Objective:This study aimed to evaluate the anti-inflammatory effects of petal and stamen extracts of saffron crocus(Crocus sativus)and explore the underlying mechanism.Methods:Local and systemic inflammation models we...Objective:This study aimed to evaluate the anti-inflammatory effects of petal and stamen extracts of saffron crocus(Crocus sativus)and explore the underlying mechanism.Methods:Local and systemic inflammation models were used to investigate the anti-inflammatory effects of C.sativus.A xyleneinduced inflammation model or lipopolysaccharide(LPS)-induced inflammation model was used in this study.C.sativus petal and stamen extracts were each administered to the mice in the xylene and LPS models by gavage for 14 d at 0.1 and 0.4 g/kg doses,respectively.Enzyme-linked immunosorbent assay(ELISA)was used to measure the concentrations of tumor necrosis factor(TNF)-αand interleukin(IL)-1βin mouse serum.Hematoxylin and eosin(H&E)staining was used to observe the pathological changes in the ear in the xylene-induced inflammation model and in the spleen in the LPS-induced inflammation model.NOD-like receptor thermal protein domain associated protein 3(NLRP3)protein levels within the nuclear factor-kappa B(NF-κB)pathway were assessed using western blotting.RAW264.7 cells were treated with LPS(5μg/mL)and LPS+C.sativus(0.05,0.1,and 0.2 mg/mL)for 24 h,and a Cell Counting Kit-8 was used to measure cell proliferation.Changes in NLRP3 and NF-κB levels were evaluated by western blotting.Results:Petal and stamen extracts of C.sativus attenuated the anti-inflammatory effects in local or systemic inflammatory models and repaired pathological changes in the ear in the xylene-induced inflammation model and spleen in the LPS-induced inflammation model.These extracts also decreased the concentrations of TNF-αand IL-1βin the mouse serum in the LPS-induced inflammation model.C.sativus downregulated NLRP3 protein level through the NF-κB pathway and downregulated LC-3 and BECLIN1 in vivo and in vitro.Carbonyl Cyanide3-ChloroPhenylhydrazone(CCCP)weakened the effects of C.sativus on the NLRP3–NF-κB pathway.Conclusion:C.sativus has anti-inflammatory effects and regulates the NLRP3-NF-κB pathway.展开更多
Hepatocyte nuclear factor 4-alpha (HNF4-α) is a nuclear receptor regulating metabolism, cell junctions, differentiation and proliferation in liver and intestinal epithelial cells. Mutations within the HNF4...Hepatocyte nuclear factor 4-alpha (HNF4-α) is a nuclear receptor regulating metabolism, cell junctions, differentiation and proliferation in liver and intestinal epithelial cells. Mutations within the HNF4A gene are associated with human diseases such as maturity-onset diabetes of the young. Recently, HNF4A has also been described as a susceptibility gene for ulcerative colitis in genome-wide association studies. In addition, specific HNF4A genetic variants have been identified in pediatric cohorts of Crohn’s disease. Results obtained from knockout mice supported that HNF4-α can protect the intestinal mucosae against inflammation. However, the exact molecular links behind HNF4-α and inflammatory bowel diseases remains elusive. In this review, we will summarize the current knowledge about the role of HNF4-α and its isoforms in inflammation. Specific nature of HNF4-α P1 and P2 classes of isoforms will be summarized. HNF4-α role as a hepatocyte mediator for cytokines relays during liver inflammation will be integrated based on documented examples of the literature. Conclusions that can be made from these earlier liver studies will serve as a basis to extrapolate correlations and divergences applicable to intestinal inflammation. Finally, potential functional roles for HNF4-α isoforms in protecting the intestinal mucosae from chronic and pathological inflammation will be presented.展开更多
Inflammatory bowel disease (IBD) is a group of inflammatory disorders mainly affecting the colon and small intestine. The main types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). UC is restricted to th...Inflammatory bowel disease (IBD) is a group of inflammatory disorders mainly affecting the colon and small intestine. The main types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). UC is restricted to the large intestine whereas CD can affect any part of the gastrointestinal tract. Treating this disorder depends on the form and level of severity. Common treatment involves an anti-inflammatory drug, such as mesalazine, and an immunosuppressant, such as prednisone. Several signaling pathways, including nuclear factor (NF)-κB and nitric oxide (NO), and genetic and environmental factors are believed to play an important role in IBD. Amitriptyline is a commonly used antidepressant with known anti-inflammatory activities. Amitriptyline also acts on the NF-κB/NO pathway or cytokine production. Therefore, we hypothesize that antidepressants like amitriptyline can be pioneered and considered effective as an innovative and effective therapeutic in the treatment and attenuation of development of IBD in adjusted doses.展开更多
Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usual...Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases.Nuclear factor erythroid 2-related factor 2(NRF2)is a transcription factor that regulates the expression of antioxidant proteins,participating in COVID-19-mediated inflammation and liver injury.Here,we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury.Additionally,we describe some mechanisms and treatment strategies.展开更多
Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type ...Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.展开更多
基金supported by the National Natural Science Foundation of China(81873063)High-level talents Research project of Hefei Normal University(2020rcjj30)+2 种基金Key Project of Provincial Scientific Research Platform of Hefei Normal University in 2020(2020PTZD14)Key Project of Universities Natural Science Foundation of Anhui province(KJ2021A0935,KJ2021A0932)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202009).
文摘Objective:This study aimed to evaluate the anti-inflammatory effects of petal and stamen extracts of saffron crocus(Crocus sativus)and explore the underlying mechanism.Methods:Local and systemic inflammation models were used to investigate the anti-inflammatory effects of C.sativus.A xyleneinduced inflammation model or lipopolysaccharide(LPS)-induced inflammation model was used in this study.C.sativus petal and stamen extracts were each administered to the mice in the xylene and LPS models by gavage for 14 d at 0.1 and 0.4 g/kg doses,respectively.Enzyme-linked immunosorbent assay(ELISA)was used to measure the concentrations of tumor necrosis factor(TNF)-αand interleukin(IL)-1βin mouse serum.Hematoxylin and eosin(H&E)staining was used to observe the pathological changes in the ear in the xylene-induced inflammation model and in the spleen in the LPS-induced inflammation model.NOD-like receptor thermal protein domain associated protein 3(NLRP3)protein levels within the nuclear factor-kappa B(NF-κB)pathway were assessed using western blotting.RAW264.7 cells were treated with LPS(5μg/mL)and LPS+C.sativus(0.05,0.1,and 0.2 mg/mL)for 24 h,and a Cell Counting Kit-8 was used to measure cell proliferation.Changes in NLRP3 and NF-κB levels were evaluated by western blotting.Results:Petal and stamen extracts of C.sativus attenuated the anti-inflammatory effects in local or systemic inflammatory models and repaired pathological changes in the ear in the xylene-induced inflammation model and spleen in the LPS-induced inflammation model.These extracts also decreased the concentrations of TNF-αand IL-1βin the mouse serum in the LPS-induced inflammation model.C.sativus downregulated NLRP3 protein level through the NF-κB pathway and downregulated LC-3 and BECLIN1 in vivo and in vitro.Carbonyl Cyanide3-ChloroPhenylhydrazone(CCCP)weakened the effects of C.sativus on the NLRP3–NF-κB pathway.Conclusion:C.sativus has anti-inflammatory effects and regulates the NLRP3-NF-κB pathway.
文摘Hepatocyte nuclear factor 4-alpha (HNF4-α) is a nuclear receptor regulating metabolism, cell junctions, differentiation and proliferation in liver and intestinal epithelial cells. Mutations within the HNF4A gene are associated with human diseases such as maturity-onset diabetes of the young. Recently, HNF4A has also been described as a susceptibility gene for ulcerative colitis in genome-wide association studies. In addition, specific HNF4A genetic variants have been identified in pediatric cohorts of Crohn’s disease. Results obtained from knockout mice supported that HNF4-α can protect the intestinal mucosae against inflammation. However, the exact molecular links behind HNF4-α and inflammatory bowel diseases remains elusive. In this review, we will summarize the current knowledge about the role of HNF4-α and its isoforms in inflammation. Specific nature of HNF4-α P1 and P2 classes of isoforms will be summarized. HNF4-α role as a hepatocyte mediator for cytokines relays during liver inflammation will be integrated based on documented examples of the literature. Conclusions that can be made from these earlier liver studies will serve as a basis to extrapolate correlations and divergences applicable to intestinal inflammation. Finally, potential functional roles for HNF4-α isoforms in protecting the intestinal mucosae from chronic and pathological inflammation will be presented.
文摘Inflammatory bowel disease (IBD) is a group of inflammatory disorders mainly affecting the colon and small intestine. The main types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). UC is restricted to the large intestine whereas CD can affect any part of the gastrointestinal tract. Treating this disorder depends on the form and level of severity. Common treatment involves an anti-inflammatory drug, such as mesalazine, and an immunosuppressant, such as prednisone. Several signaling pathways, including nuclear factor (NF)-κB and nitric oxide (NO), and genetic and environmental factors are believed to play an important role in IBD. Amitriptyline is a commonly used antidepressant with known anti-inflammatory activities. Amitriptyline also acts on the NF-κB/NO pathway or cytokine production. Therefore, we hypothesize that antidepressants like amitriptyline can be pioneered and considered effective as an innovative and effective therapeutic in the treatment and attenuation of development of IBD in adjusted doses.
基金Supported by National Natural Science Foundation of China,No.82070632.
文摘Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases.Nuclear factor erythroid 2-related factor 2(NRF2)is a transcription factor that regulates the expression of antioxidant proteins,participating in COVID-19-mediated inflammation and liver injury.Here,we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury.Additionally,we describe some mechanisms and treatment strategies.
基金supported by the Natural Science Foundation of Anhui Province of China,No.2208085Y32Scientific Research Plan Project of Anhui Province of China,No.2022AH020076the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province,No.CXPJJH12000005-07-115(all to CT).
文摘Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.
