Research Paper Volume 11, Issue 21 pp 9348—9368

Figure 8. Schematic diagram illustrating the underlying mechanism of D-gal and NaNO₂ on inducing senile osteoporosis in mice and the action of Fructus Ligustri Lucidi (FLL) on it. The injection of D-gal and NaNO₂ triggers gut dysbiosis and cognition impairment followed by upregulation of circulated TMAO levels through enhancement of FMO3 expression in the liver, which further results in compromised bone quality and cognition via an increase of oxidative stress, downregulation of Sirt6, and the activation of NF-κB/CatK signaling. Administration of FLL to aging mice exerts a bone protective effect by increasing Sirt6 expression and inhibiting the NF-κB/CatK signaling through the regulation of gut microbiota composition, which contributes to the downregulation of TMA and TMAO production, and the improvement of antioxidant activity, and the subsequent increase of Sirt6 expression. However, whether FLL could directly regulate TMAO production in this process still remains unexploited. The arrow sign (↑) indicates promoting. The stop sign (┴) indicates inhibiting. The green dotted line indicates unconfirmed action.