Chlorpyrifos is a commonly used pesticide of organophosphate group, which causes toxicological effects in non-target organisms especially fish and frogs. In the present study, the genotoxicity of sublethal concentrati...Chlorpyrifos is a commonly used pesticide of organophosphate group, which causes toxicological effects in non-target organisms especially fish and frogs. In the present study, the genotoxicity of sublethal concentrations of chlorpyrifos was observed in the erythrocytes of common Indus valley toad, Bufo stomaticus, using the Alkaline Single-Cell Gel Electrophoresis (Comet) assay. In the first step, acute toxicity of chlorpyrifos was evaluated by exposing the tadpoles to high concentrations of the pesticide. The acute LC50 value of chlorpyrifos, calculated by Trimmed Spearman-Karber (TSK) in static bioassay, was found to be 930.0 μg/L. On the basis of acute LC50 value, the tadpoles were exposed to three sublethal concentrations (155, 233 and 465 μg/L) of chlorpyrifos for 96 h. Blood cells were collected at every 24 h interval and were subjected to the Alkaline Single-Cell Gel Electrophoresis assay. The observed DNA damage was concentration and time-dependent, and those levels of DNA damage in between the tested concentrations and times were significantly different (p < 0.05). The tadpoles exposed to different concentrations of chlorpyrifos also showed different morphological abnormalities. It was concluded that chlorpyrifos is a genotoxic pesticide causing DNA damage in Bufo stomaticus.展开更多
Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characte...Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain.To date,only a few Food and Drug Administration(FDA)approved drugs are available on the market for the treatment of PD.Nonetheless,these drugs show parasympathomimetic related adverse events and remarkably higher toxicity;hence,it is important to find more efficacious molecules to treat PD.In our study,We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump-the pathological hallmark of PD-and provide new avenues for its treatment.Most of these molecules exhibited good pharmacokinetic behaviors,making them decisively favorable drug candidates to cure PD.Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets.Among the examined compounds,curcumin and piperine emerged as promising phytochemicals with the highest binding affinity,key residual stable bindings and showed a good inhibitory features.Thus,the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD.Experimental validations are needed for insights into their mechanism of action and potential clinical application.展开更多
Leishmaniasis is a vector-borne parasitic neglected tropical disease caused by a group of about 30 different species of the genus Leishmania.It is transmitted by the bite of female phlebotomies sand fly.Three main cli...Leishmaniasis is a vector-borne parasitic neglected tropical disease caused by a group of about 30 different species of the genus Leishmania.It is transmitted by the bite of female phlebotomies sand fly.Three main clinical manifestations of leishmaniasis include cutaneous,visceral,and mucocutaneous leishmaniasis.Visceral leishmaniasis(VL)caused by Leishmania donovani,is an infection of reticuloendothelial system and fatal if untreated.Cholesterol,a sterol that is prominent in the mammalian cell membranes whereas stigmasterol and ergosterol are more prevalent in plants,yeast,and protozoa,respectively.Ergosterols which is absent in human being,is an important constituent of parasite membrane.Sterol C-24 reductase(LdSR)enzyme catalyzes the final step in the ergosterol biosynthesis pathway.The inhibition of biosynthesis of ergosterol may lead to decreased cell viability and growth.Here,we performed the molecular docking-based virtual screening of a library of natural ligands against LdSR to identify a potential inhibitor to fight leishmaniasis.Capsaicin,prenyletin,flavan-3-ol,resveratrol,and gingerol showed the top binding affinity towards LdSR.Based upon ADME properties and bioactivity score,gingerol showed the best lead-likeness and drug-likeness properties.Hence,we further annotated its leishmanicidal properties.We found that gingerol inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes.Gingerol exerted its antileishmanial action through the induction of reactive oxygen species(ROS)in concentration-dependent manner.Gingerol induced ROS led to apoptosis.Overall,this study described that gingerol would act as possible inhibitor to LdSR.展开更多
文摘Chlorpyrifos is a commonly used pesticide of organophosphate group, which causes toxicological effects in non-target organisms especially fish and frogs. In the present study, the genotoxicity of sublethal concentrations of chlorpyrifos was observed in the erythrocytes of common Indus valley toad, Bufo stomaticus, using the Alkaline Single-Cell Gel Electrophoresis (Comet) assay. In the first step, acute toxicity of chlorpyrifos was evaluated by exposing the tadpoles to high concentrations of the pesticide. The acute LC50 value of chlorpyrifos, calculated by Trimmed Spearman-Karber (TSK) in static bioassay, was found to be 930.0 μg/L. On the basis of acute LC50 value, the tadpoles were exposed to three sublethal concentrations (155, 233 and 465 μg/L) of chlorpyrifos for 96 h. Blood cells were collected at every 24 h interval and were subjected to the Alkaline Single-Cell Gel Electrophoresis assay. The observed DNA damage was concentration and time-dependent, and those levels of DNA damage in between the tested concentrations and times were significantly different (p < 0.05). The tadpoles exposed to different concentrations of chlorpyrifos also showed different morphological abnormalities. It was concluded that chlorpyrifos is a genotoxic pesticide causing DNA damage in Bufo stomaticus.
文摘Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain.To date,only a few Food and Drug Administration(FDA)approved drugs are available on the market for the treatment of PD.Nonetheless,these drugs show parasympathomimetic related adverse events and remarkably higher toxicity;hence,it is important to find more efficacious molecules to treat PD.In our study,We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump-the pathological hallmark of PD-and provide new avenues for its treatment.Most of these molecules exhibited good pharmacokinetic behaviors,making them decisively favorable drug candidates to cure PD.Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets.Among the examined compounds,curcumin and piperine emerged as promising phytochemicals with the highest binding affinity,key residual stable bindings and showed a good inhibitory features.Thus,the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD.Experimental validations are needed for insights into their mechanism of action and potential clinical application.
基金Deanship of Scientific Research at Majmaah University,Al Majmaah,11952,Saudi Arabia for supporting this work under the Group Project No.RGP-2019-31.
文摘Leishmaniasis is a vector-borne parasitic neglected tropical disease caused by a group of about 30 different species of the genus Leishmania.It is transmitted by the bite of female phlebotomies sand fly.Three main clinical manifestations of leishmaniasis include cutaneous,visceral,and mucocutaneous leishmaniasis.Visceral leishmaniasis(VL)caused by Leishmania donovani,is an infection of reticuloendothelial system and fatal if untreated.Cholesterol,a sterol that is prominent in the mammalian cell membranes whereas stigmasterol and ergosterol are more prevalent in plants,yeast,and protozoa,respectively.Ergosterols which is absent in human being,is an important constituent of parasite membrane.Sterol C-24 reductase(LdSR)enzyme catalyzes the final step in the ergosterol biosynthesis pathway.The inhibition of biosynthesis of ergosterol may lead to decreased cell viability and growth.Here,we performed the molecular docking-based virtual screening of a library of natural ligands against LdSR to identify a potential inhibitor to fight leishmaniasis.Capsaicin,prenyletin,flavan-3-ol,resveratrol,and gingerol showed the top binding affinity towards LdSR.Based upon ADME properties and bioactivity score,gingerol showed the best lead-likeness and drug-likeness properties.Hence,we further annotated its leishmanicidal properties.We found that gingerol inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes.Gingerol exerted its antileishmanial action through the induction of reactive oxygen species(ROS)in concentration-dependent manner.Gingerol induced ROS led to apoptosis.Overall,this study described that gingerol would act as possible inhibitor to LdSR.
