In Silico Docking of Lariciresinol: Implications for Attenuating LPS-induced Acute Lung Injury via TLR4/MyD88/NF-κB Inhibition
TL;DR
Lariciresinol effectively attenuated LPS-induced ALI in mice by suppressing inflammatory responses through the downregulation of the TLR4/MyD88/NF-κB signaling pathway and suggesting that lariciresinol may serve as a promising therapeutic candidate for the management of ALI owing to its potent anti-inflammatory activity.
Abstract
Acute lung injury (ALI) is an acute, widespread inflammatory condition characterized by pulmonary edema and severe hypoxemia, leading to high morbidity and mortality. The present study investigated the therapeutic potential of lariciresinol against lipopolysaccharide (LPS)-induced ALI in a murine model and explored its underlying molecular mechanism. ALI was induced in BALB/c mice by intratracheal administration of LPS for 3 consecutive days. Lariciresinol was administered orally for 3 days following LPS exposure. Bronchoalveolar lavage fluid (BALF) was collected to evaluate inflammatory cell infiltration. Inflammatory cytokines and pro-inflammatory markers were quantified using commercially available assay kits. Lung tissue levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF-κB) were determined using assay kits. Histopathological examination was performed to assess lung injury. Molecular docking analysis was conducted to investigate the interactions of lariciresinol with TLR4, MyD88, and NF-κB. Lariciresinol treatment significantly reduced inflammatory cell infiltration in BALF and decreased the levels of pro-inflammatory cytokines and inflammatory mediators in LPS-induced ALI mice. It also markedly suppressed the expression of TLR4, MyD88, and NF-κB in lung tissues and significantly improved lung histopathological scores. Molecular docking demonstrated favorable binding interactions of lariciresinol with TLR4 (binding affinity = −5.2 kcal/mol; RMSD = 2.983 Å), MyD88 (binding affinity = −6.5 kcal/mol; RMSD = 1.623 Å), and NF-κB (binding affinity = −6.4 kcal/mol; RMSD = 1.700 Å), supporting its inhibitory potential against the TLR4/MyD88/NF-κB signaling pathway. Lariciresinol effectively attenuated LPS-induced ALI in mice by suppressing inflammatory responses through the downregulation of the TLR4/MyD88/NF-κB signaling pathway. These findings suggest that lariciresinol may serve as a promising therapeutic candidate for the management of ALI owing to its potent anti-inflammatory activity.