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

Pulmonary fibrosis (PF) is a fibrotic interstitial lung disease caused by continuous damage and excessive repair of alveolar epithelial cells, the pathogenesis of which is not fully understood. At present, the incidence of PF has increased significantly around the world. The therapeutic arsenals against PF are relatively limited, with often poor efficacy and many adverse effects. As a conventional and effective therapeutic strategy, traditional Chinese medicine (TCM) has been widely applied in treating lung fibrosis for thousands of years in China. Due to the multi-ingredient, multi-target characteristics, Chinese medicines possess promising clinical benefits for PF treatment. This review aims to systematically analyze the clinical efficacy of Chinese medicine on PF, and further summarize the relevant mechanisms of Chinese medicine treating PF in preclinical studies, in order to provide a comprehensive insight into the beneficial effects of Chinese medicines on PF. Eight major Chinese and English databases were searched from database inception up to October 2022, and all randomized clinical trials (RCTs) investigating the effects of Chinese medicine intervention on effectiveness and safety in the treatment of PF patients were included. Subsequently, preclinical studies related to the treatment of PF in Chinese medicine, including Chinese medicine compounds, Chinese herbal materials and extracts, and Chinese herbal formulas (CHFs) were searched through PubMed and Web of science to summarize the related mechanisms of Chinese medicine against PF. A total of 56 studies with 4019 patients were included by searching the relevant databases. Total clinical efficacy, pulmonary function, blood gas analysis, lung high resolution CT (HRCT), 6 min walk test (6-MWT), St George's Respiratory Questionnaire (SGRQ) scores, clinical symptom scores, TCM syndrome scores and other outcome indicators related to PF were analyzed. Besides, numerous preclinical studies have shown that many Chinese medicine compounds, Chinese herbal materials and extracts, and CHFs play a preventive and therapeutic role in PF by reducing oxidative stress, ameliorating inflammation, inhibiting epithelial-mesenchymal transition and myofibroblasts activation, and regulating autophagy and apoptosis. Chinese medicines show potential as supplements or substitutes for treating PF. And studies on Chinese medicines will provide a new approach to better management of PF.