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Strictosamide ameliorates LPS-induced acute lung injury by targeting ERK2 and mediating NF-κB signaling pathway.

Authors :
Geng, Qi
Liu, Bin
Fan, Danping
Cao, Zhiwen
Li, Li
Lu, Peipei
Lin, Lin
Yan, Lan
Xiong, Yibai
He, Xiaojuan
Lu, Jun
Chen, Peng
Lu, Cheng
Source :
Journal of Ethnopharmacology. Mar2024, Vol. 322, pN.PAG-N.PAG. 1p.
Publication Year :
2024

Abstract

Acute lung injury (ALI) ranks among the deadliest pulmonary diseases, significantly impacting mortality and morbidity. Presently, the primary treatment for ALI involves supportive therapy; however, its efficacy remains unsatisfactory. Strictosamide (STR), an indole alkaloid found in the Chinese herbal medicine Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Wutan), has been found to exhibit numerous pharmacological properties, particularly anti-inflammatory effects. This study aimes to systematically identify and validate the specific binding proteins targeted by STR and elucidate its anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced ALI. Biotin chemical modification, protein microarray analysis and network pharmacology were conducted to screen for potential STR-binding proteins. The binding affinity was assessed through surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and molecular docking, and the anti-inflammatory mechanism of STR in ALI treatment was assessed through in vivo and in vitro experiments. Biotin chemical modification, protein microarray and network pharmacology identified extracellular-signal-regulated kinase 2 (ERK2) as the most important binding proteins among 276 candidate STR-interacting proteins and nuclear factor-kappaB (NF- κ B) pathway was one of the main inflammatory signal transduction pathways. Using SPR, CETSA, and molecular docking, we confirmed STR's affinity for ERK2. In vitro and in vivo experiments demonstrated that STR mitigated inflammation by targeting ERK2 to modulate the NF- κ B signaling pathway in LPS-induced ALI. Our findings indicate that STR can inhibit the NF- κ B signaling pathway to attenuate LPS-induced inflammation by targeting ERK2 and decreasing phosphorylation of ERK2, which could be a novel strategy for treating ALI. [Display omitted] • Strictosamide (STR) demonstrates a pronounced anti-inflammatory effect by directly targeting extracellular-signal-regulated kinase 2 (ERK2) to modulate the NF- κ B signaling pathway in lipopolysaccharide-induced acute lung injury (ALI) treatment. • Human protein microarray identifies ERK2 as the binding protein for STR, with subsequent validation through surface plasmon resonance, cellular thermal shift assay, and molecular docking confirming STR's affinity for ERK2. • The development of STR as a drug for the treatment of ALI could be a promising treatment strategy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03788741
Volume :
322
Database :
Academic Search Index
Journal :
Journal of Ethnopharmacology
Publication Type :
Academic Journal
Accession number :
174758957
Full Text :
https://doi.org/10.1016/j.jep.2023.117593