ALLICIN NEUROPROTECTIVE EFFECT DURING OXIDATIVE/INFLAMMATORY INJURY INVOLVES AT1-Hsp70-iNOS COUNTERBALANCE AXIS

LUCIANA MAZZEI; MARÍA BELÉN RUIZ-ROSO; NATALIA DE LAS HERAS; SANDRA BALLESTEROS; CAROLINA TORRES; LEÓN FERDER; ALEJANDRA CAMARGO; WALTER MANUCHA

Biocell

Tech Science Press

Lugar: Henderson, Nevada.; Año: 2020 vol. 44 p. 671 - 681

Ethnopharmacological relevance: The ancestral cultures have described many therapeutic properties of garlic (Allium sativum) and related compounds. However, it is of central interest to elucidate the molecular basis explaining this millenary empirical knowledge. To highlight, recently it has been demonstrated a neuroprotective effect of allicin -a phytochemical present in garlic- linked to oxidative-inflammatory modulation. Aim of the study: 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.Materials and Methods: 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.Results: BV-2 cells injured showed oxidative/inflammatory damage at the cellular and mitochondrial levels, consistent with high iNOS and AT1 expressions, while Hsp70 was downregulated. On the contrary, allicin produced a significant reduction in the oxidative-inflammatory process with iNOS, AT1, and Hsp70 proteins expression recovery. Unprecedented, iNOS-Hsp70 and AT1-Hsp70 protein-protein interactions were established by immunoprecipitation, and to highlight these interactions were increased during the neuroinflammatory model, while allicin treatment significantly reduced these protein interactions.Conclusions: These data prove 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.