IN SILICO INVESTIGATION OF PIPER CHABA HUNTER PHYTOCHEMICALS FOR MODULATING KEY PROTEIN TARGETS IN ALZHEIMER'S DISEASE

• Dr. Nireya K. Dassun

  Department of Bioinformatics, University of Dhaka, Dhaka, Bangladesh

  Author

• Dr. Feliks M. Orenzi

  Computational Biology Unit, Institute of Neurodegenerative Research, Ljubljana, Slovenia

  Author

• Prof. Sarvith N. Thevakaran

  Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, India

  Author

Alzheimer's disease (AD) is a relentless neurodegenerative condition that slowly erodes memory and cognitive function, leaving a profound impact on patients and their families. The complexity of its causes, rooted in a tangle of genetic and environmental factors, has so far stymied efforts to find a cure. Current treatments offer only temporary relief from symptoms, creating a pressing need for new therapeutic strategies that can tackle the disease's underlying mechanisms. In the search for new solutions, we turn to nature's vast apothecary. Medicinal plants like Piper chaba Hunter, a traditional spice and remedy, offer a rich source of bioactive compounds and have long been noted for their anti-inflammatory properties—a key feature in the fight against AD. This study embarks on a computational journey to unlock the therapeutic secrets of Piper chaba. Using a powerful suite of in silico tools, we aimed to identify its key bioactive compounds and map out how they might work together to combat the molecular machinery of Alzheimer's disease. Our investigation began by compiling a library of phytochemicals from Piper chaba and putting them through a rigorous virtual screening to assess their drug-like potential. We predicted their protein targets and cross-referenced them with AD-related gene databases to build a network of interactions, revealing the most influential protein "hubs." We then used high-precision molecular docking, extended 100-nanosecond molecular dynamics (MD) simulations, and Density Functional Theory (DFT) to investigate the binding and stability of these compounds with their targets. Our results show that compounds from Piper chaba, particularly piperine, have excellent drug-like qualities and are predicted to cross the blood-brain barrier. Our network analysis pointed to three key protein hubs—PTGS2 (COX-2), PLA2G4A, and CYP2C19—that are central to the neuroinflammatory and metabolic chaos of AD. The docking and MD simulations confirmed that lead compounds form strong, stable complexes with these proteins. This computational exploration strongly suggests that the humble Piper chaba plant holds a sophisticated arsenal of compounds that can wage a multi-pronged assault on Alzheimer's disease, representing promising candidates for a new generation of multi-target AD therapies.

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