Ligustrum lucidum W.T. Aiton attenuates ovariectomy-induced bone loss by improving intestinal integrity and reducing NLRP3 inflammasome-related signaling

Objective To investigate whether Ligustrum lucidum W.T. Aiton ( L. lucidum , Nu Zhen Zi) attenuates ovariectomy (OVX)-induced bone loss and whether this effect is associated with preserved intestinal integrity and reduced inflammatory signaling. Methods Female C57BL/6J mice underwent OVX and were assigned to treatment groups ( n = 6), with estradiol valerate as a positive control. Mice received 4.9 g/(kg·d) oral L. lucidum for 14 weeks. Bone microarchitecture was assessed using micro-computed tomography and histology. Serum bone-turnover and inflammatory markers were measured using enzyme-linked immunosorbent assay. Intestinal morphology, barrier-associated features, tight-junction proteins, and NLR family pyrin domain-containing 3 (NLRP3) inflammasome-related protein expression in the intestine and bone marrow were evaluated by western blotting. Fecal butyrate concentrations were also measured by gas chromatography. Results Compared with mice in the OVX group, L. lucidum improved trabecular microarchitecture and attenuated OVX-induced bone loss (all P < .050), with corresponding changes in bone formation- and resorption-related markers (all P < .050). It also preserved intestinal mucosal architecture, increased goblet-cell abundance ( P < .001) and tight-junction protein expression (all P < .050), reduced circulating inflammatory mediators (all P < .010), and decreased NLRP3 inflammasome-related protein expression in intestinal tissue and bone marrow (all P < .010). Fecal butyrate concentrations ( P = .049) and GPR43 expression ( P = .015) were increased, suggesting a possible association between intestinal changes and skeletal protection. Conclusion L. lucidum attenuated OVX-induced bone loss in mice and was associated with preserved intestinal homeostasis and reduced inflammation and NLRP3 inflammasome-related protein expression. Further studies are needed to determine whether gut–bone axis modulation causally contributes to these effects.