Water Extract of Fritillariae thunbergii Bulbus Inhibits RANKL-Mediated Osteoclastogenesis and Ovariectomy-Induced Trabecular Bone Loss

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 1; p. 169
• Main Authors: Shim, Ki-Shuk, Gu, Dong-Ryun, Hwang, Youn-Hwan, Yang, Hyun, Ryuk, Jin-Ah, Ha, Hyunil
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.12.2021; MDPI
• Subjects: Accumulation; Animals; Atrophy; Biomedical materials; Bone density; Bone loss; Bone marrow; Cancellous bone; Cancellous Bone - drug effects; Cancellous Bone - metabolism; Cancellous Bone - pathology; Cell differentiation; Cell Differentiation - drug effects; Cells, Cultured; Chromatography; Chromatography, High Pressure Liquid; Disease Models, Animal; Fractures; Fritillaria - chemistry; Fritillariae thunbergii bulbus; Gene expression; Gene Expression Regulation - drug effects; Glucosides; Herbal medicine; Humans; Ligands; Liquid chromatography; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Mass spectrometry; Mass spectroscopy; Menopause; NF-κB protein; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; Oophorectomy; osteoclast differentiation; Osteoclastogenesis; Osteoclasts - drug effects; Osteogenesis - drug effects; Osteogenesis - genetics; Osteoporosis; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - etiology; Osteoporosis, Postmenopausal - metabolism; Ovariectomy; Pharmacology; Phytochemicals; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; RANK Ligand - genetics; RANK Ligand - metabolism; Scientific imaging; Tandem Mass Spectrometry; TRANCE protein; Uterus; Fritillariae thunbergii bulbus; osteoclast differentiation; osteoporosis; ovariectomy
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27010169

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 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.