[논문]난소 적출 마우스 모델에서 Oryza sativa L.의 뿌리 추출물에서 분리된 화합물의 골다공증 개선 효과에 관한 예비연구

김선희; 최은용; 양희진; 배준상

doi:10.15188/kjopp.2023.02.37.2.30

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 원문보기

동의생리병리학회지 = Journal of physiology & pathology in Korean Medicine, v.37 no.2, 2023년, pp.30 - 35

김선희 ((주)성균바이오텍) , 최은용 ((주)성균바이오텍) , 양희진 ((주)성균바이오텍) , 배준상 (원광대학교 한의과대학 병리학교실)

Abstract ▼ AI-Helper

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.

주제어

표/그림 (6)

표 Table 1. Group composition and dose administered
그림 Fig. 2. Plasma and metabolic stability assessment of oryzativol A. (A) In the plasma stability test, oryzativol A was mixed with serum and reacted for 1, 4, 8, and 24 hours, after which the supernatant was analyzed by HPLC. (B) In the metabolic stability test, lysate was prepared from mouse liver tissue, and the activity of CYP3A4 was measured using a fluorescence spectrophotometer at 5 minute intervals for 40 minutes after treating the lysate with oryzativol A. There was no significant difference in the plasma stability and metabolism of oryzativol A-treated mouse and mouse liver primary cells compared to the control group.
그림 Fig. 3. Changes in body weight and bone mineral density of ovariectomized mouse treated with oryzavitol A. The ICR mice were divided into four groups; normal control group(G1), experimental control group(G2), oryzativol A low-dose group(G3), oryzativol A high-dose group(G4). Except for the G1 group, the experimental group(G2-G4) underwent ovariectomy. After 12 weeks, oryzativol A was prepared and orally administered for 8 weeks. Body weight was measured every week after administration of oryzativol A, and bone mineral density was measured 4 weeks and 8 weeks after oryzativol A administration. (A) Body weight, (B) bone mineral density. Results are expressed as the mean ± SD. Bars labeled with different superscripts are significantly different (*p<0.05, vs. G2; ^#p<0.05, ^##p<0.01, vs. G2).
그림 Fig. 1. (A) Chemical structures of oryzativols A. (B) 1H-H COSY correlations (blue bond) and key HMBC correlations (H → C) of oryzativol A.
표 Table 2. Bone Mineral Density of ovariectomized mouse treated with oryzativol A for 8 weeks administration
그림 Fig. 4. Effects of oryzavitol A on serum (A) AST, (B) ALT, (C) ALP, (D) Ca and (E) P levels in ovariectomized mouse. The ICR mice were divided into four groups; normal control group(G1), experimental control group(G2), oryzativol A low-dose group(G3), oryzativol A high-dose group(G4). Results are expressed as the mean ± SD. Bars labeled with different superscripts are significantly different (*p<0.05, vs. G2; ^#p<0.05, vs. G2).

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