Jasurolignoside from Ilex pubescens exerts a therapeutic effect on acute lung injury in vitro and in vivo by binding to TLR4.
10.1016/S1875-5364(25)60972-1
- Author:
Shan HAN
1
;
Chi Teng VONG
2
;
Jia HE
1
;
Qinqin WANG
1
;
Qiumei FAN
3
;
Siyuan LI
3
;
Jilang LI
3
;
Min LIAO
3
;
Shilin YANG
3
;
Renyikun YUAN
4
,
5
;
Hongwei GAO
5
,
6
Author Information
1. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, China; National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal. Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
3. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, China.
4. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, China. Electronic address: yryk0808@
5. com.
6. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, China. Electronic address: gaohongwei06@
- Publication Type:Journal Article
- Keywords:
Acute lung injury;
Jasurolignoside;
NF-κB/MAPKs;
NLRP3;
TLR4
- MeSH:
Toll-Like Receptor 4/chemistry*;
Animals;
Acute Lung Injury/chemically induced*;
Mice;
Humans;
Ilex/chemistry*;
Molecular Docking Simulation;
Male;
NF-kappa B/immunology*;
Mice, Inbred C57BL;
NLR Family, Pyrin Domain-Containing 3 Protein/immunology*;
Tumor Necrosis Factor-alpha/genetics*;
Interleukin-1beta/genetics*;
RAW 264.7 Cells;
Disease Models, Animal
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(9):1058-1068
- CountryChina
- Language:English
-
Abstract:
Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
