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

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, our results show that baicalein may serve as a new clinical therapeutic strategy in ALI by modulating Drp1-induced mitochondrial impairment, restraining inflammatory responses, and reducing the severity of lung injury.

A traditional herbal formula, Deng-Shi-Qing-Mai-Tang, regulates TLR4/NF-κB signaling pathway to reduce inflammatory response in PM2.5-induced lung injury.

BACKGROUND: Studies revealed that particulate matter 2.5 (PM2.5) enters the lung through the respiratory tract and can damage lung tissue resulting in lung injury primarily via imbalance between pro-inflammatory and anti-inflammatory responses. Moreover, TLR4/NF-κB signaling pathways are reported to play a role in PM2.5-induced inflammation and lung injury, which is closely related to the inflammatory responses. Therefore, the traditional herbal formula, Deng-Shi-Qing-Mai-Tang (DSQMT), has been applied to improve patients' clinical symptoms with lung injury induced by PM2.5. It can reduce inflammatory reactions in lung injury and relieve cough and phlegm. However, the underlying mechanism of DSQMT treatment is still exclusive. PURPOSE: To clarify the preventive and therapeutic effects of DSQMT on PM2.5-induced lung injury and explore its underlying mechanism. STUDY DESIGN: PM2.5-induced lung injury rat model was established, and DSQMT was administered. METHODS: First, PM2.5 was collected, and PM2.5 suspension was prepared. Then, a rat model with PM2.5-induced lung injury was established, and the effects of DSQMT were evaluated in vivo. Finally, the roles of DSQMT in inhibiting the TLR4/NF-κB signaling pathway were investigated in vitro using the NR8383 cell line via Western blot analysis, real-time PCR, electrophoretic mobility shift assay (EMSA), and immunofluorescence staining, respectively and analyzed. RESULTS: We found that DSQMT significantly attenuated pathological lung tissue damage and inflammatory responses in PM2.5-induced lung injury. We also found that after PM2.5 stimulation in vitro, DSQMT regulates the expression of TLR4, MyD88, IKK, IκB-α, NF-κB p65 in the TLR4/NF-κB signaling pathway. It also constrains activated NF-κB entry into the nucleus and further limits its binding to target DNA. In addition, we revealed that DSQMT down-regulated interleukin (IL)-1ß, IL-6, IL-10, THF-α, NO, PGE2 to reduce the inflammatory response. CONCLUSION: We demonstrated that DSQMT has preventive and therapeutic effects on PM2.5-induced lung injury by down-regulation of the TLR4/NF-κB signaling pathway. Therefore, the efficacy of traditional Chinese medicine (TCM) in PM2.5 lung injury can be taken into consideration and may be improved in the future through further researches.