AUTHOR=Fonseca Susanne Suely Santos , S. Port’s Natacha M. , Aguiar Gisele Priscila Soares , Botelho Eliã P. , Couto Nádia M. G. , Pinheiro Wandson Braamcamp Souza , Khayat André Salim , Yamada Elizabeth S. , Costa Edmar T. , Sena Chubert Bernardo C. , Arruda Mara Silvia P. , Bahia Carlomagno P. , Pereira Antonio 

TITLE=Brosimine B and the biphasic dose-response: insights into hormesis and retinal neuroprotection

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1558726

DOI=10.3389/fphar.2025.1558726

ISSN=1663-9812

ABSTRACT=IntroductionThe biphasic dose-response behavior, also known as hormesis, is a characteristic feature of numerous natural products. It is defined by beneficial effects at low concentrations and toxicity at higher doses. This study investigates the hormetic effects of Brosimine B, a flavonoid derived from Brosimum acutifolium, on retinal cell viability under oxidative stress.MethodsTo simulate ischemic conditions, we used an oxygen-glucose deprivation (OGD) model. Retinal cells were treated with varying concentrations of Brosimine B, and analyses of cell viability, reactive oxygen species (ROS) production, and antioxidant enzyme activity were performed.ResultsBrosimine B at 10 µM significantly enhanced cell viability and reduced ROS production, likely through modulation of oxidative stress-protective enzymes such as catalase. However, higher concentrations (>10 µM) induced cytotoxic effects. A computational modeling approach using a hormetic (inverted U-shaped) model revealed biologically interpretable parameters, including a peak response at 10.2 µM and a hormetic zone width (σ = 6.5 µM) (R2 = 0.984).DiscussionThese results confirm that Brosimine B exhibits hormetic neuroprotective effects within a well-defined concentration window, supporting its potential as a therapeutic agent for oxidative stress–related retinal damage. The study highlights the value of computational modeling in optimizing dose–response analyses, offering a framework for refining natural product therapies and predicting toxicological thresholds in pharmacological applications.