State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, PR China.
State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, PR China.
Phytochemistry. 2022 Apr;196:113085. doi: 10.1016/j.phytochem.2022.113085. Epub 2022 Jan 8.
The mature fruit of Psoralea corylifolia L. is a common traditional Chinese medicine used to tonify the kidney and yang, and as well as to treat osteoporosis. Systematic phytochemical investigations have established the most comprehensive constituent library to date, covering over 180 compounds. In this study, 109 chemical constituents containing 37 undescribed compounds were reported and incorrect structures of four known coumarins were corrected. The structures of these undescribed compounds were elucidated using spectroscopic methods, single-crystal X-ray diffraction, Rh(OCOCF) and Mo(OAc)-induced circular dichroism spectra. To identify potentially active compounds and investigate their structure-activity relationship (SAR), 89 constituents in the library were evaluated for their osteogenic differentiation and mineralisation activities in MC3T3-E1 cells. We found that coumarins, isoflavones, flavonones, and meroterpenoids were the material basis for Psoralea corylifolia-based treatment of osteoporosis, with some compounds exhibiting excellent activities. These compounds function via the estrogen receptor (ER) pathway and were natural phytoestrogen. Further SAR analysis showed that compounds with an intact isopentenyl replacement possessed superior activities, which was explained by their improved affinity with the ER.
成熟的补骨脂果实是一种常用的传统中药，具有补肾壮阳、治疗骨质疏松症的功效。系统的植物化学研究已经建立了迄今为止最全面的成分库，涵盖了超过 180 种化合物。在这项研究中，报告了 109 种含有 37 种未描述化合物的化学成分，并纠正了四种已知香豆素的错误结构。这些未描述化合物的结构是通过光谱方法、单晶 X 射线衍射、Rh(OCOCF)和 Mo(OAc)诱导的圆二色光谱来阐明的。为了鉴定潜在的活性化合物并研究其结构-活性关系(SAR)，对库中的 89 种成分进行了评估，以研究它们在 MC3T3-E1 细胞中的成骨分化和矿化活性。我们发现香豆素、异黄酮、黄酮和倍半萜是补骨脂治疗骨质疏松症的物质基础，其中一些化合物具有优异的活性。这些化合物通过雌激素受体(ER)途径发挥作用，是天然的植物雌激素。进一步的 SAR 分析表明，具有完整异戊烯取代基的化合物具有更好的活性，这可以通过它们与 ER 的亲和力提高来解释。
