BackgroundThe intensive use of Praziquantel for the treatment of schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes. As drug treatment is an important feature of schistosome control programs, the search for alternative drugs is therefore a priority. The aim of this study was to assess the schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from Clerodendrum umbellatum Poir leaves aqueous extract.MethodsA phytochemical screening of the fraction of C. umbellatum was conducted. The fraction was administered orally and daily to Schistosoma mansoni-infected mice (BALB/c) from the 36th day post-infection for 28 days at 100, 200 and 400 mg/kg. Praziquantel (500 mg/kg) was used as reference drug. Non-infected and infected-untreated mice served as controls. All mice were sacrificed at 65th day post-infection. Body weight, liver/body and spleen/body weights, as well as worm burden, fecal egg count, liver and intestine egg load were determined. In the plasma, levels of total protein, transaminases (ALT, AST), alkaline phosphatase and total bilirubin were monitored to assess the possibility of liver damage. Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) levels were measured in the liver as biomarkers of the oxidative stress.ResultsThe phytochemical analysis of the fraction from C. umbellatum aqueous leaves extract revealed the presence of alkaloids, flavonoids, cardiac glycosides, phenols, saponins, tannins and terpenoids. The worm burden, fecal egg count and egg load in the liver and intestine of infected mice treated with the fraction were significantly (p < 0.001) fewer than in infected-untreated mice. Only the highest-fraction dose reduced the worm and egg burdens in a similar way as praziquantel. Hepatosplenomegaly induced by S. mansoni infection was reduced by the treatment. The liver function on infected mice was ameliorate after administration of the fraction by significant reduction of ALT activity (35.43 to 45.25 %) and increase of total protein level (44.79 to 70.03 %). The methanolic fraction of C. umbellatum prevents the elevated MDA level induced by the infection while significant increase in catalase activity (297.09 to 438.98 %) and glutathione level (58.23 to 95.88 %) were observed after treatment.ConclusionsThis study disclosed the schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from C. umbellatum leaves aqueous. These fraction’s activities were similar to those of praziquantel. This fraction can be considered as a promising source for schistosomicidal agents.

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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.

Background Undernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a low-protein diet on the efficacy of praziquantel. Methodology/Principal findings Thirty-day-old mice were fed with a low-protein diet, and 40 days later, they were individually infected with fifty Schistosoma mansoni cercariae. A 28-day-treatment with praziquantel at 100 mg/kg for five consecutive days followed by distilled water begins on the 36th day post-infection. Mice were sacrificed on the 64th day post-infection. We determined the parasitological burden, liver and intestine histomorphometry, liver injury, and immunomodulation parameters. Praziquantel treatment of infected mice fed with a standard diet (IN-PZQ) resulted in a significant reduction of worm and egg burdens and a normalization of iron and calcium levels. The therapy also improved schistosomiasis-induced hepatopathy and oxidative stress. The anti-inflammatory and immunomodulatory activities of praziquantel were also significant in these mice. When infected mice receiving the low-protein diet were treated with praziquantel (ILP-PZQ), the body weight loss and hepatomegaly were not alleviated, and the worm and liver egg burdens were significantly higher than those of IN-PZQ mice (P < 0.001). The treatment did not reduce the increased activities of ALT and γ-GGT, the high malondialdehyde concentration, and the liver granuloma volume. The iron and calcium levels were not ameliorated and differed from those of IN-PZQ mice (P < 0.001 and P < 0.05). Moreover, in these mice, praziquantel treatment did not reverse the high level of IL-5 and the low mRNA expression of CCL3/MIP-1α and CXCL-10/IP-10 induced by S. mansoni infection. Conclusion/Significance These results demonstrated that a low-protein diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel.

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.