Terpenoid-enriched Curcuma wenyujin nanovesicles for suppressing inflammation and restoring lipid homeostasis in MASH.

Authors

Lin Liu, Jiale Niu, Yulong Sun, Zhuoyan He, Ziming Jiao, Guoen Li, Ganglin Wang, Fangjun Luo, Wei Li

Published in

Extracellular vesicles and circulating nucleic acids. Volume 7. Issue 2. Pages 1010-1028. Epub Jun 30, 2026.

Abstract

Aim: This study investigates the potential of Curcuma wenyujin-derived nanovesicles (CW-DNVs) to ameliorate metabolic dysfunction-associated steatohepatitis (MASH) and explores their underlying mechanism, focusing on hepatic macrophage accumulation and the regulation of lipid metabolism. Methods: CW-DNVs were isolated via ultracentrifugation and sucrose gradient purification, and their physicochemical properties, cellular uptake, and in vivo biodistribution were characterized. Anti-inflammatory and lipid-lowering effects were evaluated in liver macrophages, hepatocytes, and a high-fat diet (HFD)-induced MASH mouse model. Lipidomic, small-molecule, and small RNA (sRNA) cargoes were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA sequencing. Results: CW-DNVs were spherical (~211 nm diameter), had a zeta potential of -27.4 mV, and were enriched in lipids, proteins, sRNAs, and terpenoids like well-known bioactive curcumenol and germacrone. Following intraperitoneal injection, they preferentially accumulated in Kupffer cells and were cleared within 7 days. In HFD-fed mice, CW-DNVs reduced body weight gain, hepatic steatosis, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), and hepatic interleukin (IL)-6 levels. Mechanistically, they upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and microsomal triglyceride transfer protein (MTTP), and downregulated fatty acid synthase (FASN), promoting lipid oxidation and export. In vitro, CW-DNVs suppressed lipopolysaccharide-activated IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in macrophages and reduced oleic acid-induced lipid accumulation in hepatocytes. sRNA sequencing identified predominantly rRNA-derived fragments (not canonical miRNAs); however, anti-inflammatory activity was primarily attributed to terpenoid components. Conclusion: CW-DNVs exert dual functionality in modulating macrophage inflammation and lipid metabolism. Loaded with bioactive terpenoids, they represent an effective natural nanoplatform for MASH therapy.

PMID:
42454197
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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