Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung ...Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.展开更多
盆腔器官脱垂(pelvic organ prolapse,POP)是一种多因素导致的疾病,发病机制复杂,主要与盆底肌肉和结缔组织缺损有关。这些缺损导致盆底组织支持功能丧失,引起盆腔器官疝入阴道,并伴有膀胱、直肠和性功能障碍的症状[1]。据报道,我国POP...盆腔器官脱垂(pelvic organ prolapse,POP)是一种多因素导致的疾病,发病机制复杂,主要与盆底肌肉和结缔组织缺损有关。这些缺损导致盆底组织支持功能丧失,引起盆腔器官疝入阴道,并伴有膀胱、直肠和性功能障碍的症状[1]。据报道,我国POP患病率约20%,其中有症状表现的POP占成年女性群体的9.6%[2]。展开更多
Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin...Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.展开更多
Directly correlating the morphology and composition of interfacial water is vital not only for studying water icing under critical conditions but also for understanding the role of protein–water interac-tions in bio-...Directly correlating the morphology and composition of interfacial water is vital not only for studying water icing under critical conditions but also for understanding the role of protein–water interac-tions in bio-relevant systems.In this study,we present a model system to study two-dimensional(2D)water layers under ambient conditions by using self-assembled monolayers(SAMs)supporting the physisorp-tion of the Cytochrome C(Cyt C)protein layer.We observed that the 2D island-like water layers were uniformly distributed on the SAMs as characterized by atomic force microscopy,and their composition was confirmed by nano-atomic force microscopy-infrared spectroscopy and Raman spectroscopy.In addition,these 2D flakes could grow under high-humidity conditions or melt upon the introduction of a heat source.The formation of these flakes is attributed to the activation energy for water desorption from the Cyt C being nearly twofold high than that from the SAMs.Our results provide a new and effective method for further understanding the water–protein interactions.展开更多
A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata.var.villosa resulted in the isolation of 23 withanolide derivatives,including one novel 13,20-γ-lactone withanolide derivative(...A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata.var.villosa resulted in the isolation of 23 withanolide derivatives,including one novel 13,20-γ-lactone withanolide derivative(1)and three new withanolide derivatives(2-4).Architecturally,physalinin A(1)represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety.The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance(NMR)spectroscopy,mass spectrometry(MS),infrared(IR)spectroscopy,and quantum chemical calculations to confirm structural assignments.The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines(HEL,HCT-116,Colo320DM,and MDA-MB-231).Among them,eight derivatives(2,5–8,14,15,and 23)exhibited significant inhibitory effects,with half-maximal inhibitory concentration(IC50)values of 0.18±0.03 to 17.02±0.21μmol·L-1.Structureactivity relationship(SAR)analysis suggested that the presence of an epoxide ring enhances anticancer activity,potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression.These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.展开更多
Three novel matrine-type alkaloids(1-3)and two unprecedented aloperine-type alkaloids(4 and 5)were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides respectively.Notably,compound 1 p...Three novel matrine-type alkaloids(1-3)and two unprecedented aloperine-type alkaloids(4 and 5)were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides respectively.Notably,compound 1 possessed an unprecedented 6/5/6 tricyclic skeleton,while compounds 2 and 3 characterized by rare 6/6/5/6 tetracyclic system and 6/6/6/6/6 pentacyclic system respectively.Moreover,compound 4 possessed an unprecedented 6/7/6/6 tetracyclic core,and compound 5 characterized by rare 6/6/6/6tetracyclic skeleton.Their structures were elucidated by comprehensive spectroscopic data analysis and electronic circular dichroism(ECD)calculations.Biological tests indicated that compound 5 displayed significant anti-tobacco mosaic virus(TMV)activity compared with the positive control ningnanmycin.展开更多
BACKGROUND In the past decade,the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity,risk assessment of osteoporotic fractures,and zoledronic...BACKGROUND In the past decade,the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity,risk assessment of osteoporotic fractures,and zoledronic acid and denosumab in the treatment of osteoporosis to treatment guidelines for osteoporosis and the side effects caused by anti-osteoporotic drugs.AIM To understand the trends and hotspots in osteoporotic fracture research.METHODS Original articles were retrieved between January 1,2010,and December 31,2019,from the Web of Science Core Collection database.CiteSpace software facilitated the analysis and visualization of scientific productivity and emerging trends.RESULTS Nine studies were identified using bibliometric indices,including citation,centrality,and sigma value,which might indicate a growing trend.Through clustering,we identified six major hot subtopics.Using burst analysis,top-5 references with the strongest bursting strength after 2017 were identified,indicating a future hotspot in this field.CONCLUSION Current hot subtopics in osteoporotic fracture research include atypical femoral fractures,androgen deprivation therapy,denosumab discontinuation,hip fractures,trabecular bone score(TBS),and bone phenotype.Management and prevention of secondary fractures in patients with osteoporotic fractures,TBSs,and long-term administration strategy for zoledronic acid are expected to become research hotspots.展开更多
AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal...AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
AIM: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. METHODS: The model of insulin resistance in 3T3-L1 adipocy...AIM: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. METHODS: The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium. Berberine treatment was performed at the same time. Glucose uptake rate was determined by the 2-deoxy-[3H]-D-glucose method. The levels of IkB kinase beta (IKKβ) Ser181 phosphorylation, insulin receptor substrate-1(IRS-1) Ser307 phosphorylation, expression of IKKβ, IRS-1, nuclear transcription factor kappaB p65 (NF-κB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy (CLSM). RESULTS: After the intervention of palmic acid for 24 h, the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%. Meanwhile, the expression of IRS-1 and PI-3K p85 protein was reduced, while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation, and nuclear translocation of NF-κB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKβ and total NF-κB p65 protein were not changed during this study. CONCLUSION: Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine. Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.展开更多
基金Supported by a grant from the National Natural Science Foundation of China(no.82174457)。
文摘Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.
文摘盆腔器官脱垂(pelvic organ prolapse,POP)是一种多因素导致的疾病,发病机制复杂,主要与盆底肌肉和结缔组织缺损有关。这些缺损导致盆底组织支持功能丧失,引起盆腔器官疝入阴道,并伴有膀胱、直肠和性功能障碍的症状[1]。据报道,我国POP患病率约20%,其中有症状表现的POP占成年女性群体的9.6%[2]。
基金financially supported by the National Natural Science Foundation of China(Nos.32270413,82060631,82160808,and 82360035)the Science and Technology Department of Guizhou Province(Nos.QKHJC 2020–1Z076,QKHJC-ZK[2023]YB156,QKHJC-ZK[2021]YB569,and QKHPTRC[2020]5008)+4 种基金Excellent Young Talents Plan of Guizhou Medical University(2023,No.106)the 13thbatch of outstanding young scientific and technological talents in Guizhou Province(No.QKHPTRC[2021]5633)Guizhou Science and Technology Innovation Talent Team(No.QKHPTRC–CXTD[2022]007)High-level Innovative Talents in Guizhou Province(Thousand Levels of Talent for Chunmao Yuan in 2018)the project of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University(Nos.FAMP202102K and QJJ[2023]113)。
文摘Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.
基金supported by the National Natural Science Foundation of China(22273045,52488101 and 22472043)Ningbo Youth Science and Technology Innovation Leading Talent(2023QL041)Tsinghua University Independent Scientific Research Plan for Young Investigator,Tsinghua University Dushi Program,and Initiative Scientific Research Program。
文摘Directly correlating the morphology and composition of interfacial water is vital not only for studying water icing under critical conditions but also for understanding the role of protein–water interac-tions in bio-relevant systems.In this study,we present a model system to study two-dimensional(2D)water layers under ambient conditions by using self-assembled monolayers(SAMs)supporting the physisorp-tion of the Cytochrome C(Cyt C)protein layer.We observed that the 2D island-like water layers were uniformly distributed on the SAMs as characterized by atomic force microscopy,and their composition was confirmed by nano-atomic force microscopy-infrared spectroscopy and Raman spectroscopy.In addition,these 2D flakes could grow under high-humidity conditions or melt upon the introduction of a heat source.The formation of these flakes is attributed to the activation energy for water desorption from the Cyt C being nearly twofold high than that from the SAMs.Our results provide a new and effective method for further understanding the water–protein interactions.
基金supported by the National Natural Science oundation of China(Nos.31960087,82060631,and 32270413)the Science and Technology Department of Guizhou Province(No.QKHJC[2020]1Z076)+6 种基金the Excellent Young Talents Plan of Guizhou Medical University(2023,No.106)the 13~(th)Batch of Outstanding Young Scientific and Technological Talents in Guizhou Province(No.QKHPTRC[2021]5633)the Natural Science Foundation of Guizhou Province(No.QKHZYD[2022]4015)the High-level Innovative Talents in Guizhou Province(Thousand Levels of Talent for Chunmao Yuan in 2018 and Jue Yang in 2023)2022 Guiyang Science and Technology Talent Training Project(No.ZKH[2023]48-5)Guizhou Science and Technology Innovation Talent Team(No.QKHPTRC-CXTD[2022]007)the“Light of the West”Talent Cultivation Program of Chinese Academy of Sciences for Chunmao Yuan(No.RZ[2020]82)。
文摘A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata.var.villosa resulted in the isolation of 23 withanolide derivatives,including one novel 13,20-γ-lactone withanolide derivative(1)and three new withanolide derivatives(2-4).Architecturally,physalinin A(1)represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety.The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance(NMR)spectroscopy,mass spectrometry(MS),infrared(IR)spectroscopy,and quantum chemical calculations to confirm structural assignments.The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines(HEL,HCT-116,Colo320DM,and MDA-MB-231).Among them,eight derivatives(2,5–8,14,15,and 23)exhibited significant inhibitory effects,with half-maximal inhibitory concentration(IC50)values of 0.18±0.03 to 17.02±0.21μmol·L-1.Structureactivity relationship(SAR)analysis suggested that the presence of an epoxide ring enhances anticancer activity,potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression.These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.
基金financially supported by the National Natural Science Foundation of China(Nos.32160103 and U1812403)the Science and Technology Department of Guizhou Province(Nos.QKH ZC-[2021]-YB181,QKH CXTD-[2022]-007 and QKH ZYD-[2022]-4015)Guizhou Provincial Engineering Research Center for Natural Drugs。
文摘Three novel matrine-type alkaloids(1-3)and two unprecedented aloperine-type alkaloids(4 and 5)were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides respectively.Notably,compound 1 possessed an unprecedented 6/5/6 tricyclic skeleton,while compounds 2 and 3 characterized by rare 6/6/5/6 tetracyclic system and 6/6/6/6/6 pentacyclic system respectively.Moreover,compound 4 possessed an unprecedented 6/7/6/6 tetracyclic core,and compound 5 characterized by rare 6/6/6/6tetracyclic skeleton.Their structures were elucidated by comprehensive spectroscopic data analysis and electronic circular dichroism(ECD)calculations.Biological tests indicated that compound 5 displayed significant anti-tobacco mosaic virus(TMV)activity compared with the positive control ningnanmycin.
文摘BACKGROUND In the past decade,the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity,risk assessment of osteoporotic fractures,and zoledronic acid and denosumab in the treatment of osteoporosis to treatment guidelines for osteoporosis and the side effects caused by anti-osteoporotic drugs.AIM To understand the trends and hotspots in osteoporotic fracture research.METHODS Original articles were retrieved between January 1,2010,and December 31,2019,from the Web of Science Core Collection database.CiteSpace software facilitated the analysis and visualization of scientific productivity and emerging trends.RESULTS Nine studies were identified using bibliometric indices,including citation,centrality,and sigma value,which might indicate a growing trend.Through clustering,we identified six major hot subtopics.Using burst analysis,top-5 references with the strongest bursting strength after 2017 were identified,indicating a future hotspot in this field.CONCLUSION Current hot subtopics in osteoporotic fracture research include atypical femoral fractures,androgen deprivation therapy,denosumab discontinuation,hip fractures,trabecular bone score(TBS),and bone phenotype.Management and prevention of secondary fractures in patients with osteoporotic fractures,TBSs,and long-term administration strategy for zoledronic acid are expected to become research hotspots.
基金Supported by National Natural Science Foundation of China,No.30973836
文摘AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.
基金The National Natural Science Foundation of China, No. 30371816
文摘AIM: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. METHODS: The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium. Berberine treatment was performed at the same time. Glucose uptake rate was determined by the 2-deoxy-[3H]-D-glucose method. The levels of IkB kinase beta (IKKβ) Ser181 phosphorylation, insulin receptor substrate-1(IRS-1) Ser307 phosphorylation, expression of IKKβ, IRS-1, nuclear transcription factor kappaB p65 (NF-κB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy (CLSM). RESULTS: After the intervention of palmic acid for 24 h, the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%. Meanwhile, the expression of IRS-1 and PI-3K p85 protein was reduced, while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation, and nuclear translocation of NF-κB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKβ and total NF-κB p65 protein were not changed during this study. CONCLUSION: Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine. Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.
