Caulerpa okamurae extract alleviates pulmonary fibrosis in vitro and in vivo by modulating Tgfβ/SMAD/MAPK signaling and NLRP3 inflammasome activation

Abstract

Pulmonary fibrosis (PF) characterized by fibroblast dysfunction and inflammation, in driven by transforming growth factor beta (Tgfβ) plays a crucial role. Caulerpa okamurae extract (COE), drived from a green seaweed widely consumed in East Asia, is known for its anti-obesity properties, but its effects on PF remain unexplored. This study investigated the potential of the COE in PF using Tgfβ-stimulated MRC-5 lung fibroblasts and bleomycin (BLM)-induced PF in C57BL/6 mice. In vitro, COE significantly reduced fibrotic markers (α-Sma, Mmp1, Col1a1, and Vimentin) and suppressed inflammatory mediators (Il-1β, Il-6, and Cox2) by downregulating Tgfβ/SMAD2/3 and MAPK signaling. In vivo, COE attenuated fibrotic features in BLM-treated mice by modulating the Tgfβ/SMAD/MAPK pathway. Interestingly, COE decreased plasma levels of IL-1β, an indicative of suppressed NLRP3 inflammasome activation. This effect was further validated in lipopolysaccharide and nigericin-treated bone marrow-derived macrophages, where COE inhibited NLRP3 inflammasome activation. These finding highlight COE's action in mitigating fibrosis and inflammation by modulation of Tgfβ/SMAD2/3 and MAPK signaling, along with the NLRP3 inflammasome pathway, underscoring its potential as a novel therapeutic for PF.