Investigation of Potential Mechanisms of Yerba Santa Compounds Against Alzheimer’s Disease
- 1Department of Chemical and Biological Engineering, Villanova University, Villanova, PA 19085, USA
- 2Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which chronic neuroinflammation plays a central role in disease initiation and progression. Yerba Santa (Eriodictyon spp.) is a medicinal plant with reported anti-inflammatory and neuroprotective properties, although its molecular mechanisms remain poorly understood. This study investigated whether chemically characterized Yerba Santa compounds show predicted docking interactions with neuroinflammation-related protein targets implicated in AD. Thirty-six ligand structures, representing 30 mass spectrometry peak assignments, were docked against 30 neuroinflammation-related proteins using the MolSoft ICM molecular docking platform. To improve reproducibility, each ligand–target pair was evaluated by replicated docking simulations followed by statistical analysis, with apo and holo targets evaluated against separate statistical references and expanded docking where applicable. Under the apo −25 kcal/mol screening reference, 11 ligand–target pairs were retained after BH-FDR correction and expanded docking for the apo C1r-C1s (PDB:6F39). Separately, 23 holo ligand–target pairs were retained after comparison with their corresponding redocked native-ligand references: Complement C1q (PDB:2JG8), GABA-A receptor α1β2γ2 (PDB:6D6U), and NLRP3 (PDB:7PZC). The pairs retained under these separate criteria involved multiple Yerba Santa compounds, predominantly flavonoids, while Rosmarinic acid (L21) was retained for both Complement C1q (PDB:2JG8) and NLRP3 (PDB:7PZC). These findings support a selective predicted multi-target interaction profile for Yerba Santa compounds and identify complement signaling, GABA-A receptor-associated neurotransmission, and NLRP3 inflammasome signaling as testable pathways for future experimental studies of neuroinflammation in AD.
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BibTeX
@article{navarro2026investigation,
title = {{Investigation of Potential Mechanisms of Yerba Santa Compounds Against Alzheimer’s Disease}},
author = {Magally Arevalo Navarro and Charles Alfano and Jonathan Cross and Tianhua Zhai and Li Shen and Zuyi Huang},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203757},
url = {https://www.mdpi.com/1420-3049/31/20/3757},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Investigation of Potential Mechanisms of Yerba Santa Compounds Against Alzheimer’s Disease
AU - Magally Arevalo Navarro
AU - Charles Alfano
AU - Jonathan Cross
AU - Tianhua Zhai
AU - Li Shen
AU - Zuyi Huang
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203757
UR - https://www.mdpi.com/1420-3049/31/20/3757
AB - Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which chronic neuroinflammation plays a central role in disease initiation and progression. Yerba Santa (Eriodictyon spp.) is a medicinal plant with reported anti-inflammatory and neuroprotective properties, although its molecular mechanisms remain poorly understood. This study investigated whether chemically characterized Yerba Santa compounds show predicted docking interactions with neuroinflammation-related protein targets implicated in AD. Thirty-six ligand structures, representing 30 mass spectrometry peak assignments, were docked against 30 neuroinflammation-related proteins using the MolSoft ICM molecular docking platform. To improve reproducibility, each ligand–target pair was evaluated by replicated docking simulations followed by statistical analysis, with apo and holo targets evaluated against separate statistical references and expanded docking where applicable. Under the apo −25 kcal/mol screening reference, 11 ligand–target pairs were retained after BH-FDR correction and expanded docking for the apo C1r-C1s (PDB:6F39). Separately, 23 holo ligand–target pairs were retained after comparison with their corresponding redocked native-ligand references: Complement C1q (PDB:2JG8), GABA-A receptor α1β2γ2 (PDB:6D6U), and NLRP3 (PDB:7PZC). The pairs retained under these separate criteria involved multiple Yerba Santa compounds, predominantly flavonoids, while Rosmarinic acid (L21) was retained for both Complement C1q (PDB:2JG8) and NLRP3 (PDB:7PZC). These findings support a selective predicted multi-target interaction profile for Yerba Santa compounds and identify complement signaling, GABA-A receptor-associated neurotransmission, and NLRP3 inflammasome signaling as testable pathways for future experimental studies of neuroinflammation in AD.
SN - 1420-3049
ER -