No abstract

The roots of Ozoroa pulcherrima Schweinf are used in traditional medicine to treat intestinal helminthiasis. The aim of this study was to assess the effect of Ozoroa pulcherrima roots methanolic extract (OPME) on liver injury induced by Schistosoma mansoni in mice. A preliminary phytochemical study of OPME was conducted. OPME was given daily and orally to S. mansoni -infected mice at 100, 200 or 400 mg/kg for 28 days, starting from the 36th day post-infection. Praziquantel was used as reference drug. Non-infected and infected-untreated mice served as controls. Worm burden and egg output, transaminases, total bilirubin, alkaline phosphatase and total protein; as well as malondialdehyde, catalase and reduced glutathione were evaluated. In OPME, total phenolic was 79.61 ± 0.25 mg gallic acid equivalent/g, while total flavonoid was 7.98 ± 0.04 mg rutin equivalent/g. Treatment of S. mansoni -infected mice with OPME produced significant reduction of worm burden and ova count in the faeces, liver and intestine. Significant reduction of alanine aminotransferase activity (p < 0.001) as well as significant increase of total protein content (p < 0.001) was recorded after OPME treatment at all doses. Total bilirubin level was also reduced (p < 0.01). Administration of OPME at all doses corrected the high malondialdehyde level (p < 0.001) induced by the infection. At 200 mg/kg, catalase activity and reduced glutathione concentration were significantly increased (p < 0.001). OPME at 200 mg/kg showed moderate schistosomicidal effect, but was effective as the standard drug praziquantel in restoring the liver function after S. mansoni infection.

Aim: The schistosomicidal activity of Clerodendrum umbellatum leaves aqueous extract (CuAE) has been previously demonstrated. The present study was performed to establish the acute and sub-chronic oral toxicity profile of CuAE in mice. Methods: For acute oral toxicity study, CuAE was administered per os to female mice at a single dose of 2,000 mg/kg. Animals were observed for 14 days in order to identify the signs of toxicity or death. In the repeated dose 28-day oral toxicity study, the extract was administered daily and per os to female and male mice at doses of 200, 400, and 800 mg/kg for 28 consecutive days. A satellite group was also set up. Body weight was measured weekly. Hematological, biochemical, and histopathological parameters were analyzed. Results: CuAE at 2,000 mg/kg produced no sign of toxicity or mortality. In the sub-chronic toxicity study, no mortality, no significant change in the body weight, the relative organ weights, and the hematological parameters were recorded in all treated mice. CuAE at 400 mg/kg significantly increased transaminases activities in male mice. Except for creatinine and high-density lipoprotein-cholesterol in which concentrations are increased after administration of CuAE at 800 mg/kg, the levels of others biochemical markers didn't change. Histopathological abnormalities found in the kidneys were reversible. Conclusion: These results indicated that the LD 50 of CuAE is greater than 2,000 mg/kg and CuAE, therefore, belongs to the category five of relatively non-toxic substances. From the sub-chronic toxicity study, the no-observed-adverse-effect level of CuAE for both male and female mice was considered to be 200 mg/kg/day.

Aims: Continuous attempts are being made to develop new and more effective drugs for the treatment of schistosomiasis. Ozoroa pulcherrima Schweinf. is a medicinal plant used in Africa for the treatment of dysmenorrhea, lower abdominal pain, dystocia and intestinal helminthiasis. This study provides findings on the cercaricidal and schistosomicidal activity of extracts and fractions of Ozoroa pulcherrima in in vitro assays. Methodology: The aqueous and methanolic extracts from Ozoroa pulcherrima root parts (62.5 – 2000 µg/mL), as well as the methanol derived fractions (n-hexane and ethyl acetate: 31.25 – 1000 µg/mL) were tested on cercariae and adult worms of Schistosoma mansoni. Niclosamide-olamine 5% (1 µg/mL) and praziquantel (10 µg/mL) were respectively used as reference drugs. During the assays, the mortality of cercariae after 2 hours, and adult worms’ mobility and mortality after 48 hours of incubation were evaluated. Results: Ozoroa pulcherrima extracts and fractions significantly increased cercariae and worm mortality in a concentration-dependent manner. The methanolic extract was the most active on cercariae with a LC50of 20.65 µg/mL after 30 minutes, while the n-hexane fraction was the most active on worm with a LC50 of 79.54 μg/mL (65.58 – 96.47 μg/mL) after 48 hours. Significant reduction of motor activity (18.47 to 100%) was recorded for surviving worms incubated in different concentrations of the extracts and fractions. Conclusion: This study proves that Ozoroa pulcherrima extracts and fractions have cercaricidal and schistosomicidal activities. Ozoroa pulcherrima may have great potential as an anti-schistosomal agent for further research.

Aims: Treatment against schistosomiasis relies on praziquantel. Its treatment failure and the possible development of resistant schistosomes strains have been reported in the literature. Clerodendrum umbellatum leaves are used in Africa for the treatment of intestinal helminthiasis. The aim of this study was to evaluate the in vitro activity of C. umbellatum leaves aqueous extract and derived fractions on Schistosoma mansoni adult worms. Methodology: Five male and five female Schistosoma mansoni adult worms were incubated in each well for 48 h in a GMEM culture medium with C. umbellatum aqueous extract (125 to 4000 µg/mL) or its n-hexane, ethyl acetate and methanol fractions or the aqueous residue (62.5 to 2000 µg/mL). The main parameters assessed were the worm’s mortality and the reduction of motor activity. Phytochemical screening of all our tested substances was also performed. The cytotoxicity assay using mouse melanoma liver cells line was performed on the aqueous extract and on the most active fraction. Results: Our study shown that C. umbellatum leaves aqueous extract and its derived fractions promoted worm mortality. The aqueous extract disclosed a LC50 of 805.21 µg/mL while the LC50 of the methanol fraction was 343.10 µg/mL. With this lowest LC50, the methanol fraction from C. umbellatum aqueous extract was therefore the most active. Moreover, it showed low level of toxicity on hepatocytes. Incubation of worms with C. umbellatum aqueous extract and fractions also resulted in a significant reduction of the motor activity of survival worms with a 39.54 to 100% reduction after 48h. The phytochemical screening of C. umbellatum aqueous extract and fractions revealed the presence of alkaloids, phenols, flavonoids, tannins, saponins and terpenoids. Conclusion: The present study demonstrated the in vitro activity of C. umbellatum aqueous extract and derived fractions on S. mansoni adult worms and could then justify its empirical use to combat schistosomiasis.

Schistosomiasis control remains a public health concern, and there is a need to evaluate new strategies for targeting larval and adult stages of the parasite. As Pedilanthus tithymaloides is empirically used to treat schistosomiasis, it becomes essential to know its e ective action scienti cally. is study assessed the cercaricidal and schistosomicidal activity of P. tithymaloides stem barks ra a wine extract (RwPt) and hydroethanolic extract (HePt). Di erent concentrations of these extracts were tested against cercariae (31.25-1000 μg/mL) and adult worms (62.5-2000 μg/mL) of Schistosoma mansoni. Niclosamide-olamine 5% (1 μg/mL) and praziquantel (10 μg/mL) were used as pharmacological controls. Cercariae viability was determined every 30 min for 180 min, and adult worms' motor activity and viability after 24 and 48 h incubation. In addition, cytotoxicity and phytochemical analysis were performed. HePt was lethal to cercariae and adult worms with LC 50 of 73.91 μg/mL after 60 min of incubation and 731.17 μg/ mL after 48 h of incubation, respectively. Furthermore, a signi cant reduction of 94.44% in motor activity was observed in surviving worms at the concentration of 2000 μg/mL. RwPt was less e ective on S. mansoni cercariae with an LC 50 of 617.86 μg/mL after 180 min and on adult worms with a mortality rate of 9.83% at 2000 μg/mL for 48 h incubation. Both extracts showed a weak cytotoxicity pro le with an IC 50 of 983.50 μg/mL for HePt and more than 1000 μg/mL for RwPt. e LC-MS analysis of HePt allowed the detection of two annotated diterpenoids. Based on the selectivity index, the hydroethanolic extract of P. tithymaloides stem barks disclosed an intense cercaricidal activity and a moderate schistosomicidal e ect with low cytotoxicity. ese ndings may support the potential use of Pedilanthus tithymaloides as a natural product or a source of natural-derived compounds for interrupting schistosomiasis transmission.

Background One of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice. Methodology/Principal findings Two months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-β gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2. Conclusion/Significance This study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.