BDE-209 exposure induced male reproductive toxicity with sperm quality decline. However, the role of autophagy in this was unclear. The purpose was to evaluate the protective effect and its potential mechanism of trehalose (Tre, autophagy inducer) on reproductive damage during spermiogenesis induced by BDE-209. We used 2% w/v Tre and 75 mg/kg/d BDE-209 cotreated mice for 42 days. GC-2 spd cells were cotreated with Tre, chloroquine (CQ, inhibition of autophagic flux), compound C (CC, AMPK inhibitor), and BDE-209. Tre intake significantly recovered decrease in sexual organ ratio and poor sperm quality in BDE-209-exposed mice. Supplementation with Tre rescued sperm head malformation by improving aberrant histone-protamine exchange in BDE-209-exposed mice. However, Tre intake couldn't restore the acrosome biogenesis. In addition, Tre supplementation improved testicular damage induced by BDE-209. BDE-209 blocked autophagic flux with increased P62 and LC3BⅡ/Ⅰ levels. Mechanistically, CQ treatment aggravated elevation of P62 and LC3BⅡ/Ⅰ levels induced by BDE-209, otherwise, CC and Tre treatments inhibited the rise in p-AMPK, p-ULK1, P62 and LC3BⅡ/Ⅰ levels induced by BDE-209. Tre supplementation improved reproductive injury in BDE-209-exposed mice by regulating autophagic flow via AMPK-ULK1 signaling pathways, which providing a new theoretical basis and possible therapeutic targets for male reproductive toxicity.
Alzheimer's disease (AD) pathology involves amyloid-beta (Aβ) accumulation and neuronal toxicity, highlighting the need for therapeutic strategies that can both inhibit Aβ aggregation and promote pathogenic protein clearance. In this study, we identified Gaultheria leucocarpa as a medicinal plant with promising neuroprotective potential. Thioflavin T (ThT) fluorescence screening revealed that extracts from G. leucocarpa (GE), particularly the petroleum ether fraction of G. leucocarpa extract (GPF), effectively inhibited Aβ fibril formation in vitro . In cell-based assays, GPF significantly improved the viability of PC-12 cells exposed to Aβ peptides and fibrils, indicating protection against Aβ-induced cytotoxicity. Furthermore, GPF enhanced mitophagic activity, as demonstrated by increased GFP-LC3 puncta, elevated LC3-II/I ratio, and colocalization of GFP-LC3 with MitoTracker Red. Mechanistic investigations showed that GPF activates mitophagy via the AMPK/ULK1 pathway and inhibits the PI3K/AKT/mTOR pathway, resulting in enhanced degradation of APP and Tau proteins. In Caenorhabditis elegans models relevant to AD, GPF administration led to reduced Aβ deposits, delayed paralysis onset, improved food perception, and decreased oxidative stress. Collectively, these findings demonstrate that GPF exerts dual actions by inhibiting Aβ fibrillization and promoting mitophagy-mediated degradation of pathogenic proteins. The active ingredients identified from GPF extracts represent promising leads for the development of novel neuroprotective agents targeting AD-related pathological mechanisms.
危险品化学品经营许可证（带存储）