Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress
Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress
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柑橘皮提取物可预防柴油废气颗粒引起的慢性阻塞性肺病，如肺部病变和氧化应激
DOI：
10.1039/d3fo02010j
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发表时间：
2023-10-18
期刊：
影响因子：
6.1
通讯作者：
Zhong，Nan-shan
中科院分区：
文献类型：
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作者：
Fang，Zhang-fu;Fu，Yu;Zhong，Nan-shan
慢性阻塞性肺疾病（COPD）是全球第三大死亡原因，其特征在于肺气肿、小气道重塑和粘液分泌过多。柑橘皮已被广泛用作食品香料和慢性肺病的传统中药。鉴于柑橘皮已知含有抗氧化剂和抗炎化合物，我们假设柑橘皮摄入量可以抑制氧化应激和对空气污染暴露的炎症反应，从而缓解COPD样病变。本研究旨在探讨柑橘皮提取物（GC）对柴油机尾气颗粒物（DEPs）所致慢性阻塞性肺疾病（COPD）的预防作用及其可能机制。在体内和体外检查DEP诱导的COPD样肺病理学、炎症反应和氧化应激（有或无GC治疗）。我们的体内研究表明，GC可有效降低支气管肺泡灌洗液（BALF）中的炎性细胞计数和炎性介质（IL-17 A和TNF-α）浓度。GC提取物预处理也显着降低DEP诱导的COPD大鼠血清和肺组织中的氧化应激。此外，GC预处理有效地减少杯状细胞增生（PAS阳性细胞）和纤维化的小气道，减少巨噬细胞浸润以及碳负荷在周围肺，并促进肺气肿和小气道重塑的决议在DEP诱导的COPD大鼠。体外自由基清除试验表明，GC在清除DPPH自由基方面具有强大的抗氧化潜力。此外，GC表现出有效的能力，减少ROS的产生和增强SOD活性的BEAS-2B细胞由DEP刺激。GC处理显著减弱DEP处理的BEAS-2B细胞中IL-8和MUC 5AC水平的增加。GC处理上调了Nrf-2的蛋白水平，并通过MAPK/NF-κB信号通路抑制p38、JNK和p65的磷酸化发挥作用。柑橘皮提取物可有效降低暴露于DEP的外周肺的氧化应激和炎症反应。这些保护作用进一步促进了COPD样病理的解决。
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.