Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation.
Stanzin AngmoShilpa RanaKamalendra YadavRajat SandhirNitin Kumar SinghalPublished in: Scientific reports (2018)
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.
Keyphrases
- iron deficiency
- oxidative stress
- artificial intelligence
- induced apoptosis
- transcription factor
- chronic kidney disease
- signaling pathway
- liver failure
- room temperature
- metabolic syndrome
- staphylococcus aureus
- biofilm formation
- insulin resistance
- cell cycle arrest
- immune response
- protein kinase
- human health
- cystic fibrosis
- electronic health record
- mechanical ventilation