Standardized Herbal Formula PM014 Inhibits Radiation-Induced Pulmonary Inflammation in Mice

Abstract

Radiation therapy is widely used for thoracic cancers. However, it occasionally causes radiation-induced lung injuries, including pneumonitis and fibrosis. Chung-Sang-Bo-Ha-Tang (CSBHT) has been traditionally used to treat chronic pulmonary disease in Korea. PM014, a modified herbal formula derived from CSBHT, contains medicinal herbs of seven species. In our previous studies, PM014 exhibited anti-inflammatory effects in a chronic obstructive pulmonary disease model. In this study, we have evaluated the effects of PM014 on radiation-induced lung inflammation. Mice in the treatment group were orally administered PM014 six times for 2 weeks. Effects of PM014 on radiation pneumonitis were evaluated based on histological findings and differential cell count in bronchoalveolar lavage fluid. PM014 treatment significantly inhibited immune cell recruitment and collagen deposition in lung tissue. Normal lung volume, evaluated by radiological analysis, in PM014-treated mice was higher compared to that in irradiated control mice. PM014-treated mice exhibited significant changes in inspiratory capacity, compliance and tissue damping and elastance. Additionally, PM014 treatment resulted in the downregulation of inflammatory cytokines, chemokines, and fibrosis-related genes and a reduction in the transforming growth factor-β1-positive cell population in lung tissue. Thus, PM014 is a potent therapeutic agent for radiation-induced lung fibrosis and inflammation.

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

“…An herbal formula, PM014 is composed of 7 components of CSBHT (Chung-Sang-Bo-Ha-Tang), which has been widely used in Korea for the treatment of pulmonary diseases 10 . Our previous study showed that PM014 possessed an anti-inflammatory role in radiation-induced pulmonary inflammation, mainly due to the inhibition of inflammasome activation, with inducing a global improvement of lung function 11 . We also found that PM014 intervention effectively decreased several pro-inflammatory cytokines and chemokines which were elevated in pulmonary inflammation induced by radiation.…”

“…Medical plants of the seven species that constitute PM014 were prepared by Hanlim Pharm Co. LTD (Yongin, Korea) as described previously 11 . Briefly, each herb was mixed, dissolved, and extracted using a reflex condenser presented in Supplementary Table 1 .…”

“…PM014 is a novel herb extract derived from the herbal compound Chung-Sang-Bo-Ha-Tang (CSBHT), which has been widely used for treating lung disorders in traditional medicine 10 . Recently, we found that PM014 suppressed the inflammatory response in radiotherapy-induced pulmonary inflammation by regulating inflammasome activation 11 . PM014 was also documented to inhibit LPS-induced lung neutrophilia in chronic obstructive pulmonary disease (COPD) 12 .…”

PM014 attenuates radiation-induced pulmonary fibrosis via regulating NF-kB and TGF-b1/NOX4 pathways

“…To study the radiation-induced damage of normal tissues adjacent to tumours that underwent radiotherapy, we previously established an in vivo mouse model that mimicked clinical SBRT 23,24 . Using this model, inflammatory responses of the irradiated lung were studied at 2 weeks after irradiation with 75 Gy 8 , and fibrosis could be clearly observed at 6 weeks. PM014 comprises seven major herbal components found in Chung-Sang-Bo-Ha-Tang, a well-known herbal mixture for treating pulmonary diseases in traditional Korean medicine 8,25 .…”

“…Using this model, inflammatory responses of the irradiated lung were studied at 2 weeks after irradiation with 75 Gy 8 , and fibrosis could be clearly observed at 6 weeks. PM014 comprises seven major herbal components found in Chung-Sang-Bo-Ha-Tang, a well-known herbal mixture for treating pulmonary diseases in traditional Korean medicine 8,25 . The optimal dosing and timing of PM014 administration to treat radiation-induced lung injury have been previously assessed in our laboratory, with the optimal conditions being 200 mg/kg, 3 times a week 8 .…”