Salidroside ameliorates severe acute pancreatitis-induced cell injury and pyroptosis by inactivating Akt/NF-κB and caspase-3/GSDME pathways

Wang, Xiaohong; Qian, Jing; Meng, Yun; Wang, Ping; Cheng, Ruizhi; Zhou, Guoqing; Zhu, Shunxing; Li, Chun

doi:10.1016/j.heliyon.2023.e13225

Cited by 6 publications

(3 citation statements)

References 49 publications

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“…Recent studies showed that inhibiting pyroptosis alleviates pancreatic injury and significantly affects the progression of AP [12]. This study showed that MARCH9 expression is downregulated in AP patients' serum and has the ability to regulate pyroptosis in PA cells.…”

Section: Discussionmentioning

confidence: 73%

MARCH9, a potential target for the treatment of acute pancreatitis, inhibits NLRP3 inflammasome mediated pyroptosis

Jin,

Ma,

Lin

et al. 2024

Trop. J. Pharm Res

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Purpose: To investigate the regulatory mechanism of membrane associated ring-CH-type finger 9 (MARCH9) in acute pancreatitis (AP). Methods: Fifteen AP patients admitted in Changzhou Second People's Hospital Nanjing, China and fifteen healthy individuals participated in this study. MARCH9 expression in serum samples taken from the subjects was assayed. To establish an AP cell model, rat pancreatic acinar (PA) cells were induced with ceruletide and then transfected with MARCH9 overexpression vector. The MARCH9 level and molecular structure, which are related to pyroptosis and inflammatory cytokines, were determined. Cell survival rate and caspase 1 activity was assessed. Results: MARCH9 was lowly expressed in AP patients’ serum and in ceruletide-induced PA cells. Overexpression of MARCH9 enhanced the survival rate of ceruletide-induced PA cells and reduced the levels of inflammatory cytokines and molecules associated with pyroptosis. MARCH9 overexpression led to a decrease in caspase 1 activity in ceruletide-induced PA cells. Additionally, the overexpression of MARCH9 had a negative regulatory effect on the levels of IL6, p-STAT3/STAT3 and p-JAK2/JAK2 in PA cells induced by ceruletide. Conclusion: Overexpression of MARCH9 suppresses NLRP3-induced pyroptosis in PA cells through the regulation of IL6/JAK/STAT3 pathway, thus offerimg insights for the potential management of AP.

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Section: Discussionmentioning

confidence: 73%

MARCH9, a potential target for the treatment of acute pancreatitis, inhibits NLRP3 inflammasome mediated pyroptosis

Jin,

Ma,

Lin

et al. 2024

Trop. J. Pharm Res

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“…NF-κB requires signaling pathway to activate from the inactivation state in cytoplasm. The activating pathway of NF-κB were trigger by various of extracellular stimuli, which may result in phosphorylation of NF-κB inhibitor and subsequent proteasome-mediated degradation [ 27 ]. Activated NF-κB migrates into the nucleus to regulate the expression of multiple target genes.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic potential of salidroside in preserving rat cochlea organ of corti from gentamicin-induced injury through modulation of NRF2 signaling and GSK3β/NF-κB pathway

Zhang,

Yu,

Guo

et al. 2024

PLoS ONE

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Salidroside (SAL) is a phenol glycoside compound found in plants of the Rhodiola genus which has natural antioxidant and free radical scavenging properties. SAL are able to protect against manganese-induced ototoxicity. However, the molecular mechanism by which SAL reduces levels of reactive oxygen species (ROS) is unclear. Here, we established an in vitro gentamicin (GM) ototoxicity model to observe the protective effect of SAL on GM-induced hair cells (HC) damage. Cochlear explants of postnatal day 4 rats were obtained and randomly divided into six groups: two model groups (treatment with 0.2 mM or 0.4 mM GM for 24 h); two 400 μmol/L SAL-pretreated groups pretreatment with SAL for 3 h followed by GM treatment (0.2 mM or 0.4 mM) for 24 h; 400 μmol/L SAL group (treatment with SAL for 24 h); control group (normal cultured cochlear explants). The protective effects of SAL on GM-induced HC damage, and on mRNA and protein levels of antioxidant enzymes were observed. HC loss occurred after 24 h of GM treatment. Pretreatment with SAL significantly reduced GM-induced OHC loss. In cochlear tissues, mRNA and protein levels of NRF2 and HO-1 were enhanced in the GM alone group compared with the SAL pretreatment GM treatment group. SAL may protect against GM-induced ototoxicity by regulating the antioxidant defense system of cochlear tissues; SAL can activate NRF2/HO-1 signaling, inhibit NF-κB activation, activate AKT, and increase inhibitory phosphorylation of GSK3β to decrease GSK3 activity, all of which exert antioxidant effects.

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“…This indicated that luteolin can target the regulation of AKT1 levels and thereby improve pyroptosis. The latest study found that AKT1 was involved in pyroptosis in severe pancreatitis through AKT1/NF-κB pathway ( 47 ). Interestingly, we found a correlation between AKT1 and iNOS in the STRING database.…”

Section: Discussionmentioning

confidence: 99%

A Network Pharmacology-Based Treatment Analysis of Luteolin for Regulating Pyroptosis in Acute Lung Injury

Zhang

Jiang

et al. 2023

Shock

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Background: Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome, are complicated pulmonary inflammatory conditions for which standard therapeutics are still not well established. Although increasing research has indicated the anti-inflammatory, anticancer, and antioxidant effects of luteolin, especially in lung diseases, the molecular mechanisms underlying luteolin treatment remain largely unclear. Methods: The potential targets of luteolin in ALI were explored using a network pharmacology-based strategy and further validated in a clinical database. The relevant targets of luteolin and ALI were first obtained, and the key target genes were analyzed using a protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The targets of luteolin and ALI were then combined to ascertain the relevant pyroptosis targets, followed by Gene Ontology analysis of core genes and molecular docking of key active compounds to the antipyroptosis targets of luteolin in resolving ALI. The expression of the obtained genes was verified using the Gene Expression Omnibus database. In vivo and in vitro experiments were performed to explore the potential therapeutic effects and mechanisms of action of luteolin against ALI. Results: Fifty key genes and 109 luteolin pathways for ALI treatment were identified through network pharmacology. Key target genes of luteolin for treating ALI via pyroptosis were identified. The most significant target genes of luteolin in ALI resolution included AKT1, NOS2, and CTSG. Compared with controls, patients with ALI had lower AKT1 expression and higher CTSG expression. Luteolin simply reduced systemic inflammation and lung tissue damage in septic mice. Furthermore, we blocked AKT1 expression and found luteolin reduced the degree of lung injury and affected NOS2 levels. Conclusions: As demonstrated by a network pharmacology approach, luteolin may exert an antipyroptosis effect on ALI via AKT1, NOS2, and CTSG.

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Salidroside ameliorates severe acute pancreatitis-induced cell injury and pyroptosis by inactivating Akt/NF-κB and caspase-3/GSDME pathways

Cited by 6 publications

References 49 publications

MARCH9, a potential target for the treatment of acute pancreatitis, inhibits NLRP3 inflammasome mediated pyroptosis

MARCH9, a potential target for the treatment of acute pancreatitis, inhibits NLRP3 inflammasome mediated pyroptosis

Therapeutic potential of salidroside in preserving rat cochlea organ of corti from gentamicin-induced injury through modulation of NRF2 signaling and GSK3β/NF-κB pathway

A Network Pharmacology-Based Treatment Analysis of Luteolin for Regulating Pyroptosis in Acute Lung Injury

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