Isolation of Antiosteoporotic Compounds from Seeds of <i>Sophora japonica</i>

<div><p>Chemical investigation of <i>Sophora japonica</i> seeds resulted in the isolation of seven metabolites identified as: genistin (<b>1</b>), sophoricoside (<b>2</b>), sophorabioside (<b>3</b>), sophoraflavonoloside (<b>4</b>), genistein 7,4’-di-<i>O</i>-<i>β</i>-D-glucopyransoide (<b>5</b>), kaempferol 3-<i>O</i>-<i>α</i>–L-rhamnopyranosyl(1→6)<i>β</i>-D-glucopyranosyl(1→2)<i>β</i>-D-glucopyranoside (<b>6</b>) and rutin (<b>7</b>). Compounds <b>1</b>, <b>2</b> and <b>5</b> showed significant estrogenic proliferative effect in MCF-7 cell in sub-cytotoxic concentration range. Compounds <b>1</b> and <b>2</b> showed minimal cell membrane damaging effect using LDH leakage assay. Accordingly, compound <b>2</b> (sophoricoside, (SPH)) was selected for further <i>in-vivo</i> 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.</p>