Extracellular Vesicle from Chlorella vulgaris Alleviates Hepatic Fibrosis in a Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease Through Modulation of Inflammatory Signaling

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a major chronic liver disorder that progresses through inflammation and fibrosis to cirrhosis, yet no effective pharmacological therapy is available. Extracellular vesicles (EVs), which are key mediators of intercellular communication, have recently been reported to exert preventative and therapeutic effects in disease models. This study evaluated the oral efficacy of EVs derived from the microalga Chlorella vulgaris (CEVs) in an MASLD mouse model. Male C57BL/6J mice were assigned to a control group (normal diet), an MASLD group (choline- and methionine-deficient high-fat diet; CDHF), or CEV group (CDHF + CEVs). Twelve-week CEV administration did not alter the CDHF-induced reduction in circulating lipid levels or produce an increase in hepatic lipid content. However, CEV treatment significantly suppressed CDHF-induced fibrosis with collagen accumulation and reduced the mRNA expression of fibrosis-related genes, including Col1a1, Acta2, Mmp2, and Timp1. CEVs also significantly downregulated the expression of macrophage-derived inflammatory mediators—Ccl2, Ccr2, Il6 and Il1b—and reduced lobular inflammatory foci. These findings suggest that CEVs attenuate hepatic fibrosis by modulating early inflammation associated with steatosis and inhibiting hepatic stellate cell activation. This study supports the potential of CEVs as a novel oral intervention for slowing MASLD progression.