Nortropane alkaloids as pharmacological chaperones in the rescue of equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome through mitochondrial potentiation, endoplasmic reticulum stress mitigation and insulin resistance alleviation
Authors: Lynda Bourebaba, F. Bedjou, M. Röcken, K. Marycz
Journal: Stem Cell Research & Therapy
Summary
Equine metabolic syndrome impairs the function of adipose-derived mesenchymal stem cells (ASCs), limiting their therapeutic value despite their regenerative potential; Bourebaba and colleagues investigated whether calystegines—plant-derived polyhydroxylated alkaloids with established antioxidant and antidiabetic properties—could restore the viability and metabolic competence of EMS-affected ASCs. Using flow cytometry, confocal microscopy and quantitative RT-qPCR, they treated ASCs harvested from metabolic syndrome horses with varying calystegine concentrations and measured effects on cell survival, mitochondrial function, apoptotic pathways, endoplasmic reticulum stress and insulin-responsive gene expression. Treatment significantly improved cell viability and proliferation whilst reducing apoptosis through enhanced mitochondrial potentiation, suppression of ER stress, and upregulation of GLUT4 and insulin receptor substrate transcripts—suggesting improved insulin sensitivity at the cellular level. Additionally, calystegines functioned as pharmacological chaperones to promote autophagy, enabling cells to maintain homeostasis under metabolic stress. These findings suggest that nortropane alkaloid supplementation may offer a novel therapeutic avenue to improve cellular metabolic dynamics in EMS horses, potentially enhancing the efficacy of stem cell-based treatments and addressing the systemic metabolic dysfunction underlying the condition.
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Practical Takeaways
- •This in vitro research suggests nortropane alkaloids may have therapeutic potential for horses with metabolic syndrome, though clinical application requires further development and testing in living animals
- •The findings support exploring natural compounds with antioxidant and antidiabetic properties as adjunctive treatments for managing equine metabolic syndrome
- •Results are preliminary laboratory work; translation to clinical practice for EMS management remains years away and requires in vivo validation
Key Findings
- •Calystegines improved viability and proliferation of EMS-affected adipose-derived stem cells while reducing apoptosis
- •Treatment enhanced mitochondrial function and suppressed endoplasmic reticulum stress in metabolically compromised cells
- •Nortropane alkaloids upregulated GLUT4 and IRS transcripts, suggesting insulin sensitization effects
- •Calystegines promoted autophagy as a cellular survival mechanism in metabolic syndrome-affected stem cells