Exploring Phacellanthus tubiflorus Sieb. et Zucc. (Orobanchaceae) as a Novel Herbal Therapeutic: Efficacy and Mechanisms in Alzheimer’s Disease

Alzheimer's disease (AD) is a major public health concern due to its widespread prevalence and limited effective treatments, highlighting the urgent need for innovative therapies.This study explores the therapeutic potential of Phacellanthus tubiflorus Sieb.et Zucc.(P.tubiflorus), a traditional Chinese medicine, as a potential source of neuroprotective agents.Systematically phytochemical analysis, employing UPLC-Q-TOF/MS, identified 1,536 compounds within P. tubiflorus including a notable abundance of Magnoloside D, Acteoside, and Cordycepin.Network pharmacology analyses, integrated with molecular docking studies, predicted a convergence between P. tubiflorus-derived compounds and central regulators of AD pathophysiology, notably SRC proto-oncogene (SRC), Tumor necrosis factor (TNF), AKT Serine/Threonine Kinase 1 (AKT1), Interleukin 1 Beta (IL-1B), and Interleukin 6 (IL-6).Enrichment analyses further implicated these interactions in key biological processes and signaling pathways, including neuroactive ligand-receptor interaction, cAMP signaling pathway, PI3k-Akt signaling pathway, all of which are dysregulated in AD.Importantly, these in silico predictions were substantiated by in vitro experiments using an A 1-42 -challenged SH-SY5Y cell model, demonstrating that Magnoloside D can attenuate neuroinflammatory responses and modulate post-translational phosphorylation.These findings provide mechanistic insights into the potential therapeutic effects of P. tubiflorus and highlights its promise as a novel avenue for AD intervention.