Allicin Neuroprotective Effect During Oxidative/inflammatory Injury Involves AT1-Hsp70-iNOS Counterbalance Axis

The ancestral cultures have described many therapeutic properties of garlic; therefore, it is of central interest to elucidate the molecular basis explaining this millenary empirical knowledge. Indeed, it has been demonstrated a neuroprotective effect of allicin-a phytochemical present in garlic-linked to oxidative-inflammatory modulation. Allicin improved neuronal injury by heat shock protein 70 (Hsp70) and inducible nitric oxide synthase (iNOS) regulation. Also, allicin exerts renal protection involving a possible angiotensin type 1 receptor (AT1) interaction. In connection, AT1 overexpression has been recognized as a central deleterious factor in many brain diseases. However, there are no studies that evaluate AT1-Hsp70-iNOS interaction as a mechanism linked to neuroinflammation. Thus, our central aim is to evaluate if the allicin protective effect is associated with an AT1-Hsp70-iNOS counterbalance axis. For this study, a murine microglial cell line (BV-2) was injured with lipopolysaccharides and treated or not with allicin. Then, it was evaluated cell viability, proinflammatory cytokine levels, cellular oxidative stress, iNOS, Hsp70, and AT1 protein expression (cellular and mitochondrial fractions), nitrite levels, and protein-protein interactions. The results demonstrated that allicin could prevent neuronal injury due to a reduction in oxidative stress and inflammatory status mediated by an AT1-Hsp70-iNOS counterbalance axis linked to direct protein-protein interaction.