Nuciferine reduces ovariectomy-induced bone loss in rats by activating autophagy
The lotus leaf alkaloid promoted bone formation and osteogenic differentiation in ovariectomized rats through the TFEB autophagy-lysosomal pathway.
In a study using six-month-old female ovariectomized rats, researchers tested whether nuciferine protects against bone loss caused by estrogen deficiency. The team administered the compound by oral gavage for 12 weeks with ten rats per group, while also testing rat bone marrow mesenchymal stem cells in vitro. Nuciferine significantly increased bone mineral density and improved microarchitecture in the rats. It elevated serum markers of bone formation, including BALP, PINP, and osteocalcin, and reduced the resorption marker TRAP. Nuciferine also restored osterix and TFEB expression, increased the LC3-II/LC3-I ratio, and lowered p62, signaling enhanced autophagy. In cultured stem cells, nuciferine promoted osteogenic differentiation and TFEB nuclear translocation, which were both suppressed by TFEB silencing.
Why it matters
Age-related estrogen decline triggers postmenopausal osteoporosis by impairing bone formation and turnover. Targeting autophagy-lysosomal signaling through TFEB offers a biological mechanism to preserve bone density during reproductive aging.
Caveats
The research was conducted exclusively in a rat model with ten animals per group and in cultured rat stem cells. It remains unknown whether nuciferine will have safe, comparable effects on bone metabolism in humans.
- Nuciferine
- Disabled macroautophagy
- Stem cell exhaustion
- Autophagy
- Map1lc3b
- Sp7
- Sqstm1
- Tfeb
- Osteoporosis
- Postmenopausal osteoporosis
- Bone mineral density
- Bone-specific alkaline phosphatase
The paper
Nuciferine Ameliorates Ovariectomy-Induced Bone Loss via TFEB-Mediated Autophagy-Lysosomal Pathway
Shi B, Gao Z, Chen SY et al.
Biomolecules · 21 Sep 2026