RESUMO
A fungal metabolite, diatretol, has shown to be a promising antimalarial agent. Diatretol displayed potent in vitro antiparasitic activity against the Plasmodium falciparum K1 strain, with an IC50 value of 378 ng ml-1, as well as in vivo efficacy in a Plasmodium berghei-infected mice model, with ca. 50% inhibition at 30 mg/kg (p.o.).
Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Animais , Antimaláricos/química , Dicetopiperazinas/química , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/parasitologia , Humanos , Malária/parasitologia , Camundongos Endogâmicos ICR , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Plasmodium berghei/parasitologia , Plasmodium falciparum/efeitos dos fármacosRESUMO
The aim of the present study was chemical clarification of in vitro Peyer's patch-immunomodulating polysaccharides in sugar cane molasses, and evaluation of in vivo modulating activity on immune function of T lymphocytes in Peyer's patches and on microenvironment of hemopoietic system. Five kinds of glucans, comprising of dextranase-sensitive and activity-related d-glucosyl moieties, were purified as in vitro Peyer's patch-immunomodulating polysaccharides from the molasses. Oral administration of a glucan-enriched subfraction induced IL-2 and GM-CSF-producing T lymphocytes in Peyer's patches, resulting in enhancement of IL-6 production in a hemopoietic microenvironment to boost neutrophil numbers in the peripheral blood stream. Oral administration of purified glucan or glucan-enrich sub-fraction of sugar cane reduced the number of Plasmodium berghei- or P. yoelii-infected erythrocytes in a murine infection model, using polysaccharide alone or via co-administration with the antimalarial drug, artesunate. These results suggested that Peyer's patch-immunomodulating glucans enhanced protective immunity through axis of Peyer's patches-hemopoietic system.
Assuntos
Glucanos/farmacologia , Hematopoese/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Malária/tratamento farmacológico , Nódulos Linfáticos Agregados/efeitos dos fármacos , Saccharum/química , Administração Oral , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Feminino , Expressão Gênica/efeitos dos fármacos , Glucanos/química , Glucanos/isolamento & purificação , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Hematopoese/imunologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Malária/genética , Malária/imunologia , Malária/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Nódulos Linfáticos Agregados/imunologia , Extratos Vegetais/química , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium yoelii/efeitos dos fármacos , Plasmodium yoelii/crescimento & desenvolvimento , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
A Kampo medicine, maoto, has been prescribed in an early phase of influenza-like illness and used for a treatment of influenza clinically in Japan these days. However, the efficacy of maoto against the virus infection remains to be elucidated. This study was conducted to evaluate the alleviative effects of maoto against early phase of influenza virus infection and its preliminary mode of actions through immune systems. When maoto (0.9 and 1.6 g/kg/day) was orally administered to A/J mice on upper respiratory tract infection of influenza virus A/PR/8/34 from 4 hours to 52 hours postinfection (p.i.) significant antipyretic effect was shown in comparison with water-treated control. Administration of maoto (0.8 and 1.3 g/kg/day) significantly decreased the virus titers in both nasal (NLF) and bronchoalveolar lavage fluids (BALF) at 52 hours p.i., and significantly increased the anti-influenza virus IgM, IgA, and IgG1 antibody titers in NLF, BALF, and serum, respectively. Maoto also increased significantly the influenza virus-bound IgG1 and IgM antibody titers in serum and the virus-bound IgM antibody titer in even the BALF of uninfected A/J mice. These results indicate that maoto exerts antipyretic activity in influenza virus-infected mice and virus reducing effect at an early phase of the infection through probably augmentation of the virus-bound natural antibodies.
RESUMO
Background. A Kampo medicine, Shahakusan (SHS), has been prescribed in late phase of infection that causes inflammations in the lung. But effect of SHS on viral infection in respiratory tract has never been reported. Objectives. To evaluate anti-influenza virus activity of SHS and its mode of actions through immune systems. Methods. SHS (0.3 g/kg/day) was orally administered to BALB/c miceforupper (URI) or lower respiratory tract infection (LRI) of influenza virus A/PR/8/34. The virus titer of nasal lavage fluid (NLF) at 5 or 2 day postinfection (p.i.) and cytokine mRNA expressions in mandibular lymph node or lung at 5 or 4 day p.i. were evaluated for URI or LRI, respectively. The histopathological examinations of lung tissue and NK cell activity in the splenocytes were also evaluated at 4 day p.i. on LRI. Results. When SHS was administered from 7 days before to 4 days p.i. for URI, the virus titer was significantly decreased in comparison with water-treated control, and IL-4, IL-1ß, and IL-10 mRNA expression was decreased, but IL-12A mRNA expression was increased. Administration of SHS from one day before to one day p.i. for LRI significantly decreased the virus titer. SHS also decreased infiltration of inflammatory cells in the bronchoalveolar spaces and damage of desquamated mucosal epithelia of bronchiole, decreased IP-10 mRNA expression, and increased NK cell activity. Conclusion. SHS has no direct effect on influenza virus infection but exerts antiviral effect in mice by its immunomodulating activity through action of NK cells and anti-inflammatory activity in the lung.