Discovery of natural agents potentially effective in preventing post-menopausal osteoporosis based on Greek flora

Osteoporosis is a major cause of morbidity in the elderly, women in particular. Treatment regiments include hormone replacement therapy (HRT) with estrogen and selective estrogen receptor modulators (SERMs, raloxifene). It is also known, that exogenous estrogen increases breast and uterine cancer risk and that raloxifene is less effective in preventing osteoporosis compared to HRT. Plant derived supplements are used by numerous women to prevent postmenopausal diseases including osteoporosis. Although Greece is one of the richest floral diversity regions, housing nearly 6,300 species of which 950 are found only in Greece, there are scarcely any reports connecting Greek flora herbs with prevention of osteoporosis. The aim of our study was to identify and characterize plant derived extracts and isolated compounds that display structural and/or functional similarity to estrogen and are potentially capable of safely preventing postmenopausal osteoporosis. Based on traditional medicine sources and our previous research experience on natural products with estrogenic properties [1, 2], 25 plant species were selected and 55 extracts were prepared using conventional (maceration) and modern-green techniques (accelerated solvent extraction, microwave assisted extraction and supercritical fluid extraction). Phytochemical profiling and preliminary biological screening revealed Glycyrrhiza glabra, Genista hassertiana and Lathyrus clymenum extracts as capable of inducing MC3T3-E1 differentiation to osteoblasts. Since this differentiation is promoted by antioxidants as well as estrogens, the estrogenic and antioxidant neuroprotective activities of the extracts were determined [3]. Biological evaluation of isolated compounds using cell-based assays revealed flavonoids (flavanons, flavanols, flavonols, etc.) and ionones as the most bioactive constituents. The correlation of pro-differentiation, estrogenic and antioxidant properties of selected compounds will be discussed.

Keywords: Osteoporosis, Greek flora, Osteoblasts, Estrogenic-antiestrogenic activity, Antioxidant neuroprotective properties

References:

[1] Halabalaki M, Alexi X, Aligiannis N, Lambrinidis G, Pratsinis H, Florentin I, Mitakou S, Mikros E, Skaltsounis AL, Alexis MN. Estrogenic activity of isoflavonoids from Onobrychis ebenoides. Planta Med. 2006; 72(6): 488 – 93

[2] Polasek J, Queiroz EF, Marcourt L, Meligova AK, Halabalaki M, Skaltsounis AL, Alexis MN, Prajogo B, Wolfender JL, Hostettmann K. Peltogynoids and 2-phenoxychromones from Peltophorum pterocarpum and evaluation of their estrogenic activity. Planta Med. 2013; 79(6): 480 – 6

[3] Villalonga-Barber C, Meligova AK, Alexi X, Steele BR, Kouzinos CE, Screttas CG, Katsanou ES, Micha-Screttas M, Alexis MN. New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription. Bioorg Med Chem. 2011; 19(1): 339 – 51