Sirtuins, as classic NAD⁺-dependent class III histone deacetylases (HDACs), have been the focus of extensive research since their discovery, primarily centered on the mechanisms by which their deacetylase activity mediates the pathogenesis of various diseases and regulates key biological processes. With the rapid advancement of epigenetics, numerous novel acylation modifications, including lysine malonylation (Kma), lysine β-hydroxybutyrylation (Kbhb), lysine succinylation (Ksucc), and have been identified to date. Notably, the recently discovered lysine lactylation (Kla) modification has fundamentally revised long-held perception of lactic acid as a mere "metabolic waste". Importantly, SIRT1-3 have been shown to possess robust delactylase activity. To date, SIRT1-7 have been discovered to exert over ten distinct novel enzymatic functions. Herein, we summarized the functions of SIRT1-7 and their associated metabolic regulatory pathways in the context of post-translational modifications.
Previous study demonstrated that Hypnea cervicornis lectin (HCA) reduces inflammation and nociception via interaction with the lectin carbohydrate-binding site, modulating gene expression of the interleukins IL-1β, TNF-α and of iNOS. This study evaluated the effect of HCA in the rat model of arthritis induced by zymosan in the tibiotarsal joint and the involvement of macrophage-derived mediators. In vitro, macrophages were stimulated with zymosan before being incubated with HCA and the supernatant was injected into the joint. In vivo, HCA was administered by intravenous route after intra-articular injection of zymosan, fMLP, or macrophages supernatant. Hypernociception, edema and leukocyte influx were evaluated in the joints, and inflammatory mediators in the macrophage supernatant or periarticular tissue. In vitro, HCA (100 µg/ml) reduced NO2− and IL-1β in the supernatant of macrophages. In vivo, HCA (3 mg/kg) reduced articular hypernociception, edema and leukocyte influx elicited by zymosan, fMLP or by the supernatant of zymosan activated macrophages, as well as the zymosan-induced rolling and adhesion, and gene expression of iNOS and IL-1. HCA attenuated edema and leukocyte influx in the periarticular tissue, revealing preserved chondrocytes in the cartilage. In conclusion, HCA exerts anti-inflammatory effect in the arthritis induced by zymosan in rat tibio-tarsal joints, involving NO and IL-1 released by resident macrophages.
