Lactoferrin's role in modulating NF-κB pathway to alleviate diabetes-associated inflammation: A novel in-silico study.

Autor:	Arain MA; Faculty of Animal Husbandry & Veterinary Sciences, Sindh Agriculture University, Tandojam, 70060, Pakistan.; Faculty of Veterinary and Animal Sciences, Lasbela University of Agriculture Water and Marine Sciences, Uthal, 90150, Pakistan., Khaskheli GB; Faculty of Animal Husbandry & Veterinary Sciences, Sindh Agriculture University, Tandojam, 70060, Pakistan., Barham GS; Faculty of Animal Husbandry & Veterinary Sciences, Sindh Agriculture University, Tandojam, 70060, Pakistan., Marghazani IB; Faculty of Veterinary and Animal Sciences, Lasbela University of Agriculture Water and Marine Sciences, Uthal, 90150, Pakistan.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Jul 03; Vol. 10 (14), pp. e34051. Date of Electronic Publication: 2024 Jul 03 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e34051
Abstrakt:	Lactoferrin (LF), a multifunctional glycoprotein found in mammalian milk and various exocrine secretions, plays a pivotal role in modulating various responses. Lactoferrin plays a significant role in type-2 diabetes by improving hepatic insulin resistance and pancreatic dysfunction however, the exact mechanism for this improvement is not thoroughly elucidated. To this date, there are no evidence that attributes the direct interaction of lactoferrin with components of NF-κB pathway. Considering this precedent, the current study aimed to investigate the interaction of LF with key components of NF-κB pathway using molecular docking and simulation approaches. Results indicated that LF has shown highly stable interactions with IL-1β, IL-6, IκBα and NF-κB, and relatively weaker interactions with IKK and TNF-α. All four trajectories, including root mean square of deviations (RMSD), root mean square of fluctuation (RMSF), hydrogen bond interactions, and radius of gyration (RoG), confirmed the stable interactions of LF with NF-κB pathway components. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis further supports their stable interactions. To the best of our knowledge, this is the first study to provide convincing evidence that LF can interact with all six major components of the NF-κB pathway. This study provides pioneering in-silico evidence that lactoferrin (LF) can interact with all six major components of the NF-κB pathway, demonstrating highly stable interactions with IL-1β, IL-6, IκBα, and NF-κB, and relatively weaker interactions with IKK and TNF-α. These findings suggest that LF and its peptides have significant potential for both preventive and therapeutic applications by targeting the NF-κB pathway to inhibit inflammation, thereby improving insulin sensitivity and aiding in the management of diabetes. Competing Interests: The authors of this manuscript declared that they have no potential conflict of interest. (© 2024 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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