ABSTRACT
Acute central nervous system (CNS) trauma, including spinal cord injury (SCI) and traumatic brain injury (TBI), always leads to severe sensory, motor and autonomic nervous system dysfunction due to a series of processes, including cell death, oxidative stress, inflammation, and excitotoxicity. In recent years, ferroptosis was reported to be a type of programmed cell death characterized by the consumption of polyunsaturated fatty acids and the accumulation of membrane lipid peroxides. The processes that induce ferroptosis include iron overload, imbalanced glutathione metabolism and lipid peroxidation. Several studies have indicated a novel association of ferroptosis and acute CNS trauma. The present paper reviews recent studies of the occurrence of ferroptosis, stressing the definition and process of ferroptosis and metabolic pathways related to ferroptosis. Furthermore, a summary of the existing knowledge of the role of ferroptosis in CNS trauma is presented. The aim here is to effectively understand the mechanisms underlying the occurrence of ferroptosis, as well as the relevant effect on the pathophysiological process of CNS trauma, to present a novel perspective and frame of reference for subsequent investigations.
ABSTRACT
Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1ß (IL-1ß) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1ß-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.
