title: Mangiferin attenuate sepsis-induced acute kidney injury via antioxidant and anti-inflammatory effects.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nephrology Department, 2nd Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, Hunan, PR China.
authors.forename: Liyu
authors.initials: L
authors.lastname: He
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Peng
authors.forename: Jiefu
authors.initials: J
authors.lastname: Zhu
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Tang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
authors.forename: Youming
authors.initials: Y
authors.lastname: Peng
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D018805:Sepsis / Q000150:complications*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002352:Carrier Proteins; D058847:Inflammasomes; D007375:Interleukin-1; D020382:Interleukin-18; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D044004:Xanthones; C013592:mangiferin