Gu Lanxin, Yin Yue, Liu Manling, Yu Lu
Yale School of Public Health, New Haven, CT, 06510, United States.
Department of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
Heliyon. 2024 Sep 4;10(17):e37083. doi: 10.1016/j.heliyon.2024.e37083. eCollection 2024 Sep 15.
Acacetin is one of the natural flavone components found in many plants and possesses diverse pharmacological activities. The anti-inflammatory properties and definite mechanism of acacetin remains incompletely illuminated. Here, we evaluated the efficacy of acacetin on lipopolysaccharide (LPS)-induced acute lung injury and TNF-α-stimulated cellular injury . As indicated by survival experiments, acacetin reduced mortality and improved survival time of LPS-induced acute lung injury in mice. 50 mg/kg of acacetin obtained higher survival (about 60 %), and 20 mg/kg of acacetin was about 46.7 %. In addition, 20 mg/kg of acacetin rescued lung histopathologic damage in LPS treated mice, lowered lung-to-body weight and lung wet-to-dry ratios, suppressed myeloperoxidase activity in lung tissue, the contents of protein, the numbers of total cells and neutrophils in bronchoalveolar lavage fluid (BALF), and the contents of inflammatory cytokines such as TNF-α, IL-6, IL-17 and IL-1β in BALF. Acacetin also increased the activity and expression of SIRT1, thereby suppressing acetylation-dependent activation NF-κB. Similarly, , acacetin increased cell viability, reduced levels of TNF-α, IL-6, IL-17, and IL-1β, increased NAD levels as well as NAD/NADH ratio, and then up-regulated the activity and expression of SIRT1, and restrained acetylation-dependent activation NF-κB in TNF-α-stimulated A549 cells, which could be abolished by SIRT1 siRNA. Collectively, the current study showed that acacetin exerts a protective effiect on acute lung injury by improving the activity and expression SIRT1, thereby suppressing the acetylation-dependent activation of NF-κB-p65 and the release of downstream inflammatory cytokines.
刺槐素是许多植物中含有的天然黄酮成分之一，具有多种药理活性。刺槐素的抗炎特性和确切机制仍未完全阐明。在此，我们评估了刺槐素对脂多糖（LPS）诱导的急性肺损伤和肿瘤坏死因子-α（TNF-α）刺激的细胞损伤的疗效。生存实验表明，刺槐素可降低LPS诱导的小鼠急性肺损伤的死亡率并延长存活时间。50mg/kg的刺槐素使存活率更高（约60%），20mg/kg的刺槐素使存活率约为46.7%。此外，20mg/kg的刺槐素可挽救LPS处理小鼠的肺组织病理损伤，降低肺脏与体重比及肺湿重与干重比，抑制肺组织中的髓过氧化物酶活性、蛋白质含量、支气管肺泡灌洗液（BALF）中的总细胞数和中性粒细胞数，以及BALF中TNF-α、白细胞介素-6（IL-6）、白细胞介素-17（IL-17）和白细胞介素-1β（IL-1β）等炎性细胞因子的含量。刺槐素还增加了沉默信息调节因子1（SIRT1）的活性和表达，从而抑制了依赖乙酰化的核因子-κB（NF-κB）激活。同样，刺槐素可提高TNF-α刺激的A549细胞的活力，降低TNF-α、IL-6、IL-17和IL-1β的水平，增加烟酰胺腺嘌呤二核苷酸（NAD）水平以及NAD与烟酰胺腺嘌呤二核苷酸磷酸（NADH）的比率，进而上调SIRT1的活性和表达，并抑制依赖乙酰化的NF-κB激活，而SIRT1小干扰RNA（siRNA）可消除这种作用。总体而言，当前研究表明，刺槐素通过提高SIRT1的活性和表达对急性肺损伤发挥保护作用，从而抑制NF-κB-p65依赖乙酰化的激活及下游炎性细胞因子的释放。
