Schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from Clerodendrum umbellatum Poir leaves aqueous extract in Schistosoma mansoni infection in mice

Abstract

Background: The 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.

Methods: A 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.

Results: The 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.

Conclusions: This 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.

Fig. 1

Effect of the methanolic fraction from Clerodendrum umbellatum leaves aqueous extract on the worm burden, fecal egg count and egg load in the liver and intestine of mice on the 65th day post-infection. Data are expressed as mean ± SEM; n = 5 (NIC) or n = 6 (IC, PZQ, CuF100, CuF200 and CuF400). NIC non-infected mice, IC infected-untreated mice, PZQ infected mice treated with praziquantel; CuF100, CuF200 and CuF400, infected mice treated with the methanolic fraction from C. umbellatum leaves aqueous extract at 100, 200 and 400 mg/kg respectively. ANOVA followed by Newman-Keuls multiple comparison test: ^**, ^***: statistically different from IC group at p < 0.01 and p < 0.001 respectively. ^§, ^§§: statistically different from PZQ group at p < 0.05 and p < 0.01 respectively

Fig. 2

Effect of the methanolic fraction from Clerodendrum umbellatum leaves aqueous extract on some biomarkers of the oxidative stress on the 65th day post-infection. Data are expressed as mean ± SEM; n = 5 (NIC) or n = 6 (IC, PZQ, CuF100, CuF200 and CuF400). NIC non-infected mice, IC infected-untreated mice, PZQ infected mice treated with praziquantel; CuF100, CuF200 and CuF400: infected mice treated with the methanolic fraction from C. umbellatum leaves aqueous extract at 100, 200 and 400 mg/kg respectively. ANOVA followed by Newman-Keuls multiple comparison test: ^£, ^££, ^£££: statistically different from NIC group at p < 0.05, p < 0.01 and p < 0.001 respectively. ^*, ^**, ^***: statistically different from IC group at p < 0.05, p < 0.01 and p < 0.001 respectively