Effect of the in vivo activity of dihydroartemisinin against Schistosoma mansoni infection in mice

Abstract

Dihydroartemisinin, formerly known as an antimalarial drug, is the main metabolite of the mother compound artemisinins, as well as of artemether and artesunate. It has been shown that the drug exhibits antischistosomal efficacy against Schistosoma japonicum.The purpose of the current study was to assess the in vivo effect of dihydroartemisinin against Schistosoma mansoni infection in mice. Drugs at a single oral dose of 300 mg/kg were given to mice to assess the efficacy against different developmental stages of the parasite; juvenile and adult S. mansoni were treated with single doses of dihydroarteminisin with different regimens (at 200, 300, 400 or 600 mg/kg) in the stage of drug sensitivity, and the dose-response relationship was assessed; and the effect of multiple doses (at 200, 300 or 400 mg/kg) on juvenile and adult S. mansoni was also observed. The results showed that a single oral dose (300 mg/kg) of dihydroartemisinin reduced total worm burdens by 13.8-82.1% and female worm burdens by 13-82.8%, and the greatest reductions were seen when treatment was given on day 21 post-infection, with total and female worm burden reductions of 82.1% and 82.8%. Administration of a single oral dose of dihydroartemisinin on day 21 post-infection with different drug dosage (at 200, 300, 400 or 600 mg/kg) reduced total worm burdens by 70.3-87.3% and female worm burdens by 73.5-92.4%, depending on dosage. Similar treatments given on day 49 post-infection reduced total worm burdens by 48.7-68.73% and female worm burdens by 63.25-94.6%. There was obvious dose-response relationship of dihydroartemisinin against the schistosomula and adult worms of S. mansoni observed. Administration with dihydroartemisinin at oral doses of 200, 300 and 400 mg/kg, given once on each of days 20-22 post-infection of three successive days, reduced total worm burdens by 88.5-90.1% and female worm burdens by 89.2-92.1%, depending on dosage. Similar treatments given once on each of days 48-50 post-infection reduced total worm burdens by 60-70.3% and female worm burdens by 77.5-94.9%. It is concluded that dihydroartemisinin exhibits in vivo activity against various developmental stages of S. mansoni, particularly the 21-day schistosomula, and there is obvious dose-response relationship of dihydroartemisinin against the schistosomula and adult worms of S. mansoni observed.

Epiisopilosine alkaloid has activity against Schistosoma mansoni in mice without acute toxicity

“…Our observation of higher activity of EPIIS on female S . mansoni worms accords with results from a previous in vivo study investigating natural antischistosomal products and natural product-derived compounds such as dihydroartemisinin [ 34 ]. We therefore speculate that EPIIS may act on different targets in males and females, however, the mechanism of action remains to be elucidated.…”

“…In the literature however, we note that the majority of compounds tested against S . mansoni showed activity at doses higher than 100 mg/kg, e.g., dihydroartemisinin [ 34 ], and nerolidol [ 30 ], whereas (-)-6,6'-dinitrohinokinin reduced total worm burden at a concentration of 100 mg/kg [ 35 ] but to a lesser extent than did EPIIS in the present study. In addition, the treatment produced significant reduction in female worms; this is important as the females are responsible for oviposition, producing about 300 eggs/day, all of which are viable, metabolically active, and highly antigenic [ 36 ].…”

Evaluation of the schistosomicidal activity of the steroidal alkaloids from Solanum lycocarpum fruits

“…Crude aqueous extract of Zingiber officinale (Mostafa et al 2011) and pure compounds as artemether (AbdulGhani et al 2011) and dihydroartemisinin (Li et al 2011) have showed in vivo schistosomicidal effects, but so far, no new drug has been marketed for the treatment of schistosomiasis.…”

Natural Products as Leads in Schistosome Drug Discovery

“…The administration of drug 2 in S. japonicum -infected mice at a single dose of 300 mg/kg during on days 7 and 35 post-infection reduced the total worm burden by 65% and 61%, respectively, indicating the satisfactory activity of the drug against schistosomula and adult S. japonicum worms [ 39 ]. An extended study to evaluate the efficacy against S. mansoni infected mice using the same dose, showed that drug 2 exhibited best activity at 14–21 days (schistosomula) and 49–56 days (adult worms) post-infection, with corresponding worm reduction rates of 77%–82% and 61%–63%, respectively [ 40 ].…”