Boldine Ameliorates Estrogen Deficiency-Induced Bone Loss via Inhibiting Bone Resorption

Abstract

Osteoporosis is an enormous health problem caused by the imbalance between bone resorption and bone formation. The current therapeutic strategies for osteoporosis still have some limitations. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects in vivo. For the first time, we discover that boldine has a protective effect for the estrogen deficiency-induced bone loss in mice. According to the Micro-CT and histomorphometry assays, boldine conducts this protective effect through inhibiting bone resorption without affecting bone formation in vivo. Moreover, we showed that boldine can inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation via impairing the AKT signaling pathways, while SC79 (an AKT agonist) partially rescue this effect. In conclusion, our results suggest that boldine can prevent estrogen deficiency-induced osteoporosis by inhibiting osteoclastogenesis. Thus, boldine may be served as a novel therapeutic agent for anti-osteoporotic therapy.

Boldine inhibits the alveolar bone resorption during ligature‐induced periodontitis by modulating the Th17/Treg imbalance

“…Alveolar bone resorption, however, remains an important clinical problem, and none of the approaches proposed to date have proven to be very effective 1,33 . In this context, boldine is a plausible alternative, since recent in vivo studies have reported its beneficial effects on pathological osteoclast activity and bone loss 6,12 . In the present study, we have demonstrated for the first time that boldine ameliorates periodontitis by inhibiting the alveolar bone resorption, and this inhibition is associated with the modulation of the Th17/Treg imbalance that determines the RANKL‐mediated osteoclast activity in the periodontal lesions.…”

“…In particular, boldine induced an increase in the expression levels of OPG and a decrease in the expression levels of RANKL in the joint lesions 6 . Similarly, using an animal model of ovariectomy‐induced osteoporosis, boldine prevented pathological bone loss and conducted this protective effect through the inhibition of RANKL‐induced osteoclastogenesis 12 . Consistent with these findings, in the present study, ligature‐induced periodontitis was inhibited after oral administration of boldine, and this inhibition was associated with changes in the production of RANKL and OPG in the periodontal tissues, which resulted in attenuation of the RANKL/OPG signal pathway that determines osteoclast‐mediated periodontal bone resorption.…”

“…Mounting evidence has shown that boldine has a beneficial effect in distinct human diseases 6‒11 . In the context of osteoimmunological diseases, it is noteworthy that boldine has also been demonstrated to protect against bone loss 6,12 . By using an animal model of collagen‐induced rheumatoid arthritis, oral administration of boldine inhibited osteoclast differentiation and the consequent sub‐chondral articular bone loss 6 .…”

“…Indeed, accumulating scientific evidence has supported its therapeutic use against hypertension, diabetes mellitus, cancer, cerebrovascular injury, and rheumatoid arthritis 6‒11 . Recent studies reported that the oral administration of boldine or its lower homolog norboldine in experimental animal models of rheumatoid arthritis or osteoporosis inhibited pathological bone resorption, and this inhibition was associated with the downregulation of the pro‐bone‐resorptive factor termed receptor activator of nuclear factor κB ligand (RANKL) and the upregulation of its soluble decoy osteoprotegerin (OPG) in the affected tissues 6,12 . Notably, the decreased bone resorption was associated with modulation of the imbalance between T‐helper type‐17 (Th17) and T‐regulatory (Treg) lymphocyte activity, which directly determines the decreased local RANKL/OPG ratio 12‒16 …”

Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome

“…The data from the Micro-CT and histomorphometry assay show that boldine conducts a protective effect for estrogen deficiency-induced bone loss in mice through inhibiting bone resorption, without affecting bone formation in vivo. Boldine also inhibits RANKL-induced osteoclast formation via regulating the AKT signaling pathway [ 103 ]. In addition, rheumatoid arthritis, a chronic autoimmune inflammatory disease, is associated with multiple metabolic alterations [ 104 ].…”