Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea; University of Science & Technology (UST), Korean Convergence Medicine Major KIOM, Daejeon 34054, Republic of Korea.
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
Biomed Pharmacother. 2021 Dec;144:112300. doi: 10.1016/j.biopha.2021.112300. Epub 2021 Oct 12.
Osteoporosis and resulting bone fractures are the major health issues associated with morbidity in the aging population; however, there is no effective treatment that does not cause severe side effects. In East Asia, dried seeds of Psoralea corylifolia L. (PC) have traditionally been used as an herbal medicine to manage urinary tract, cutaneous, and gastrointestinal disorders, as well as bone health. However, the mechanism of action and active biocomponents of PC are unclear. Here, we adopted a pharmacokinetic (PK) study aiming to identify the bioavailable phytochemicals in aqueous and ethanolic extracts of PC (APC) and (EPC), respectively. In addition, we aimed to determine anti-resorptive constituents of PC, which accounted for its beneficial effects on bone health. To this end, we used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A rapid, sensitive, and reliable UPLC-MS/MS method was developed and determined the 17 PC ingredients. In the PK study, nine components (two chalcones, two coumarins, one coumestan, two flavonoids, and two isoflavonoids) were observed between 36 and 48 h after oral administration of APC or EPC. Among the bioavailable ingredients, four PC constituents (psoralidin, isobavachin, corylifol A, and neobavaisoflavone) inhibited M-CSF-and RANKL-induced osteoclast differentiation in bone marrow-derived macrophages. In addition, two chalcones and two isoflavonoids markedly inhibited cathepsin K activity, and their binding modes to cathepsin K were determined by molecular docking. In summary, our data suggest that bioavailable multicomponents of PC could contribute to the management of bone health.
骨质疏松症及其导致的骨折是与人口老龄化相关的主要健康问题；然而，目前还没有既有效又无严重副作用的治疗方法。在东亚，补骨脂（Psoralea corylifolia L.）的干种子传统上被用作草药，用于治疗尿路、皮肤和胃肠道疾病以及骨骼健康。然而，补骨脂的作用机制和有效生物成分尚不清楚。在这里，我们采用了一项药代动力学（PK）研究，旨在分别鉴定补骨脂水提物和醇提物（APC 和 EPC）中的生物可利用的植物化学成分。此外，我们旨在确定补骨脂的抗吸收成分，这是其对骨骼健康有益的原因。为此，我们使用了超高效液相色谱-串联质谱法（UPLC-MS/MS）。建立了一种快速、灵敏、可靠的 UPLC-MS/MS 方法，用于测定 17 种补骨脂成分。在 PK 研究中，在口服 APC 或 EPC 后 36 至 48 小时之间观察到九种成分（两种查尔酮、两种香豆素、一种香豆雌酚、两种类黄酮和两种异黄酮）。在生物可利用的成分中，四种补骨脂成分（补骨脂定、异补骨脂查耳酮、补骨脂醇 A 和新补骨脂异黄酮）抑制了巨噬细胞来源的破骨细胞分化。此外，两种查尔酮和两种异黄酮显著抑制组织蛋白酶 K 的活性，并通过分子对接确定了它们与组织蛋白酶 K 的结合模式。综上所述，我们的数据表明，补骨脂的生物可利用的多种成分可能有助于骨骼健康的管理。
