난소 적출 마우스 모델에서 Oryza sativa L.의 뿌리 추출물에서 분리된 화합물의 골다공증 개선 효과에 관한 예비연구
Preliminary Study on the Osteoporosis Improvement Effect of Compounds Isolated from Oryza sativa L. root Extract in the Ovariectomized Mouse Model
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Bisphosphonates, estrogen, and calcium supplements are commonly used medications for postmenopausal osteoporosis, but they are associated with various side effects such as vaginal bleeding, deep vein thromembolism, and breast cancer. In this study, we aimed to investigate the potential of a compound isolated from the roots of Oryza sativa L. to improve osteoporosis using an ovariectomized mouse model. We isolated and identified oryzativol A, a lignan compound, through chemical analysis of an ethanol extract using a bioassay-guided fractionation protocol. We also examined the metabolism, clearance, and CYP enzyme activity of oryzativol A, and found that it showed plasma stability of over 80% at all analysis times, and indicating a low likelihood of inactivation or excretion by the CYP3A4 enzyme. Our results showed that the high-dose group of oryzativol A exhibited a significant increase in bone mineral density compared to the control group. Although the ALP concentration did not differ significantly compared to the control group, it showed a tendency to increase in the high-dose group of oryzativol A. Furthermore, the abnormal ratio of serum Ca/P, caused by osteoporosis, was improved to a level closer to that of the normal group as the dosage of oryzativol A increased. Taken together, these findings suggest that oryzativol A is stable in vivo and has potential as a therapeutic agent for osteoporosis, particularly when administered in high doses.
Abstract
Bisphosphonates, estrogen, and calcium supplements are commonly used medications for postmenopausal osteoporosis, but they are associated with various side effects such as vaginal bleeding, deep vein thromembolism, and breast cancer. In this study, we aimed to investigate the potential of a compound isolated from the roots of Oryza sativa L. to improve osteoporosis using an ovariectomized mouse model. We isolated and identified oryzativol A, a lignan compound, through chemical analysis of an ethanol extract using a bioassay-guided fractionation protocol. We also examined the metabolism, clearance, and CYP enzyme activity of oryzativol A, and found that it showed plasma stability of over 80% at all analysis times, and indicating a low likelihood of inactivation or excretion by the CYP3A4 enzyme. Our results showed that the high-dose group of oryzativol A exhibited a significant increase in bone mineral density compared to the control group. Although the ALP concentration did not differ significantly compared to the control group, it showed a tendency to increase in the high-dose group of oryzativol A. Furthermore, the abnormal ratio of serum Ca/P, caused by osteoporosis, was improved to a level closer to that of the normal group as the dosage of oryzativol A increased. Taken together, these findings suggest that oryzativol A is stable in vivo and has potential as a therapeutic agent for osteoporosis, particularly when administered in high doses.
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