Preventive effect of total flavonoids of on a chronic obstructive pulmonary disease rat model based on the TLR4/NF-κB pathway.

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is diagnosed based on the clinical symptoms, risk factors, and pulmonary function tests. Exposure to cigarette smoke (CS), microbial infection stimulates monocytes and macrophages to rapidly synthesise and release inflammatory factors. A previous study of (TAF) revealed that it had significant anti-inflammatory and anti-oxidation effects on a pneumonia disease. Based on recent studies of the inflammatory pathway of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB), we will explore the influence of TAF on COPD.

METHODS

Wistar rats were randomly divided into blank control group, Model Group, low-dose TAF + model group, middle-dose TAF + model group, high-dose TAF + model group, positive control + model group. Except for the blank control group, COPD inflammation models were established in all groups by CS poisoning and LPS. Prior to the daily poisoning, 125 mg/kg, 250 mg/kg, and 500 mg/kg of TAF were administered by gavage in the low-, middle-, and high-dose groups, respectively, and dexamethasone solution (1 mg/kg, once daily) was administered continuously in the positive control group on the last 5 days of modelling. General signs, lung function indices, lung imaging results, complete blood count, lung histopathological changes, inflammatory factors in the alveolar lavage fluid, relative expressions of TLR4, IκB kinase α (IKKα), p65, as well as IL-1β proteins and their mRNA relative expressions were measured and compared between each group.

RESULTS

Compared with the blank control group, TAF effectively reduced pulmonary parenchymal oedema (wet-to-dry ratio) and respiratory secretions. It also significantly delayed lung function injury. Lung X-ray imaging and haematoxylin and eosin staining. Blood routine examination results showed that TAF effectively inhibited the increase of white blood cell, lymphocyte, and eosinophil counts, decreased the release of inflammatory cytokines [IL-1β, IL-6, IL-8, TNF-α, and transforming growth factor-1β (TGF-1β)] and promoted the release of IL-10. It also inhibited the relative expressions of TLR4, IKKα, p65, IL-1β proteins, as well as IL-1 receptor-associated kinase (IRAK-1), IKKɑ, p65, and IL-1β mRNA.

CONCLUSIONS

Early intervention of TAF can reduce the occurrence of COPD, reduce the development of inflammation via TLR/NF-κB pathway, and provide reference for further study of the medicinal value of TAF.