Cheng Chang
Key Laboratory of Forest Plant Ecology, Engineering Research Center of Forest Bio-preparation, Ministry of Education, The College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China.
Wenjie Yu
Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Provincial Key Laboratory of Research and Development on Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou 571199, China
Yuguang Fan
Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Provincial Key Laboratory of Research and Development on Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou 571199, China;
Fengkun Cai
Jilin Provincial Joint Key Laboratory of Changbai Mountain Biocoenosis and Biodiversity, Changbai Mountain Academy of Sciences, Antu 133613, China.
Shen Lu
Jilin Provincial Joint Key Laboratory of Changbai Mountain Biocoenosis and Biodiversity, Changbai Mountain Academy of Sciences, Antu 133613, China.
Jiao Jiao
Key Laboratory of Forest Plant Ecology, Engineering Research Center of Forest Bio-preparation, Ministry of Education, The College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China
Zhiguo Liu
Key Laboratory of Forest Plant Ecology, Engineering Research Center of Forest Bio-preparation, Ministry of Education, The College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China.
Chenlu Wang
The College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
Yujie Fu
The College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
Abstract
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 Aβ1–42-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.
