The Dibenzyl Isoquinoline Alkaloid Berbamine Ameliorates Osteoporosis by Inhibiting Bone Resorption

Abstract

Postmenopausal osteoporosis (PMOP) is a kind of primary osteoporosis that is characterized by decreased bone density and strength. Berbamine is a nonbasic quaternary benzylisoquinoline plant alkaloid that has been widely used in the clinic to treat leukopenia in China. We found that berbamine inhibited RANKL-induced osteoclastogenesis of bone marrow-derived macrophages (BMMs) in vitro, which mainly occurred in the middle phase and late phase. The gene and protein expression levels of osteoclast-related molecules, including CTSK, MMP-9, NFATc1, CD44 and DC-STAMP, were also downregulated by berbamine. In vivo, we treated PMOP mice with berbamine for 8 weeks and found that the extent of osteoporosis was alleviated significantly according to micro-CT scanning, hematoxylin-eosin staining, DC-STAMP immunohistochemical staining and TRAP immunohistochemical staining in the distal femurs of the mice. Our findings demonstrate that berbamine has an inhibitory effect on the osteoclastogenesis of BMMs and can prevent bone loss after ovariectomy in vivo. This study provides evidence that berbamine is a potential drug for the prevention and treatment of PMOP.

NFATc1-mediated expression of SLC7A11 drives sensitivity to TXNRD1 inhibitors in osteoclast precursors

“…In previous studies, we have identified a number of small molecule drugs that could alleviate OVX-induced bone loss in mice by preventing pre-OC fusion or inhibiting osteoclast differentiation [ 39 , [52] , [53] , [54] ]. In the course of these studies, we found that the susceptibility of cells to certain drugs changes during osteoclast differentiation.…”

“…BMDMs were isolated from wild-type or SLC7A11 −/− mice as previously described [ 39 ]. Briefly, 4-week-old C57BL/6J mice were dissected under Zoletil 50 (50 mg/kg) anaesthesia, and the tibiae and femora were collected.…”

“…Bone resorption activity was assessed as described previously [ 39 ]. Briefly, BMDMs were seeded onto bone slices in 96-well plates at a density of 8000 cells/well, then cultured for seven days with a medium containing 20 ng/mL M-CSF and 50 ng/mL RANKL.…”

Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis

“…The application of these drugs will inevitably bring certain side effects. For example, bisphosphonates can cause hypocalcemia, osteonecrosis of the jaw, and atrial fibrillation ( 106 , 107 ). Denosumab, a human anti-RANKL antibody, potently blocks the interaction between RANK and its ligands to inhibit bone resorption, but long-term use can lead to infection, rash, and atypical femoral fractures ( 108 , 109 ).…”

Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

“…It also has the effects of beneficial Qi, invigorating the spleen, and reducing edema. The active ingredients in FJ are mainly dibenzyl isoquinoline alkaloids, such as tetrandrine, fangchinoline, and rocinoline, which have analgesic, antitumor, antifibrotic, and anti-inflammatory effects [ 7 , 8 ]. Our previous study found that N-methylfangchinoline, fangchinoline, tetrandrine, tetrandrine-M3, and tetrandrine-M4 have the same structure, which can cooperatively improve kidney injury [ 9 ].…”