Pheretima protein inhibits epithelial-mesenchymal transition and extracellular matrix deposition and reduces inflammation, as published in the Journal of Ethnopharmacology.

“These findings provide evidence that the Pheretima protein may be used to treat [idiopathic pulmonary fibrosis] (IPF),” the authors wrote. The protein was also shown to alleviate pulmonary fibrosis in a mouse model.

Pheretima is a genus of earthworms that has been used as a traditional Chinese medicine for thousands of years to treat many pulmonary diseases including asthma, pneumonia, and lung cancer. However, only a few studies have been conducted to date on the potential effect of Pheretima protein in treating lung diseases.

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Here, a team of researchers from China aimed to explain the antipulmonary fibrosis mechanism of the Pheretima protein. To do so, they first obtained Pheretima protein from freeze-dried pheretima.

They then treated control mice and mice in which pulmonary fibrosis was induced using bleomycin with Pheretima protein and pirfenidone, a medicine commonly used to treat IPF. Three weeks later, lung fibrosis, injury, and inflammation were assessed.

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The results demonstrated that Pheretima protein inhibited epithelial-mesenchymal transition and extracellular matrix deposition and reduced inflammation. These are processes that are closely related to the development of pulmonary fibrosis. 

Preliminary mechanistic studies showed that Pheretima protein exerted its activity by reducing the levels of Smad2/3, pSmad2/3, and transforming growth factor-beta 1 (TGF-β1) or in other words, downregulating the TGF-β1/Smad2/3 pathway.

IPF is a chronic and progressive lung disease characterized by the buildup of fibrotic tissue in the pulmonary parenchyma. There is currently no cure for the disease and there are only 2 treatments available that may slow its progression.

However, these treatments do not have an effect on fibrosis that has already occurred and do not improve symptoms. There is still an unmet medical need for treatments that can halt or reverse the progression of the disease.


Li S, Yang Q, Chen F, et al. The antifibrotic effect of pheretima protein is mediated by the TGF-β1/Smad2/3 pathway and attenuates inflammation in bleomycin-induced idiopathic pulmonary fibrosis. J Ethnopharmacol. 2021;286(7):114901. doi:10.1016/j.jep.2021.114901