Abstract
Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.
Highlights
Chronic obstructive pulmonary disease (COPD), one of the most widespread chronic respiratory diseases with a prevalence of about 3.9% (Soriano et al, 2020) and the third leading cause of death (World Health Organization, 2019) worldwide, has impacted disastrously on mankind’s health and caused heavy economic burden around the world (Soriano et al, 2017)
Extensive infiltration of inflammatory cells into peribronchial and perivascular regions was observed in COPD mice with significantly increased inflammatory scores, while, they were substantially ameliorated with PLE treatment (200 and 400 mg/kg, p < 0.01) and with RFST (20 mg/kg, p < 0.05 or p < 0.01) and DEX (0.5 mg/kg, p < 0.01) treatment
Significant inhibitions were shown in TNF-α (p < 0.01), IFN-γ (p < 0.05), and IL-17A (p < 0.01) with RFST treatment, but no significance was observed with DEX treatment, the exact reason of which still needs to be explored
Summary
COPD, one of the most widespread chronic respiratory diseases with a prevalence of about 3.9% (Soriano et al, 2020) and the third leading cause of death (World Health Organization, 2019) worldwide, has impacted disastrously on mankind’s health and caused heavy economic burden around the world (Soriano et al, 2017). Among the complex pathogenesis of COPD, chronic airway inflammation is thought to be a key driving factor in its pathological progression, which results in largely and gradually irreversible obstruction in the patient’s entire respiratory tract from the center to the periphery. Anti-inflammatory therapy has been an effective and key means in clinical treatment of COPD. In severe COPD patients, longacting β-agonist (LABA) or long-acting muscarinic antagonist (LAMA)/inhaled corticosteroid (ICS) combination treatment showed curative effects by controlling symptoms such as dyspnea and cough and preventing exacerbations. ICS treatment can reduce COPD airway inflammation, it is related with varieties of side effects, such as a higher risk of pneumonia (Rabe and Watz, 2017), and often developed corticosteroid resistance. The development of a new anti-inflammatory drug is still very urgent and imperative for COPD clinical treatment
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