Paederosidic acid (PA) has shown beneficial effects in anti-inflammatory studies, but it is unclear whether PA has positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of PA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, PA has demonstrated the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiments also show that PA significantly upregulates SOD2 expression while downregulating TNF-α expression (all, p < 0.05), leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density (all, p < 0.05), compared to the control group. The collective experimental findings strongly suggest that PA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation; hence mitigating bone loss in LPS-treated rat models.
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