Punicalagin alleviates senile osteoporosis by inhibiting the senescence of bone mesenchymal stem cells via NRF2/HO-1 pathway.
Punicalagin may help reduce the aging-related decline in bone health by affecting bone mesenchymal stem cells, but further research is needed to confirm these effects in humans.
Where it sits
this study against the rest of the p21 (p021) corpusSummary and findings
This study investigated the effects of Punicalagin (PUN) on bone mesenchymal stem cells (BMSCs) and senile osteoporosis in aging rats. PUN was administered via intraperitoneal injection, and its impact on BMSC senescence and osteogenic differentiation was evaluated. The findings suggest a dose-dependent effect of PUN on BMSC senescence and osteogenesis.
Abstract
<h4>Background</h4>The senescence and abnormal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) are important causes of senile osteoporosis. Punicalagin (PUN), a natural polyphenol extracted from pomegranate peel, has demonstrated antioxidant activity in preclinical studies. This study aims to investigate the inhibitory effect of PUN on the aging of BMSCs and its therapeutic effect on senile osteoporosis.<h4>Methods</h4>The senescence of BMSCs were induced by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to assess the therapeutic effect of PUN. Intracellular reactive oxygen species measurements, the senescence β-galactosidase staining, western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were conducted to evaluate the senescence of BMSCs. Alkaline phosphatase staining, Alizarin red S staining, western blotting, and RT-qPCR were performed to assess the osteogenic differentiation of senescent BMSCs. Transcriptome sequencing was conducted to explore the underlying mechanism. In vivo, the therapeutic effects of PUN were investigated in aging rats with senile osteoporosis.<h4>Results</h4>PUN reversed the senescence of BMSCs and promoted the osteogenic differentiation in a dose-dependent manner. Mechanistically, PUN activated the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway to protect BMSCs from oxidative stress. In aging rats with senile osteoporosis, intraperitoneal injection of PUN can promote osteogenesis and reduce aging-related bone loss in vivo.<h4>Conclusion</h4>PUN alleviates senile osteoporosis by inhibiting the senescence of BMSCs via NRF2/HO-1 pathway, representing a candidate therapeutic drug for aging-related bone diseases.