Gallic Acid-L-Leucine Conjugate Protects Mice against LPS-Induced Inflammation and Sepsis via Correcting Proinflammatory Lipid Mediator Profiles and Oxidative Stress

Oxidative Medicine and Cellular Longevity
Yuanyuan ChengJianhui Rong

Abstract

The pathology of endotoxin LPS-induced sepsis is hallmarked by aberrant production of proinflammatory lipid mediators and nitric oxide (NO). The aim of the present study was to determine whether the new product gallic acid-L-leucine (GAL) conjugate could ameliorate the LPS-induced dysregulation of arachidonic acid metabolism and NO production. We first investigated the effects of GAL conjugate on the expression of proinflammatory enzymes and the production of proinflammatory NO and lipid mediators in mouse macrophage cell line RAW264.7, primary peritoneal macrophages, and mouse model. Western blot analyses revealed that GAL attenuated LPS-induced expression of iNOS, COX-2, and 5-LOX in a concentration-dependent manner. Consistently, probing NO-mediated fluorescence revealed that GAL antagonized the stimulatory effect of LPS on iNOS activity. By profiling of lipid mediators with ESI-MS-based lipidomics, we found that GAL suppressed LPS-induced overproduction of prostaglandin E2, prostaglandin F2, leukotriene B4, and thromboxane B2. We further discovered that GAL might exhibit anti-inflammatory activities by the following mechanisms: (1) suppressing LPS-induced activation of MAP kinases (i.e., ERK1/2, JNK, and p38); (2) reducing ...Continue Reading

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Citations

Nov 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jinrong BaiXianli Meng
Feb 7, 2020·Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry·Ozkan Karatas, Fikret Gevrek

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Methods Mentioned

BETA
NMR
lavage
electrophoresis
Assay
nuclear
fluorescence microscopy
nuclear translocation

Software Mentioned

SPSS
NIH Image J
Analyst
Image J

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