Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, SAS Nagar, Punjab 140306, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS, Nagar, Punjab, 160062, India.
Life Sci. 2022 Aug 1;302:120655. doi: 10.1016/j.lfs.2022.120655. Epub 2022 May 20.
Inflammatory Bowel Disease is characterised by abdominal pain, diarrhoea, rectal bleeding and weight loss. Sometimes it may leads to severe health complications resulting in death of an individual. Current research efforts to highlight the role of melatonin in regulating EZH2, a master epigenetic regulator and its beneficiary effect in case of IBD management.
Murine macrophages (RAW 264.7) were treated with lipopolysaccharides (LPS) to activate them for generating inflammatory response to investigate efficacy of melatonin in-vitro models. Similarly, for developing in vivo models, Dextran sodium sulphate (36-50 kDa) was used. Evaluations of anti-inflammatory activities were carried out by nitrite assay, western blotting, q-PCR, immunofluorescence, and histological studies.
Reduction of epigenetic target, EZH2 by melatonin significantly improves the clinical symptoms of dextran sodium sulphate induced colitis and may be implicated as a potential therapeutic target in IBD management. The present study evaluates the efficacy of melatonin by epigenetic regulation in IBD models. Down regulation of EZH2 by melatonin reduced the chemical induced inflammatory insults in in vitro and in vivo models. Exploration of molecular pathways has revealed interlink of EZH2 and NOS2, a hallmark of inflammation. Molecular mechanistic action of melatonin is attributed to inhibition of the expression and physical interaction of EZH2 and NOS2.
Our study highlights melatonin therapeutic effect via attenuating interaction between EZH2 and NOS2 which is beneficial in managing IBD treatment.
炎症性肠病的特征是腹痛、腹泻、直肠出血和体重减轻。有时它可能导致严重的健康并发症，导致个体死亡。目前的研究努力强调了褪黑素在调节 EZH2 中的作用，EZH2 是一种主要的表观遗传调节剂，及其在 IBD 管理中的有益作用。
用脂多糖（LPS）处理鼠源巨噬细胞（RAW 264.7）以激活它们，以产生炎症反应，从而在体外模型中研究褪黑素的疗效。同样，为了开发体内模型，使用了葡聚糖硫酸钠（36-50 kDa）。通过亚硝酸盐测定、western blot、q-PCR、免疫荧光和组织学研究来评估抗炎活性。
褪黑素对表观遗传靶标 EZH2 的抑制显著改善了葡聚糖硫酸钠诱导的结肠炎的临床症状，可能作为 IBD 管理的潜在治疗靶点。本研究通过 IBD 模型评估了褪黑素的疗效。褪黑素下调 EZH2 可减少体外和体内模型中的化学诱导炎症损伤。对分子途径的探索揭示了 EZH2 与 NOS2 之间的相互联系，NOS2 是炎症的标志。褪黑素的分子机制作用归因于抑制 EZH2 和 NOS2 的表达和物理相互作用。
我们的研究强调了褪黑素通过减轻 EZH2 和 NOS2 之间的相互作用来发挥治疗作用，这有利于管理 IBD 治疗。
