Senegenin alleviates Aβ1-42 induced cell damage through triggering mitophagy
Yihong Tian1, Yongmei Qi1, Hui Cai2
1Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.
Journal of Ethnopharmacology
|May 31, 2022
Summary
Senegenin (SEN) protects neurons from amyloid-beta damage by activating mitophagy, a process that clears damaged mitochondria via the PINK1/Parkin pathway. This study confirms SEN
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Senegenin (SEN), derived from Polygala tenuifolia Willd., shows neuroprotective potential.
- Alzheimer's disease (AD) involves amyloid-beta (Aβ) induced mitochondrial damage and oxidative stress.
- Mitophagy, mediated by the PINK1/Parkin pathway, removes damaged mitochondria and is crucial in neuronal health.
Purpose of the Study:
- To investigate SEN's effects on Aβ-induced neuronal damage.
- To determine if SEN activates mitophagy.
- To elucidate mitophagy's role in SEN's neuroprotective mechanism.
Main Methods:
- Established an in vitro Aβ1-42-induced neuronal damage model using HT22 cells.
- Assessed cell viability, LDH release, ROS levels, mitochondrial membrane potential (MMP), and apoptosis.
- Utilized transmission electron microscopy, immunofluorescence, and immunoblotting to detect mitophagy markers and pathway activation.
Main Results:
- Aβ1-42 significantly damaged HT22 cells, reducing viability and MMP, and increasing ROS and apoptosis.
- SEN treatment dose-dependently protected cells against Aβ1-42-induced damage.
- SEN activated mitophagy by upregulating PINK1/Parkin pathway components and LC3 conversion, evidenced by increased mitophagosomes and decreased p62 and HSP60.
- Inhibition of mitophagy with CsA abolished SEN's protective effects.
Conclusions:
- SEN alleviates Aβ1-42-induced neuronal damage by activating PINK1/Parkin-mediated mitophagy.
- Findings support the traditional use of P. tenuifolia for anti-aging and anti-neurodegenerative effects.
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