Research Paper Volume 11, Issue 21 pp 9348—9368
Fructus Ligustri Lucidi preserves bone quality through the regulation of gut microbiota diversity, oxidative stress, TMAO and Sirt6 levels in aging mice
- 1 Diabetes Research Centre, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
- 2 The First Affiliated Hospital of He’nan University of Traditional Chinese Medicine, Zhengzhou 45000, China
- 3 The Scientific Research Centre, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
- 4 Department of Histology, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China
- 5 Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russia
- 6 Faculty of Dentistry, University of British Columbia, Vancouver BC V6T 1Z3, Canada
Received: May 12, 2019 Accepted: October 14, 2019 Published: November 12, 2019
https://doi.org/10.18632/aging.102376How to Cite
Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Gut dysbiosis and oxidative stress may trigger senile osteoporosis. Fructus Ligustri Lucidi (FLL) has bone-preserving properties and affects the intestinal microecology. However, the mechanism of the anti-osteoporotic effect of FLL and its link to the gut microbiota remains to be elucidated. Here, we demonstrated that sustained exposure of ICR mice to D-galactose / sodium nitrite for 90 days causes aging-related osteoporosis and reduced cognitive performance. The aging phenotype is also characterized by increased oxidative stress in serum. This is likely triggered by abnormal changes in the gut microbiota population of Bifidobacterium and the ratio of Firmicutes/ Bacteroidetes that resulted in increased levels of flavin-containing monooxygenase-3 and trimethylamine-N-oxide (TMAO). Moreover, the increased oxidative stress further accelerated aging by increasing tumor necrosis factor-α levels in serum and reducing Sirtuin 6 (Sirt6) expression in long bones, which prompted nuclear factor kappa-B acetylation as well as over-expression and activation of cathepsin K. FLL-treated aging mice revealed a non-osteoporotic bone phenotype and an improvement on the cognitive function. The mechanism underlying these effects may be linked to the regulation of gut microbiota diversity, antioxidant activity, and the levels of TMAO and Sirt6. FLL may represent a potential source for identifying anti-senile osteoporotic drug candidates.