Feikang granules ameliorate pulmonary inflammation in the rat model of chronic obstructive pulmonary disease via TLR2/4-mediated NF-\u03baB pathway

Liuliu Yang,Xiaohong Liu,Yong Wang,Minyong Wen,Kai Wang

doi:10.1186/s12906-020-02964-x

Abstract

PurposeSeveral reports have shown that traditional Chinese medicine could be an alternative therapeutic approach for COPD patients, but the mechanism remains unknown. The present study aimed to examine the effects of Feikang granules in a COPD model rat and investigate the possible mechanisms via Toll-like receptor (TLR)/ nuclear factor kappa B (NF-κB) signaling.MethodsThe COPD model rats were treated with Feikang granules, dexamethasone, or normal saline. The pulmonary function; lung tissue histology; levels of inflammatory cytokines; mRNA levels of TNFα, IL-6, TLR4, and TLR2; and protein levels of TLR4, TLR2, p-IκB, IκB and P65 in lung tissues were evaluated.ResultsThe present study confirmed that the pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and IL-17 levels were elevated and the pulmonary function and morphology are altered in COPD model rats. The TLR2 and TLR4 -mediated NF-kB signaling pathway plays a role in the mechanism of action. Feikang granules, a type of Chinese herbal medicine, significantly reduced LPS induced inflammatory cytokines release from lung tissue and alveolar macrophage in a dose-dependent manner. These medical herbs also prevented TLR2/4 and IκB downregulation and reversed the p-IκB and NF-κB p65 upregulation of the lung tissue in the COPD rats. Feikang granules were also found to protect against pulmonary dysfunction and pathological changes in the COPD rats.ConclusionThe Chinese herbal medicine formula Feikang granules prevent pulmonary inflammation and improve pulmonary function, suggesting that Feikang granules may be an effective treatment for chronic pulmonary diseases, such as COPD.

Highlights

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic bronchitis, airway obstruction, and emphysema, which is one of the leading causes of morbidity and mortality [1, 2]
The results showed that the indexes of Peak of inspiratory flow (PIF), Peak of expiratory flow (PEF), and EF50 of lung function in COPD model group decreased significantly (P = 0.005, Fig. 1), suggesting that airway resistance increased, airflow was blocked, and lung compliance decreased after a longterm smoking; all doses of Feikang granules could significantly improve the airway hyperresponsiveness of COPD rats (P = 0.037) in a dose-dependent manner
The results showed that the levels of IL-1β, TNF-α, IL-6 and IL-17 secreted by alveolar macrophages in COPD model rats were significantly higher than those in control group (P < 0.001, Fig. 6) like in bronchoalveolar lavage fluid (BALF)

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic bronchitis, airway obstruction, and emphysema, which is one of the leading causes of morbidity and mortality [1, 2]. Cigarette smoke may stimulate the airway epithelial cells and release noxious molecules that bind to cell surface Toll-like receptors (TLRs). TLR function forms part of the innate immune system and induces pro-inflammatory cytokine release. TLR4 signaling pathways involve various transcription factors, including Nuclear factor kappa-light-chain-enhancer (NF-κB), Signal Transducers and Activators of Transcription family of transcription factors (STAT1), Interferon regulatory factors (IRF’s), and activator protein 1(AP1), which are all crucial players in the regulation of inflammatory response [7]. Several studies have reported that the TLR4/NF-kB signaling pathway mediates the pulmonary inflammation in COPD model animals or patients [8,9,10]

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Discussion

Conclusion