Immunomodulatory Effects of Glutathione, Garlic Derivatives, and Hydrogen Sulfide

Abstract

Glutathione and aged garlic extract are sulfur-containing products that play important protective and regulatory roles within the immune system and in oxidative processes. Hydrogen sulfide (H₂S), an endogenous, gaseous, signaling transmitter, has also been shown to be involved in the regulation of inflammation. Recent studies have shown that sulfur-containing compounds from garlic have beneficial effects in attenuating outcomes associated with cardiovascular disease and inflammation by a mechanism that may be related to the H₂S signaling pathway. In this review, we summarize the main functions of glutathione (GSH), garlic derivatives and H₂S and their role in the immune response and impact on health and disease.

Keywords: aged garlic extract; glutathione; hydrogen sulfide; immune response; inflammation.

Figure 1

Schematic illustration of the proposed mechanism by which GSH, SAC and H₂S affect the activation of the canonical NF-κB pathway. The canonical NF-κB pathway is the major pathway responsible for controlling inflammatory events through translocation of p50/p65 heterodimer to the nucleus. This event induces the production of pro-inflammatory cytokines and other chemochines, such as IL-6, TNF-α, IL-1β, MIP-1α, MPC-1 and COX-2 enzyme. It has been suggested that GSH has anti-inflammatory effects by reducing the levels of pro-inflammatory cytokines production. SAC, a constituent from AGE, has been shown to inhibit p50/p65 activation and the levels of pro-inflammatory cytokines. Contrarily, H₂S seems to have both inhibitory and activating effects in the NF-κB pathway. Abbreviations: R (receptor); NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells); NEMO (NF-kB essential modulator); IκB (inhibitor of kappa B); IκBα (inhibitor of kappa B alpha); IKKα (IκB kinase alpha); IKKβ (IκB kinase beta); P (phosphorylation); Ub (ubiquitination); TNF-α (tumor necrosis factor-alpha); MIP-1 (macrophage inflammatory protein-1); MCP-1 (monocyte chemoattractant protein-1); COX2 (cyclooxygenase-2), SAC (S-allyl cysteine); GSH (glutathione), H₂S (hydrogen sulfide).