Il potenziale ruolo di un nuovo approccio nutraceutico nel contrastare gli effetti dannosi dei prodotti finali della glicazione avanzata in un modello murino di squilibrio metabolico.

Advanced glycation end products (AGEs) are compounds formed, following the Maillard reaction, when proteins combine with sugars. AGEs are well known to hurt tissues by different pathogenic pathways: the first, is the receptor-independent manner, the second, and the most common, is the receptor-mediated manner through the specific receptor for advanced glycation end products (RAGE), that can cause the activation of pro-oxidative and pro-inflammatory pathways. Spirulina Platensis is a microscopic blue-green algae (from Oscillatoriacea family) that is supposed to have beneficial effects on oxidative stress and on inflammatory pathways. The aim of this study was to evaluate the effects of Zinc enriched-Spirulina Platensis (Zn-SP) supplementation in counteracting diet-induced AGEs production in an in-vivo model. Spirulina Platensis was enriched in Zinc because it has been reported to have different beneficial biological functions. The in-vivo protocol was conducted on thirty male mice for 12-weeks. Mice were randomized in 3 different groups: one fed with Standard Diet (SD, 10% fat), one with High-Fat-High-Sugar diet (HFHS, 58% fat – 25% sucrose), one with High fat high sugar diet and then treated (after 5 weeks of dietary manipulation) with Zn-Spirulina Platensis (HFHS + Zn-Sp, 350 mg/kg). The treatment was administered orally for 3 days per week, for the remaining 7 weeks. Liver and plasma samples were collected to measure inflammatory parameters (Western Blot, ELISA), oxidative stress markers and AGEs levels (Western Blot, HPLC). Two different AGEs were analyzed both in liver samples: CML (carboxymethyl-lysin) and CEL (carboxyethyl-lysin). In HFHS fed mice higher amounts of both CML and CEL were detected compared to SD mice. In HFHS-Zn+SP mice, both CML and CEL levels were similar to those recorded in SD mice. Blood markers (IL-6, IFN-γ and IL-1β) were used to analyze the inflammatory state, resulting in increased levels in HFHS mice compared to SD mice, while administration of Zn-Spirulina Platensis reduced these values. Inflammatory pathways were analyzed in liver samples, showing a higher activation of the NFκB and NLRP3 signaling pathway in HFHS mice, while in Zn-SP treated mice this levels were drastically reduced. Consistently, antioxidant and anti-glycation defense mechanisms (Nrf2 and glo-1 activity) were drastically decreased in HFHS mice, while in treated mice the levels were restored. In conclusion, the results suggest that Zn-SP could be used for prevention and/or adjuvant treatments for diet-induced metabolic disorders. Zn-SP could act directly on AGEs, avoiding their formation, thus decreasing the levels of inflammatory and pro-oxidative markers both locally and systemically. Additional studies are needed to elucidate the contribution of Spirulina components.