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

Herbal self-assembled nanoplatforms (H-SANs) represent an emerging strategy in herbal nanomedicine by integrating the intrinsic bioactivity of phytochemica

Non‑small cell lung cancer (NSCLC) remains a leading cause of cancer‑associated mortality and urgently requires new therapeutic agents. In the present study, phenotypic screening of natural herbal extracts was performed, identifying Disporum cantoniense extract as a selective inhibitor of NSCLC cell viability. Bioactivity‑guided fractionation further revealed that the petroleum ether fraction (DPF) was the major active fraction. DPF suppressed the viability, proliferation, colony formation, migration and invasion of A549 and H1299 cells while exhibiting weaker cytotoxicity toward BEAS‑2B cells. In addition, DPF increased propidium iodide (PI)‑positive cell death and lactate dehydrogenase release in NSCLC cells, indicating that DPF‑induced viability loss was accompanied by membrane‑damaging cytotoxicity. Transcriptomic and network pharmacology analyses indicated significant enrichment of autophagy‑, apoptosis‑, AMPK‑, mTOR‑, and MAPK‑associated pathways. Mechanistically, DPF increased LC3‑II accumulation, promoted green fluorescent protein‑LC3 puncta formation and autophagic flux, and activated the AMPK/mTOR/unc‑51 like autophagy activating kinase 1 and MEK/ERK signaling pathways. DPF also induced apoptosis, as demonstrated by increased Annexin V positivity, elevated cleaved caspase‑3 and Bax expression, reduced Bcl‑2 expression, and reduced cytotoxicity in Bax‑Bak double‑knockout mouse embryonic fibroblast (MEF) cells. Notably, pharmacological inhibition of autophagy or its upstream regulators attenuated DPF‑induced cytotoxicity. In addition, autophagy‑deficient Atg7^‑/‑ MEF cells exhibited reduced DPF‑induced PI‑positive cell death, loss of cell viability, and caspase‑3 activation, further supporting the involvement of Atg7‑dependent autophagy in DPF‑induced apoptosis. In a xenograft model, DPF significantly inhibited tumor growth and increased apoptosis‑ and autophagy‑associated markers in tumor tissues without evident systemic toxicity. Collectively, these findings identify DPF as a principal anti‑NSCLC fraction of Disporum cantoniense and suggest that it suppresses NSCLC progression through AMPK/mTOR/unc‑51 like autophagy activating kinase 1‑ and MEK/ERK‑mediated autophagy‑dependent apoptosis.

Ferroptosis, an iron‑dependent and lipid peroxidation‑driven form of regulated cell death, has emerged as a key contributor to neuronal degeneration in protein misfolding disorders. However, how cellular energy metabolism modulates ferroptotic susceptibility in neurodegenerative proteinopathies remains incompletely defined. The present study investigated whether the previously described energy stress‑AMP-activated protein kinase (AMPK)‑acetyl‑CoA carboxylase (ACC) ferroptosis checkpoint operates in disease‑relevant neuronal proteinopathy models. Pharmacological and genetic interventions, cell viability assays, lipid peroxidation measurements, western blotting, RNA interference, and behavioral analyses were performed in SH‑SY5Y cells, transgenic Caenorhabditis elegans (C. elegans), and 3xTg‑AD mice. In SH‑SY5Y cells, glucose deprivation, 2‑deoxy‑D‑glucose (2DG), or 5‑aminoimidazole‑4‑carboxamide ribonucleoside reduced ferroptotic cell death induced by erastin or RSL3 and attenuated ferroptosis‑associated neuronal injury induced by amyloid precursor protein, α‑synuclein A53T, and polyQ74. This protection was associated with AMPK activation, ACC1 phosphorylation, reduced lipid peroxidation, sensitivity to ferroptosis inhibition, glutathione peroxidase 4 restoration, and acyl‑CoA synthetase long‑chain family member 4 suppression. AMPK inhibition or knockdown weakened the protection conferred by glucose deprivation, while aak‑2 RNAi attenuated the protective effects of 2DG in C. elegans, supporting a substantial contribution of AMPK‑ACC1‑associated signaling to ferroptosis suppression under energy stress. Consistently, 2DG or liproxstatin‑1 reduced ferroptosis‑associated oxidative damage and improved behavioral or cognitive deficits in transgenic C. elegans and 3xTg‑AD mice. These findings extend the established AMPK‑ACC ferroptosis checkpoint to neurodegenerative proteinopathy models and support energy stress‑associated AMPK‑ACC1 signaling as an important metabolic defense mechanism against ferroptosis‑related neuronal injury.