ABSTRACT
Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund's adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1ß and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1ß and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.
Subject(s)
Anti-Inflammatory Agents , Antioxidants , Carotenoids , Encephalomyelitis, Autoimmune, Experimental , Mice, Inbred BALB C , Vitamin A , Animals , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/pathology , Mice , Antioxidants/pharmacology , Antioxidants/therapeutic use , Female , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Carotenoids/pharmacology , Carotenoids/therapeutic use , Vitamin A/analogs & derivatives , Vitamin A/therapeutic use , Mice, Inbred C57BL , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Ubiquitin-Protein Ligases/metabolism , Oxidative Stress/drug effects , Interleukin-1beta/metabolismABSTRACT
Curcumin, an orange-yellow lipophilic polyphenolic molecule, is the active component of Curcuma longa, which is extensively used as a spice in most of the Asian countries. This natural compound is able to interact with a large number of molecular structures like proteins, enzymes, lipids, DNA, RNA, transporter molecules, and ion channels. It has been reported to possess several biological effects such as antioxidant, anti-inflammatory, wound healing, antimicrobial, anticancer, antiangiogenic, antimutagenic, and antiplatelet aggregation properties. These beneficial effects of curcumin are because of its extraordinary chemical interactions such as extensive hydrogen and covalent bonding, metal chelation, and so on. Therefore, the aim of this review was to outline the evidence in which curcumin could affect different types of ion channels and ion channel-related diseases, and also to elucidate basic molecular mechanisms behind it. © 2019 IUBMB Life, 2019.
