A study from the University of Madras, India, showed that celastrol — a component of an extract from the Thunder God Vine root — was able to reduce inflammation, collagen deposition, and alveolar damage in a rat model of pulmonary fibrosis (PF). The effects were likely the result of a broad activation of antioxidant and antifibrotic activities.
The Thunder God Vine is a traditional Chinese remedy reported to have anti-tumor and antioxidative properties. Studies have shown that the compound blocks activation of pro-inflammatory cytokines such as IL-1, TNF-α, IL-6 and IL-8, and blocks cell division. A recent study in the journal Cell also showed that the substance might be a potential obesity treatment.
Researchers, in the study titled “Celastrol enhances Nrf2 mediated antioxidant enzymes and exhibits anti-fibrotic effect through regulation of collagen production against bleomycin-induced pulmonary fibrosis“ and published in the journal of Chemico-Biological Interactions, induced pulmonary fibrosis in rats by injecting bleomycin, a well-known PF model. The fibrotic rats had reduced antioxidant enzyme activity, and increased levels of reactive oxygen species (ROS) in their lungs.
Celastrol treatment increased the activity of the antioxidant enzymes almost to the levels found in control rats, and also substantially reduced ROS levels. The drug prominently reduced changes in the lungs of the animals, such as the thickening of alveolar walls and alveolar collapse, and reduced lung collagen deposits.
Next, the researchers analyzed inflammatory cells in the rats’ lungs, and found that celastrol normalized the increased numbers of macrophage and neutrophil immune cells, as well as the histamine-secreting mast cells. The treatment also reduced the levels of the fibrotic mediator molecules TNF-α, MMP-2, and MMP-9. Finally, the team observed that Nrf2 — a factor regulating gene expression responses to oxidative stress — was increased.
The authors argued that the increase in Nrf2 signaling is likely the source of the anti-inflammatory and anti-oxidant effects of celastrol, but they are only now performing studies to demonstrate the mechanisms behind celastrol’s effects. Still, considering the broad beneficial outcomes in this widely used lung fibrosis model, celastrol is a promising agent to explore for the development of new PF treatments.