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.

Pancreatic cancer remains a formidable challenge in oncology due to its aggressive nature and limited treatment options. In this study, we investigate the potential therapeutic efficacy of elaiophylin, a novel compound, in targeting BxPC-3 and PANC-1 pancreatic cancer cells. We comprehensively explore elaiophylin’s impact on apoptosis induction, proliferation inhibition, migration suppression, invasion attenuation, and angiogenesis inhibition, key processes contributing to cancer progression and metastasis. The results demonstrate that elaiophylin exerts potent pro-apoptotic effects, inducing a substantial increase in apoptotic cells. Additionally, elaiophylin significantly inhibits proliferation, migration, and invasion of BxPC-3 and PANC-1 cells. Furthermore, elaiophylin exhibits remarkable anti-angiogenic activity, effectively disrupting tube formation in HUVECs. Moreover, elaiophylin significantly inhibits the Wnt/β-Catenin signaling pathway. Our findings collectively demonstrate the multifaceted potential of elaiophylin as a promising therapeutic agent against pancreatic cancer via inhibition of the Wnt/β-Catenin signaling pathway. By targeting diverse cellular processes crucial for cancer progression, elaiophylin emerges as a prospective candidate for future targeted therapies. Further investigation of the in vivo efficacy of elaiophylin is warranted, potentially paving the way for novel and effective treatment approaches in pancreatic cancer management.

Background: Alzheimer’s disease (AD) is characterized by Tau aggregation, mitochondrial dysfunction, and oxidative stress, yet effective interventions targeting these pathological cascades remain limited. Therapeutic strategies that enhance autophagic and mitophagic clearance, attenuate Tau toxicity, and restore mitochondrial homeostasis are crucial for AD management. Methods: This study investigated the neuroprotective effects of Pulsatilla chinensis extract (PCE) in SH-SY5Y neuronal cells and Caenorhabditis elegans ( C. elegans ) models of Tauopathy. Autophagic flux was evaluated by GFP-LC3 puncta formation, LC3-II conversion, and p62 degradation. Mitochondrial function was assessed through reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and ultrastructural analysis. The roles of autophagy and mitophagy were examined using 3-methyladenine (3-MA) and the Parkin inhibitor AC220. In C. elegans , locomotion, Tau aggregation, oxidative stress, and mitophagosome formation were assessed, and pink-1 knockdown was used to confirm mitophagy dependence. Results: PCE significantly enhanced autophagic flux, decreased total and phosphorylated Tau (p-Tau Ser404) levels, and improved neuronal viability. It significantly reduced ROS accumulation, maintained MMP, and preserved mitochondrial morphology under both Tau overexpression and H ₂ O ₂ -induced oxidative stress. Inhibition of autophagy or Parkin-mediated mitophagy negated these protective effects. In C. elegans , PCE ameliorated neuromuscular dysfunction, suppressed Tau inclusions, and reduced oxidative injury, while the loss of pink-1 abolished its benefits, underscoring the critical role of mitophagy. Conclusion: PCE exerts potent neuroprotective effects by promoting mitophagy, reducing Tau phosphorylation and aggregation, and restoring mitochondrial integrity. These findings reveal a novel mechanism linking mitochondrial quality control with Tau proteostasis and highlight PCE as a promising natural therapeutic candidate for AD. Graphical