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- Title
Genistein Modified with 8-Prenyl Group Suppresses Osteoclast Activity Directly via Its Prototype but Not Metabolite by Gut Microbiota.
- Authors
Qiu, Zuo-Cheng; Zhang, Feng-Xiang; Hu, Xue-Ling; Zhang, Yang-Yang; Tang, Zi-Ling; Zhang, Jie; Yang, Li; Wong, Man-Sau; Chen, Jia-Xu; Xiao, Hui-Hui
- Abstract
Postmenopausal osteoporosis is a significant threat to human health globally. Genistein, a soy-derived isoflavone, is regarded as a promising anti-osteoporosis drug with the effects of promoting osteoblastogenesis and suppressing osteoclastogenesis. However, its oral bioavailability (6.8%) is limited by water solubility, intestinal permeability, and biotransformation. Fortunately, 8-prenelylated genistein (8PG), a derivative of genistein found in Erythrina Variegate, presented excellent predicted oral bioavailability (51.64%) with an improved osteoblastogenesis effect, although its effects on osteoclastogenesis and intestinal biotransformation were still unclear. In this study, an in vitro microbial transformation platform and UPLC-QTOF/MS analysis method were developed to explore the functional metabolites of 8PG. RANKL-induced RAW264.7 cells were utilized to evaluate the effects of 8PG on osteoclastogenesis. Our results showed that genistein was transformed into dihydrogenistein and 5-hydroxy equol, while 8PG metabolites were undetectable under the same conditions. The 8PG (10−6 M) was more potent in inhibiting osteoclastogenesis than genistein (10−5 M) and it down-regulated NFATC1, cSRC, MMP-9 and Cathepsin K. It was concluded that 8-prenyl plays an important role in influencing the osteoclast activity and intestinal biotransformation of 8PG, which provides evidence supporting the further development of 8PG as a good anti-osteoporosis agent.
- Subjects
OSTEOCLASTOGENESIS; BIOAVAILABILITY; GENISTEIN; GUT microbiome; OSTEOCLASTS; OSTEOPOROSIS in women; BIOCONVERSION; PHARMACODYNAMICS
- Publication
Molecules, 2022, Vol 27, Issue 22, p7811
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules27227811