Dietary Isoquercetin Ameliorates Bone Loss via Restoration of the Gut Microbiota and Lipopolysaccharide-Triggered Inflammatory Status in Ovariectomy Mice

Osteoporosis is one of the skeletal degenerative diseases accompanied by bone loss and microstructure disruption. Given that the gut–bone signaling axis highly contributes to bone health, here, dietary isoquercetin (IQ) was shown to effectively improve postmenopausal osteoporosis (PMO) in an ovariectomy (OVX) mouse model through the modulation of the gut–bone cross-talk. An in vivo study showed that OVX induced striking disruption of the microbial community, subsequently causing gut leakage and gut barrier dysfunction. As a result, lipopolysaccharide (LPS)-triggered inflammatory cytokines released from the intestine to bone marrow were determined to be associated with bone loss in OVX mice. Long-term dietary IQ effectively improved microbial community and gut barrier function in the OVX mice and thus markedly improved bone loss and host inflammatory status by repressing the NF-κB signaling pathway. An in vitro study further revealed that IQ treatments dose-dependently inhibited LPS-induced inflammation and partly promoted the proliferation and differentiation of osteoblasts. These results provide new evidence that dietary IQ has the potential for osteoporosis treatment.