Polygalasaponin F alleviates cerebral ischemia-reperfusion injury through inhibiting mitophagy

Oct 24, 2025Metabolic brain disease

Polygalasaponin F may reduce brain damage after blood flow loss by blocking damaged mitochondria removal

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Abstract

Polygalasaponin F (PGSF) was found to reduce mitochondrial reactive oxygen species and apoptosis in models of cerebral ischemia-reperfusion injury.

Oxidative stress from ischemia-reperfusion injury may disrupt mitochondrial function.
Mitophagy plays a complex role, where both excessive and insufficient activation can worsen mitochondrial dysfunction.
PGSF improved mitochondrial function by preserving mitochondrial membrane potential and altering mitochondrial morphology.
Inhibition of mitophagy by PGSF was indicated by a reduced LC3II/LC3I ratio and decreased colocalization of LC3 with mitochondria.
Enhanced levels of TOM20 and p62 were observed with PGSF treatment, suggesting modulation of mitophagy.

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Neurological recovery after ischemic stroke (IS) remains clinically challenging, primarily due to cerebral ischemia-reperfusion injury (CIRI). Oxidative stress contributes to the pathogenesis of CIRI by causing reactive oxygen species excessive accumulation, which disrupts mitochondrial function. Mitophagy maintains mitochondrial function by eliminating damaged or dysfunctional mitochondria. Nevertheless, mitophagy exerts dual effects, either excessive or insufficient activation exacerbates mitochondrial dysfunction. Polygalasaponin F (PGSF), a natural triterpenoid saponin, has been demonstrated to regulate mitochondrial function. Therefore, in this study, we investigated whether PGSF protects against CIRI through inhibiting the mitophagy in vitro and in vivo. Results showed that PGSF attenuated apoptosis both in vivo and in vitro. Moreover, PGSF preserved mitochondrial membrane potential (MMP), reduced mitochondrial reactive oxygen species (mtROS), and ameliorated mitochondrial morphology to improve mitochondrial function in vitro. Furthermore, we revealed that PGSF ameliorates CIRI via modulation of mitophagy, evidenced by a reduced LC3II/LC3I ratio, decreased colocalization of LC3 with mitochondria, while enhancing the levels of TOM20 and p62. In conclusion, our findings imply that PGSF alleviates CIRI through inhibiting mitophagy and reducing apoptosis, demonstrating its therapeutic potential.

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Polygalasaponin F alleviates cerebral ischemia-reperfusion injury through inhibiting mitophagy

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