Ursolic Acid Inhibits Collagen Production and Promotes Collagen Degradation in Skin Dermal Fibroblasts: Potential Antifibrotic Effects

• Published in: Biomolecules (Basel, Switzerland) Vol. 15; no. 3; p. 365
• Main Authors: He, Tianyuan, Xiang, Yaping, Quan, Hehui, Liu, Yingchun, Guo, Chunfang, Quan, Taihao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.03.2025; MDPI
• Subjects: Activator protein 1; Animals; Antibodies; Antifibrotic Agents - pharmacology; Biopsy; Bleomycin; Cell culture; Cells, Cultured; Chronic diseases; Chronic illnesses; Collagen; Collagen - metabolism; Degradation; Enzymes; Ethylenediaminetetraacetic acid; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Fibrosis - drug therapy; Homeostasis; Human subjects; Humans; Interstitial collagenase; Kinases; Liver cirrhosis; MAKP; MAP kinase; Matrix metalloproteinase; Matrix Metalloproteinase 1 - metabolism; Medical research; Metalloproteinase; Mice; MMP-1; Protein kinases; Proteins; Signal Transduction - drug effects; Skin; Skin - cytology; Skin - drug effects; Skin - metabolism; Skin - pathology; Smad protein; TGF-β/Smad; Transcription factors; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Transforming growth factors; Triterpenes - pharmacology; Ursolic Acid; California; United States; Massachusetts; Germany; St Louis Missouri; United States > US; TGF-β/Smad; MMP-1; collagen; MAKP; fibrosis; AP-1; ursolic acid
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom15030365

Tissue fibrosis, characterized by excessive collagen accumulation, leads to impaired organ function and is a hallmark of various chronic diseases. Fibroblasts play a central role in collagen production and deposition. This study examines the impact of ursolic acid, a pentacyclic triterpenoid compound present in various fruits and vegetables, on collagen homeostasis in primary human dermal fibroblasts. Ursolic acid (UA) was observed to significantly reduce collagen production while markedly increasing the activity of matrix metalloproteinase-1 (MMP-1), an enzyme responsible for collagen degradation. Mechanistically, ursolic acid was found to inhibit TGF-β/Smad signaling, leading to decreased collagen production, and to activate mitogen-activated protein kinase (MAPK) pathways and activator protein 1 (AP-1), resulting in enhanced MMP-1 production. These in vitro findings were further validated in an in vivo mouse model of fibrosis, where ursolic acid significantly mitigated bleomycin-induced skin fibrosis. These results suggest that UA could be a promising candidate for treating skin fibrosis due to its dual effects on collagen homeostasis: inhibiting collagen production and promoting collagen degradation.