Isolation of antiosteoporotic compounds from seeds of Sophora japonica

• Published in: PloS one 2014-06, Vol.9 (6), p.e98559
• Main Authors: Abdallah, Hossam M, Al-Abd, Ahmed M, Asaad, Gihan F, Abdel-Naim, Ashraf B, El-halawany, Ali M
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Acid phosphatase; Acid Phosphatase - metabolism; Alkaline phosphatase; Alkaline Phosphatase - metabolism; Animals; Benzopyrans - chemistry; Benzopyrans - pharmacology; Biocompatibility; Biology and Life Sciences; Biomedical materials; Bone resorption; Cancer; Cardiovascular disease; Cell Line; Cell Proliferation - drug effects; Cytotoxicity; Enzymes; Estradiol - chemistry; Estrogens; Genistein; Hormone replacement therapy; Humans; Isoflavones; Kaempferol; MCF-7 Cells; Medicine and Health Sciences; Menopause; Metabolites; Natural products; Oral administration; Osteoblasts; Osteocalcin; Osteocalcin - blood; Osteoid; Osteoporosis; Ovariectomy; Pharmacology; Pharmacy; Phosphatase; Physical Sciences; Rats; Rutin; Seeds; Seeds - chemistry; Sex hormones; Sophora - chemistry; Sophora japonica; Toxicology; Womens health; Xenoestrogens
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098559

Chemical investigation of Sophora japonica seeds resulted in the isolation of seven metabolites identified as: genistin (1), sophoricoside (2), sophorabioside (3), sophoraflavonoloside (4), genistein 7,4'-di-O-β-D-glucopyransoide (5), kaempferol 3-O-α-L-rhamnopyranosyl(1 → 6)β-D-glucopyranosyl(1 → 2)β-D-glucopyranoside (6) and rutin (7). Compounds 1, 2 and 5 showed significant estrogenic proliferative effect in MCF-7 cell in sub-cytotoxic concentration range. Compounds 1 and 2 showed minimal cell membrane damaging effect using LDH leakage assay. Accordingly, compound 2 (sophoricoside, (SPH)) was selected for further in-vivo studies as a potential anti-osteoporosis agent. The anti-osteoporotic effect of SPH was assessed in ovarectomized (OVX) rats after oral administration (15 mg/kg and 30 mg/kg) for 45 days compared to estradiol (10 µg/kg) as a positive control. Only in a dose of 30 mg/kg, SPH regained the original mechanical bone hardness compared to normal non-osteoporotic group. However, SPH (15 mg/kg) significantly increased the level of alkaline phosphatase (ALP) to normal level. Treatment with SPH (30 mg/kg) increased the level of ALP to be higher than normal group. SPH (15 mg/kg) did not significantly increase the serum level of osteocalcin (OC) compared to OVX group. On the other hand, treatment with SPH (30 mg/kg) significantly increased the level of OC to 78% higher than normal non-ovarectomized animals group. In addition, SPH (15 mg/kg) decreased the bone resorption marker, acid phosphatase (ACP) to normal level and SPH (30 mg/kg) further diminished the level of serum ACP. Histopathologically, sophoricoside ameliorated the ovarectomy induced osteoporosis in a dose dependent manner. The drug showed thicker bony trabeculae, more osteoid, and more osteoblastic rimming compared to OVX group.