Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-i...Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI,CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis.ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress,respectively.Western blot was applied to determine the expression of apoptosis-and AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor-2(Nrf-2)/heme oxygenase-1(HO-1)signaling-associated proteins.JC-1 staining,adenosine triphosphate(ATP)assay kit,and MitoSOX Red assays were performed to detect mitochondrial membrane potential,ATP content,and mitochondrial ROS formation,respectively.Moreover,lung injury was evaluated by measuring lung morphological alternations,lung wet-to-dry ratio,myeloperoxidase content,and total protein concentration.Results:Oleuropein reduced inflammatory reaction,oxidative damage,and apoptosis,and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI.Besides,oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway.However,these effects of oleuropein were abrogated by an AMPK inhibitor compound C.Conclusions:Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling,which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.展开更多
BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence a...BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence and development of DFU,focusing on the therapeutic mechanisms of X-Paste(XP)of wound healing in diabetic mice.METHODS Employing traditional Chinese medicine ointment preparation methods,XP combines various medicinal ingredients.High-performance liquid chromatography(HPLC)identified XP’s main components.Using streptozotocin(STZ)-induced diabetic,we aimed to investigate whether XP participated in the process of diabetic wound healing.RNA-sequencing analyzed gene expression differences between XP-treated and control groups.Molecular docking clarified XP’s treatment mechanisms for diabetic wound healing.Human umbilical vein endothelial cells(HUVECs)were used to investigate the effects of Andrographolide(Andro)on cell viability,reactive oxygen species generation,apoptosis,proliferation,and metastasis in vitro following exposure to high glucose(HG),while NF-E2-related factor-2(Nrf2)knockdown elucidated Andro’s molecular mechanisms.RESULTS XP notably enhanced wound healing in mice,expediting the healing process.RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment.HPLC identified 21 primary XP components,with Andro exhibiting strong Nrf2 binding.Andro mitigated HG-induced HUVECs proliferation,metastasis,angiogenic injury,and inflammation inhibition.Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation,with Nrf2 knockdown reducing Andro’s proliferative and endothelial protective effects.CONCLUSION XP significantly promotes wound healing in STZ-induced diabetic models.As XP’s key component,Andro activates the Nrf2/HO-1 signaling pathway,enhancing cell proliferation,tubule formation,and inflammation reduction.展开更多
Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were...Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were randomly assigned to the normal control group(NC),model group,ischemia-reperfusion group(IR),hesperidin group,SIRT1 inhibitor group and hesperidin plus SIRT1 inhibitor group.In addition to NC,the rats in the remaining groups were replicated by intraperitoneal of high-fat diet combined with injection of streptozotocin for type 2 diabetic rats.After then,the myocardial ischemia/reperfusion injury(MIRI)rat model was established by LAd for 30 minutes with 2 hours reperfusion.He staining was used to observe the pathological changes of myocardial tissue,and the levels of serum LDH,CK-MB and SOD,GSH and MDA in myocardial tissue were detected by kit methods,and the expression abundance of related proteins in 4-HNE and SIRT1/Nrf2/HO-1 signal pathway were detected by immunohistochemistry and Western blot;Results:Hesperidin could significantly inhibit cardiomyocyte necrosis and inflammatory cell infiltration,reduce LDH activity,CK-MB and MDA level,and increase SOD activity,GSH and 4-HNE level,the differences were statistically significant when compared with IR group(P<0.01).In addition,compared with the ischemia-reperfusion group,the expressions of SIRT1,Nrf2 and HO-1 proteins in hesperidin group were significantly up-regulated,the differences were statistically significant(P<0.01);Conclusion:Hesperidin inhibits oxidative stress by activating SIRT1/Nrf2/HO-1 signaling pathway,and play a protective effect of myocardial ischemia reperfusion injury in diabetic rats.展开更多
Objective:This study aimed to explore the therapeutic effect of nuciferine on high-fat diet-induced obesity in rats and the influence of nuciferine on nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1...Objective:This study aimed to explore the therapeutic effect of nuciferine on high-fat diet-induced obesity in rats and the influence of nuciferine on nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in the adipose tissue.Methods:A total of 40 male Sprague Dawley(SD)rats were evenly divided into the normal,model,positive control,and nuciferine groups,using the random number table method.Except for the normal group,rats in the other groups were fed with high-fat diet for 12 weeks to establish the obesity model.During the model establishment,rats in the positive control group received atorvastatin calcium 2 mg/kg,rats in the nuciferine group received nuciferine 20 mg/kg,and rats in the normal and model groups received normal saline 2 mL,daily through intragastric administration for 12 consecutive weeks.After model establishment and administration,the body weight,Lee’s index,and blood lipids of rats in each group were measured,and hematoxylin and eosin(HE)staining was performed on the liver and adipose tissues to evaluate the therapeutic effect of nuciferine on obesity rat model.Additionally,the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in the serum of rats in each group were determined,and the gene expressions of Nrf2 and HO-1 in the adipose tissue of rats in each group were detected through quantitative polymerase chain reaction(qPCR)to investigate the mechanism of action of nuciferine in the treatment of obesity.Results:After 12 weeks of model establishment and administration,we observed that compared with the model group,nuciferine could significantly reduce the body weight,Lee’s index,and serum triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels and increase the serum high-density lipoprotein cholesterol(HDL-C)level in obesity rat model(P<0.05 or P<0.01).HE staining revealed that nuciferine could significantly alleviate liver steatosis in obesity rat model and improve the cell morphology in epididymal adipose tissue.Moreover,nuciferine could elevate serum SOD and GSH-Px activities in obesity rat model and lower the serum MDA level(P<0.05 or P<0.01).The qPCR indicated that nuciferine could upregulate the gene expression of Nrf2 and HO-1 in the adipose tissue of obesity rat model(P<0.05 or P<0.01).展开更多
We investigated the liver protective activity of dandelion polyphenols(DP)against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity.Mice were acclimated for 1 week and randomly divided into the following groups(n...We investigated the liver protective activity of dandelion polyphenols(DP)against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity.Mice were acclimated for 1 week and randomly divided into the following groups(n=9 per group):Control,APAP,APAP+DP(100 mg·kg^–1),APAP+DP(200 mg·kg^–1),and APAP+DP(400 mg·kg^–1)groups.Mice were pretreated with DP(100,200,and 400 mg·kg^–1)by oral gavage for 7 d before being treated with 350 mg·kg^–1 APAP for 24 h to induced hepatotoxicity.Severe liver injury was observed,and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers,protein expressions levels,and liver histopathology.Pretreatment with DP was able to restore serum liver characteristics(aspartate transaminase,AST;alanine aminotransferase,ALT;alkaline phosphatase,AKP),improve redox imbalance(superoxide dismutase,SOD;glutathione,GSH;malondialdehyde,MDA),and decrease inflammatory factors(tumor necrosis factor-α,TNF-α;interleukin-1β,IL-1β).Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).Furthermore,DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein.DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1.The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration,congestion,and necrosis.Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.展开更多
The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2 O2-induced oxidative damage in...The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2 O2-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit Et OAc fraction(fruit-EFr., 12.5–50 μmol·L^(-1)) of G. xanthochymus for 24 h prior to H_2O_2 exposure markedly improved cell viability and increased the activities of antioxidant enzymes(superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases(MMP), and scavenged reactive oxygen species(ROS). Fruit-EFr. also reduced BAX and cytochrome C expression and improved BCL-2 expression, thereby decreasing the ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect was abolished by LY294002, a specific inhibitor of PI3 K. Taken together, the above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular antioxidant defense capacity, at least in part, through upregulating HO-1 expression and activating the PI3 K/AKT pathway and that it could suppress H_2O_2-induced oxidative damage via PI3 K/AKT and NRF2/HO-1 signaling pathways.展开更多
基金supported by Wenzhou Scientific Research Project(Y20210290).
文摘Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI,CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis.ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress,respectively.Western blot was applied to determine the expression of apoptosis-and AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor-2(Nrf-2)/heme oxygenase-1(HO-1)signaling-associated proteins.JC-1 staining,adenosine triphosphate(ATP)assay kit,and MitoSOX Red assays were performed to detect mitochondrial membrane potential,ATP content,and mitochondrial ROS formation,respectively.Moreover,lung injury was evaluated by measuring lung morphological alternations,lung wet-to-dry ratio,myeloperoxidase content,and total protein concentration.Results:Oleuropein reduced inflammatory reaction,oxidative damage,and apoptosis,and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI.Besides,oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway.However,these effects of oleuropein were abrogated by an AMPK inhibitor compound C.Conclusions:Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling,which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.
基金Supported by the Shanghai Science and Technology Innovation Project,One Belt One Road International Joint Laboratory of Medical Mycology,No.21410750500。
文摘BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence and development of DFU,focusing on the therapeutic mechanisms of X-Paste(XP)of wound healing in diabetic mice.METHODS Employing traditional Chinese medicine ointment preparation methods,XP combines various medicinal ingredients.High-performance liquid chromatography(HPLC)identified XP’s main components.Using streptozotocin(STZ)-induced diabetic,we aimed to investigate whether XP participated in the process of diabetic wound healing.RNA-sequencing analyzed gene expression differences between XP-treated and control groups.Molecular docking clarified XP’s treatment mechanisms for diabetic wound healing.Human umbilical vein endothelial cells(HUVECs)were used to investigate the effects of Andrographolide(Andro)on cell viability,reactive oxygen species generation,apoptosis,proliferation,and metastasis in vitro following exposure to high glucose(HG),while NF-E2-related factor-2(Nrf2)knockdown elucidated Andro’s molecular mechanisms.RESULTS XP notably enhanced wound healing in mice,expediting the healing process.RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment.HPLC identified 21 primary XP components,with Andro exhibiting strong Nrf2 binding.Andro mitigated HG-induced HUVECs proliferation,metastasis,angiogenic injury,and inflammation inhibition.Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation,with Nrf2 knockdown reducing Andro’s proliferative and endothelial protective effects.CONCLUSION XP significantly promotes wound healing in STZ-induced diabetic models.As XP’s key component,Andro activates the Nrf2/HO-1 signaling pathway,enhancing cell proliferation,tubule formation,and inflammation reduction.
基金Construction Project of Traditional Chinese Medicine Academic Genre Inheritance Studio of the State Administration of Traditional Chinese Medicine(No.LPGZS2012-14)Construction Project of National Famous and old Traditional Chinese Medicine Expert Inheritance Studio of the State Administration of Traditional Chinese Medicine。
文摘Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were randomly assigned to the normal control group(NC),model group,ischemia-reperfusion group(IR),hesperidin group,SIRT1 inhibitor group and hesperidin plus SIRT1 inhibitor group.In addition to NC,the rats in the remaining groups were replicated by intraperitoneal of high-fat diet combined with injection of streptozotocin for type 2 diabetic rats.After then,the myocardial ischemia/reperfusion injury(MIRI)rat model was established by LAd for 30 minutes with 2 hours reperfusion.He staining was used to observe the pathological changes of myocardial tissue,and the levels of serum LDH,CK-MB and SOD,GSH and MDA in myocardial tissue were detected by kit methods,and the expression abundance of related proteins in 4-HNE and SIRT1/Nrf2/HO-1 signal pathway were detected by immunohistochemistry and Western blot;Results:Hesperidin could significantly inhibit cardiomyocyte necrosis and inflammatory cell infiltration,reduce LDH activity,CK-MB and MDA level,and increase SOD activity,GSH and 4-HNE level,the differences were statistically significant when compared with IR group(P<0.01).In addition,compared with the ischemia-reperfusion group,the expressions of SIRT1,Nrf2 and HO-1 proteins in hesperidin group were significantly up-regulated,the differences were statistically significant(P<0.01);Conclusion:Hesperidin inhibits oxidative stress by activating SIRT1/Nrf2/HO-1 signaling pathway,and play a protective effect of myocardial ischemia reperfusion injury in diabetic rats.
基金This work was supported by the Science and Technology Project of Jiaxing.(No.2018AY3207)。
文摘Objective:This study aimed to explore the therapeutic effect of nuciferine on high-fat diet-induced obesity in rats and the influence of nuciferine on nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in the adipose tissue.Methods:A total of 40 male Sprague Dawley(SD)rats were evenly divided into the normal,model,positive control,and nuciferine groups,using the random number table method.Except for the normal group,rats in the other groups were fed with high-fat diet for 12 weeks to establish the obesity model.During the model establishment,rats in the positive control group received atorvastatin calcium 2 mg/kg,rats in the nuciferine group received nuciferine 20 mg/kg,and rats in the normal and model groups received normal saline 2 mL,daily through intragastric administration for 12 consecutive weeks.After model establishment and administration,the body weight,Lee’s index,and blood lipids of rats in each group were measured,and hematoxylin and eosin(HE)staining was performed on the liver and adipose tissues to evaluate the therapeutic effect of nuciferine on obesity rat model.Additionally,the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in the serum of rats in each group were determined,and the gene expressions of Nrf2 and HO-1 in the adipose tissue of rats in each group were detected through quantitative polymerase chain reaction(qPCR)to investigate the mechanism of action of nuciferine in the treatment of obesity.Results:After 12 weeks of model establishment and administration,we observed that compared with the model group,nuciferine could significantly reduce the body weight,Lee’s index,and serum triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels and increase the serum high-density lipoprotein cholesterol(HDL-C)level in obesity rat model(P<0.05 or P<0.01).HE staining revealed that nuciferine could significantly alleviate liver steatosis in obesity rat model and improve the cell morphology in epididymal adipose tissue.Moreover,nuciferine could elevate serum SOD and GSH-Px activities in obesity rat model and lower the serum MDA level(P<0.05 or P<0.01).The qPCR indicated that nuciferine could upregulate the gene expression of Nrf2 and HO-1 in the adipose tissue of obesity rat model(P<0.05 or P<0.01).
基金supported by the National Natural Science Foundation of China(Nos.81202935 and 81773893)the National Major Scientific and Technological Special Project of China for “Significant New Drugs Development”(No.2017ZX09301060-001)+1 种基金the Natural Science Foundation of Hubei Province,China(No.2015CFB302)Fundamental Research Funds for the Central Universities “South-Central University for Nationalities”(No.CZY20025)。
文摘We investigated the liver protective activity of dandelion polyphenols(DP)against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity.Mice were acclimated for 1 week and randomly divided into the following groups(n=9 per group):Control,APAP,APAP+DP(100 mg·kg^–1),APAP+DP(200 mg·kg^–1),and APAP+DP(400 mg·kg^–1)groups.Mice were pretreated with DP(100,200,and 400 mg·kg^–1)by oral gavage for 7 d before being treated with 350 mg·kg^–1 APAP for 24 h to induced hepatotoxicity.Severe liver injury was observed,and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers,protein expressions levels,and liver histopathology.Pretreatment with DP was able to restore serum liver characteristics(aspartate transaminase,AST;alanine aminotransferase,ALT;alkaline phosphatase,AKP),improve redox imbalance(superoxide dismutase,SOD;glutathione,GSH;malondialdehyde,MDA),and decrease inflammatory factors(tumor necrosis factor-α,TNF-α;interleukin-1β,IL-1β).Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).Furthermore,DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein.DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1.The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration,congestion,and necrosis.Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.
基金supported by the National Natural Science Foundation of China(No.31370379)the National Natural Science Foundation Youth Project Financing(No.81201610)+1 种基金State Ethnic Affairs Commission Research Project(No.CMZY13012)Universities of Hubei Province Outstanding Youth Scientific Innovation Team Plan(No.T201220)
文摘The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2 O2-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit Et OAc fraction(fruit-EFr., 12.5–50 μmol·L^(-1)) of G. xanthochymus for 24 h prior to H_2O_2 exposure markedly improved cell viability and increased the activities of antioxidant enzymes(superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases(MMP), and scavenged reactive oxygen species(ROS). Fruit-EFr. also reduced BAX and cytochrome C expression and improved BCL-2 expression, thereby decreasing the ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect was abolished by LY294002, a specific inhibitor of PI3 K. Taken together, the above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular antioxidant defense capacity, at least in part, through upregulating HO-1 expression and activating the PI3 K/AKT pathway and that it could suppress H_2O_2-induced oxidative damage via PI3 K/AKT and NRF2/HO-1 signaling pathways.