Food Science and Technology Department, National Agri-Food Biotechnology Institute (NABI) Sector-81(Knowledge City), PO Manauli, S.A.S. Nagar, Mohali, 140306, Punjab, India.
Department of Biochemistry, Panjab University, 160014, Chandigarh, India.
Sci Rep. 2018 Dec 6;8(1):17684. doi: 10.1038/s41598-018-35992-2.
Hepcidin, master regulator of iron homeostasis, causes anemia under infectious and inflammatory conditions by reducing intestinal absorption of iron with decreased release of iron from macrophages and liver despite adequate iron stores leading to Anemia of Inflammation (AI). Many therapeutic trials have been carried out but none have been effective due to its adverse effects. In present study, we discover that Guanosine 5'-diphosphate (GDP) encapsulated in lipid vesicle (NH+) was found to inhibit NF-ҝB activation by limiting phosphorylation and degradation of IҝBα, thus, attenuating IL-6 secretion from macrophage cells. Moreover, the suppressed IL-6 levels down regulated JAK2/STAT3 pathway with decrease inflammation-mediated Hamp mRNA transcription (HepG2) and increase iron absorption (Caco2) in HepG2/Caco2 co-culture model. Analogous results were obtained in acute and chronic AI mice model thus, correcting haemoglobin level. These results proved NH + GDP as novel therapeutic agent to overcome limitations and suggests it as potential drug to ameliorate AI.
亚铁调素是铁稳态的主要调节剂，在感染和炎症条件下会导致贫血，其机制是通过减少肠道铁吸收，同时巨噬细胞和肝脏中铁的释放减少，尽管铁储存充足，但这会导致炎症性贫血（AI）。已经进行了许多治疗试验，但由于其副作用，没有一种是有效的。在本研究中，我们发现，包裹在脂质囊泡（NH+）中的鸟苷 5'-二磷酸（GDP）通过限制 IκBα的磷酸化和降解来抑制 NF-κB 的激活，从而减少巨噬细胞细胞中 IL-6 的分泌。此外，抑制的 IL-6 水平下调 JAK2/STAT3 通路，减少炎症介导的 Hamp mRNA 转录（HepG2），并增加 HepG2/Caco2 共培养模型中的铁吸收。在急性和慢性 AI 小鼠模型中也得到了类似的结果，从而纠正了血红蛋白水平。这些结果证明 NH+ GDP 是一种克服局限性的新型治疗剂，并提示其可能是改善 AI 的潜在药物。
