Natural Compounds and Glutathione: Beyond Mere Antioxidants

Abstract

The tripeptide glutathione plays important roles in many cell processes, including differentiation, proliferation, and apoptosis; in fact, disorders in glutathione homeostasis are involved both in the etiology and in the progression of several human diseases, including cancer. Natural compounds have been found to modulate glutathione levels and function beyond their role as mere antioxidants. For example, certain compounds can upregulate the expression of glutathione-related enzymes, increase the availability of cysteine, the limiting amino acid for glutathione synthesis, or directly interact with glutathione and modulate its function. These compounds may have therapeutic potential in a variety of disease states where glutathione dysregulation is a contributing factor. On the other hand, flavonoids’ potential to deplete glutathione levels could be significant for cancer treatment. Overall, while natural compounds may have potential therapeutic and/or preventive properties and may be able to increase glutathione levels, more research is needed to fully understand their mechanisms of action and their potential benefits for the prevention and treatment of several diseases. In this review, particular emphasis will be placed on phytochemical compounds belonging to the class of polyphenols, terpenoids, and glucosinolates that have an impact on glutathione-related processes, both in physiological and pathological conditions. These classes of secondary metabolites represent the most food-derived bioactive compounds that have been intensively explored and studied in the last few decades.

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

“…The source of oxidative stress is generally derived from the imbalance of redox homeostasis [ 14 ], such as the downregulation of cellular antioxidants. Several drugs, such as METS [ 33 ] and fucoidan [ 28 ], downregulate the GSH, causing oxidative stress for antiproliferation in oral cancer cells [ 34 ]. Consistently, SAMA depletes the GSH of oral ( Figure 9 ), liver [ 21 ], and lung [ 22 ] cancer cells, accompanied by upregulating oxidative stress.…”

“…GSH depletion is one of the indicators of oxidative stress [ 34 ]. A GSH-reacting dye, specifically 5-chloromethylfluorescein diacetate (CMF-DA) (Thermo Fisher Scientific, Carlsbad, CA, USA), was selected for GSH detection.…”

Roles of Glutathione and AP-1 in the Enhancement of Vitamin D-Induced Differentiation by Activators of the Nrf2 Signaling Pathway in Acute Myeloid Leukemia Cells

“…Nrf2, AP-1, and nuclear factor kappa B (NFκB) are among the key transcription factors that regulate the expression of these enzymes [33]. The reduced form of glutathione (GSH) functions as the principal cellular reducing agent and antioxidant and participates in various regulatory processes, including cytoprotection, cell signaling, metabolism of xenobiotics, gene expression, protein synthesis and modification, cell cycle, apoptosis, and immunomodulation [26,[45][46][47][48].…”

Untitled

“…The molecule consists of 3 amino acids: glutamate, cysteine, and glycine. Glutathione also contains S -H groups, which can neutralize free radicals (hydroperoxides), namely radicals that can increase O2 pressure in erythrocytes [7]. Apart from glutathione, an enzymatic antioxidant that is no less important is Superoxide dismutase (SOD).…”