Abstract
Artemisinin (ART) is an anti-malaria natural compound with a moderate anticancer action. As a metabolite of ART, dihydroartemisinin (DHA) may have stronger anti-colorectal cancer (CRC) bioactivities. However, the effects of DHA and ART on CRC chemoprevention, including adaptive immune regulation, have not been systematically evaluated and compared. Coupled with a newly-established HPLC analytical method, enteric microbiome biotransformation was conducted to identify if the DHA is a gut microbial metabolite of ART. The anti-CRC potential of these compounds was compared using two different human CRC cell lines for cell cycle arrest, apoptotic induction, and anti-inflammation activities. Naive CD4+T cells were also obtained for testing the compounds on the differentiation of Treg, Th1 and Th17. Using compound extraction and analytical methods, we observed for the first time that ART completely converted into its metabolites by gut microbiome within 24h, but no DHA was detected. Although ART did not obviously influence cancer cell growth in the concentration tested, DHA very significantly inhibited the cancer cell growth at relatively low concentrations. DHA included G2/M cell cycle arrest via upregulation of cyclin A and apoptosis. Both ART and DHA downregulated the pro-inflammatory cytokine expression. The DHA significantly promoted Treg cell proliferation, while both ART and DHA inhibited Th1 and Th17 cell differentiation. As a metabolite of ART, DHA possessed stronger anti-CRC activities. The DHA significantly inhibited cell growth via cell cycle arrest, apoptosis induction and anti-inflammation actions. The adaptive immune regulation is a related mechanism of actions for the observed effects.
Highlights
Artemisia annua L. or artemisia, is an herb traditionally used in Chinese medicine to treat fever, inflammation, and malaria infections [1]
Coupled with a newly-established HPLC analytical method, enteric microbiome biotransformation was conducted to identify if the DHA is a gut microbial metabolite of ART
A HPLC method for ART and DHA identification was developed, and accompanying this method with ethyl ether extraction significantly increased the efficacy of sample processing
Summary
Artemisia annua L. or artemisia, is an herb traditionally used in Chinese medicine to treat fever, inflammation, and malaria infections [1]. One of its active compounds, artemisinin, a sesquiterpene trioxane lactone agent, was identified by Chinese scientists in 1970s. This novel compound has been used in combination with other drugs to treat drug-resistant malaria and has saved millions of lives. Medicinal herbs and their derivatives, including ART, are almost always taken orally. After intake, their parent compounds could be biotransformed by enteric microbiome, and the metabolites could possess even higher bioactivities compared with the parent ones [5]. After ART oral ingestion, whether the parent compound ART is metabolized by the enteric microbiome into DHA has not been examined
Sign-in/Register to view highlights & summary 
Submitted Version (
Free)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call