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

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.

Hydroethanolic Extract of Fritillariae thunbergii Bulbus Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Enhancing Intestinal Barrier Integrity

“…In this study, UPLC-tandem mass spectrometry analysis was utilized to characterize the components of FTB. Using retention time (Rt) and mass spectral data from reference standards and reported studies, eight alkaloids (yibeissine, peiminoside, sipeimine glucoside, sipeimine, peimisine, peimine, peiminine, and solanidine) and xanthurenic acid, which are basic components of FTB, were identified in FTB ( Table 1 and Supplementary Figure S1 ) [ 21 , 22 ].…”

“…To analyze the FTB, a Dionex UltiMate 3000 UPLC system equipped with a Thermo Q-Exactive mass spectrometer was used. Chromatographic separation was performed using an Acquity BEH C18 column (100 × 2.1 mm, 1.7 µm) and the gradient setting was performed as described by Shim et al, using 0.1% formic acid in water and acetonitrile [ 21 ]. The identification of phytochemicals in FTB was performed by comparing their retention time (Rt) and mass spectral data with reference standards or based on a previous report [ 21 , 22 ].…”

Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss

“…Bone marrow cells (BMCs) were isolated from the femora and tibiae of 8-week-old C57BL/6J mice following the previously described method [54]. The BMCs were cultured in α-minimal essential medium (α-MEM; HyClone, Logan, UT, USA) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Thermo Fisher Scientific, Waltham, MA, USA) and 20 ng/mL of M-CSF.…”

Peiminine regulates bone‐fat balance by canonical Wnt/β‐catenin pathway in an ovariectomized rat model

“…Pm also played an important role in suppressing the differentiation and function of osteoclasts and alleviating osteolysis and bone resorption (Zhu et al, 2021). Further study revealed that water extract of Fritillariae thunbergii Bulbus Inhibits RANKL‐Mediated osteoclastogenesis and ovariectomy‐induced trabecular bone loss (Shim et al, 2021). A recent study suggested that parathyroid hormone can treat bone loss by inhibiting adipogenesis and osteoclast function (Fan et al, 2017).…”