Synergistic Anti-inflammatory Effect of Radix Platycodon in Combination with Herbs for Cleaning-heat and Detoxification and Its Mechanism

Objective： To investigate the synergistic anti-inflammatory effect of Radix Platycodon in combination with herbs for cleaning-heat and detoxification and its mechanism for Fei （肺）-targeting. Methods： Forty Wistar rats were randomly divided into five groups （8 per group）： the sham-operated group, model group, Radix P/atycodon group, Flos Lonicera and Fructus Forsythia （LF） group, and Radix Platycodon, Flos Lonicera and Fructus Forsythia combination （PLF） group, using a random number table. A rat chronic obstructive pulmonary disease （COPD） model was established by passive smoking and intratracheal instillation of lipopolysaccharide （LPS）. The treatments started from the 15th day of passive smoking for a total duration of 14 days. At the end of the treatment, changes in the following measurements were determined： lung histopathology, inflammatory cytokines including tumor necrosis factor α （TNF- α）, transforming growth factor 13 （TGF- 13 ） and interleukin IL-1 13 （IL-1 13 ） in bronchoalveolar lavage fluid （BALF）, and mRNA expression of endogenous active substance intestinal trefoil factor 3 （TFF3） in the lung tissue. Results： Light microscopy showed that compared with the sham-operated group, rats in the COPD model group had disrupted alveolar structure, collapsed local alveoli, significantly widened or even fused alveolar septa, and massive infiltration of inflammatory cells in the alveolar wall and interstitium. In addition, significant bronchial epithelium hyperplasia, partially shed epithelia, and marked inflammatory cell infiltration in the bronchial wall and its surrounding tissues were noticed. Electron microscopy showed that rats in the model group had degeneration of alveolar type Ⅱ epithelial cell; reduction, breakage or even loss of cell surface microvilli; swollen mitochondria with disappearing cristae and vacuole-like structure; and, increased secondary lysosomes in alveolar macrophages. The TNF- α, TGF- β and IL-β levels and white blood cell （WBC） count in BALF were significantly increased （P〈0.01 or P〈0.05） and TFF3 mRNA expression in the lung tissue was significantly reduced （P〈0.01）. After treatment, the pathological morphology of lung injury was less severe in all three treatment groups. In addition, TGF- 13 and IL-1 13 and WBC count in BALF were decreased （P〈0.01 or P〈0.05）, and TFF3 mRNA expression in the lung tissue was significantly increased in the PLF group （P〈0.01）. Compared with the LF group, the IL-1 13 in BALF was significantly decreased （P〈0.05）, and TFF3 mRNA expression was significantly increased （P〈0.05） in the PLF group. Conclusions： Radix Platycodon synergizes with herbs for cleaning-heat and detoxification in reducing inflammatory injury in a rat model of COPD. The synergistic anti-inflammatory effect is reflected in the improvement in pathological changes and in the reduction of IL-1 β levels in BALF. The mechanism of such synergistic action may be related to its effect on maintaining the TFF3 mRNA expression and Fei-targeting function.