Mechanistic insights into phlorizin’s multi-target potential in Alzheimer’s disease: A network pharmacological and in-vivo study

Title : Mechanistic insights into phlorizin’s multi-target potential in Alzheimer’s disease: A network pharmacological and in-vivo study

Abstract:

This study investigated the therapeutic potential of phlorizin for Alzheimer's disease (AD) using an integrated computational and experimental pharmacology approach. The research aimed to determine how phlorizin modulates key AD biomarkers, including AChE, Bcl-2, caspase-3, and GSH. The initial computational phase involved using several databases and tools to predict and analyze phlorizin's interactions. DisGeNET and SwissTargetPrediction identified a strong association between phlorizin's predicted targets and AD, with important proteins like TNF, AKT1, AChE, Bcl-2, and caspase-3 being highlighted. Gene ontology enrichment analysis confirmed the compound's potential involvement in amyloid-beta clearance, regulation of neuron death, and oxidative stress responses. Molecular docking and subsequent molecular dynamics simulations demonstrated that phlorizin forms stable and favorable bindings with AChE, Bcl-2, and caspase-3. Experimentally, AD was induced in male Wistar rats with aluminum chloride (AlCl3?). Phlorizin treatment in these rats significantly alleviated AD-like symptoms. Behavioral tests showed marked improvements in cognition, while biochemical analysis confirmed the neuroprotective effects. Phlorizin successfully restored levels of GSH and AChE, and it modulated apoptosis by upregulating the anti-apoptotic protein Bcl-2 and downregulating the pro-apoptotic protein caspase-3. In conclusion, phlorizin demonstrated significant neuroprotective effects in AD models by improving cognitive function, reducing oxidative stress, and modulating apoptosis-related biomarkers, validating its potential as a therapeutic agent.

Biography:

Dr. Nilay Solanki is an Associate Professor at Ramanbhai Patel College of Pharmacy, CHARUSAT Campus, India. He had completed his Ph.D. in 2016 from CHARUSAT University and his post-graduation in 2007 from LMCP, Gujarat University. Dr. Nilay has over 16 years of academic, research, administrative and leadership experience in the field of Pharmacology. His expertise is in the area of preclinical animal model development neurodegenerative disease, diabetes, cancer, NAFLD, obesity. Dr. Nilay has several collaborations with multispecialty hospitals in Gujarat, where major clinical studies were conducted. Dr. Nilay has published over 45 research, review papers & book chapters in Scopus and Web of Science-listed high-impact factor journals. He has also completed multiple consultancy projects. He had received various awards at national conferences and CHARUSAT research paper awards for five consecutive years. He had also provided his services as a resource person at national and international conferences in India. He is also associated as a reviewer and editor in national and international journals.