Sesamin as a Context-Dependent Redox Modulator: Interactions with Organelle Quality Control and Regulated Cell Death

Abstract

Sesamin is a furofuran lignan in sesame with reported antioxidant, anti-inflammatory, metabolic, and anticancer activities. However, its biological effects vary according to exposure, metabolism, cellular state, and stress-response capacity. This review examines sesamin as a context-dependent redox modulator, focusing on bioavailability, metabolite-dependent activity, organelle quality control, and regulated cell death. We integrate evidence on cytochrome P450-mediated metabolism, catechol formation, conjugation, tissue availability, mitochondrial redox regulation, mitophagy, autophagic flux, lysosomal function, innate immune signalling, and their intersections with apoptosis, ferroptosis, and pyroptosis. In non-malignant injury models, sesamin generally attenuates oxidative damage, preserves organelle function, and limits inflammatory or ferroptotic injury, whereas higher concentrations in selected malignant-cell models may increase oxidative stress, disrupt survival signalling, or enhance susceptibility to cell death. These divergent outcomes appear to depend on molecular species, dose, metabolic competence, baseline redox pressure, and organelle reserve. Translational limitations include sparse human pharmacokinetic and efficacy data, uncertain tissue exposure, frequent use of pharmacologically unverified micromolar concentrations, and limited metabolite-specific testing. Future studies should therefore combine exposure-matched experimental systems with quantitative redox measurements, organelle-flux assays, and pathway-specific validation to define the biological relevance of sesamin-mediated redox regulation and cell-fate control.