Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China.
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
J Pharm Pharmacol. 2021 Sep 7;73(10):1319-1329. doi: 10.1093/jpp/rgab074.
Acute lung injury (ALI) is a pulmonary manifestation of an acute systemic inflammatory response, which is associated with high morbidity and mortality. Accordingly, from the perspective of treating ALI, it is important to identify effective agents and elucidate the underlying modulatory mechanisms. β-Caryophyllene (BCP) is a naturally occurring bicyclic sesquiterpene that has anti-cancer and anti-inflammatory activities. However, the effects of BCP on ALI have yet to be ascertained.
ALI was induced intratracheally, injected with 5 mg/kg LPS and treated with BCP. The bone marrow-derived macrophages (BMDMs) were obtained and cultured then challenged with 100 ng/ml LPS for 4 h, with or without BCP pre-treatment for 30 min.
BCP significantly ameliorates LPS-induced mouse ALI, which is related to an alleviation of neutrophil infiltration and reduction in cytokine production. In vitro, BCP was found to reduce the expression of interleukin-6, interleukin-1β and tumour necrosis factor-α, and suppresses the MAPK signalling pathway in BMDMs, which is associated with the inhibition of TAK1 phosphorylation and an enhancement of MKP-1 expression.
Our data indicate that BCP protects against inflammatory responses and is a potential therapeutic agent for the treatment of LPS-induced acute lung injury.
急性肺损伤(ALI)是全身炎症反应的肺部表现,与高发病率和死亡率相关。因此,从治疗 ALI 的角度来看,确定有效的药物并阐明其潜在的调节机制非常重要。β-石竹烯(BCP)是一种天然存在的双环倍半萜烯,具有抗癌和抗炎活性。然而,BCP 对 ALI 的影响尚未确定。
通过气管内注射 5mg/kg LPS 诱导 ALI,并给予 BCP 治疗。获得骨髓来源的巨噬细胞(BMDMs)并进行培养,然后用 100ng/ml LPS 刺激 4 小时,或用 BCP 预处理 30 分钟。
BCP 显著改善 LPS 诱导的小鼠 ALI,与中性粒细胞浸润减轻和细胞因子产生减少有关。体外,BCP 降低了白细胞介素-6、白细胞介素-1β和肿瘤坏死因子-α的表达,并抑制了 BMDMs 中的 MAPK 信号通路,这与 TAK1 磷酸化的抑制和 MKP-1 表达的增强有关。
我们的数据表明,BCP 可防止炎症反应,是治疗 LPS 诱导的急性肺损伤的潜在治疗药物。