哮喘(bronchial asthma)以气道炎症和高反应性为主要特征,严重危害人类健康^([1])。AMP-activated protein kinase(AMPK)作为氧化还原蛋白,能有效调节细胞内氧化应激,可通过激活高度保守的NAD+依赖性去乙酰化酶Sirtuin 1(SIRT1)/NF-κB...哮喘(bronchial asthma)以气道炎症和高反应性为主要特征,严重危害人类健康^([1])。AMP-activated protein kinase(AMPK)作为氧化还原蛋白,能有效调节细胞内氧化应激,可通过激活高度保守的NAD+依赖性去乙酰化酶Sirtuin 1(SIRT1)/NF-κB通路抑制哮喘^([2])。PPARγcoactivator-1α(PGC-1α)在线粒体生物合成和功能调节中得到广泛应用^([3])。人参皂苷Rb1是人参根茎的重要提取物,具有抗炎,抗凋亡,能够抑制哮喘气道高反应性等作用^([4])。本研究探讨了Rb1可能通过激活AMPK/SIRT1/PGC-1α信号轴改善小鼠支气管上皮细胞在CRE诱导下发生的氧化应激线粒体动力学障碍,最终有效缓解哮喘气道炎症的发生和发展。展开更多
BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(...BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(Cor)has hepatoprotective,anti-inflammatory,antibacterial,antioxidant,anti-hypertensive,antidiabetic,and anti-tumor activities.AIM To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms.METHODS Streptozotocin and a high-fat diet were combined to generate DN mice models,which were then divided into either a Cor group or a DN group(n=8 in each group).Mice in the Cor group were intraperitoneally injected with Cor(30 mg/kg/d)for 12 wk,and mice in the DN group were treated with saline.Biochemical analysis was used to measure the blood lipid profiles.Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue.Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin.Mouse podocyte cells(MPC5)were cultured and treated with glucose(5 mmol/L),Cor(50μM),high glucose(HG)(30 mmol/L),and HG(30 mmol/L)plus Cor(50μM).Real-time quantitative PCR and Western blotting RESULTS Compared with the control group,the DN mice models had increased fasting blood glucose,glycosylated hemoglobin,triglycerides,and total cholesterol,decreased nephrin and podocin expression,increased apoptosis rate,elevated inflammatory cytokines,and enhanced oxidative stress.All of the conditions mentioned above were alleviated after intervention with Cor.In addition,Cor therapy improved SIRT1 and AMPK expression(P<0.001),inhibited reactive oxygen species and oxidative stress,and elevated autophagy in HG-induced podocytes(P<0.01).CONCLUSION Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway,thereby exerting its protective impact on renal function in DN mice.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedent...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.展开更多
[Objectives]Non-alcoholic fatty liver disease(NAFLD)rat model was established by feeding high-fat and high-sugar fodder to rats,and the protective effect of Dicliptera chinensis polysaccharide(DCP)on NAFLD rats was st...[Objectives]Non-alcoholic fatty liver disease(NAFLD)rat model was established by feeding high-fat and high-sugar fodder to rats,and the protective effect of Dicliptera chinensis polysaccharide(DCP)on NAFLD rats was studied to explore its potential mechanism.[Methods]45 SD rats were randomly divided into 4 groups:normal control group,model control group and DCP treatment groups(100 and 300 mg/kg).The rats in the normal control group were fed with ordinary fodder,and the rats in other groups were fed with high-fat and high-sugar diet for 14 weeks to establish NAFLD model.From the 9^(th)week,the rats in the DCP treatment groups were given different doses of DCP by intragastric administration(5 mL/kg)for 6 weeks.After the last intragastric administration,the rats fasted for 16 h,and the serum and liver of rats were collected for detection.Hematoxylin-eosin(HE)staining was conducted to observe the histopathological changes of rat liver,and alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C)were detected by biochemical method.Interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor(TNF-α)and micrornA-141(micro RNA-141)were detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression of SIRT1 and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)in rat liver was detected by western blot.[Results]Compared with the model control group,the inflammatory damage and steatodegeneration of rats in the DCP groups were relieved to varying degrees,and the number of lipid vacuoles significantly reduced.The ALT,AST,TC,TG and LDL-C content in the serum and MDA content in the liver tissue decreased to varying degrees,while the HDL-C,SOD and GSH-Px content increased.The expression of SIRT1 and AMPK increased,while the expression of miR-141,TNF-α,IL-6 and IL-1βdeclined,and the DCP 300 mg/kg treatment group had better improvement effect.[Conclusions]DCP had a certain protective effect on NAFLD rats,which may be related to the regulation of miR-141/AMPK/SIRT1 signaling pathway.展开更多
文摘哮喘(bronchial asthma)以气道炎症和高反应性为主要特征,严重危害人类健康^([1])。AMP-activated protein kinase(AMPK)作为氧化还原蛋白,能有效调节细胞内氧化应激,可通过激活高度保守的NAD+依赖性去乙酰化酶Sirtuin 1(SIRT1)/NF-κB通路抑制哮喘^([2])。PPARγcoactivator-1α(PGC-1α)在线粒体生物合成和功能调节中得到广泛应用^([3])。人参皂苷Rb1是人参根茎的重要提取物,具有抗炎,抗凋亡,能够抑制哮喘气道高反应性等作用^([4])。本研究探讨了Rb1可能通过激活AMPK/SIRT1/PGC-1α信号轴改善小鼠支气管上皮细胞在CRE诱导下发生的氧化应激线粒体动力学障碍,最终有效缓解哮喘气道炎症的发生和发展。
基金Supported by Shanghai Pudong New Area Leading Talents Training Program Project,No.PWR12020-02Shanghai Pudong New Area Excellent Young Medical Talents Training Program Project,No.PWRq2023-40Shanghai Pudong New Area Health and Family Planning Scientific Research Project,No.PW2022A-91.
文摘BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(Cor)has hepatoprotective,anti-inflammatory,antibacterial,antioxidant,anti-hypertensive,antidiabetic,and anti-tumor activities.AIM To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms.METHODS Streptozotocin and a high-fat diet were combined to generate DN mice models,which were then divided into either a Cor group or a DN group(n=8 in each group).Mice in the Cor group were intraperitoneally injected with Cor(30 mg/kg/d)for 12 wk,and mice in the DN group were treated with saline.Biochemical analysis was used to measure the blood lipid profiles.Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue.Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin.Mouse podocyte cells(MPC5)were cultured and treated with glucose(5 mmol/L),Cor(50μM),high glucose(HG)(30 mmol/L),and HG(30 mmol/L)plus Cor(50μM).Real-time quantitative PCR and Western blotting RESULTS Compared with the control group,the DN mice models had increased fasting blood glucose,glycosylated hemoglobin,triglycerides,and total cholesterol,decreased nephrin and podocin expression,increased apoptosis rate,elevated inflammatory cytokines,and enhanced oxidative stress.All of the conditions mentioned above were alleviated after intervention with Cor.In addition,Cor therapy improved SIRT1 and AMPK expression(P<0.001),inhibited reactive oxygen species and oxidative stress,and elevated autophagy in HG-induced podocytes(P<0.01).CONCLUSION Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway,thereby exerting its protective impact on renal function in DN mice.
基金the Scientific Research Project of Jiangsu Health Commission,No.Z2022078the Natural Science Foundation of Jiangsu Province,No.BK20220299.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
基金Supported by National Natural Science Foundation of China(81960779,82160811)Project for Degree and Graduate Education Reform in Guangxi(JGY2022215)。
文摘[Objectives]Non-alcoholic fatty liver disease(NAFLD)rat model was established by feeding high-fat and high-sugar fodder to rats,and the protective effect of Dicliptera chinensis polysaccharide(DCP)on NAFLD rats was studied to explore its potential mechanism.[Methods]45 SD rats were randomly divided into 4 groups:normal control group,model control group and DCP treatment groups(100 and 300 mg/kg).The rats in the normal control group were fed with ordinary fodder,and the rats in other groups were fed with high-fat and high-sugar diet for 14 weeks to establish NAFLD model.From the 9^(th)week,the rats in the DCP treatment groups were given different doses of DCP by intragastric administration(5 mL/kg)for 6 weeks.After the last intragastric administration,the rats fasted for 16 h,and the serum and liver of rats were collected for detection.Hematoxylin-eosin(HE)staining was conducted to observe the histopathological changes of rat liver,and alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C)were detected by biochemical method.Interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor(TNF-α)and micrornA-141(micro RNA-141)were detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression of SIRT1 and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)in rat liver was detected by western blot.[Results]Compared with the model control group,the inflammatory damage and steatodegeneration of rats in the DCP groups were relieved to varying degrees,and the number of lipid vacuoles significantly reduced.The ALT,AST,TC,TG and LDL-C content in the serum and MDA content in the liver tissue decreased to varying degrees,while the HDL-C,SOD and GSH-Px content increased.The expression of SIRT1 and AMPK increased,while the expression of miR-141,TNF-α,IL-6 and IL-1βdeclined,and the DCP 300 mg/kg treatment group had better improvement effect.[Conclusions]DCP had a certain protective effect on NAFLD rats,which may be related to the regulation of miR-141/AMPK/SIRT1 signaling pathway.
