{"paper_id":"7d9db7a1-cefc-464d-90a2-40e6ecfc1160","body_text":"Multiple articles converge on the Nrf2/GPX4 axis as a critical defense against ferroptosis, an iron-dependent, lipid peroxidation-driven cell death pathway implicated in AD, PD, and other neurodegenerative disorders.  Hong et al.  demonstrate that culinary spices (curcumin, allicin, cinnamaldehyde, capsaicin, and piperine) function as natural ferroptosis inhibitors through electrophilic modification of Keap1, releasing Nrf2 to activate GPX4. Curcumin additionally chelates iron, while piperine co-administration increases curcumin bioavailability up to 2,000%. Complementing this,  Zhang L. et al.  review how herbal compounds (baicalein, curcumin, astragaloside IV) modulate neuroinflammation through TLR4/NF-κB, NLRP3 inflammasome, and JAK-STAT pathways, while promoting microglial M1-to-M2 and astrocytic A1-to-A2 phenotypic shifts.  Lu et al.  detail quercetin's multi-target cerebrovascular protection via Nrf2/HO-1 activation, Wnt/β-catenin-mediated BBB stabilization, and BDNF-TrkB-PI3K/Akt anti-apoptosis, while candidly acknowledging the “delivery gap” (oral bioavailability < 6%).  Zhong et al.  review the antidepressant effects of culinary spices, emphasizing “food synergy”—curcumin with piperine—and multi-pathway actions including monoamine regulation, HPA axis inhibition, and BDNF activation.  Tang et al.  experimentally validate Danggui Shaoyao San, demonstrating that this medicinal-food formula exerts antidepressant effects through coordinated TLR4/NF-κB, JAK2/STAT3, and AKT-GSK3β modulation, promoting hippocampal neurogenesis.  Li L. et al.  employ machine learning and network pharmacology to identify daidzein from Pueraria as an antidepressant compound targeting CDK5R1 (binding energy −8.3 kcal/mol).  Wang Q. et al.  show that MgSO4 supplementation alleviates CMS-induced depression by suppressing IKK/NF-κB and NLRP3 inflammasome signaling, reducing microglial activation, and repairing BBB integrity—linking mineral nutrition directly to neuroinflammation control.  Liu G. et al.  bridge neuroimaging with nutrition, demonstrating that recurrent MDD patients show bilateral amygdala dysfunction and reduced BDNF levels, with BDNF positively correlating with amygdala functional connectivity.\n\nWang Y. et al.  use quantitative proteomics in 5 × FAD mice to show that Modified Sanjia Powder (containing six medicine-food homology components) downregulates ACSL4, a key regulator linking lipid metabolism to ferroptosis, reduces Aβ plaques and tau pathology, and improves cognitive function.  Ye et al.  identify PFKFB3 as a therapeutic target for Pueraria in AD, showing that daidzein and formononetin bind PFKFB3 (energy < −8.0 kcal/mol) and reverse Aβ 1 − 42 -induced cognitive deficits.  Wang M. et al.  synthesize evidence for medicine-food homology compounds in PD, detailing PD-specific oxidative stress (dopamine auto-oxidation, neuromelanin-iron catalysis) and proposing a quality standardization framework including function-linked release assays (Nrf2/ARE reporter, iPSC-derived TH +  neuron protection).\n\nJin et al.  comprehensively review phytochemical strategies for BBB protection across VCI etiologies (stroke, hypertension, diabetes, and aging), identifying five core mechanisms: tight junction restoration, MMP inhibition, neuroinflammation mitigation, oxidative stress alleviation, and gut-brain axis modulation.  Yu et al.  apply multi-omics integration to Xianyu Capsule, revealing a “gut microbiota-glycerophospholipid metabolism-neuroinflammation” axis in epilepsy treatment.\n\nZhang Z. et al.  addressed persistent neuropsychiatric symptoms in thyroid disease by linking them to specific dietary components and their underlying mechanisms: selenium through its cofactor role in deiodinases, iodine via its characteristic U-shaped risk curve, the Mediterranean diet by reducing neuroinflammation and oxidative stress, and cruciferous vegetables by the trade-off between neuroprotective sulforaphane and goitrogenic compounds.  Li W. et al.  systematically review the clinical evidence for plant food-derived nutrients in preventing CIPN. This includes a landmark Level I trial for curcumin, alongside promising findings for green tea catechins (notably EGCG), vitamin E, omega-3 fatty acids, carotenoids, and anthocyanins.  Liu X. et al.  review plant-derived compounds for women's reproductive health, covering polyphenols (EGCG, curcumin, and resveratrol) and phytoestrogens (isoflavones, lignans). They detail mechanisms targeting the HPO axis and neuroinflammation (NF-κB, Nrf2), applications in menopausal cognition, PMS, and endometriosis, as well as formulation strategies for improved bioavailability.\n\nThe articles in this Research Topic collectively demonstrate that plant-derived nutrients are mechanistically sophisticated, multi-target neuroprotective agents converging on Nrf2/ARE, NF-κB/NLRP3, BDNF-TrkB, and AKT-GSK3β pathways. While bioavailability bottlenecks and the need for large-scale clinical trials remain challenges, the integration of traditional dietary wisdom with modern formulation science and precision nutrition offers a transformative roadmap for neurological health.","source_license":"CC-BY-4.0","license_restricted":false}