A standardized herbal extract PM014 ameliorates pulmonary fibrosis by suppressing the TGF-β1 pathway

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating and common chronic lung disease pathologically characterized by loss of epithelial cells and activation of fibroblasts and myofibroblasts. The etiology of IPF remains unclear and the disease pathology is poorly understood with no known efficacious therapy. PM014 is an herbal extract that has been shown to have beneficial effects in pulmonary diseases, which are likely to exert anti-inflammatory bioactions. In the present study, we observed that bleomycin (BLM) caused increased inflammatory infiltration as well as collagen deposition in lungs of mice on day 14 after treatment. Administration of PM014 suppressed BLM-induced inflammatory responses and fibrotic changes in dose-dependent manner in mice. Additionally, we provided in vitro evidence suggesting that PM014 inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) and fibroblast activation in alveolar epithelial cells and human lung fibroblasts from healthy donor and IPF patients. PM014 appeared to target TGF-β1 signaling via Smad-dependent pathways and p38 mitogen-activated protein kinases (MAPKs) pathways. Taken together, our data suggest that PM014 administration exerts a protective effect against lung fibrosis and highlight PM014 as a viable treatment option that may bring benefits to patient with IPF.

Standardized herbal extract PM014 alleviates fine dust-induced lung inflammation in mice

“…In vitro and in vivo results from other studies shows a similar effect of PM014 in murine models of chronic obstructive pulmonary disease (COPD) [4,5] and cockroach allergen-induced asthma [6]. In addition, PM014 has recently been shown to improve pulmonary fibrosis induced by bleomycin [7]. Furthermore, a thirteen-week study of PM014 showed no subchronic oral toxicity in animal model, providing supportive evidence of the safety of PM014.…”

“…The components of PM014 were purchased from Kyung Hee Herb Pharm (Seoul, South Korea) and prepared by Hanlim Pharm Co. LTD (Yongin, Korea) as described in a previous studies [3,7]. The preparation of the medicinal herbs was based on the standards provided by The Korean Herbal Pharmacopoeia published by the Korean Food and Drugs Administration (KFDA).…”

“…Undesirable materials were removed by filtration (Sigma, St. Louis, MO, USA). The solvent was concentrated at 60°C using an evaporator under vacuum, and the final product of PM014 was collected in the form of dried extract powder [7]. PM014 (20 mg/ml) was dissolved in high-performance liquid chromatography (HPLC)-grade methanol and filtered using Minisart RC15 (Sartorius Stedim Biotech, Germany).…”

“…For the evaluation of different doses used in this study those administered therapeutically, we referred to the guidance for industry prepared by the Office of New Drugs in the Center for Drug Evaluation and Research at the Food and Drug Administration [3,8]. The optimal timing for the administration of PM014 was applied based on another preliminary experiment [7], and we decided to use continual treatment of PM014 to examine the significant impact on fine dust-induced inflammation. Both PM014 and DEXA were administered orally (peroral administration, p.o.).…”

“…After all of the animals were euthanized, bronchial alveolar lavage fluid (BALF) was collected by washing the lungs three times with 1 ml of PBS. BALF samples were centrifuged at 2000 rpm for 10 min at 4°C and the cell pellet was resuspended in 1 ml of PBS [7]. A hemocytometer was used to count the total number of live immune cells.…”