Salidroside pretreatment alleviates PM2.5 caused lung injury via inhibition of apoptosis and pyroptosis through regulating NLRP3 Inflammasome

Shi, Shihua; Huang, Demei; Wu, Yongcan; Pei, Caixia; Wang, Yilan; Shen, Zherui; Zhao, Sijing; Jia, Nan; Wang, Xiaomin; Chen, Bonan; Pan, Jie; Wang, Fei; Wang, Zhenxing

doi:10.1016/j.fct.2023.113858

Cited by 15 publications

(4 citation statements)

References 53 publications

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“…Moreover, a 2023 study indicated that the traditional Chinese medicine salidroside can protect against PM2.5-induced lung injury by inhibiting cell pyroptosis and apoptosis through the NF-κB pathway. 56 These findings further confirm the comprehensive and overall protective effect of traditional Chinese medicine on lung injury. Therefore, based on previous research and our current results, we believe that CAP may have a certain therapeutic effect on inflammatory lung diseases by modulating the NF-κB and Pi3k/AKT pathways.…”

Section: Discussionsupporting

confidence: 55%

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Hu,

Liu,

Wang

et al. 2024

JIR

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Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI. Methods: The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPSinduced autophagy. Results: Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression. Conclusion: Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy.

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Section: Discussionsupporting

confidence: 55%

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Hu,

Liu,

Wang

et al. 2024

JIR

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“…For example, Salidroside pretreatment was found to alleviate PM 2.5 -induced lung injury via inhibition of apoptosis and pyroptosis through regulating NLRP3 inflammasome pathway. 52 A CLP-induced SLI mouse model was constructed to confirm the effect of CD14, GSDMD, IL1β, and FAS on SLI. The results of qRT-PCR consistently showed that CD14, IL1β, and FAS expression was significantly increased in SLI, only the expression of GSDMD was not inconsistent with our bioinformatics analysis.…”

Section: Discussionmentioning

confidence: 99%

Identification and Analysis of PANoptosis-Related Genes in Sepsis-Induced Lung Injury by Bioinformatics and Experimental Verification

Yang,

Kao,

Huang

et al. 2024

JIR

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Purpose Sepsis-induced lung injury (SLI) is a serious complication of sepsis. PANoptosis, a novel form of inflammatory programmed cell death that is not yet to be fully investigated in SLI. Our research aims to screen and validate the signature genes of PANoptosis in SLI by bioinformatics and in vivo experiment. Methods SLI-related datasets were downloaded from NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of SLI were identified and intersected with the PANoptosis gene set to obtain DEGs related to PANoptosis (SPAN_DEGs). Then, Protein–Protein Interaction (PPI) network and functional enrichment analysis were conducted based on SPAN_DEGs. SVM-REF, LASSO and RandomForest three algorithms were combined to identify the signature genes. The Nomogram and ROC curves were performed to predict diagnostic value. Immune infiltration analysis, correlation analysis and differential expression analysis were used to explore the immunological characterization, correlation and expression levels of the signature genes. Finally, H&E staining and qRT-PCR were conducted for further verification in vivo experiment. Results Twenty-four SPAN_DEGs were identified by intersecting 675 DEGs with the 277 PANoptosis genes. Four signature genes (CD14, GSDMD, IL1β, and FAS) were identified by three machine learning algorithms, which were highly expressed in the SLI group, and had high diagnostic value in the diagnostic model. Moreover, immune infiltration analysis showed that most immune cells and immune-related functions were higher in the SLI group than those in the control group and were closely associated with the signature genes. Finally, it was confirmed that the cecum ligation and puncture (CLP) group mice showed significant pathological damage in lung tissues, and the mRNA expression levels of CD14, IL1β, and FAS were significantly higher than the sham group. Conclusion CD14, FAS, and IL1β may be the signature genes in PANoptosis to drive the progression of SLI and involved in regulating immune processes.

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“…It is reported that Centella asiatica contributes to the clearance of ROS [ 59 ]. Some herbal ingredients, such as salidroside (NF- κ B/NLRP3 axis) [ 60 ], lonicerin (mitochondrial autophagy) [ 61 ], andrographolide (triggering mitochondrial dysfunction) [ 62 ], and celastrol (K63 deubiquitination) [ 63 ], have been found to play a role in lung injury, ulcerative colitis, renal tubulointersticial injury, and liver damage through targeting the NLRP3 inflammasome. Additionally, ginsenosides have been reported to have a strong affinity for NLRP3 and can directly bind to the NLRP3 amino acid site [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Huajuxiaoji Formula Alleviates Phenyl Sulfate‐Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis

Zhang,

Bi,

Zhou

et al. 2024

Journal of Diabetes Research

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Background: One of the most common microvascular complications of diabetes is diabetic kidney disease (DKD). The Huajuxiaoji formula (HJXJ) has shown clinical efficacy for DKD; however, its regulatory mechanisms against DKD remain elusive. We investigated NLRP3 inflammasome and the mechanisms of HJXJ by which HJXJ alleviates DKD.Methods: Phenyl sulfate (PS) was used to establish DKD models. HJXJ was administered to mice through intragastric or made into a pharmaceutical serum for the cell cultures. Biological indicator levels in mouse blood and urine were analyzed, and kidney tissues were used for HE, Masson, and PAS staining. ELISA and western blotting were used to detect inflammatory cytokines and protein levels, respectively. Reactive oxygen species (ROS) production and pyroptosis were evaluated using flow cytometry. Lentiviral vector‐mediated overexpression of NLRP3 was performed to determine whether NLRP3 participates in the antipyroptotic effect of HJXJ.Results: HJXJ significantly reduced the severity of the injury and, in a dose‐dependent manner, decreased the levels of biological markers including creatinine, blood urea nitrogen, urine protein, and endotoxin, as well as inflammatory cytokines such as interleukin (IL)‐1β, IL‐18, tumor necrosis factor‐α, and IL‐6 in DKD mice. Treatment with HJXJ reversed the downregulation of podocin, nephrin, ZO‐1, and occludin and upregulated ROS, NLRP3, Caspase‐1 P20, and GSDMD‐N induced by PS. Moreover, the upregulation of NLRP3 expression increased the number of cells positive for pyroptosis. HJXJ suppressed pyroptosis and inflammasome activation by inhibiting NLRP3 expression.Conclusions: Generally, HJXJ has the potential to reduce DKD injury and exerts anti‐DKD effects by inhibiting the NLRP3‐mediated NLRP3 inflammasome activation and pyroptosis in vitro and in vivo.

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Salidroside pretreatment alleviates PM2.5 caused lung injury via inhibition of apoptosis and pyroptosis through regulating NLRP3 Inflammasome

Cited by 15 publications

References 53 publications

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Identification and Analysis of PANoptosis-Related Genes in Sepsis-Induced Lung Injury by Bioinformatics and Experimental Verification

Huajuxiaoji Formula Alleviates Phenyl Sulfate‐Induced Diabetic Kidney Disease by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis

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