Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages

作者：Cheng Jiang, Jiechun Zhang, Huiwen Xie, Huiting Guan, Rui Li, Caixia Chen, Hongzhen Dong, You Zhou, Wei Zhang · 发表于：Biomedicine & Pharmacotherapy · 年份：2021 · DOI：10.1016/j.biopha.2021.112408 · 被引用次数：45 · 研究领域：Inflammasome and immune disorders、Flavonoids in Medical Research、Sphingolipid Metabolism and Signaling

Acute lung injury (ALI) and its serious form, the acute respiratory distress syndrome (ARDS) are devastating diseases without effective chemotherapy. Exuberant or uncontrolled proinflammation responses in the lung, also known as "cytokine storms", is one of the main culprits in the pathogenesis of organ failure, and anti-inflammatory therapy is essential to alleviate ALI/ARDS-associated injuries. Emerging evidence suggests that baicalein has potent anti-inflammatory and antioxidant properties. However, the underlined mechanism of baicalein to mitigate inflammation in ALI remains unclear. Herein, we demonstrated a critical role for baicalein in suppressing the inflammatory response of LPS-activated macrophages. We found that mitochondria function was restored in the condition of baicalein. Interestingly, results showed that mitochondrial dysfunction positively correlates with inflammatory cytokine generation at each corresponding baicalein concentration. Further mRNA analysis revealed that baicalein mitigates mitochondrial defects via attenuation of dynamin-related protein 1 (Drp1) expression. These reprogrammed mitochondria prevent their function shift from the ATP synthesis to reactive oxygen species (ROS) production after the LPS challenge, thereby dampening NF-κB-dependent inflammatory cytokine transcription. Baicalein reduces the production of inflammatory mediators TNF-α, MIP-1, IL-6, and diminishes neutrophil influx and severity of endotoxin-mediated ALI. Taken together...