當藥黃素抑制脂多醣誘發肺損傷和鐵死亡之作用

肺損傷(pulmonary injury)是由感染、毒素、創傷或吸入有害物質等因素引起的肺部損害。內毒素脂多醣(lipopolysaccharide, LPS)是革蘭氏陰性細菌細胞壁的一種主要成分，具有促發炎活性，常被用作研究肺損傷的模型。近年來，研究表明許多從草藥中提取的生物活性成分能透過多種機制有效改善肺損傷。當藥黃素(Swertisin)是一種植物來源的C-葡萄糖基黃酮(C-glucosyl flavone)，已知具有抗糖尿病、抗發炎和抗氧化作用。鐵死亡(ferroptosis)是一種與鐵依賴性脂質過氧化相關的受調節的非凋亡細胞死亡形式，過去研究顯示鐵死亡作為LPS誘導肺損傷的關鍵因素，然而，swertisin與調控鐵死亡之間的關係仍未闡明。本研究旨在探討swertisin對LPS誘導的肺損傷的保護作用及其潛在分子機制。首先建立LPS和彈性蛋白酶(LPS/E)誘導的肺損傷小鼠模型，研究結果顯示，swertisin改善小鼠肺部病理變化、呼吸率及血氧異常，並有效減輕肺水腫及鐵死亡的程度。在體外實驗中，證明swertisin能抑制LPS在人類支氣管上皮細胞BEAS-2B中誘導的活性氧(reactive oxygen species, ROS)生成與鐵死亡特徵，此外，swertisin還能促進核因子類紅血球2相關因子2 (nuclear factor erythroid 2-related factor 2, Nrf2)路徑活化及下游抗氧化酵素的活性。總而言之，本研究表明swertisin在LPS誘導的肺損傷中具有顯著的保護作用，並透過分子伴侶蛋白(kelch-like ECH-associated protein 1, Keap1)-Nrf2途徑，進而減少氧化損傷與鐵死亡，為治療肺損傷提供了新的思路和研究基礎。

Pulmonary injury is a pathological condition caused by infection, toxins, trauma, or inhalation of harmful substances. Lipopolysaccharide (LPS), a major pro-inflammatory component of the outer membrane of Gram-negative bacteria, is widely used to establish an experimental model of pulmonary injury. In recent years, numerous bioactive compounds extracted from medicinal herbs have demonstrated therapeutic potential in improving pulmonary injury via multiple mechanisms. Swertisin, a plant-derived C-glycosyl flavonoid, is known for its antidiabetic, anti-inflammatory, and antioxidant properties. Ferroptosis is a regulated, non-apoptotic form of cell death associated with iron-dependent lipid peroxidation and has been identified as a key contributor to LPS-induced pulmonary injury. However, the relationship between Swertisin and ferroptosis remains unclear. This study aimed to investigate the protective effects and underlying mechanisms of Swertisin on the LPS-induced pulmonary injury. The mouse model of pulmonary injury was first established using combined lipopolysaccharide and elastase (LPS/E) induction. The results showed that Swertisin significantly improved lung histopathological changes, respiratory rate, and oxygenation, effectively reducing pulmonary edema and ferroptosis in lung tissues. In vitro experiments, Swertisin was shown to inhibit LPS-induced reactive oxygen species (ROS) generation and ferroptosis features in human bronchial epithelial BEAS-2B cells. Additionally, Swertisin promoted activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and enhanced the activity of downstream antioxidant enzymes. In conclusion, this study reveals that Swertisin exerts protective effects against LPS-induced lung injury by attenuating oxidative stress and ferroptosis by regulating the Keap1–Nrf2 signaling pathway, providing a novel insight for therapeutic development in lung injury.