Objective:To investigate thein vitroandin vivoeffect of whole plant extracts ofPeristrophe bicalyculataonTrypanosoma brucei brucei-infected rats.Methods:The experiment wasdivided into two phases:In the first phase,the...Objective:To investigate thein vitroandin vivoeffect of whole plant extracts ofPeristrophe bicalyculataonTrypanosoma brucei brucei-infected rats.Methods:The experiment wasdivided into two phases:In the first phase,the anti-trypanosomal activity of the hot water,cold water,methanol and butanol extracts of the whole plant were determined by incubatingwithTrypanosoma brucei brucei.The cold water extract was partially-purified and the anti-trypanosomal activity of the fractions determined.In the second phase,Trypanosoma brucei brucei-infected rats were treated with fraction 2c for nine days.Packed cell volume(PCV),highdensity lipoprotein(HDL),low density lipoprotein(LDL),total cholesterol(TC),triacylglycerol(TAG),aspartate aminotransferase,alanine aminotransferases(ALT),alkaline phosphatase(ALP),total and direct bilirubin levels were determined at the end of the experiment.Results:Cold water extract immobilized 90%of the parasites after 60 min of incubation,and fraction 2ccompletely immobilized the parasites after 35 min.It significantly increased PCV inTrypanosoma brucei brucei-infected rats.Decreased TC,TAG,HDL and LDL levels of infected rats increasedsignificantly when rats were treated with the fraction,while elevated levels of total bilirubinand ALT also decreased.The difference in urea,direct bilirubin and ALP was not significantwhen infected rats were compared to rats in other groups.Conclusions:The ability of the plantto ameliorate the infection-induced biochemical changes calls for detailed investigation of thepotentials of the plant for antitrypanosomiasis drug delivery.展开更多
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi.This disease is also known as American trypanosomiasis and approximately 7-8 million people are currently infected(WHO,2014.Nifurtimox has been used...Chagas disease is caused by the protozoan parasite Trypanosoma cruzi.This disease is also known as American trypanosomiasis and approximately 7-8 million people are currently infected(WHO,2014.Nifurtimox has been used for over 40 years to treat Chagas disease,however,this drug is only effective during the acute phase of infection,and certain protozoan strains have developed resistance展开更多
American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the ...American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the objective of finding new drug targets and to know better the biology of the agent causal (Trypano-soma cruzi). T. cruzi is an RNAi-negative parasite, therefore the silencing genes strategies by RNAi is not possible;for that reason, antibodies may be taken as a tool for studying the parasite proteins function by blocking these molecules with specific antibodies. The aim of this work was to establish a methodology for antibody delivery (antibody transfection) into viable parasites. We used anti-cyclin-A antibody (human origin) in western blot assay with epimastigote of T. cruzi proteins and this recognized a ~55 kDa polypeptide. Several methods for antibody transfection (electroporation, saponin permeabilization and a lipid-based formulation) were tested. The first two methods were unsuccessful. In electroporation was impossible to visualize the antibody inside parasites and with saponin permeabilization, antibodies were successfully introduced, but with loss of parasites viability. The lipid-based formulation method forms noncovalent complexes with antibodies. These complexes are internalized by cells and antibodies are released into the cytoplasm. With this method, a successful antibody delivery was achieved. Anti-cyclin antibodies were visualized in the cytoplasm from fixed transfected parasites (immunofluorescence assays). At 24 h post-transfection, parasites maintained their viability (90%) and were able to arrest the cell cycle in G0/G1-phase of cultured epimastigotes (cell population increased in G0/G1-phase from 50.5% to 66.2% and decreased in S-phase from 47.2% to 26%). It was also observed that anti-cyclin-A antibodies inhibit the parasite population doubling (p T. cruzi, with a simple and cheap technique, which will allows carrying out further studies of this protozoan.展开更多
Background:Malaria and neglected communicable protozoa parasitic diseases,such as leishmaniasis,and trypanosomiasis,are among the otherwise called diseases for neglected communities,which are habitual in underprivileg...Background:Malaria and neglected communicable protozoa parasitic diseases,such as leishmaniasis,and trypanosomiasis,are among the otherwise called diseases for neglected communities,which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa,Asia,and the Americas.Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period,which have encouraged resistance.These have prompted many researchers to focus on fin ding new drugs that are safe,effective,and affordable from marine environ merits.The aim of this review was to show the diversity,structural scaffolds,in-vitro or in-vivo efficacy,and recent progress made in the discovery/isolation of marine natural products(MNPs)with potent bioactivity against malaria,leishmaniasis,and trypanosomiasis.Main text:We searched PubMed and Google scholar using Boolean Operators(AND,OR,and NOT)and the combination of related terms for articles on marine natural products(MNPs)discovery published only in English language from January 2016 to June 2020.Twenty nine articles reported the isolation,identification and antiparasitic activity of the isolated compounds from marine environment.A total of 125 compounds were reported to have been isolated,out of which 45 were newly isolated compounds.These compounds were all isolated from bacteria,a fungus,sponges,algae,a bryozoan,cnidarians and soft corals.In recent years,great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds.Comparably,some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs.However,very few of these MNPs have a pharmaceutical destiny due to lack of the following:sustainable production of the bioactive compounds,stan da rd efficient screening methods,knowledge of the mechanism of action,partnerships between researchers and pharmaceutical industries.Conclusions:It is crystal clear that marine organisms are a rich source of antiparasitic compounds,such as alkaloids,terpenoids,peptides,polyketides,terpene,coumarins,steroids,fatty acid derivatives,and lactones.The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.展开更多
基金Supported by Education Trust Fund of Nigeria with the grant number ETF/DESS/AS&D/UNIV/ABU/ZARIA/V2
文摘Objective:To investigate thein vitroandin vivoeffect of whole plant extracts ofPeristrophe bicalyculataonTrypanosoma brucei brucei-infected rats.Methods:The experiment wasdivided into two phases:In the first phase,the anti-trypanosomal activity of the hot water,cold water,methanol and butanol extracts of the whole plant were determined by incubatingwithTrypanosoma brucei brucei.The cold water extract was partially-purified and the anti-trypanosomal activity of the fractions determined.In the second phase,Trypanosoma brucei brucei-infected rats were treated with fraction 2c for nine days.Packed cell volume(PCV),highdensity lipoprotein(HDL),low density lipoprotein(LDL),total cholesterol(TC),triacylglycerol(TAG),aspartate aminotransferase,alanine aminotransferases(ALT),alkaline phosphatase(ALP),total and direct bilirubin levels were determined at the end of the experiment.Results:Cold water extract immobilized 90%of the parasites after 60 min of incubation,and fraction 2ccompletely immobilized the parasites after 35 min.It significantly increased PCV inTrypanosoma brucei brucei-infected rats.Decreased TC,TAG,HDL and LDL levels of infected rats increasedsignificantly when rats were treated with the fraction,while elevated levels of total bilirubinand ALT also decreased.The difference in urea,direct bilirubin and ALP was not significantwhen infected rats were compared to rats in other groups.Conclusions:The ability of the plantto ameliorate the infection-induced biochemical changes calls for detailed investigation of thepotentials of the plant for antitrypanosomiasis drug delivery.
基金the Universidad Autonoma de Nuevo León(Mexico)for PAICYT grants CN-422-10 and CN-662-11
文摘Chagas disease is caused by the protozoan parasite Trypanosoma cruzi.This disease is also known as American trypanosomiasis and approximately 7-8 million people are currently infected(WHO,2014.Nifurtimox has been used for over 40 years to treat Chagas disease,however,this drug is only effective during the acute phase of infection,and certain protozoan strains have developed resistance
文摘American trypanosomiasis is a zoonosis of worldwide medical importance and currently there is no effective treatment in chronic patients, hence the importance of the study of protein function of the parasite with the objective of finding new drug targets and to know better the biology of the agent causal (Trypano-soma cruzi). T. cruzi is an RNAi-negative parasite, therefore the silencing genes strategies by RNAi is not possible;for that reason, antibodies may be taken as a tool for studying the parasite proteins function by blocking these molecules with specific antibodies. The aim of this work was to establish a methodology for antibody delivery (antibody transfection) into viable parasites. We used anti-cyclin-A antibody (human origin) in western blot assay with epimastigote of T. cruzi proteins and this recognized a ~55 kDa polypeptide. Several methods for antibody transfection (electroporation, saponin permeabilization and a lipid-based formulation) were tested. The first two methods were unsuccessful. In electroporation was impossible to visualize the antibody inside parasites and with saponin permeabilization, antibodies were successfully introduced, but with loss of parasites viability. The lipid-based formulation method forms noncovalent complexes with antibodies. These complexes are internalized by cells and antibodies are released into the cytoplasm. With this method, a successful antibody delivery was achieved. Anti-cyclin antibodies were visualized in the cytoplasm from fixed transfected parasites (immunofluorescence assays). At 24 h post-transfection, parasites maintained their viability (90%) and were able to arrest the cell cycle in G0/G1-phase of cultured epimastigotes (cell population increased in G0/G1-phase from 50.5% to 66.2% and decreased in S-phase from 47.2% to 26%). It was also observed that anti-cyclin-A antibodies inhibit the parasite population doubling (p T. cruzi, with a simple and cheap technique, which will allows carrying out further studies of this protozoan.
文摘Background:Malaria and neglected communicable protozoa parasitic diseases,such as leishmaniasis,and trypanosomiasis,are among the otherwise called diseases for neglected communities,which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa,Asia,and the Americas.Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period,which have encouraged resistance.These have prompted many researchers to focus on fin ding new drugs that are safe,effective,and affordable from marine environ merits.The aim of this review was to show the diversity,structural scaffolds,in-vitro or in-vivo efficacy,and recent progress made in the discovery/isolation of marine natural products(MNPs)with potent bioactivity against malaria,leishmaniasis,and trypanosomiasis.Main text:We searched PubMed and Google scholar using Boolean Operators(AND,OR,and NOT)and the combination of related terms for articles on marine natural products(MNPs)discovery published only in English language from January 2016 to June 2020.Twenty nine articles reported the isolation,identification and antiparasitic activity of the isolated compounds from marine environment.A total of 125 compounds were reported to have been isolated,out of which 45 were newly isolated compounds.These compounds were all isolated from bacteria,a fungus,sponges,algae,a bryozoan,cnidarians and soft corals.In recent years,great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds.Comparably,some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs.However,very few of these MNPs have a pharmaceutical destiny due to lack of the following:sustainable production of the bioactive compounds,stan da rd efficient screening methods,knowledge of the mechanism of action,partnerships between researchers and pharmaceutical industries.Conclusions:It is crystal clear that marine organisms are a rich source of antiparasitic compounds,such as alkaloids,terpenoids,peptides,polyketides,terpene,coumarins,steroids,fatty acid derivatives,and lactones.The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.
