Spermidine inhibits LPS-induced pro-inflammatory activation of macrophages by acting on Nrf2 signaling but not autophagy

Spermidine-Eugenol Supplement Preserved Inflammation-Challenged Intestinal Cells by Stimulating Autophagy

“…The shared etiology of defective autophagy and chronic inflammation constitute the “hallmarks” of many non-communicable and auto-immune diseases, for which research on natural products has attracted attention in drug discovery fields. This interest is paralleled with investigating the effects of products on the interrelationship between autophagy and inflammation [ 2 , 11 , 25 , 26 , 27 , 28 , 36 , 37 ]. Within this framework, the tolerability and protective effects of an economically priced SUPPL, composed of pressed wheat germ matrix containing SPD with adsorbed clove EUG, on inflammation status and autophagy were investigated in intestinal Caco-2 and NCM460 cell lines.…”

“…As regards the SPD component, published results are still scarce on this topic. Within a 24 h timeline, autophagy has either been directly implicated in modulating inflammation [ 26 , 27 ], or not [ 28 ]. In the present study, over a short timeline of 2–4 h, the SUPPL was shown to significantly increase steady state LC3-II levels compared to the untreated control.…”

“…We attempted to address this question by examining the effect of the SUPPL in reducing LPS-induced inflammation in NCM460 cells in which AMPK-mediated autophagy was effectively blocked using CC (indicated by the absence of LC3-II expression) over a period of 4 h. In the absence of autophagy (CC-treated NCM460 cells), the SUPPL was shown to reduce MDK expression, suggesting that, over a short timeline, non-autophagy-dependent antioxidant pathways may have been activated to reduce inflammation. Interestingly, in a recently published paper, SPD was shown to inhibit the LPS-induced pro-inflammatory activation of murine-derived macrophages by acting on Nrf2 signaling but not autophagy when blocked with the late autophagy blocker bafilomycin for 24 h [ 28 ]. These results contrasted with previous results also using murine-derived immune cells where SPD was shown to attenuate inflammation in an autophagy-dependent manner [ 26 , 27 ].…”

“…For example, the involvement of SPD in the direct autophagy-mediated reduction of inflammation has been shown using either autophagy inhibitors or autophagy-related (ATG) protein knockouts [ 25 , 26 , 27 ]. Yet, SPD was also shown for the first time in 2022 to directly suppress the NF-κB signaling pathway via the nuclear factor erythroid 2–related factor 2 (Nrf2) that did not involve autophagy [ 28 ]. Instead, EUG has been reported to reduce inflammation via NF-κB signaling and inflammasome inactivation [ 24 , 29 , 30 ], with no reports of the role of autophagy in this process.…”

Spermidine‐Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ

“…[ 6 ] Consistent with this hypothesis, animal experiments have shown that SPD can improve the success rate of embryo implantation and development. [ 7 ] More intriguingly, several recent works have demonstrated a broader immunomodulatory function for SPD, such as anti‐inflammatory effects [ 8 ] and improvement in anti‐tumor immunity. [ 9 ] Hence, we have envisioned that the local administration of SPD in biomaterials can reduce the inflammation induced by exogenous biomaterials and promote wound healing, thus avoiding the undesirable adverse reactions caused by immunosuppressive drugs.…”