Thymol protects against bleomycin-induced pulmonary fibrosis via abrogation of oxidative stress, inflammation, and modulation of miR-29a/TGF-β and PI3K/Akt signaling in mice

Idiopathic pulmonary fibrosis is a terminal lung ailment that shares several pathological and genetic mechanisms with severe COVID-19. Thymol (THY) is a dietary compound found in thyme species that showed therapeutic effects against various diseases. However, the effect of THY against bleomycin (BLM)-induced lung fibrosis was not previously investigated. The current study investigated the ability of THY to modulate oxidative stress, inflammation, miR-29a/TGF-beta expression, and PI3K/phospho-Akt signaling in lung fibrosis. Mice were divided into Normal, THY (100 mg/kg, p.o.), BLM (15 mg/kg, i.p.), BLM + THY (50 mg/kg, p.o.), and BLM + THY (100 mg/kg, p.o.) groups and treated for four weeks. The obtained results showed that BLM + THY (50 mg/kg) and BLM + THY (100 mg/kg) reduced fibrotic markers; alpha-SMA and fibronectin, inflammatory mediators; TNF-alpha, IL1 beta, IL-6, and NF-kB and oxidative stress biomarkers; MDA, GSH, and SOD, relative to BLM group. Lung histopathological examination by H&E and Masson's trichrome stains confirmed the obtained results. Remarkably, expression levels of TGF-beta, PI3K, and phospho-Akt were decreased while miR-29a expression was elevated. In conclusion, THY effectively prevented BLM-induced pulmonary fibrosis by exerting significant anti-oxidant and anti-inflammatory effects. Our novel findings that THY upregulated lung miR-29a expression while decreased TGF-beta and PI3K/Akt signaling are worthy of further investigation as a possible molecular mechanism for THY's anti-fibrotic actions.

Automated summary

This study found that thymol (THY) from thyme species can inhibit oxidative stress, inflammation, and lung fibrosis-related miR-29a/TGF-beta and PI3K/phospho-Akt signaling pathways. The results showed that THY effectively alleviated pulmonary fibrosis, upregulated miR-29a expression, and downregulated TGF-beta and PI3K/Akt signaling pathways. These findings are worthy of further investigation as a possible mechanism for THY's anti-fibrotic effects.