Indole-4-carboxaldehyde Isolated from Seaweed, Sargassum thunbergii, Attenuates Methylglyoxal-Induced Hepatic Inflammation.

Seon-Heui Cha,Hee-Sook Jun,Soo-Jin Heo,Yongha Hwang

doi:10.3390/md17090486

Abstract

Glucose degradation is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Glyoxalase-1 (Glo-1) is a ubiquitous cellular enzyme that participates in the detoxification of methylglyoxal (MGO), a cytotoxic byproduct of glycolysis that induces protein modification (advanced glycation end-products, AGEs) and inflammation. Here, we investigated the anti-inflammatory effect of indole-4-carboxaldehyde (ST-I4C), which was isolated from the edible seaweed Sargassum thunbergii, on MGO-induced inflammation in HepG2 cells, a human hepatocyte cell line. ST-I4C attenuated the MGO-induced expression of inflammatory-related genes, such as tumor necrosis factor (TNF)-α and IFN-γ by activating nuclear factor-kappa B (NF-κB) without toxicity in HepG2 cells. In addition, ST-I4C reduced the MGO-induced AGE formation and the expression of the receptor for AGE (RAGE). Interestingly, both the mRNA and protein expression levels of Glo-1 increased following ST-I4C treatment, and the decrease in Glo-1 mRNA expression caused by MGO exposure was rescued by ST-I4C pretreatment. These results suggest that ST-I4C shows anti-inflammatory activity against MGO-induced inflammation in human hepatocytes by preventing an increase in the pro-inflammatory gene expression and AGE formation. Therefore, it represents a potential therapeutic agent for the prevention of hepatic steatosis.

Highlights

Methylglyoxal (MGO), a dicarbonyl compound, is a ubiquitous product of cellular metabolism and is present in all cells, under both normal and pathological conditions
In addition to the direct changes in protein function caused by MGO modifications, advanced glycation end-products (AGEs)-modified proteins exert cellular effects through their interaction with the specific AGE receptor, receptor for AGE (RAGE) [6,7], which triggers an inflammatory response at the cellular level and accounts for AGE toxicity
Some derivatives isolated from natural sources, including seaweed, have indicated that they have various reports on indole derivatives isolated from natural sources, including seaweed, have indicated that biological activities [29,30]

Summary

Introduction

Methylglyoxal (MGO), a dicarbonyl compound, is a ubiquitous product of cellular metabolism and is present in all cells, under both normal and pathological conditions. MGO can be produced as a by-product of protein and fatty acid metabolism [1,2], and the glycolytic pathway represents the most important endogenous source of MGO [3]. MGO is one of the most potent glycating agents; MGO readily reacts with lipids, nucleic acids, and lysine and arginine residues of proteins to form advanced glycation end-products (AGEs) [4,5]. In addition to the direct changes in protein function caused by MGO modifications, AGE-modified proteins exert cellular effects through their interaction with the specific AGE receptor, RAGE (receptor for AGE) [6,7], which triggers an inflammatory response at the cellular level and accounts for AGE toxicity.

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