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Isolation of antiosteoporotic compounds from seeds of Sophora japonica.

Abdallah HM, Al-Abd AM, Asaad GF, Abdel-Naim AB, El-halawany AM - PLoS ONE (2014)

Bottom Line: SPH (15 mg/kg) did not significantly increase the serum level of osteocalcin (OC) compared to OVX 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.The drug showed thicker bony trabeculae, more osteoid, and more osteoblastic rimming compared to OVX group.

View Article: PubMed Central - PubMed

Affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

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.

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Assessing the estrogenic properties of compounds isolated from S. japonica in estrogen dependent MCF-7 cell line.Sub-cytotoxic concentrations of the isolated compounds were determined using LDH leakage assay (A); and proliferative effect was determined using SRB assay (B).
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pone-0098559-g002: Assessing the estrogenic properties of compounds isolated from S. japonica in estrogen dependent MCF-7 cell line.Sub-cytotoxic concentrations of the isolated compounds were determined using LDH leakage assay (A); and proliferative effect was determined using SRB assay (B).

Mentions: Effect of compounds under investigation on the cell membrane integrity was further confirmed using more sensitive technique (LDH leakage assay). Exposure to 1 µM of compounds 3, 4 and 6 induced 2.2, 2.6 and 2.8 folds LDH leakage that in the control group, respectively. The concentration of LDH in media was about 5 folds control group after exposure to 100 µM of compounds 3, 4 and 6. On the other hand, the amount of LDH in media over cells treated with concentrations less than 10 µM of compounds 1, 2, 5, and 7 did not exceed double the concentration of LDH leakage in control group. These indicate the harmless effect of these compounds on cell membrane (Figure 2-A).


Isolation of antiosteoporotic compounds from seeds of Sophora japonica.

Abdallah HM, Al-Abd AM, Asaad GF, Abdel-Naim AB, El-halawany AM - PLoS ONE (2014)

Assessing the estrogenic properties of compounds isolated from S. japonica in estrogen dependent MCF-7 cell line.Sub-cytotoxic concentrations of the isolated compounds were determined using LDH leakage assay (A); and proliferative effect was determined using SRB assay (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043785&req=5

pone-0098559-g002: Assessing the estrogenic properties of compounds isolated from S. japonica in estrogen dependent MCF-7 cell line.Sub-cytotoxic concentrations of the isolated compounds were determined using LDH leakage assay (A); and proliferative effect was determined using SRB assay (B).
Mentions: Effect of compounds under investigation on the cell membrane integrity was further confirmed using more sensitive technique (LDH leakage assay). Exposure to 1 µM of compounds 3, 4 and 6 induced 2.2, 2.6 and 2.8 folds LDH leakage that in the control group, respectively. The concentration of LDH in media was about 5 folds control group after exposure to 100 µM of compounds 3, 4 and 6. On the other hand, the amount of LDH in media over cells treated with concentrations less than 10 µM of compounds 1, 2, 5, and 7 did not exceed double the concentration of LDH leakage in control group. These indicate the harmless effect of these compounds on cell membrane (Figure 2-A).

Bottom Line: SPH (15 mg/kg) did not significantly increase the serum level of osteocalcin (OC) compared to OVX 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.The drug showed thicker bony trabeculae, more osteoid, and more osteoblastic rimming compared to OVX group.

View Article: PubMed Central - PubMed

Affiliation: Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

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.

Show MeSH
Related in: MedlinePlus