Identification and pharmacokinetics of bioavailable anti-resorptive phytochemicals after oral administration of Psoralea corylifolia L

• Published in: Biomedicine & pharmacotherapy 2021-12, Vol.144, p.112300, Article 112300
• Main Authors: Lee, Ami, Yang, Hyun, Kim, Taesoo, Ha, Hyunil, Hwang, Youn-Hwan
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological Availability; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - isolation & purification; Bone Density Conservation Agents - pharmacokinetics; Bone Resorption - metabolism; Bone Resorption - pathology; Bone Resorption - prevention & control; Cathepsin K; Cathepsin K - metabolism; Cell Differentiation - drug effects; Cells, Cultured; Male; Mass spectrometry; Osteoclast; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoclasts - pathology; Osteogenesis - drug effects; Osteoporosis; Pharmacokinetics; Phytochemicals - administration & dosage; Phytochemicals - isolation & purification; Phytochemicals - pharmacokinetics; Plant Extracts - administration & dosage; Plant Extracts - isolation & purification; Plant Extracts - pharmacokinetics; Psoralea - chemistry; Psoralea corylifolia L; Rats; Rats, Sprague-Dawley
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.112300

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. [Display omitted] •Rapid and reliable UPLC-MS/MS method quantified 17 PC phytochemicals in rat serum.•Pharmacokinetic characteristics of nine bioactive phytochemicals were determined.•Bioavailable compounds inhibited osteoclast differentiation and function.•Our data will be useful for improving the therapeutic regimen of PC in bone disorders.