Chen Jiyu, Huang Yanli, Bian Xiaohong, He Yan
Clinical Trials Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Office of Academic Research, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Front Nutr. 2022 Feb 25;9:851255. doi: 10.3389/fnut.2022.851255. eCollection 2022.
The inflammatory response is the key pathophysiological character of acute lung injury (ALI). Berberine (BBR), a natural quaternary ammonium alkaloid, plays a functional role in anti-inflammation both and . However, the underlying mechanism between BBR and ALI has not been expounded. Here, we found that BBR improved the permeability of pulmonary and repressed the inflammatory factors in the lipopolysaccharides (LPSs)-induced ALI model. We demonstrated that BBR could suppress the expression of phosphorylated nuclear factor-kappa B (NF-κB) and further restrain the downstream gene nucleotide-binding domain and leucine-rich repeat protein-3 (Nlrp3). Moreover, we also revealed that BBR could directly interact with Nlrp3 protein. After knocked down of Nlrp3 by using siRNA, the protective role of BBR was abrogated . The expression of IL-1β and IL-18 was downregulated by BBR the two signaling pathways. Notably, in Nlrp3 deficient mice, the protective effect of BBR was abolished. These findings demonstrate that BBR has a depressant effect on inflammatory response caused by LPS regulating NF-κB/Nlrp3 signaling pathway, providing a potential therapeutic strategy in ALI.
炎症反应是急性肺损伤（ALI）的关键病理生理特征。黄连素（BBR）是一种天然的季铵生物碱，在抗炎方面发挥着功能性作用。然而，BBR与ALI之间的潜在机制尚未阐明。在此，我们发现BBR改善了肺的通透性，并抑制了脂多糖（LPS）诱导的ALI模型中的炎症因子。我们证明BBR可以抑制磷酸化核因子-κB（NF-κB）的表达，并进一步抑制下游基因核苷酸结合域富含亮氨酸重复蛋白3（Nlrp3）。此外，我们还发现BBR可以直接与Nlrp3蛋白相互作用。使用小干扰RNA（siRNA）敲低Nlrp3后，BBR的保护作用被消除。BBR通过两条信号通路下调白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的表达。值得注意的是，在Nlrp3基因敲除小鼠中，BBR的保护作用被消除。这些发现表明，BBR通过调节NF-κB/Nlrp3信号通路对LPS引起的炎症反应具有抑制作用，为ALI提供了一种潜在的治疗策略。
