Abstract
Fritillariae thunbergii bulbus has been widely used to treat symptoms of coughs and airway congestion in the chest due to pathological colds and damp phlegm in traditional Chinese medicine. Despite its long history of traditional use, its pharmacological activities on osteoclastogenesis and osteoporosis have not been evaluated. This study investigated the effects of the water extract of Fritillariae thunbergii bulbus (WEFT) on osteoclast differentiation in bone marrow-derived macrophage cells and on ovariectomy (OVX)-induced osteoporosis in mice. We found that WEFT significantly inhibited osteoclastogenesis by downregulating the receptor activator of the NF-κB ligand (RANKL) signaling-induced nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression. In an OVX-induced osteoporosis model, WEFT significantly prevented the OVX-induced trabecular loss of femurs, accompanied by a reduction in fat accumulation in the bone marrow and liver. In addition, WEFT significantly prevented weight gain and gonadal fat gain without recovering uterine atrophy. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, seven alkaloids (peimisine glucoside, yibeissine, peiminoside, sipeimine-glucoside, peimisine, peimine, and peiminine) were identified in WEFT. The results of this study suggest that WEFT can be a potential pharmacological candidate to reduce menopausal osteoporosis and menopause-related symptoms, such as fat accumulation.
Highlights
Osteoporosis is a bone disease characterized by a decrease in bone volume and bone mineral density, a gradual shortage of calcium, and an imbalance in bone remodeling [1]
RANKL/RANK signaling is initiated by the activation of tumor necrosis factor receptor-associated factor 6 (TRAF6) to stimulate MAPK, NF-κB, and AP-1 activation during the early phase of osteoclast differentiation [6,7]
There are some negative regulators of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) at the tra scriptional level, including v-maf avian musculoaponeurotic fibrosarcoma oncogen homolog B (MafB) and interferon regulatory factor-8 (Irf-8), which repress NFATc1 e pression in osteoclast precursors [10,11]
Summary
Osteoporosis is a bone disease characterized by a decrease in bone volume and bone mineral density, a gradual shortage of calcium, and an imbalance in bone remodeling [1]. These results suggest that WEFT inhibits osteoclastogenesis by suppressing the RANKL-induced positive and negative regulation of NFATc1 expression. The activation of NF-κB and MAPK ine glucoside, yibeissine, peiminoside, sipeimine glucoside, peimisine, peimine, and peiminine) were identified in WEFT (Figure 6 and Table 1) by using the retention time and mass spectral data of reference standards and previous studies [35,36]. These alkaloids are characterized by a cevane skeleton, which is composed of an isosteroid structure with a quinolizidine system. The extract was filtered and dried in a vacuum freeze dryer
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