Chinese medicine as a therapeutic option for pulmonary fibrosis: Clinical efficacies and underlying mechanisms

Fibrosis can occur in any organ and is responsible for up to 45% of all deaths in the industrialized world (Henderson et al., 2020). Pulmonary fibrosis (PF) is an interstitial lung change characterized by alveolar damage, over-restoration of the alveolar epithelium, destruction of lung tissue structure, excessive fibroblast proliferation and massive extracellular matrix (ECM) deposition due to various causes (Moss et al., 2022). Idiopathic pulmonary fibrosis (IPF) is one of the most common idiopathic interstitial pneumonia and the common end-stage pathological pathway of many interstitial lung diseases, with a median survival of only 3–5 years after diagnosis, which seriously threatens human health (Moon et al., 2021). Besides, data from the COVID-19 pandemic show there could be substantial fibrotic consequences following COVID-19 infection (George et al., 2020).

The current paradigm suggests that PF occurs as a result of epithelial injury and dysregulation of epithelial/mesenchymal crosstalk. Recurrent alveolar epithelial cell (AEC) injury leads to metabolic dysfunction, senescence, abnormal epithelial cell activation and dysregulated epithelial repair, which activates multiple interconnected downstream profibrotic pathways, ultimately leading to an aberrant reparative response characterized by excessive collagen deposition (Ma et al., 2022; Moss et al., 2022). Related signaling pathways and targets involve oxidative stress, inflammatory response, epithelial-mesenchymal transition (EMT), myofibroblast (MFs) activation, metabolic disorders, etc (Spagnolo et al., 2021). Currently, there is no universally accepted treatment for PF. Nintedanib and pirfenidone are the only two drugs known to be recommended by evidence-based guidelines for the treatment of IPF. In addition, glucocorticoids, antioxidants, receptor inhibitors and other drugs are also used to treat PF. However, these drugs have limited efficacy in preventing disease progression, and some side effects of long-term medication such as nausea and diarrhea also affect the clinical application of the drugs (Galli et al., 2017). In China, traditional Chinese medicine (TCM) or the integration of traditional Chinese and western medicine is widely used in the treatment of PF. The above treatments can effectively delay the progress of PF and improve the quality of life of patients. And using a combination of Chinese and western medicine is considered to be more effective than monotherapy in treating PF.

In recent years, Chinese medicine, which includes Chinese medicine compounds, Chinese herbal materials and extracts, and Chinese herbal formulas (CHFs), and their compatibility has attracted considerable attention due to its multi-ingredient, multi-target, multi-pathway therapeutic characteristics and potential anti-fibrotic effects. To date, many researchers have investigated Chinese medicine with anti-PF properties through in vitro, in vivo and clinical trials, attempting to better understand the molecular mechanisms and clinical efficacy of Chinese medicine against PF. Although there have been systematic reviews reporting on the application of Chinese medicine in PF (Li and Kan., 2017), a more thorough review summarizing the clinical efficacy and mechanisms of action of Chinese medicine in this field has not yet been conducted. Relevant reviews urgently need to be updated. In this review, the potential of Chinese medicine for PF is comprehensively discussed. We aim to provide updated and extensive evidence into the clinical efficacies of Chinese medicine and emphasize the underlying mechanisms and molecular targets.