Dietary oleuropein and its new acyl-derivate attenuate murine lupus nephritis through HO-1/Nrf2 activation and suppressing JAK/STAT, NF-κB, MAPK and NLRP3 inflammasome signaling pathways.

Systemic lupus erythemathosus (SLE) is a chronic inflammatory and autoimmune disease which can affect multiple organ systems, without an effective and safe treatment. Olive leaf extracts are of special interest for their therapeutic effects. Oleuropein (OL) is the most abundant constituents of olive leaf extract and possesses many beneficial properties. In this study, we evaluated the effects of dietary OL and its new derivate, peracetylated oleuropein (Per-OL), in a pristane-induced SLE model. Mice received an injection of pristane or saline solution and were fed with experimental diets: enriched with OL and Per-OL. The levels of proinflammatory cytokines and markers were evaluated by enzyme-linked immunosorbent assay. The protein expressions of inducible nitric oxide synthase, microsomal prostaglandin E synthase 1, heme oxygenase (HO-1), nuclear factor E2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear transcription factor-kappa B (NF-κB) and inflammasome nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) pathways activation were determined in kidneys by Western blot. OL and Per-OL significantly reduced renal damage and decreased serum matrix metalloproteinase 3 and prostaglandine E2 kidneys levels. Our findings indicate that Nrf2 and HO-1 antioxidant protein expressions were up-regulated in mice fed with OL and Per-OL diets, whereas the activation of JAK/STAT, MAPK, NF-κB and NLRP3 inflammasome pathways was significantly ameliorated. These results suggest that OL and Per-OL supplementation might provide a new alternative approach as a preventive/palliative treatment of nephritis in SLE management.

Castejon ML ，Sánchez-Hidalgo M ，Aparicio-Soto M ，Montoya T ，Martín-LaCave I ，Fernández-Bolaños JG ，Alarcón-de-la-Lastra C ... -  《-》

A New Peracetylated Oleuropein Derivative Ameliorates Joint Inflammation and Destruction in a Murine Collagen-Induced Arthritis Model via Activation of the Nrf-2/Ho-1 Antioxidant Pathway and Suppression of MAPKs and NF-κB Activation.

Castejón ML ，Alarcón-de-la-Lastra C ，Rosillo MÁ ，Montoya T ，Fernández-Bolaños JG ，González-Benjumea A ，Sánchez-Hidalgo M ... -  《Nutrients》

Dietary extra virgin olive oil attenuates kidney injury in pristane-induced SLE model via activation of HO-1/Nrf-2 antioxidant pathway and suppression of JAK/STAT, NF-κB and MAPK activation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a widespread organ involvement. Recent studies have suggested that extra virgin olive oil (EVOO) might possess preventive effects on this immunoinflammation-related disease. However, its role in SLE remained unknown. In this work, we evaluated the effects of EVOO diet in a pristane-induced SLE model in mice. Three-month-old mice received an injection of pristane or saline solution and were fed with different experimental diets: sunflower oil diet or EVOO diet. After 24weeks, mice were sacrificed, spleens were collected and kidneys were removed for immunoinflammatory detections. The kidney expression of microsomal prostaglandin E synthase 1, heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf-2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear transcription factor-kappa B (NF-κB) pathways were studied by western blotting. In addition to macroscopic and histological analyses, serum matrix metalloproteinase 3 (MMP-3) levels and proinflammatory cytokines production in splenocytes were evaluated by enzyme-linked immunoassay. We have demonstrated that EVOO diet significantly reduced renal damage and decreased MMP-3 serum and PGE2 kidney levels as well as the proinflammatory cytokines production in splenocytes. Our data indicate that Nrf-2 and HO-1 protein expressions were up-regulated in those mice fed with EVOO and the activation of JAK/STAT, MAPK and NF-κB pathways were drastically ameliorated. These results support the interest of EVOO as a beneficial functional food exerting a preventive/palliative role in the management of SLE.

Aparicio-Soto M ，Sánchez-Hidalgo M ，Cárdeno A ，Rosillo MÁ ，Sánchez-Fidalgo S ，Utrilla J ，Martín-Lacave I ，Alarcón-de-la-Lastra C ... -  《-》

Ligstroside aglycon, an extra virgin olive oil secoiridoid, prevents inflammation by regulation of MAPKs, JAK/STAT, NF-κB, Nrf2/HO-1, and NLRP3 inflammasome signaling pathways in LPS-stimulated murine peritoneal macrophages.

Castejón ML ，Montoya T ，Ortega-Vidal J ，Altarejos J ，Alarcón-de-la-Lastra C ... -  《-》

Peracetylated hydroxytyrosol, a new hydroxytyrosol derivate, attenuates LPS-induced inflammatory response in murine peritoneal macrophages via regulation of non-canonical inflammasome, Nrf2/HO1 and JAK/STAT signaling pathways.

Montoya T ，Aparicio-Soto M ，Castejón ML ，Rosillo MÁ ，Sánchez-Hidalgo M ，Begines P ，Fernández-Bolaños JG ，Alarcón-de-la-Lastra C ... -  《-》