Effects of dihydroartemisinin on the gut microbiome of mice

Mol Med Rep. 2020 Aug;22(2):707-714. doi: 10.3892/mmr.2020.11165. Epub 2020 May 20.

Abstract

Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which has been found to exhibit a broad range of biological activities, excluding antimalarial effects; however its effects on the gut microbiota remain poorly understood. The present study aimed to investigate the effects of DHA on the gut microbiome in mice and to determine its potential biological and pharmaceutical activities through its alteration of the gut microbiota. Serum glucose, triglyceride (TG), total cholesterol, lipopolysaccharide, high density lipoprotein‑cholesterol, low density lipoprotein‑cholesterol, alanine aminotransferase and aspartate aminotransferase levels in mice treated with DHA were analyzed using the corresponding detection kits. In addition, hematoxylin and eosin staining was performed to determine the pathological effects of DHA on the liver, kidney and intestinal tissues of mice, and the effects of DHA on the gut microbiome were analyzed using 16S ribosomal (r)DNA gene analysis. The results demonstrated that the TG serum levels of mice treated with DHA were significantly decreased compared with the control group. Furthermore, 16S rDNA gene analysis demonstrated that the bacterial diversity of mice treated with DHA was enriched compared with the control group. The DHA group exhibited increased numbers of Firmicutes and Saccharibacteria, and decreased Deferribacteres and Actinobacteria compared with the control group at the phylum level. Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis also revealed that the signaling pathways associated with 'Energy metabolism' and 'Nucleotide metabolism' were upregulated, whereas the signaling pathways associated with 'Infectious diseases and 'Neurodegenerative diseases' were downregulated in the DHA group compared with the control group. In conclusion, the findings of the present study indicated that DHA may significantly decrease the serum TG levels and alter the gut microbiota, which suggested its potential to be used for the treatment of hyperlipidemia, inflammatory and neurodegenerative disorders.

Keywords: dihydroartemisinin; lipid metabolism; triglyceride; gut microbiome; 16S ribosomal dna gene analysis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Artemisinins / pharmacology*
  • Databases, Genetic
  • Energy Metabolism
  • Gastrointestinal Microbiome / drug effects*
  • Gene Expression Regulation / drug effects
  • Intestines / cytology
  • Intestines / drug effects
  • Kidney / cytology
  • Kidney / drug effects
  • Liver / cytology
  • Liver / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / pharmacology*
  • Nucleotides / metabolism
  • RNA, Ribosomal, 16S / analysis
  • Signal Transduction / drug effects
  • Triglycerides / blood

Substances

  • Anti-Inflammatory Agents
  • Artemisinins
  • Neuroprotective Agents
  • Nucleotides
  • RNA, Ribosomal, 16S
  • Triglycerides
  • artenimol