for compound-protein and compound-gene interactions, respectively. DAVID Bioinformatics Resources 6.7 and Cytoscape 3.01 with Jepetto plugin software were used to perform a network pharmacological analysis of EXD. RESULTS: A total of 721 compounds were identified in EXD, of which 155 exhibited 2,656 compound-protein interactions with 1,963 associated proteins determined by STITCH4.0 database, and of which 210 had 14,893 compound-gene interactions with 8,536 associated genes determined by Comparative Toxicogenomics Database. Sixty three compounds of EXD followed the Lipinski's Rule with OB ≥30% and DL index ≥0.18, of which 20 related to 34 significant pathway- or 12 gene- associated with menopause. CONCLUSIONS: Twenty compounds were identified by network pharmacology as potential effective ingredients of EXD for relieving menopause with acceptable oral bioavailability and druggability.