Paeoniflorin attenuates particulate matter-induced acute lung injury by inhibiting oxidative stress and NLRP3 inflammasome-mediated pyroptosis through activation of the Nrf2 signaling pathway.

Particulate matter (PM), the main component of air pollutants, emerges as a research hotspot, especially in the area of respiratory diseases. Paeoniflorin (PAE), known as anti-inflammatory and immunomodulatory effects, has been reported to alleviate acute lung injury (ALI). However, the effect of PAE on PM-induced ALI and the underlying mechanisms are still unclear yet. In this study, we established the PM-induced ALI model using C57BL/6J mice and BEAS-2B cells to explore the function of PAE. In vivo, mice were intraperitoneally injected with PAE (100 mg/kg) or saline 1 h before instilled with 4 mg/kg PM intratracheally and were euthanized on the third day. For lung tissues, HE staining and TUNEL staining were used to evaluate the degree of lung injury, ELISA assay was used to assess inflammatory mediators and oxidative stress level, Immunofluorescence staining and western blotting were applied to explore the role of pyroptosis and Nrf2 signaling pathway. In vitro, BEAS-2B cells were pretreated with 100 μM PAE before exposure to 200 μg/ml PM and were collected after 24h for the subsequent experiments. TUNEL staining, ROS staining, and western blotting were conducted to explore the underlying mechanisms of PAE on PM-induced ALI. According to the results, PAE can attenuate the degree of PM-induced ALI in mice and reduce PM-induced cytotoxicity in BEAS-2B cells. PAE can relieve PM-induced excessive oxidative stress and NLRP3 inflammasome-mediated pyroptosis. Additionally, PAE can also activate Nrf2 signaling pathway and inhibition of Nrf2 signaling pathway can impair the protective effect of PAE by aggravating oxidative stress and pyroptosis. Our findings demonstrate that PAE can attenuate PM-induced ALI by inhibiting oxidative stress and NLRP3 inflammasome-mediated pyroptosis, which is mediated by Nrf2 signaling pathway.

Zhou W ，Zuo H ，Qian Y ，Miao W ，Chen C ... -  《-》

5-Methoxytryptophan ameliorates endotoxin-induced acute lung injury in vivo and in vitro by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway.

Endotoxin-induced acute lung injury (ALI) is a complicated and fatal condition with no specific or efficient clinical treatments. 5-Methoxytryptophan (5-MTP), an endogenous metabolite of tryptophan, was revealed to block systemic inflammation. However, the specific mechanism by which 5-MTP affects ALI still needs to be clarified. The purpose of this study was to determine whether 5-MTP protected the lung by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway. We used lipopolysaccharide (LPS)-stimulated C57BL/6 J mice and MH-S alveolar macrophages to create models of ALI, and 5-MTP (100 mg/kg) administration attenuated pathological lung damage in LPS-exposed mice, which was associated with decreased inflammatory cytokines and oxidative stress levels, upregulated protein expression of Nrf2 and HO-1, and suppressed Caspase-1 activation and NLRP3-mediated pyroptosis protein levels. Moreover, Nrf2-deficient mice or MH-S cells were treated with 5-MTP to further confirm the protective effect of the Nrf2/HO-1 pathway on lung damage. We found that Nrf2 deficiency partially eliminated the beneficial effect of 5-MTP on reducing oxidative stress levels and inflammatory responses and abrogating the inhibition of NLRP3-mediated pyroptosis induced by LPS. These findings suggested that 5-MTP could effectively ameliorate ALI by inhibiting NLRP3-mediated pyroptosis via the Nrf2/HO-1 signaling pathway.

Ma Y ，Wang Z ，Wu X ，Ma Z ，Shi J ，He S ，Li S ，Li X ，Li X ，Li Y ，Yu J ... -  《-》

Glycyrrhizin protects against particulate matter-induced lung injury via regulation of endoplasmic reticulum stress and NLRP3 inflammasome-mediated pyroptosis through Nrf2/HO-1/NQO1 signaling pathway.

Particulate matter (PM) is a major environmental pollutant that contributes considerably to deaths worldwide. The pathogenesis of PM-induced lung injury (PILI) is far from elucidated and warrants effective intervention. An effective component of licorice, glycyrrhizin (GL), has been the subject of much research due to its anti-inflammatory and anti-oxidative capabilities. Although preventive properties of GL are well-known, the precise mechanism of GL in PILI has not yet been investigated. A mouse model of PILI was used to examine the protective effects of GL in vivo, and a human bronchial epithelial cells (HBECs) model was used in vitro. In order to determine whether GL mitigates PILI, its effects on endoplasmic reticulum (ER) stress, NLRP3 inflammasome-mediated pyroptosis and the oxidative response were examined. According to the findings, GL reduced PILI and activate anti-oxidative Nrf2/HO-1/NQO1 signaling in mice. Notably, the effect of GL on PM-induced ER stress and NLRP3 inflammasome-mediated pyroptosis was significantly attenuated by the Nrf2 inhibitor ML385. The data suggest that via the anti-oxidative Nrf2 signaling, GL may reduce oxidative stress-mediated ER stress and NLRP3 inflammasome-mediated pyroptosis. Therefore, GL may serve as a promising treatment for PILI.

Shi Q ，Qian Y ，Wang B ，Liu L ，Chen Y ，Chen C ，Feng L ，Chen J ，Dong N ... -  《-》

Oridonin protects LPS-induced acute lung injury by modulating Nrf2-mediated oxidative stress and Nrf2-independent NLRP3 and NF-κB pathways.

Yang H ，Lv H ，Li H ，Ci X ，Peng L ... -  《Cell Communication and Signaling》

Tangeretin attenuates acute lung injury in septic mice by inhibiting ROS-mediated NLRP3 inflammasome activation via regulating PLK1/AMPK/DRP1 signaling axis.

Liu Y ，Zhang Y ，You G ，Zheng D ，He Z ，Guo W ，Antonina K ，Shukhrat Z ，Ding B ，Zan J ，Zhang Z ... -  《-》