Currently,the performance,cost,and environmental sustainability of saturable absorbers(SAs)represent major bottlenecks in the development of ultrafast fiber lasers.However,the development of high-performance SAs remai...Currently,the performance,cost,and environmental sustainability of saturable absorbers(SAs)represent major bottlenecks in the development of ultrafast fiber lasers.However,the development of high-performance SAs remains challenging due to intricate fabrication processes and inadequate nonlinear performance.In this context,this work presents the natural alkaloid berberine as a promising alternative for mode-locked erbium-doped fiber lasers.The berberine-based SA exhibits excellent nonlinear optical properties,including a modulation depth of 24.40%and a saturation intensity of 1.281MW/cm^(2),and successfully enables stable femtosecond pulse generation.By employing time-stretched dispersive Fourier transform technology,the transient dynamics results indicate that the berberine-based SA significantly shortens the relaxation oscillation time and effectively suppresses pulse intensity fluctuations,thereby accelerating the self-starting process of mode-locking.This work provides a new strategy for developing high-performance,low-cost,and environmentally friendly ultrafast photonic devices,significantly advancing the practical application of green SAs.展开更多
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
OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Avail...OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.展开更多
Hyperglycemia in individuals with diabetes causes cognitive impairment,called diabetic encephalopathy(DE).The pathogenesis of DE is closely related to angiopathy,and effective treatment is highly desirable.The botanic...Hyperglycemia in individuals with diabetes causes cognitive impairment,called diabetic encephalopathy(DE).The pathogenesis of DE is closely related to angiopathy,and effective treatment is highly desirable.The botanical agent berberine(BBR)effectively lowers blood glucose in diabetic patients.Here,we show for the first time that BBR significantly improved cognitive function in type 2 diabetic encephalopathy KK-Ay(2DEK)mice.High-resolution imaging via fluorescence micro-optical sectioning tomography(fMOST)revealed that the integrity of brain vessels was improved by BBR treatment.The improvements in average vessel diameter,vessel length,and total vessel volume were significant in the parietal association cortex(PtA),as well as in the CA1 and CA3 regions.A mechanistic study revealed that oral BBR inhibited δ-valerobetaine(δ-VB,a metabolite of the gut microbiota)production in the intestine.As intestinal δ-VB can enter the circulation and activate the Toll-like receptor-4(TLR-4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa B(NF-jB)inflammatory pathway in the epithelial cells of blood vessels through interacting with TLR-4,BBR might reduce the intestinal level of δ-VB to protect the cerebral blood vessels of DE mice and improve their brain function.Fecal microbiota transplantation(FMT)using the gut microbiota from BBR-treated mice confirmed the vital role of the gut microbiota.BBR showed a wide range of effects on the gut flora,also increasing short-chain fatty acid(SCFA)production and decreasing lipopolysaccharide(LPS)levels in the intestine by adjusting the abundance of SCFA-or LPS-producing bacteria.The observed therapeutic efficacy in vivo revealed a synergistic effect of BBR on the gut microbiota.Conclusively,we found an association between the gut microbiota and blood vessels,of which intestinal δ-VB might be a chemical link.Mainly through downregulating δ-VB in the intestine,BBR protected cerebral vessels and alleviated DE.展开更多
Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary a...Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.展开更多
Diabetes mellitus(DM)is a serious health problem in the world,and infections are common complications in diabetic patients,particularly methicillin-resistant Staphylococcus aureus(MRSA)infections,which substantially i...Diabetes mellitus(DM)is a serious health problem in the world,and infections are common complications in diabetic patients,particularly methicillin-resistant Staphylococcus aureus(MRSA)infections,which substantially increases mortality in patients.In clinical practice,the treatment of diabetic complicationrelated infections involves multiple issues such as drug resistance when combining antidiabetic drugs with antibiotics.In this study,a series of derivatives were synthesized with alkyl radicals with different chain lengths substituted at the C8 and C12 positions of berberine,with compounds CY1 and CY3with good antidiabetic and antibacterial activities screened out after identification.Then,oral liposomes(CY1-Lip and CY3-Lip)were prepared,and their particle sizes,stability,and pharmacokinetics were investigated.In acquired mouse models of diabetes,induced with an acute MRSA lung infection,we demonstrate that CY1-Lip and CY3-Lip can effectively reduce levels of fasting blood glucose(FBG),fasting insulin(FINS),and insulin resistance index among diabetic mice with pneumonia,thus exerting their multitargets effects.Furthermore,both preparations significantly reduced lung MRSA loads and improved lung tissue lesions,reduced high infiltration of M1 macrophages in lung,and suppressed the expression levels of pro-infiammatory factors such as necrosis factor-α(TNF-α)and interleukin-6(IL-6).This provides new insights into the clinical treatment of diabetes complicated with pulmonary infections.展开更多
This study explored the therapeutic effect of trimebutine maleate dispersible tablets combined with berberine on PI-IBS rats with liver depression and spleen deficiency.Fifty male rats were divided into five groups:no...This study explored the therapeutic effect of trimebutine maleate dispersible tablets combined with berberine on PI-IBS rats with liver depression and spleen deficiency.Fifty male rats were divided into five groups:normal,model,berberine(XB),trimebutine(QM),and combination(XB+QM).The PI-IBS model was established using maternal separation,TNBS perfusion,and chronic restraint.After 20 days of drug intervention,DAI,CMDI,TDI,AWR scores,histopathology,and expression levels of c-Fos,VIP,NOS,and CHAT in the hippocampus and colon were assessed.The model group showed significant gut and brain changes,while the combination group(XB+QM)improved fecal characteristics,reduced inflammation,regulated brain-gut peptide expression,and alleviated visceral hypersensitivity and colon tissue damage(P<0.05).展开更多
Atherosclerosis(AS)is the core pathological basis of Cardiovascular Disease(CVD)worldwide.Its occurrence and development involve endothelial dysfunction,lipid deposition,chronic inflammation and abnormal proliferation...Atherosclerosis(AS)is the core pathological basis of Cardiovascular Disease(CVD)worldwide.Its occurrence and development involve endothelial dysfunction,lipid deposition,chronic inflammation and abnormal proliferation of smooth muscle cells.Berberine(BBR),also known as berberine,is an isoquinoline alkaloid extracted from traditional Chinese medicine such as Coptis coptidis and Phelloberia angustifolia.It has traditionally been used for antibacterial and anti-inflammatory treatment.In recent years,it has been found that it has multi-target metabolic regulation and anti-inflammatory properties,showing significant potential in the prevention and treatment of AS.This article systematically reviews the research progress of berberine in the treatment of AS by improving endothelial function,regulating lipid metabolism,inhibiting inflammatory response,regulating smooth muscle cell phenotypic transformation,and anti-oxidative stress,and discusses the current status and challenges of its clinical application.展开更多
Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was perform...Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.展开更多
Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distil...Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distilled water freely with different doses of BER （15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1） or sallcylazosulfapyridine （SASP, 520 mg·kg^-1）, and solvent （0. 2 mL/10 mg Wt） once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）. Myeloperoxidase （MPO） and superoxide dismutase （SOD） activities and malondialdehyde （MDA） content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.展开更多
Berberine （BBR） has a variety of pharmacological activities. Studies have reported that BBR not only reduces heat stress-induced fever but also inhibits lower body temperatures due to cold stress. Heat stress can be...Berberine （BBR） has a variety of pharmacological activities. Studies have reported that BBR not only reduces heat stress-induced fever but also inhibits lower body temperatures due to cold stress. Heat stress can be reduced via BBR treatment, which antagonizes HSP70-TNFa to regulate the body temperature alteration. In cold stress, however, the molecular mechanism of BBR-induced inhibition of hypothermia remains unclear. Therefore, we studied whether BBR promoted uncoupling protein 1 （UCP1, a crucial protein of thermogenesis） expression and its mechanism under cold stress. Wild type mice and Ucpl-/- mice were used for the in vivo experiments, and primary brown adipocytes and brown adipocytes HIB-1B were used for the in vitro studies. The cold stress was set at 4℃. The results showed that at 4℃, the body temperature of mice was decreased. BBR effectively inhibited this hypothermia. Simultaneously, Ucpl expression in brown adipose tissue （BAT） cells was significantly increased, and BBR promoted Ucpl expression. However, in Ucpl-knockout mice, the effect of BBR on hypothermia disappeared during cold stress, indicating that the main target for BBR regulation of body temperature was Ucpl. Further studies showed that the transcriptional response element NFE2 （nuclear factor erythroid-derived 2） in the upstream of the Ucpl promoter region contributed to the positive regulatory role on Ucpl expression at lower temperature. BBR could bind to the sequence of NFE2 response element in a temperature-dependent manner. Increased affinity of BBR binding to NFE2 response element in cold stress significantly strengthened and enhanced the expression of Ucpl. This work was important for understanding the role of BBR on thermogenesis in BAT, body temperature regulation and temperature tolerance under cold conditions.展开更多
Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ...Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.展开更多
The intestinal absorption ofberberine （Ber） and its structural modified compound 8-hydroxy dihydroberberine （Hdber） was compared, and their effects on the intestinal absorption of sugar by per- fusion experiment w...The intestinal absorption ofberberine （Ber） and its structural modified compound 8-hydroxy dihydroberberine （Hdber） was compared, and their effects on the intestinal absorption of sugar by per- fusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography （HPLC） was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than I0%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 ~tg/mL. However, Hdber presented stronger activity than Bet （P〈0.01）. It is suggested that Hdber is ab- sorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.展开更多
Effects of berberine (Ber) on platelet aggregation and TXB2 and 6 keto PGF1a plasma levels were studied in rabbits with uncomplete cerebral ischemia. Ber inhibited uncomplete cerebral ischemic rabbit platelet aggreg...Effects of berberine (Ber) on platelet aggregation and TXB2 and 6 keto PGF1a plasma levels were studied in rabbits with uncomplete cerebral ischemia. Ber inhibited uncomplete cerebral ischemic rabbit platelet aggregation triggered by collagen, ADP, and arachidonic acid (AA) with the IC 50 of 0.15, 0.46, and 0.51 mg·ml 1 , respectively. In rabbits, Ber 25, or 50 mg·kg 1 iv 30 min after uncomplete cerebral ischemia, restrained the collagen ADP and AA induced platelet aggregation determined 90 min later. With radioimmunoassay, we measured the thromboxane B2 (TXB 2) and 6 ketoprostaglandin F 1α (6 keto PGF 1α ) contents in rabbit plasma. The results indicated that the TXB 2 level in rabbit 120 min after uncomplete cerebral ischemia (921±539 pg·ml 1 ) was higher than that (230±71 pg·ml 1 ) in normal rabbits ( P < 0.01), but 6 keto PGF 1α level after ischemia (73±23pg·ml 1 ) was lower than that (262±988pg·ml 1 ) in normal rabbit. Ber (5, 25 or 50 mg·kg 1 ) reduced obviously the plasma TXB 2 level in rabbit with uncomplete cerebral ischemia (504±196, 386±174, or 272±183 vs 921±539 pg·ml 1 , respectively, P < 0.01). We conclude that the decrease of TXB 2 content is one of the possible mechanisms of Ber anti cerebral ischemic effect.展开更多
The content of berberine hydrochloride(BH)in compound berberine tablets(CBTs)is subject to strict requirements.Its content is usually measured based on chemical analysis.In this paper,the fluorescence spectral imaging...The content of berberine hydrochloride(BH)in compound berberine tablets(CBTs)is subject to strict requirements.Its content is usually measured based on chemical analysis.In this paper,the fluorescence spectral imaging method was used to study the relative content of BH from a physics perspective.By comparing the relative fluorescence intensity of self-made CBTs with di®erent mass percentages of BH,a linear positive relationship was observed between the BH content and the relative fluorescence intensity,and accordingly the quality of CBTs of different brands was evaluated.The results indicate that the fluorescence spectral imaging method can be a simple,fast and nondestructive semi-quantitative analysis method to determine the content of BH in CBTs,and this method has great potential in the quality control of CBTs.展开更多
Berberine, an isoquinoline alkaloid component of Rhizoma Coptidis has been demonstrated to be the key active ingredient involved in its protective effect against cerebral ischemia-reperfusion. However, the comparison ...Berberine, an isoquinoline alkaloid component of Rhizoma Coptidis has been demonstrated to be the key active ingredient involved in its protective effect against cerebral ischemia-reperfusion. However, the comparison among the analogues to the protective effect against oxygen and glucose deprivation/reoxygenation （OGD-R） was mediated by inhibition of cyclooxygenase-2 （COX-2） has never been reported. The aim of this study is to investigate the protective effect of berberine and its five analogues against OGD-R in PC 12 cells, as well as to determine whether the protective effect was regulated through COX-2. An established in vitro OGD-R model of PC12 cells by oxygen glucose deprivation of 4 h and reperfusion of 24 h was used in our study. After cells were treated with berberine or its five analogues, we examined the cell viability assay by 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） assay. Cells were also collected to determine the levels of mRNA and protein of COX-2 by real time PCR and Western blot. We found that berberine and its analogues improved the viability of PC12 cells against OGD-R. Whereas berberine and berberrubine presented stronger activity with the most effective dose of 0.31 lag/mL and the minimum effective doses of 0.02 and 0.04 gg/mL. Palmatine possessed potentially weaker protective effect. The mRNA level of COX-2 in cells treated with berberine, coptisine and epiberberine was decreased significantly. The protein level of COX-2 was significantly down-regulated in cells treated with berberine. Studies suggested the important role of methylenedioxy groups （R2 and R3） of berberine analogues in COX-2 inhibitory effect, and methylenedioxy groups （R2, R3, R9 and R10） in berberine analogues in binding affinity with COX-2. Substituted hydroxyl group at R9 did not affect the activity of berberine. In summary, our study illustrated the protective effects of berberine and its analogues in PCI2 cells against OGD-R and to elucidate the structure-activity relationships. Docking analysis indicates that methylenedioxys at R2 and R3 is involved in the effect. More studies in other cells are needed to confirm our results.展开更多
AIM： To investigate the relationship between the inhibited growth （cytotoxic activity） of berberine and apoptotic pathway with its molecular mechanism of action. METHODS： The in vitro cytotoxic techniques were com...AIM： To investigate the relationship between the inhibited growth （cytotoxic activity） of berberine and apoptotic pathway with its molecular mechanism of action. METHODS： The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub431 group （apoptosis） were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting. RESULTS： For SNU-5 cell line, the IC （50） was found to be 48 μmol/L of berberine. In SNU-5 cells treated with 25-200 μmol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-Go cell population in cell cycle measurement was proved in 25-200 μmol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-Go cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca^2＋, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis. CONCLUSION： Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.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
This study aimed to verify the effects of berberine(BBR)on the fat metabolism proteins involved in the sirtuin 3(SIRT3)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)pat...This study aimed to verify the effects of berberine(BBR)on the fat metabolism proteins involved in the sirtuin 3(SIRT3)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)pathway in the liver tissues of rats with high-fat diet(HFD)-induced non-alcoholic fatty liver disease(NAFLD).Forty-eight rats were randomly divided into the normal control(NC)group,HFD group or BBR group,with 16 rats in each group.After 8 and 16 weeks of treatment,serum and liver samples were collected.Subsequently,body parameters,biochemical parameters and liver pathology were examined.The expression levels of proteins involved in the SIRT3/AMPK/ACC pathway in the liver were detected by Western blotting.After 8 and 16 weeks of a HFD,the successful establishment of rat models with different degrees of NAFLD was confirmed by hematoxylin and eosin(H&E)and Oil Red O staining.NAFLD rat models exhibited obesity and hyperlipidemia,and the protein expression levels of SIRT3,p-AMPK.p-ACC,and CPT-1A in the liver were significantly decreased compared to those in the NC group.The concurrent administration of BBR with the HFD effectively improved serum and liver lipid profiles and ameliorated liver injury.Furthermore,the protein expression levels of SIRT3,p-AMPK,p-ACC,and CPT-1 A in the liver were significantly increased in the BBR group as compared with those in the HFD group.In conclusion,our data suggest that the mechanism by which BBR ameliorates HFD-induced hepatic steatosis may be related to the activation of the SIRT3/AMPK/ACC pathway in the liver.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 the Key Project of Science and Technology Research Program of Hubei Provincial Department of Education,China(D20231704)the Opening Foundation of Hubei Key Laboratory for New Textile Materials and Applications Research(FZXCL202410)the Wuhan Textile University Special Fund Project。
文摘Currently,the performance,cost,and environmental sustainability of saturable absorbers(SAs)represent major bottlenecks in the development of ultrafast fiber lasers.However,the development of high-performance SAs remains challenging due to intricate fabrication processes and inadequate nonlinear performance.In this context,this work presents the natural alkaloid berberine as a promising alternative for mode-locked erbium-doped fiber lasers.The berberine-based SA exhibits excellent nonlinear optical properties,including a modulation depth of 24.40%and a saturation intensity of 1.281MW/cm^(2),and successfully enables stable femtosecond pulse generation.By employing time-stretched dispersive Fourier transform technology,the transient dynamics results indicate that the berberine-based SA significantly shortens the relaxation oscillation time and effectively suppresses pulse intensity fluctuations,thereby accelerating the self-starting process of mode-locking.This work provides a new strategy for developing high-performance,low-cost,and environmentally friendly ultrafast photonic devices,significantly advancing the practical application of green SAs.
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.
基金Natural Science Foundation-funded Project:Study on the Mechanism of Mechanical Stress Sensing Element Piezo Type Mechanosensitive Ion Channel Component 2 Interacting with Nuclear Receptor Subfamily 4 Group A Member 2 Mediating Traumatic Brain Injury(No.82172190)。
文摘OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.
基金funded by the National Key Research and Devel-opment Program of China(2022YFA0806400)the CAMS Innova-tion Fund for Medical Sciences(CIFMS)(2023-I2M-2-006,2021-1-I2M-027,and 2021-1-I2M-028)+1 种基金the National Natural Science Foundation of China(82173888 and 81973290)the Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study(Z141102004414062).
文摘Hyperglycemia in individuals with diabetes causes cognitive impairment,called diabetic encephalopathy(DE).The pathogenesis of DE is closely related to angiopathy,and effective treatment is highly desirable.The botanical agent berberine(BBR)effectively lowers blood glucose in diabetic patients.Here,we show for the first time that BBR significantly improved cognitive function in type 2 diabetic encephalopathy KK-Ay(2DEK)mice.High-resolution imaging via fluorescence micro-optical sectioning tomography(fMOST)revealed that the integrity of brain vessels was improved by BBR treatment.The improvements in average vessel diameter,vessel length,and total vessel volume were significant in the parietal association cortex(PtA),as well as in the CA1 and CA3 regions.A mechanistic study revealed that oral BBR inhibited δ-valerobetaine(δ-VB,a metabolite of the gut microbiota)production in the intestine.As intestinal δ-VB can enter the circulation and activate the Toll-like receptor-4(TLR-4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa B(NF-jB)inflammatory pathway in the epithelial cells of blood vessels through interacting with TLR-4,BBR might reduce the intestinal level of δ-VB to protect the cerebral blood vessels of DE mice and improve their brain function.Fecal microbiota transplantation(FMT)using the gut microbiota from BBR-treated mice confirmed the vital role of the gut microbiota.BBR showed a wide range of effects on the gut flora,also increasing short-chain fatty acid(SCFA)production and decreasing lipopolysaccharide(LPS)levels in the intestine by adjusting the abundance of SCFA-or LPS-producing bacteria.The observed therapeutic efficacy in vivo revealed a synergistic effect of BBR on the gut microbiota.Conclusively,we found an association between the gut microbiota and blood vessels,of which intestinal δ-VB might be a chemical link.Mainly through downregulating δ-VB in the intestine,BBR protected cerebral vessels and alleviated DE.
基金supported by the National Natural Science Foundation of China(Grant No.82270892)Natural Science Foundation of Hubei Province(Grant No.2022CFB287)+2 种基金Xianning City Science and Technology Plan Project(Grant No.2022ZRKX052)School projects of Hubei University of Science and Technology(Grant No.2022T01,2021WG05,2021TNB01)Hubei University of Science and Technology School-level Fund(Grant No.BK202122).
文摘Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.
基金financial support provided by Young Scientists Fund of the National Natural Science Foundation of China(No.32201086)Postdoctoral Science Foundation of Chongqing Natural Science Foundation(No.cstc2021jcyj-bsh X0125)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(No.CXQT20006)。
文摘Diabetes mellitus(DM)is a serious health problem in the world,and infections are common complications in diabetic patients,particularly methicillin-resistant Staphylococcus aureus(MRSA)infections,which substantially increases mortality in patients.In clinical practice,the treatment of diabetic complicationrelated infections involves multiple issues such as drug resistance when combining antidiabetic drugs with antibiotics.In this study,a series of derivatives were synthesized with alkyl radicals with different chain lengths substituted at the C8 and C12 positions of berberine,with compounds CY1 and CY3with good antidiabetic and antibacterial activities screened out after identification.Then,oral liposomes(CY1-Lip and CY3-Lip)were prepared,and their particle sizes,stability,and pharmacokinetics were investigated.In acquired mouse models of diabetes,induced with an acute MRSA lung infection,we demonstrate that CY1-Lip and CY3-Lip can effectively reduce levels of fasting blood glucose(FBG),fasting insulin(FINS),and insulin resistance index among diabetic mice with pneumonia,thus exerting their multitargets effects.Furthermore,both preparations significantly reduced lung MRSA loads and improved lung tissue lesions,reduced high infiltration of M1 macrophages in lung,and suppressed the expression levels of pro-infiammatory factors such as necrosis factor-α(TNF-α)and interleukin-6(IL-6).This provides new insights into the clinical treatment of diabetes complicated with pulmonary infections.
基金Science and Technology Fund Project of Guizhou Provincial Health Commission(Project No.:gawkj2021-225).
文摘This study explored the therapeutic effect of trimebutine maleate dispersible tablets combined with berberine on PI-IBS rats with liver depression and spleen deficiency.Fifty male rats were divided into five groups:normal,model,berberine(XB),trimebutine(QM),and combination(XB+QM).The PI-IBS model was established using maternal separation,TNBS perfusion,and chronic restraint.After 20 days of drug intervention,DAI,CMDI,TDI,AWR scores,histopathology,and expression levels of c-Fos,VIP,NOS,and CHAT in the hippocampus and colon were assessed.The model group showed significant gut and brain changes,while the combination group(XB+QM)improved fecal characteristics,reduced inflammation,regulated brain-gut peptide expression,and alleviated visceral hypersensitivity and colon tissue damage(P<0.05).
文摘Atherosclerosis(AS)is the core pathological basis of Cardiovascular Disease(CVD)worldwide.Its occurrence and development involve endothelial dysfunction,lipid deposition,chronic inflammation and abnormal proliferation of smooth muscle cells.Berberine(BBR),also known as berberine,is an isoquinoline alkaloid extracted from traditional Chinese medicine such as Coptis coptidis and Phelloberia angustifolia.It has traditionally been used for antibacterial and anti-inflammatory treatment.In recent years,it has been found that it has multi-target metabolic regulation and anti-inflammatory properties,showing significant potential in the prevention and treatment of AS.This article systematically reviews the research progress of berberine in the treatment of AS by improving endothelial function,regulating lipid metabolism,inhibiting inflammatory response,regulating smooth muscle cell phenotypic transformation,and anti-oxidative stress,and discusses the current status and challenges of its clinical application.
基金Innovation Fund of Chinese Academy of Sciences(KGCX2 SW 213 05)
文摘Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.
基金AProject of the Health Bureau of Chongqing (No.2004-B-31)
文摘Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distilled water freely with different doses of BER （15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1） or sallcylazosulfapyridine （SASP, 520 mg·kg^-1）, and solvent （0. 2 mL/10 mg Wt） once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）. Myeloperoxidase （MPO） and superoxide dismutase （SOD） activities and malondialdehyde （MDA） content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.
基金National Natural Science Foundation of China(Grant No.81374006,81073092 and 90713043)
文摘Berberine （BBR） has a variety of pharmacological activities. Studies have reported that BBR not only reduces heat stress-induced fever but also inhibits lower body temperatures due to cold stress. Heat stress can be reduced via BBR treatment, which antagonizes HSP70-TNFa to regulate the body temperature alteration. In cold stress, however, the molecular mechanism of BBR-induced inhibition of hypothermia remains unclear. Therefore, we studied whether BBR promoted uncoupling protein 1 （UCP1, a crucial protein of thermogenesis） expression and its mechanism under cold stress. Wild type mice and Ucpl-/- mice were used for the in vivo experiments, and primary brown adipocytes and brown adipocytes HIB-1B were used for the in vitro studies. The cold stress was set at 4℃. The results showed that at 4℃, the body temperature of mice was decreased. BBR effectively inhibited this hypothermia. Simultaneously, Ucpl expression in brown adipose tissue （BAT） cells was significantly increased, and BBR promoted Ucpl expression. However, in Ucpl-knockout mice, the effect of BBR on hypothermia disappeared during cold stress, indicating that the main target for BBR regulation of body temperature was Ucpl. Further studies showed that the transcriptional response element NFE2 （nuclear factor erythroid-derived 2） in the upstream of the Ucpl promoter region contributed to the positive regulatory role on Ucpl expression at lower temperature. BBR could bind to the sequence of NFE2 response element in a temperature-dependent manner. Increased affinity of BBR binding to NFE2 response element in cold stress significantly strengthened and enhanced the expression of Ucpl. This work was important for understanding the role of BBR on thermogenesis in BAT, body temperature regulation and temperature tolerance under cold conditions.
文摘Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.
基金supported by grants from the National Natural Science Foundation of China(No.81173370)the Natural Science Foundation of Hubei Province,China(No.2012FFB02434)
文摘The intestinal absorption ofberberine （Ber） and its structural modified compound 8-hydroxy dihydroberberine （Hdber） was compared, and their effects on the intestinal absorption of sugar by per- fusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography （HPLC） was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than I0%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 ~tg/mL. However, Hdber presented stronger activity than Bet （P〈0.01）. It is suggested that Hdber is ab- sorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.
文摘Effects of berberine (Ber) on platelet aggregation and TXB2 and 6 keto PGF1a plasma levels were studied in rabbits with uncomplete cerebral ischemia. Ber inhibited uncomplete cerebral ischemic rabbit platelet aggregation triggered by collagen, ADP, and arachidonic acid (AA) with the IC 50 of 0.15, 0.46, and 0.51 mg·ml 1 , respectively. In rabbits, Ber 25, or 50 mg·kg 1 iv 30 min after uncomplete cerebral ischemia, restrained the collagen ADP and AA induced platelet aggregation determined 90 min later. With radioimmunoassay, we measured the thromboxane B2 (TXB 2) and 6 ketoprostaglandin F 1α (6 keto PGF 1α ) contents in rabbit plasma. The results indicated that the TXB 2 level in rabbit 120 min after uncomplete cerebral ischemia (921±539 pg·ml 1 ) was higher than that (230±71 pg·ml 1 ) in normal rabbits ( P < 0.01), but 6 keto PGF 1α level after ischemia (73±23pg·ml 1 ) was lower than that (262±988pg·ml 1 ) in normal rabbit. Ber (5, 25 or 50 mg·kg 1 ) reduced obviously the plasma TXB 2 level in rabbit with uncomplete cerebral ischemia (504±196, 386±174, or 272±183 vs 921±539 pg·ml 1 , respectively, P < 0.01). We conclude that the decrease of TXB 2 content is one of the possible mechanisms of Ber anti cerebral ischemic effect.
基金The authors would like to acknowledge the support of the Ph.D.research startup foundation of Guangdong Medical University (2XB14006).
文摘The content of berberine hydrochloride(BH)in compound berberine tablets(CBTs)is subject to strict requirements.Its content is usually measured based on chemical analysis.In this paper,the fluorescence spectral imaging method was used to study the relative content of BH from a physics perspective.By comparing the relative fluorescence intensity of self-made CBTs with di®erent mass percentages of BH,a linear positive relationship was observed between the BH content and the relative fluorescence intensity,and accordingly the quality of CBTs of different brands was evaluated.The results indicate that the fluorescence spectral imaging method can be a simple,fast and nondestructive semi-quantitative analysis method to determine the content of BH in CBTs,and this method has great potential in the quality control of CBTs.
基金National Natural Science Foundation of China(Grant No.81374006,81073092 and 90713043)the National S&T Major Special Project for New Drug R&D Program of China(Grant No.2012ZX09103-201-041,2012ZX09102-201-008 and 2011ZX09101-002-11)
文摘Berberine, an isoquinoline alkaloid component of Rhizoma Coptidis has been demonstrated to be the key active ingredient involved in its protective effect against cerebral ischemia-reperfusion. However, the comparison among the analogues to the protective effect against oxygen and glucose deprivation/reoxygenation （OGD-R） was mediated by inhibition of cyclooxygenase-2 （COX-2） has never been reported. The aim of this study is to investigate the protective effect of berberine and its five analogues against OGD-R in PC 12 cells, as well as to determine whether the protective effect was regulated through COX-2. An established in vitro OGD-R model of PC12 cells by oxygen glucose deprivation of 4 h and reperfusion of 24 h was used in our study. After cells were treated with berberine or its five analogues, we examined the cell viability assay by 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） assay. Cells were also collected to determine the levels of mRNA and protein of COX-2 by real time PCR and Western blot. We found that berberine and its analogues improved the viability of PC12 cells against OGD-R. Whereas berberine and berberrubine presented stronger activity with the most effective dose of 0.31 lag/mL and the minimum effective doses of 0.02 and 0.04 gg/mL. Palmatine possessed potentially weaker protective effect. The mRNA level of COX-2 in cells treated with berberine, coptisine and epiberberine was decreased significantly. The protein level of COX-2 was significantly down-regulated in cells treated with berberine. Studies suggested the important role of methylenedioxy groups （R2 and R3） of berberine analogues in COX-2 inhibitory effect, and methylenedioxy groups （R2, R3, R9 and R10） in berberine analogues in binding affinity with COX-2. Substituted hydroxyl group at R9 did not affect the activity of berberine. In summary, our study illustrated the protective effects of berberine and its analogues in PCI2 cells against OGD-R and to elucidate the structure-activity relationships. Docking analysis indicates that methylenedioxys at R2 and R3 is involved in the effect. More studies in other cells are needed to confirm our results.
基金Supported by The Grant CMU92-CM-02 from China Medical University
文摘AIM： To investigate the relationship between the inhibited growth （cytotoxic activity） of berberine and apoptotic pathway with its molecular mechanism of action. METHODS： The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub431 group （apoptosis） were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting. RESULTS： For SNU-5 cell line, the IC （50） was found to be 48 μmol/L of berberine. In SNU-5 cells treated with 25-200 μmol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-Go cell population in cell cycle measurement was proved in 25-200 μmol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-Go cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca^2＋, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis. CONCLUSION： Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.
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grants from the National Natural Science Foundation of China(No.81573844 and No.81774165)Medical Research Fund of Guangdong Province(No.A2017363).
文摘This study aimed to verify the effects of berberine(BBR)on the fat metabolism proteins involved in the sirtuin 3(SIRT3)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)pathway in the liver tissues of rats with high-fat diet(HFD)-induced non-alcoholic fatty liver disease(NAFLD).Forty-eight rats were randomly divided into the normal control(NC)group,HFD group or BBR group,with 16 rats in each group.After 8 and 16 weeks of treatment,serum and liver samples were collected.Subsequently,body parameters,biochemical parameters and liver pathology were examined.The expression levels of proteins involved in the SIRT3/AMPK/ACC pathway in the liver were detected by Western blotting.After 8 and 16 weeks of a HFD,the successful establishment of rat models with different degrees of NAFLD was confirmed by hematoxylin and eosin(H&E)and Oil Red O staining.NAFLD rat models exhibited obesity and hyperlipidemia,and the protein expression levels of SIRT3,p-AMPK.p-ACC,and CPT-1A in the liver were significantly decreased compared to those in the NC group.The concurrent administration of BBR with the HFD effectively improved serum and liver lipid profiles and ameliorated liver injury.Furthermore,the protein expression levels of SIRT3,p-AMPK,p-ACC,and CPT-1 A in the liver were significantly increased in the BBR group as compared with those in the HFD group.In conclusion,our data suggest that the mechanism by which BBR ameliorates HFD-induced hepatic steatosis may be related to the activation of the SIRT3/AMPK/ACC pathway in the liver.
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.
