ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

The urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally. The delivery of healthcare exacerbates the planetary health crisis through greenhouse gas emissions, largely due to combustion of fossil fuels for medical equipment production and operation, creation of medical and non-medical waste, and contamination of water supplies. As representatives of radiology societies from across the globe who work closely with industry, and both governmental and non-governmental leaders in multiple capacities, we advocate together for urgent, impactful, and measurable changes to the way we deliver care by further engaging our members, policymakers, industry partners, and our patients. Simultaneous challenges including global health disparities, resource allocation, and access to care must inform these efforts. Climate literacy should be increasingly added to radiology training programmes. More research is required to understand and measure the environmental impact of radiological services and inform mitigation, adaptation and monitoring efforts. Deeper collaboration with industry partners is necessary to support innovations in the supply chain, energy utilization, and circular economy. Many solutions have been proposed and are already available, but we must understand and address barriers to implementation of current and future sustainable innovations.

The urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally. The delivery of healthcare exacerbates the planetary health crisis through greenhouse gas emissions, largely due to combustion of fossil fuels for medical equipment production and operation, creation of medical and non-medical waste, and contamination of water supplies. As representatives of radiology societies from across the globe who work closely with industry, and both governmental and non-governmental leaders in multiple capacities, we advocate together for urgent, impactful, and measurable changes to the way we deliver care by further engaging our members, policymakers, industry partners, and our patients. Simultaneous challenges including global health disparities, resource allocation, and access to care must inform these efforts. Climate literacy should be increasingly added to radiology training programmes. More research is required to understand and measure the environmental impact of radiological services and inform mitigation, adaptation and monitoring efforts. Deeper collaboration with industry partners is necessary to support innovations in the supply chain, energy utilization, and circular economy. Many solutions have been proposed and are already available, but we must understand and address barriers to implementation of current and future sustainable innovations.

The urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally. The delivery of healthcare exacerbates the planetary health crisis through greenhouse gas emissions, largely due to combustion of fossil fuels for medical equipment production and operation, creation of medical and non-medical waste, and contamination of water supplies. As representatives of radiology societies from across the globe who work closely with industry, and both governmental and non-governmental leaders in multiple capacities, we advocate together for urgent, impactful, and measurable changes to the way we deliver care by further engaging our members, policymakers, industry partners, and our patients. Simultaneous challenges including global health disparities, resource allocation, and access to care must inform these efforts. Climate literacy should be increasingly added to radiology training programmes. More research is required to understand and measure the environmental impact of radiological services and inform mitigation, adaptation and monitoring efforts. Deeper collaboration with industry partners is necessary to support innovations in the supply chain, energy utilization, and circular economy. Many solutions have been proposed and are already available, but we must understand and address barriers to implementation of current and future sustainable innovations.

The urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally. The delivery of healthcare exacerbates the planetary health crisis through greenhouse gas emissions, largely due to combustion of fossil fuels for medical equipment production and operation, creation of medical and non-medical waste, and contamination of water supplies. As representatives of radiology societies from across the globe who work closely with industry, and both governmental and non-governmental leaders in multiple capacities, we advocate together for urgent, impactful, and measurable changes to the way we deliver care by further engaging our members, policymakers, industry partners, and our patients. Simultaneous challenges including global health disparities, resource allocation, and access to care must inform these efforts. Climate literacy should be increasingly added to radiology training programmes. More research is required to understand and measure the environmental impact of radiological services and inform mitigation, adaptation and monitoring efforts. Deeper collaboration with industry partners is necessary to support innovations in the supply chain, energy utilization, and circular economy. Many solutions have been proposed and are already available, but we must understand and address barriers to implementation of current and future sustainable innovations.

The urgency for climate action is recognised by international government and healthcare organisations, including the United Nations (UN) and World Health Organisation (WHO). Climate change, biodiversity loss, and pollution negatively impact all life on earth. All populations are impacted but not equally; the most vulnerable are at highest risk, an inequity further exacerbated by differences in access to healthcare globally. The delivery of healthcare exacerbates the planetary health crisis through greenhouse gas emissions, largely due to combustion of fossil fuels for medical equipment production and operation, creation of medical and non-medical waste, and contamination of water supplies. As representatives of radiology societies from across the globe who work closely with industry, and both governmental and non-governmental leaders in multiple capacities, we advocate together for urgent, impactful, and measurable changes to the way we deliver care by further engaging our members, policymakers, industry partners, and our patients. Simultaneous challenges including global health disparities, resource allocation, and access to care must inform these efforts. Climate literacy should be increasingly added to radiology training programmes. More research is required to understand and measure the environmental impact of radiological services and inform mitigation, adaptation and monitoring efforts. Deeper collaboration with industry partners is necessary to support innovations in the supply chain, energy utilization, and circular economy. Many solutions have been proposed and are already available, but we must understand and address barriers to implementation of current and future sustainable innovations.