Chronic obstructive pulmonary disease (
COPD) is the third leading cause of death worldwide and characterized by
emphysema,
small airway remodeling and mucus hypersecretion. Citrus peels have been widely used as food spices and in
traditional Chinese medicine for chronic
lung disease. Given that citrus peels are known for containing
antioxidants and anti-inflammatory compounds, we hypothesize that citrus peel intake can suppress oxidative stress and inflammatory response to air pollution exposure, thereby alleviating
COPD-like pathologies. This study aimed to investigate the efficacy of citrus peel extract, namely Guang
Chenpi (GC), in preventing the development of
COPD induced by
diesel exhaust particles (DEPs) and its potential mechanism.
DEP-induced
COPD-like lung pathologies, inflammatory responses and oxidative stress with or without GC treatment were examined in vivo and in vitro. Our in vivo study showed that GC was effective in decreasing inflammatory cell counts and inflammatory mediator (IL-17A and TNF-α) concentrations in bronchoalveolar lavage fluid (BALF). Pretreatment with GC extract also significantly decreased oxidative stress in the serum and lung tissue of
DEP-induced
COPD rats. Furthermore, GC pretreatment effectively reduced goblet cell
hyperplasia (PAS positive cells) and
fibrosis of the small airways, decreased macrophage infiltration as well as
carbon loading in the peripheral lungs, and facilitated the resolution of
emphysema and
small airway remodeling in
DEP-induced
COPD rats. An in vitro
free radical scavenging assay revealed robust
antioxidant potential of GC in scavenging DPPH
free radicals. Moreover, GC demonstrated potent capacities in reducing ROS production and enhancing SOD activity in BEAS-2B cells stimulated by DEPs. GC treatment significantly attenuated the increased level of
IL-8 and MUC5AC from
DEP-treated BEAS-2B cells. Mechanistically, GC treatment upregulated the
protein level of Nrf-2 and could function via MAPK/NF-κB signaling pathways by suppressing the phosphorylation of p38, JNK and p65. Citrus peel extract is effective in decreasing oxidative stress and inflammatory responses of the peripheral lungs to
DEP exposure. These protective effects further contributed to the resolution of
COPD-like pathologies.