Brosimine B and the biphasic dose-response: insights into hormesis and retinal neuroprotection
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...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1558726/full |
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| Summary: | 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. |
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| ISSN: | 1663-9812 |