The Effect of Artemisinin on Inflammation-Associated Lymphangiogenesis in Experimental Acute Colitis

Inflammatory bowel disease (IBD) is characterized by inflammation, angiogenesis, and lymphangiogenesis. Artemisinin (Art), a chemical compound isolated from L. (sweet wormwood), has several biochemical properties including antibacterial, anticancer, anti-inflammation, and anti-angiogenesis effects....

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Bibliographic Details
Published in:International journal of molecular sciences 2020-10, Vol.21 (21), p.8068
Main Authors: Lee, Ae Sin, Hur, Haeng Jeon, Sung, Mi Jeong
Format: Article
Language:English
Subjects:
Animals
Antimalarials - pharmacology
Artemisinins - pharmacology
Colitis - chemically induced
Colitis - drug therapy
Colitis - metabolism
Colitis - pathology
Dextran Sulfate - toxicity
Edema - drug therapy
Edema - etiology
Edema - metabolism
Edema - pathology
Inflammation - complications
Lymphangiogenesis - drug effects
Male
Mice
Mice, Inbred C57BL
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Summary:Inflammatory bowel disease (IBD) is characterized by inflammation, angiogenesis, and lymphangiogenesis. Artemisinin (Art), a chemical compound isolated from L. (sweet wormwood), has several biochemical properties including antibacterial, anticancer, anti-inflammation, and anti-angiogenesis effects. We investigated the effects of Art on inflammation-induced lymphangiogenesis in a dextran sulfate sodium (DSS)-induced mouse acute colitis model. The mice were orally administered Art for 7 days before being evaluated using the disease activity index (DAI) and documenting colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), proinflammatory cytokine levels, and vascular endothelial growth factor (VEGF)-C and VEGF-D/VEGF receptor (VEGFR)-3 mRNA expression levels in colon tissue. Art reduced DSS-induced lymphatic vessel endothelial hyaluronan receptor-1-positive LVD. Art also reduced the symptoms of colitis, improved tissue histology, and relieved inflammatory edema in mice affected by colitis. In addition, Art decreased the infiltration of immunomodulatory cells and inflammatory cytokines, which involved reduction of VEGF-C, -D, and VEGFR-3 expression. Taken together, our findings suggest that Art ameliorates inflammation-driven lymphangiogenesis in an experimental colitis mouse model via the VEGF-C/VEGFR-3 signaling pathway, implicating this pathway as a potential target for the treatment of IBD.
ISSN:1422-0067
1422-0067
DOI:10.3390/ijms21218068