RESUMO
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 effective action scientifically. This study assessed the cercaricidal and schistosomicidal activity of P. tithymaloides stem barks raffia wine extract (RwPt) and hydroethanolic extract (HePt). Different 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 LC50 of 73.91 µg/mL after 60 min of incubation and 731.17 µg/mL after 48 h of incubation, respectively. Furthermore, a significant reduction of 94.44% in motor activity was observed in surviving worms at the concentration of 2000 µg/mL. RwPt was less effective on S. mansoni cercariae with an LC50 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 profile with an IC50 of 983.50 µg/mL for HePt and more than 1000 µg/mL for RwPt. The 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 effect with low cytotoxicity. These findings may support the potential use of Pedilanthus tithymaloides as a natural product or a source of natural-derived compounds for interrupting schistosomiasis transmission.
RESUMO
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.
