title: Isolation of antiosteoporotic compounds from seeds of Sophora japonica.
abstract: 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.
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Hossam M
authors.initials: HM
authors.lastname: Abdallah
authors.affiliation: Pharmacology Department, Medical Division, National Research Center, Giza, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Al-Abd
authors.affiliation: Pharmacology Department, Medical Division, National Research Center, Giza, Egypt; Pharmacology Department, Faculty of Pharmacy, Jazan University, Jazan, Saudia Arabia.
authors.forename: Gihan F
authors.initials: GF
authors.lastname: Asaad
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ali M
authors.initials: AM
authors.lastname: El-halawany
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D012639:Seeds / Q000737:chemistry*; D029909:Sophora / Q000737:chemistry*
chemical_list: D001578:Benzopyrans; C120642:sophoricoside; D015675:Osteocalcin; D004958:Estradiol; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase