Polygonatum sibiricum polysaccharide attenuates BMSC senescence by inhibiting NCOA4-mediated ferritinophagy.
4 affiliations
- 1School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China.
- 2The First Hospital of Hunan University of Chinese Medicine, Changsha, China.
- 3Department of Radiology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China.
- 4Medicine School, Hunan University of Chinese Medicine, Changsha, China.
Abstract
Context
BMSC senescence is associated with osteoporosis progression. Polygonatum sibiricum polysaccharide (PSP) shows potential anti-senescence activity, but its effects on bone marrow mesenchymal stem cells (BMSCs) remain unclear.Objective
To investigate the protective effects and molecular mechanisms of PSP against tert-butyl hydroperoxide (TBH)-induced senescence in BMSCs.Materials and methods
Senescence was induced in primary rat BMSCs with TBH, followed by PSP intervention. Viability was assessed using the Cell Counting Kit-8 assay, while senescence-associated β-galactosidase, alkaline phosphatase, and Oil Red O staining assessed senescence and osteogenic/adipogenic differentiation. Ferritinophagy-associated proteins (NCOA4, FTH1, and LC3) and intracellular Fe²⁺ were quantified using western blot, immunofluorescence, and FerroOrange staining. Mitochondrial function was evaluated using MitoSOX and JC-1 assays and ATP quantification. Cytosolic mtDNA accumulation and the cGAS-STING pathway were assessed using immunofluorescence colocalization, quantitative polymerase chain reaction, and Western blotting. NCOA4 involvement was examined using an NCOA4-overexpressing lentiviral vector.Results
PSP concentration-dependently attenuated TBH-induced senescence phenotypes in BMSCs, partially restored osteogenic differentiation, and reduced adipogenic differentiation. PSP downregulated NCOA4 expression, attenuating ferritinophagy-associated changes and intracellular Fe²⁺ accumulation. Reduced Fe²⁺ accumulation preserved mitochondrial membrane potential, reduced mitochondrial reactive oxygen species generation, and reduced cytosolic mtDNA accumulation, alongside attenuated cGAS-STING signaling. Lentiviral overexpression of NCOA4 attenuated the protective effects of PSP on mitochondrial homeostasis and cGAS-STING pathway suppression.Discussion and conclusions
PSP may attenuate BMSC senescence by suppressing NCOA4-mediated ferritinophagy, thereby preserving mitochondrial homeostasis and inhibiting cGAS-STING signaling. These findings provide a rationale for further investigation of PSP as a potential therapeutic strategy for osteoporosis-associated BMSC dysfunction.
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BibTeX
@article{dai2026polygonatum,
title = {{Polygonatum sibiricum polysaccharide attenuates BMSC senescence by inhibiting NCOA4-mediated ferritinophagy.}},
author = {Xing Dai and Linhua Wang and Yu Sun and Zhuo He and Xiaolin Du and Xiaoming Lei and Shaofeng Yang and Muzhe Li},
journal = {Pharmaceutical biology},
year = {2026},
month = oct,
doi = {10.1080/13880209.2026.2746259},
url = {https://europepmc.org/article/MED/42872690},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Polygonatum sibiricum polysaccharide attenuates BMSC senescence by inhibiting NCOA4-mediated ferritinophagy.
AU - Xing Dai
AU - Linhua Wang
AU - Yu Sun
AU - Zhuo He
AU - Xiaolin Du
AU - Xiaoming Lei
AU - Shaofeng Yang
AU - Muzhe Li
PY - 2026
DA - 2026/10/14
JO - Pharmaceutical biology
DO - 10.1080/13880209.2026.2746259
UR - https://europepmc.org/article/MED/42872690
AB - Context BMSC senescence is associated with osteoporosis progression. Polygonatum sibiricum polysaccharide (PSP) shows potential anti-senescence activity, but its effects on bone marrow mesenchymal stem cells (BMSCs) remain unclear.Objective To investigate the protective effects and molecular mechanisms of PSP against tert-butyl hydroperoxide (TBH)-induced senescence in BMSCs.Materials and methods Senescence was induced in primary rat BMSCs with TBH, followed by PSP intervention. Viability was assessed using the Cell Counting Kit-8 assay, while senescence-associated β-galactosidase, alkaline phosphatase, and Oil Red O staining assessed senescence and osteogenic/adipogenic differentiation. Ferritinophagy-associated proteins (NCOA4, FTH1, and LC3) and intracellular Fe²⁺ were quantified using western blot, immunofluorescence, and FerroOrange staining. Mitochondrial function was evaluated using MitoSOX and JC-1 assays and ATP quantification. Cytosolic mtDNA accumulation and the cGAS-STING pathway were assessed using immunofluorescence colocalization, quantitative polymerase chain reaction, and Western blotting. NCOA4 involvement was examined using an NCOA4-overexpressing lentiviral vector.Results PSP concentration-dependently attenuated TBH-induced senescence phenotypes in BMSCs, partially restored osteogenic differentiation, and reduced adipogenic differentiation. PSP downregulated NCOA4 expression, attenuating ferritinophagy-associated changes and intracellular Fe²⁺ accumulation. Reduced Fe²⁺ accumulation preserved mitochondrial membrane potential, reduced mitochondrial reactive oxygen species generation, and reduced cytosolic mtDNA accumulation, alongside attenuated cGAS-STING signaling. Lentiviral overexpression of NCOA4 attenuated the protective effects of PSP on mitochondrial homeostasis and cGAS-STING pathway suppression.Discussion and conclusions PSP may attenuate BMSC senescence by suppressing NCOA4-mediated ferritinophagy, thereby preserving mitochondrial homeostasis and inhibiting cGAS-STING signaling. These findings provide a rationale for further investigation of PSP as a potential therapeutic strategy for osteoporosis-associated BMSC dysfunction.
SN - 1388-0209
SN - 1744-5116
ER -