Aspidin PB, a novel natural anti-fibrotic compound, inhibited fibrogenesis in TGF-β1-stimulated keloid fibroblasts via PI-3K/Akt and Smad signaling pathways

- TGF-β1 induced the expression of type I collagen, CTGF and α-SMA.
- Aspidin PB inhibited the expression of type I collagen, CTGF, and α-SMA.
- Aspidin PB inhibited TGF-β1-induced phosphorylation of Smad2 and Smad3.
- Aspidin PB inhibited TGF-β1-induced genes expression by PI-3K/Akt signaling pathway.

Keloid is an overgrowth of scar tissue that develops around a wound. The mechanisms of keloid formation and development still remain unknown, and no effective treatment is available. Searching for active natural resources may develop better prevention and treatment approaches for keloids. Aspidin PB is a natural resource with lower toxicity. We explored its effect on the regulation of TGF-β1-induced expression of type I collagen, CTGF, and α-SMA in keloid fibroblasts (KFs). Western blotting was used to detect the expression levels of type I collagen, CTGF, α-SMA, PI-3K/Akt and Smad-dependent and Smad-independent signaling pathway. The effect of aspidin PB on cell viability in human keloid fibroblasts was measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide). The percentage of the apoptotic cells was studied by flow cytometry. Based on our results, we revealed that aspidin PB inhibited the production of type I collagen, CTGF, and α-SMA in TGF-β1-induced KFs by blocking PI-3K/Akt signaling pathway. The TGF-β1-mediated phosphorylated levels of Smad2/3 were inhibited by aspidin PB pretreatment. Conclusively, our study suggests that aspidin PB has an inhibitory effect on fibrogenesis in TGF-β1-induced KFs. Our findings imply that aspidin PB has a therapeutic potential to intervene and prevent keloids and other fibrotic diseases.