Mangiferin attenuate sepsis-induced acute kidney injury via antioxidant and anti-inflammatory effects.

Acute kidney injury (AKI) is a frequent and serious complication of sepsis. A growing body of evidence now suggests that inflammatory reactions and tubular dysfunction induced by oxidative stress involved in the mechanisms of the disease. This study aimed to determine the role of anti-inflammatory and anti-oxidant activities of mangiferin (MA) in sepsis-induced AKI. We investigated the effects of MA on apoptosis of rat kidney proximal tubular cell (RPTC), together with renal function and morphological alterations of mice undergoing cecal-ligation and puncture (CLP). The levels of oxidative stress in kidney tissues were also determined. Moreover, we mainly focus on the effects of MA in regulating the production of NLRP3 and Nrf2 in the present study. The exposure to LPS (5 μg/ml) yielded a significant increase of apoptosis in RPTC cells, which was largely inhibited by MA pretreatment. MA attenuates renal dysfunction and ameliorates the morphological changes in the septic mice induced by CLP. MA inhibits oxidative stress, decreases serum levels of IL-1β and IL-18, and prevents tubular epithelial cells apoptosis in kidneys of CLP mice model. Data in this study also suggest that MA promotes Nrf2 expression and suppresses renal NLRP3 inflammasome activation. In summary, MA protects against sepsis-induced AKI through NLRP3 inflammasome inhibition and Nrf2 up-regulation. Thus, the mangiferin could thus be a promising candidate for development of a multi-potent drug.

He L ，Peng X ，Zhu J ，Chen X ，Liu H ，Tang C ，Dong Z ，Liu F ，Peng Y ... -  《-》

Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats.

Wang P ，Huang J ，Li Y ，Chang R ，Wu H ，Lin J ，Huang Z ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1β, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1β and TNF-α production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/d-GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1β and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

Pan CW ，Pan ZZ ，Hu JJ ，Chen WL ，Zhou GY ，Lin W ，Jin LX ，Xu CL ... -  《-》

Role of the nucleotide-binding domain-like receptor protein 3 inflammasome in acute kidney injury.

Acute kidney injury (AKI), which is associated with high mortality rates, involves renal inflammation related to the activation of innate immunity. The inflammatory response in AKI involves the inflammasome, which integrates danger signals into caspase-1-activating platforms, leading to the processing and secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-18. The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a role in the development of many diseases, including AKI. However, the mechanisms by which the NLRP3 inflammasome translates different danger signals into the expression of proinflammatory cytokines remain unclear. Here, we investigated the role of the NLRP3 inflammasome in renal injury in a cecal ligation and puncture (CLP) model of sepsis-induced AKI. CLP decreased blood pressure and increased serum creatinine levels and neutrophil infiltration into the kidney in parallel with the upregulation of NLRP3, the adaptor protein apoptosis-associated speck-like protein, and caspase-1 expression and activity in kidney tissues, and increases in the serum and kidney levels of IL-1β and IL-18. Genetic deletion of NLRP3 reversed the CLP-induced reduction in blood pressure and increases in serum creatinine level and neutrophil infiltration, and attenuated the CLP-induced upregulation of apoptosis-associated speck-like protein, caspase-1 expression and activity, and the secretion of IL-1β and IL-18, similarly to the effects of caspase-1 inhibition. Taken together, our results indicate that activation of the NLRP3 inflammasome contributes to the development of hypotension and the inflammatory response of AKI, suggesting its possible role as a therapeutic target for the treatment of kidney diseases.

Cao Y ，Fei D ，Chen M ，Sun M ，Xu J ，Kang K ，Jiang L ，Zhao M ... -  《-》

Malvidin promotes PGC-1α/Nrf2 signaling to attenuate the inflammatory response and restore mitochondrial activity in septic acute kidney injury.

Fan H ，Sun Y ，Zhang X ，Xu Y ，Ming Y ，Zhang L ，Zhao P ... -  《-》