Natural Compounds and Glutathione: Beyond Mere Antioxidants Original paper

What was reviewed?

This review covers and explains how food-derived natural compounds change glutathione (GSH) biology in ways that go beyond simple antioxidant action. The authors describe how selected polyphenols, terpenoids, and glucosinolates can raise or lower GSH levels, change GSH recycling, alter GSH-linked enzymes, and shift redox signaling that controls cell growth and cell death. They frame GSH as a key cell regulator that supports detox reactions, limits oxidative damage, and controls redox-sensitive signaling. At the same time, they stress that disease context can change whether higher GSH helps or harms, especially in cancer.

Who was reviewed?

The authors reviewed evidence across in vitro studies, animal studies, and human studies, and they did not define one patient group. They focused on cell systems and disease models that link GSH control to outcomes in cancer, metabolic disorders, inflammation models, and organ injury models. They discussed a wide set of cell types and settings, including cancer cell lines, immune and epithelial models, and rodent models used to test oxidative stress and inflammation pathways. They also included clinical and dietary research where authors measured GSH-related endpoints after exposure to specific food compounds or nutraceutical-like extracts.

Most important findings

The review shows that natural compounds regulate glutathione homeostasis through controlled and context-dependent mechanisms rather than simple antioxidant effects. The authors report that several polyphenols increase intracellular glutathione by inducing glutathione synthesis enzymes and supporting glutathione recycling through NRF2-linked signaling. In contrast, some flavonoids and terpenoids lower glutathione levels by promoting glutathione export, suppressing synthesis, or increasing utilization, especially in cancer cell models. The paper also highlights that glucosinolate-derived isothiocyanates enter metabolism through glutathione conjugation, which can transiently deplete glutathione while simultaneously inducing glutathione synthesis and detox enzymes. Across all compound classes, the authors emphasize dose dependence and cell-type specificity, with opposing effects observed under different stress and disease conditions.

Key implications

This review gives clinicians a clear logic for natural compounds and glutathione, when they evaluate diet, supplements, and drug interactions that touch redox biology. The paper argues that “more GSH” does not always equal “better,” since high GSH can protect normal tissue but can also support tumor survival and drug resistance in some cancers. It also warns that the same compound can raise GSH in one model and lower it in another, based on dose, cell type, and stress state, so clinicians should avoid simple claims and instead link intervention choice to the clinical goal. The review supports careful attention to NRF2 pathway activation, GSH synthesis capacity, GST-linked conjugation, and transporter-linked GSH loss when clinicians interpret lab signals of oxidative stress or when they advise on nutraceutical use in complex disease.