Abstract
In traditional oriental medicine, the fruit of Forsythia suspensa has been used as a nutritional supplement to alleviate inflammation and treat gastrointestinal diseases. However, there is no information available on its beneficial effects on bone. We investigated the beneficial effects of F. suspensa water extract (WFS) on osteoclast differentiation and bone loss. The microarchitecture of trabecular bone was analyzed by micro-computed tomography. Osteoclast differentiation was evaluated based on tartrate-resistant alkaline phosphatase activity, and bone resorption activity was examined on a bone-like mineral surface. The mechanism of action of WFS was assessed by evaluating the expression and activation of signaling molecules. Phytochemical constituents were identified and quantitated by ultrahigh-performance liquid chromatography–tandem mass spectrometry. WFS reduced ovariectomy-induced trabecular bone loss and inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and resorption activity. WFS suppressed RANKL-induced expression of nuclear factor of activated T cells cytoplasmic 1, a crucial transcription factor for osteoclast differentiation by decreasing c-Fos protein levels and suppressing the activation of p38 and c-Jun-N-terminal kinase. We also identified 12 phytochemicals in WFS including lignans, phenylethanoids, and flavonoids. Collectively, these results suggest that WFS inhibits osteoclast differentiation and can potentially be used to treat postmenopausal osteoporosis.
Highlights
Bone remodeling is a tightly regulated process that balances bone formation by osteoblasts and bone resorption by osteoclasts
The present study investigated whether the water extract of F. suspensa (WFS) can alleviate osteoporosis using a mouse model of ovariectomy-induced bone loss as well as the underlying mechanisms
We investigated the beneficial effects of WFS (200 and 500 mg/kg/day) on bone in OVX mice fed with an high-fat diet (HFD) through micro-CT analysis for bone microarchitecture and histopathological examination for fat accumulation
Summary
Bone remodeling is a tightly regulated process that balances bone formation by osteoblasts and bone resorption by osteoclasts. An imbalance in bone remodeling—especially an elevation in osteoclast activity—leads to deterioration of bone architecture, low bone mineral density, and reduced bone strength [1]. Given the critical role of osteoclasts in bone disorders, therapeutic strategies that attenuate excess osteoclast formation and resorption activity may be an effective treatment for osteoporosis. Several standard therapies are available for the treatment of osteoporosis, there is a need for safer but effective alternatives. Natural products and herbal medicines are gaining interest for their potential to improve bone health in osteoporosis patients and healthy individuals [4]
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