Owing to the widespread distribution of mosquitoes capable of transmitting Zika virus, lack of clinical vaccines and treatments, and poor immunity of populations to new infectious diseases, Zika virus has become a glo...Owing to the widespread distribution of mosquitoes capable of transmitting Zika virus, lack of clinical vaccines and treatments, and poor immunity of populations to new infectious diseases, Zika virus has become a global public health concern. Recent studies have found that Zika virus can continuously infect human brain microvascular endothelial cells.These cells are the primary components of the blood–brain barrier of the cerebral cortex, and further infection of brain tissue may cause severe damage such as encephalitis and fetal pituitary disease. The present study found that a biologically active base, piperlongumine(PL), inhibited Zika virus replication in human brain microvascular endothelial cells, Vero cells, and human umbilical vein endothelial cells. PL also significantly increased heme oxygenase-1(HO-1) gene expression, while silencing HO-1 expression and using the reactive oxygen species scavenger, N-acetylcysteine, attenuated the inhibitory effect of PL on Zika virus replication. These results suggest that PL induces oxidative stress in cells by increasing reactive oxygen species. This, in turn, induces an increase in HO-1 expression, thereby inhibiting Zika virus replication. These findings provide novel clues for drug research on the prevention and treatment of Zika virus.展开更多
Ganoderic triterpenoids(GTs)are the primary bioactive constituents of the Basidiomycotina fungus,Ganoderma lucidum.These compounds exhibit antitumor,anti-hyperlipidemic,and immune-modulatory pharmacological activities...Ganoderic triterpenoids(GTs)are the primary bioactive constituents of the Basidiomycotina fungus,Ganoderma lucidum.These compounds exhibit antitumor,anti-hyperlipidemic,and immune-modulatory pharmacological activities.This study focused on GT accumulation in mycelia of G.lucidum mediated by the heme oxygenase-1(HO-1)/carbon monoxide(CO)signaling.Compared with the control,hemin(10μmol/L)induced an increase of 60.1%in GT content and 57.1%in HO-1 activity.Moreover,carbon monoxide-releasing molecule-2(CORM-2),CO donor,increased GT content by 56.0%and HO-1 activity by 18.1%.Zn protoporphyrin IX(ZnPPIX),a specific HO-1 inhibitor,significantly reduced GT content by 26.0%and HO-1 activity by 15.8%,while hemin supplementation reversed these effects.Transcriptome sequencing showed that HO-1/CO could function directly as a regulator involved in promoting GT accumulation by regulating gene expression in the mevalonate pathway,and modulating the reactive oxygen species(ROS)and Ca2+pathways.The results of this study may help enhance large-scale GT production and support further exploration of GT metabolic networks and relevant signaling cross-talk.展开更多
基金supported by the National Natural Science Foundation (Nos. 31670168, 31470271 and 81730110)National Key R&D Program of China (Grant No. 2018YFC1602206)Guangdong Provincial Science and Technology (No. 2018B020207006)。
文摘Owing to the widespread distribution of mosquitoes capable of transmitting Zika virus, lack of clinical vaccines and treatments, and poor immunity of populations to new infectious diseases, Zika virus has become a global public health concern. Recent studies have found that Zika virus can continuously infect human brain microvascular endothelial cells.These cells are the primary components of the blood–brain barrier of the cerebral cortex, and further infection of brain tissue may cause severe damage such as encephalitis and fetal pituitary disease. The present study found that a biologically active base, piperlongumine(PL), inhibited Zika virus replication in human brain microvascular endothelial cells, Vero cells, and human umbilical vein endothelial cells. PL also significantly increased heme oxygenase-1(HO-1) gene expression, while silencing HO-1 expression and using the reactive oxygen species scavenger, N-acetylcysteine, attenuated the inhibitory effect of PL on Zika virus replication. These results suggest that PL induces oxidative stress in cells by increasing reactive oxygen species. This, in turn, induces an increase in HO-1 expression, thereby inhibiting Zika virus replication. These findings provide novel clues for drug research on the prevention and treatment of Zika virus.
基金the Applied Basic Research Project of Shanxi Province(No.201901D211402),China。
文摘Ganoderic triterpenoids(GTs)are the primary bioactive constituents of the Basidiomycotina fungus,Ganoderma lucidum.These compounds exhibit antitumor,anti-hyperlipidemic,and immune-modulatory pharmacological activities.This study focused on GT accumulation in mycelia of G.lucidum mediated by the heme oxygenase-1(HO-1)/carbon monoxide(CO)signaling.Compared with the control,hemin(10μmol/L)induced an increase of 60.1%in GT content and 57.1%in HO-1 activity.Moreover,carbon monoxide-releasing molecule-2(CORM-2),CO donor,increased GT content by 56.0%and HO-1 activity by 18.1%.Zn protoporphyrin IX(ZnPPIX),a specific HO-1 inhibitor,significantly reduced GT content by 26.0%and HO-1 activity by 15.8%,while hemin supplementation reversed these effects.Transcriptome sequencing showed that HO-1/CO could function directly as a regulator involved in promoting GT accumulation by regulating gene expression in the mevalonate pathway,and modulating the reactive oxygen species(ROS)and Ca2+pathways.The results of this study may help enhance large-scale GT production and support further exploration of GT metabolic networks and relevant signaling cross-talk.
