Using high-throughput sequencing to explore the anti-inflammatory effects of α-mangostin.

Abstract

Lipopolysaccharide (LPS) causes an inflammatory response, and α-mangostin (α-MG) is an ingredient of a Chinese herbal medicine with anti-inflammatory effects. We investigated the mechanism by which α-MG reduces LPS-stimulated IEC-6 cells inflammation. A genome-wide examination of control, LPS-stimulated, and α-MG-pretreated cells was performed with the Illumina Hiseq sequencing platform, and gene expression was verified with quantitative real-time PCR (qPCR). Among the 37,199 genes profiled, 2014 genes were regulated in the LPS group, and 475 genes were regulated in the α-MG group. GO enrichment and KEGG pathway analyses of the differentially expressed genes (DEGs) showed that they were mainly related to inflammation and oxidative stress. Based on the transcriptomic results, we constructed a rat model of inflammatory bowel disease (IBD) with LPS and investigated the effects of α-MG on NLRP3 inflammasomes. After LPS stimulation, the rat intestinal villi were significantly detached, with congestion and hemorrhage; the intestinal epithelial cell nuclei were deformed; and the mitochondria were swollen. However, after pretreatment with α-MG, the intestinal villus congestion and hemorrhage were reduced, the epithelial nuclei were rounded, and the mitochondrial morphology was intact. qPCR and western blotting were used to detect NLRP3, caspase 1, interleukin (IL)-18, and IL-1β expression at the gene and protein levels. Their expression increased at both the transcript and protein levels after LPS stimulation, whereas it decreased after pretreatment with α-MG. This study provides new methods and ideas for the treatment of inflammation. α-MG may have utility as a drug for intestinal inflammation.

• Authors: Peng Yin, Wenshu Zou, Jiandong Li, Na Jin, Qian Gao, Fenghua Liu
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 15626 (10 30 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31666566 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Drugs, Chinese Herbal
• Inflammasomes
• Interleukin-18
• Xanthones
• Caspase 1
• mangostin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Caspase 1 (genetics, immunology)
• Drug Evaluation, Preclinical (methods)
• Drugs, Chinese Herbal (pharmacology)
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Inflammasomes (drug effects, genetics, immunology)
• Inflammation (drug therapy, genetics, immunology)
• Interleukin-18 (genetics, immunology)
• Male
• Rats
• Rats, Sprague-Dawley
• Transcriptome (drug effects)
• Xanthones (pharmacology)