Sodium Butyrate Attenuates AGEs-Induced Oxidative Stress and Inflammation by Inhibiting Autophagy and Affecting Cellular Metabolism in THP-1 Cells

Abstract

In recent years, sodium butyrate has gained increased attention for its numerous beneficial properties. However, whether sodium butyrate could alleviate inflammatory damage by macrophage activation and its underlying mechanism remains unclear. The present study used an advanced glycosylation products- (AGEs-) induced inflammatory damage model to study whether sodium butyrate could alleviate oxidative stress, inflammation, and metabolic dysfunction of human monocyte-macrophage originated THP-1 cells in a PI3K-dependent autophagy pathway. The results indicated that sodium butyrate alleviated the AGEs-induced oxidative stress, decreased the level of reactive oxygen species (ROS), increased malondialdehyde (MDA) and mRNA expression of pro-inflammatory cytokines of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and increased the content of superoxide dismutase (SOD). Sodium butyrate reduced the protein expression of the NLR family, pyrin domain-containing protein 3 (NLRP3) and Caspase-1, and decreased the nucleus expression of nuclear factor-kappaB (NF-κB). Sodium butyrate decreased the expression of light-chain-associated protein B (LC3B) and Beclin-1, and inhibited autophagy. Moreover, sodium butyrate inhibited the activation of the PI3K/Akt pathway in AGEs-induced THP-1 cells. In addition, the metabolomics analysis showed that sodium butyrate could affect the production of phosphatidylcholine, L-glutamic acid, UDP-N-acetylmuraminate, biotinyl-5’-AMP, and other metabolites. In summary, these results revealed that sodium butyrate inhibited autophagy and NLRP3 inflammasome activation by blocking the PI3K/Akt/NF-κB pathway, thereby alleviating oxidative stress, inflammation, and metabolic disorder induced by AGEs.

The effects of advanced glycation end‐products on skin and potential anti‐glycation strategies

“…AGEs have been shown to impair autophagy, a cellular process responsible for recycling damaged cellular components and maintaining cellular health 40 . Impaired autophagy can lead to the accumulation of damaged cellular components, further contributing to oxidative stress and cellular dysfunction 17 …”

“…Glycation is closely related to oxidative stress, and a large number of oxygen radicals are generated during the process of sugar oxidation, which ultimately leads to the formation of AGEs. In addition, glycated proteins activate membrane receptors such as RAGE through AGEs, which can further induce oxidative stress and pro‐inflammatory states within cells 17 . Over time, the expression of RAGE increases on the cell surface, increasing the passage and amount of AGEs into the body 45 …”

“…40 Impaired autophagy can lead to the accumulation of damaged cellular components, further contributing to oxidative stress and cellular dysfunction. 17 AGEs can modulate gene expression patterns, leading to changes in the expression of genes involved in inflammation, oxidative stress and tissue remodelling. Altered gene expression can contribute to the progression of AGE-related diseases.…”

“…In addition, glycated proteins activate membrane receptors such as RAGE through AGEs, which can further induce oxidative stress and pro-inflammatory states within cells. 17 Over time, the expression of RAGE increases on the cell surface, increasing the passage and amount of AGEs into the body. 45 UV radiation in solar, also termed photoageing, is the most predominant external cause of skin ageing, and it can further catalyse the formation of AGE in the skin.…”

“…As a component of the immune response, inflammatory processes in the body can trigger glycation reactions and stimulate the production of AGEs. High blood sugar levels, as seen in diabetes, accelerate glycation reactions, leading to increased AGE production and further aggravating the disease process 17 . This is also a major reason for the association between diabetes and AGE‐related complications 18,19 .…”