Tetrandrine ameliorates pulmonary fibrosis by inhibiting ROS-mediated fibroblast activation
10.16438/j.0513-4870.2024-0313
- VernacularTitle:汉防己甲素抑制ROS介导的成纤维细胞活化治疗肺纤维化
- Author:
Ye-chao YAN
;
Chun-yi GUO
;
Jia-ming ZHANG
;
Yun-xuan LI
;
Ke LI
- Publication Type:Research Article
- Keywords:
pulmonary fibrosis;
tetrandrine;
fibroblast activation;
reactive oxygen species;
mitochondria
- From:
Acta Pharmaceutica Sinica
2024;59(8):2216-2226
- CountryChina
- Language:Chinese
-
Abstract:
Pulmonary fibrosis is a chronic and progressive lung disease that poses a threat to human health. Current treatment options are limited, highlighting the urgent need for more effective therapeutic strategies. Tetrandrine (TET), a bis-benzylisoquinoline alkaloid extracted from Stephania tetrandra, has been known for its anti-inflammatory and anti-fibrotic effects, but its specific mechanisms remain unclear. This study investigated the anti-fibrotic effects of TET in a chronic model of pulmonary fibrosis, aiming to delineate the molecular mechanisms underlying TET-mediated inhibition of fibroblast activation. The results showed that TET significantly alleviated the pathological changes in a murine model of multiple bleomycin-induced pulmonary fibrosis and effectively inhibited TGF-β1-induced fibroblast activation. Mechanistically, TET predominantly inhibited the TGF-β/SMAD signaling pathway and diminished intracellular reactive oxygen species (ROS) levels. Utilizing CRISPR-Cas9 library screening, we identified that angiotensin II type 1 receptor associated protein (AGTRAP) and membrane palmitoylated protein 6 (MPP6) played important roles in TET's suppressive impact of ROS levels, with the knockout of two genes attenuating TET's antifibrotic activity. All animal treatment procedures were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (IMB-20230406D507). This research not only elucidates the pharmacological mechanism of TET but also provides a novel therapeutic avenue for the treatment of pulmonary fibrosis.
