Osteoblasts and osteoclasts are bone cells that are specifically responsible for the formation and destruction of bone. Lack of bone formation and/or excessive bone resorption break bone homeostasis and result in bone disease, i.e. osteoporosis. Exploring better drug for osteoporosis is needed due to shortcomings of the current treatment. Chinese herbal medicine is key source in searching natural products for new drug discovery. Psoraleae Fructus, the fruit of Psoralea corylifolia L, has been used in China in treating osteoporosis for years. However, the bioactive ingredients and molecular mechanism of this herbal medicine in bone function remain largely unknown. Here, we aimed to evaluate and identify bioactive phytochemicals of Psoraleae Fructus in bone development.

The chemical HPLC...[ Read more ]

Osteoblasts and osteoclasts are bone cells that are specifically responsible for the formation and destruction of bone. Lack of bone formation and/or excessive bone resorption break bone homeostasis and result in bone disease, i.e. osteoporosis. Exploring better drug for osteoporosis is needed due to shortcomings of the current treatment. Chinese herbal medicine is key source in searching natural products for new drug discovery. Psoraleae Fructus, the fruit of Psoralea corylifolia L, has been used in China in treating osteoporosis for years. However, the bioactive ingredients and molecular mechanism of this herbal medicine in bone function remain largely unknown. Here, we aimed to evaluate and identify bioactive phytochemicals of Psoraleae Fructus in bone development.

The chemical HPLC profile of extracts deriving from Psoraleae Fructus was established. The effect of herbal extracts and identified phytochemicals from Psoraleae Fructus on cultured osteoblasts were systemically evaluated. Among these phytochemicals, corylin was identified as one of potential phytochemicals having robust effect in bone formation. In cultured osteoblasts and bone micromass, corylin increased the expressions of markers of osteogenesis and regulated the metabolic profiles. Moreover, corylin was able to trigger osteoblastic differentiation through dual pathways, i.e. estrogen and Wnt/β-catenin signalling pathways. This important role of corylin in enhancing osteoblast differentiation was validated by transcriptomic analysis. Furthermore, corylin was shown to suppress the RANKL-induced osteoclastogenesis by modulating the NF-κB signalling pathway in cultured osteoclasts. Corylin restrained the migration and commitment of the osteoclast precursor to osteoclastogenesis without influencing cell apoptosis. The molecular mechanism was revealed by transcriptomic analysis, and the inhibitory targets either direct, e.g. GLU236 on RANKL, or indirect, NF-κB essential modulators and ERK, responsible for the anti-osteoclastogenic property of corylin were identified.

This current research provided several lines of evidence for clinical application of Psoraleae Fructus, and which indicated that corylin might be helpful in the discovery of natural product as pro-osteogenic agent, either on their own or in combination with other compounds in the future, as well as the development of effective RNAKL inhibitor for bone disease therapy.