Treatment of pulmonary fibrosis and combined pulmonary fibrosis and emphysema syndrome with herbs for promoting blood circulation and removing blood stasis: A review of pharmacological studies.

[ETHNOPHARMACOLOGICAL RELEVANCE] Pulmonary fibrosis (PF) is a progressive interstitial lung disease (ILD), and combined pulmonary fibrosis and emphysema (CPFE) is a complication of this condition. Traditional Chinese medicine (TCM) considers that the deficiency of the lung, spleen, and kidney, complicated by phlegm and blood stasis obstructing the lung, is the main pathological mechanism of CPFE. Promoting blood circulation and removing blood stasis (RBCRBS) is a crucial therapeutic principle in both treating PF and CPFE. Through research on TCM literature and the clinical experience of a renowned TCM doctor, we have found that Pheretima (Dilong), Spatholobi Caulis (Jixueteng), and Rhodiola (Hongjingtian) are important blood-activating and stasis-resolving (BASR) herbs used to treat PF and COPD. They are effective in improving symptoms and the pathological state of patients with PF and CPFE in clinical practice.

[AIM OF THE STUDY] Through literature research to understand the pathological mechanism of PF and CPFE; By analyzing the traditional application, modern pharmacological research, and network pharmacological research of BASR herbs, to systematically review the effectiveness and unique advantages of these herbs in treating PF and CPFE.

[MATERIALS AND METHODS] Multiple databases, including PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI), were utilized to screen out relevant literature. The search terms were "pulmonary fibrosis", "CPFE", "promoting blood circulation and removing blood stasis", and relevant Chinese herb names such as "Dilong", "Jixueteng", and "Hongjingtian". The literature spanned mainly from 2000 to the present. Additionally, network pharmacology methods were employed to identify the key active ingredients of these herbs and predict their mechanisms of action in treating PF.

[RESULTS] The deficiency of the lung, spleen, and kidney, complicated by phlegm and blood stasis obstructing the lung, is the pathogenesis of CPFE. Pheretima, Spatholobi Caulis, and Rhodiola exert antifibrotic effects through the TGF-β1/Smad2/3 pathway, anti-inflammatory/antioxidant, immune homeostasis restoration, and EMT suppression. Subsequent network pharmacology analysis identifies 74 core targets (TP53, AKT1, SRC, STAT3, TNF), and highlights 20 pathways, including EGFR, HIF-1, FoxO, PD-1/PD-L1, and AGE-RAGE. These collectively influence IPF progression by regulating EMT, fibroblast activation, collagen deposition, and immune microenvironment disruption.

[CONCLUSIONS] This review synthesizes research on the material basis and pharmacodynamics of representative BASR herbs, providing novel insights for advancing the therapeutic application of these herbs in PF and its associated complications.