AUTHOR=Liu Honglin , He Juan , Xu Lili , Chen Yingxuan , Wang Xiaoni , Pang Xiaoni , Yang Haihui , Liang Lianhui , Chen Shuwen , Li Shuli 

TITLE=Echinocystic acid in Momordica charantia L. exosome-like nanovesicles attenuates dengue virus-induced vascular leakage associated inflammatory mediators through macrophage metabolic reprogramming and HIF-1α/p300-CBP interaction

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1653689

DOI=10.3389/fmed.2025.1653689

ISSN=2296-858X

ABSTRACT=IntroductionDengue virus (DENV) infection can progress to severe dengue hemorrhagic fever and shock syndrome, characterized by vascular leakage with high mortality. This endothelial dysfunction is primarily driven by excessive inflammatory activation of monocytes and macrophages. While Momordica charantia L. is known for its broad bioactive properties, its potential role in mitigating dengue-induced immunopathology remains unexplored.MethodsWe investigated the effects of exosome-like nanoparticles derived from Momordica charantia L. (MC-ELNs) and their highly abundant constituent, echinocystic acid (EA), on DENV-induced macrophage inflammation and endothelial dysfunction. The mechanism focused on the HIF-1α–p300/CBP transcriptional complex.ResultsMC-ELNs and EA significantly alleviated DENV-induced macrophage inflammation without affecting HIF-1α expression or nuclear translocation. They shifted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, downregulated glycolytic enzymes (HK2, PFKL, PKM1, LDHA), suppressed phagocytosis, reduced secretion of endothelial damage-associated mediators (IL-1β, IL-6, TNF-α, MMP-9), and enhanced IL-10 production. Mechanistically, both interventions inhibited the interaction between HIF-1α and p300/CBP, thereby decoupling inflammatory activation from metabolic reprogramming.DiscussionThese findings reveal a novel host-directed therapeutic strategy against severe dengue by targeting the HIF-1α–p300/CBP complex. The study highlights the potential of plant-derived nanovesicles and their bioactive components, such as MC-ELNs and EA, in treating inflammatory vascular diseases.