João Gustavo Mendes Rodrigues1, Paula Sibelly Veras Albuquerque2, Johnny R Nascimento3, Jaianna Andressa Viana Campos4, Andressa S S Godinho5, Sulayne Janayna Araújo6, Jefferson Mesquita Brito7, Caroline M Jesus8, Guilherme Silva Miranda9, Michelle C Rezende10, Deborah Aparecida Negrão-Corrêa11, Cláudia Q Rocha12, Lucilene Amorim Silva13, Rosane N M Guerra14, Flávia R F Nascimento15. 1. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: gustavorodrigues_98@hotmail.com. 2. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: paulasibelly@gmail.com. 3. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: john_nyramos@yahoo.com.br. 4. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: jaiana_campos@hotmail.com. 5. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: dessasouzaster@gmail.com. 6. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: sulaynebio@hotmail.com. 7. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: jeffersonbrito17@hotmail.com. 8. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: caroline.martinsj19@hotmail.com. 9. Laboratory of Immunohelmintology, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, CEP: 31.270-901, Belo Horizonte, MG, Brazil; Laboratory of Biology, Department of Education, Federal Institute of Education, CEP: 65.840-000, São Raimundo Das Mangabeiras, MA, Brazil. Electronic address: mirandagsbio@gmail.com. 10. Laboratory of Immunohelmintology, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, CEP: 31.270-901, Belo Horizonte, MG, Brazil. Electronic address: bio.michelle@gmail.com. 11. Laboratory of Immunohelmintology, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, CEP: 31.270-901, Belo Horizonte, MG, Brazil. Electronic address: denegrao@icb.ufmg.br. 12. Laboratory of Natural Products Chemistry, Department of Chemistry, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: claudiarocha3@yahoo.com.br. 13. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: lucileneamorimsilva@yahoo.com.br. 14. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: roguerra@globo.com. 15. Laboratory of Immunophysiology, Centre for Biological and Health Sciences, Federal University of Maranhão, CEP: 65.055-970, São Luís, MA, Brazil. Electronic address: flavia.nascimento@ufma.br.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Folk medicine reports have described the use of Chenopodium ambrosioides as an anti-inflammatory, analgesic, and anthelmintic herb. These effects, including its activity against intestinal worms, are already scientifically observed. However, the immunological mechanisms of this species in the treatment of Schistosoma mansoni infection are unknown. AIM OF THE STUDY: To evaluate the immunological and anti-Schistosoma mansoni effects of a crude Chenopodium ambrosioides hydro-alcoholic extract (HCE). MATERIALS AND METHODS: For the in vitro analysis, cercariae and adult worms were exposed to different concentrations (0 to 10,000 μg/mL) of the HCE. For the in vivo evaluation, Swiss mice were infected with 50 cercariae of S. mansoni and separated into groups according to treatment as follows: a negative control (without treatment), a positive control (treated with Praziquantel®), HCE1 Group (treated with HCE during the cutaneous phase), HCE2 Group (treated with HCE during the lung phase), HCE3 Group (treated with HCE during the young worm phase), and HCE4 Group (treated with HCE during the adult worm phase). The animals treated with HCE received daily doses of 50 mg/kg, by gavage, for seven days, corresponding to the different developmental stages of S. mansoni. For comparison, a clean control group (uninfected and untreated) was also included. All animals were euthanized 60 days post-infection to allow the following assessments to be performed: a complete blood cells count, counts of eggs in the feces and liver, the quantification of cytokines and IgE levels, histopathological evaluations of the livers, and the analysis of inflammatory mediators. RESULTS: HCE treatment increased the mortality of cercariae and adult worms in vitro. The HCE treatment in vivo reduced the eggs in feces and liver. The number and area of liver granulomas, independent of the phase of treatment, were also reduced. The treatment with HCE reduced the percentage of circulating eosinophils, IgE, IFN-γ, TNF-α, and IL-4. In contrast, the treatment with the HCE, dependent on the phase, increased IL-10 levels and the number of peritoneal and bone marrow cells, mainly of T lymphocytes, B lymphocytes, and macrophages. This effect could be due to secondary compounds presents in this extract, such as kaempferol, quercetin and derivatives. CONCLUSIONS: This study demonstrates that Chenopodium ambrosioides has antiparasitic and immunomodulatory activity against the different phases of schistosomiasis, reducing the granulomatous inflammatory profile caused by the infection and, consequently, improving the disease prognosis.
ETHNOPHARMACOLOGICAL RELEVANCE: Folk medicine reports have described the use of Chenopodium ambrosioides as an anti-inflammatory, analgesic, and anthelmintic herb. These effects, including its activity against intestinal worms, are already scientifically observed. However, the immunological mechanisms of this species in the treatment of Schistosoma mansoni infection are unknown. AIM OF THE STUDY: To evaluate the immunological and anti-Schistosoma mansoni effects of a crude Chenopodium ambrosioides hydro-alcoholic extract (HCE). MATERIALS AND METHODS: For the in vitro analysis, cercariae and adult worms were exposed to different concentrations (0 to 10,000 μg/mL) of the HCE. For the in vivo evaluation, Swiss mice were infected with 50 cercariae of S. mansoni and separated into groups according to treatment as follows: a negative control (without treatment), a positive control (treated with Praziquantel®), HCE1 Group (treated with HCE during the cutaneous phase), HCE2 Group (treated with HCE during the lung phase), HCE3 Group (treated with HCE during the young worm phase), and HCE4 Group (treated with HCE during the adult worm phase). The animals treated with HCE received daily doses of 50 mg/kg, by gavage, for seven days, corresponding to the different developmental stages of S. mansoni. For comparison, a clean control group (uninfected and untreated) was also included. All animals were euthanized 60 days post-infection to allow the following assessments to be performed: a complete blood cells count, counts of eggs in the feces and liver, the quantification of cytokines and IgE levels, histopathological evaluations of the livers, and the analysis of inflammatory mediators. RESULTS:HCE treatment increased the mortality of cercariae and adult worms in vitro. The HCE treatment in vivo reduced the eggs in feces and liver. The number and area of liver granulomas, independent of the phase of treatment, were also reduced. The treatment with HCE reduced the percentage of circulating eosinophils, IgE, IFN-γ, TNF-α, and IL-4. In contrast, the treatment with the HCE, dependent on the phase, increased IL-10 levels and the number of peritoneal and bone marrow cells, mainly of T lymphocytes, B lymphocytes, and macrophages. This effect could be due to secondary compounds presents in this extract, such as kaempferol, quercetin and derivatives. CONCLUSIONS: This study demonstrates that Chenopodium ambrosioides has antiparasitic and immunomodulatory activity against the different phases of schistosomiasis, reducing the granulomatous inflammatory profile caused by the infection and, consequently, improving the disease prognosis.