[Show abstract][Hide abstract] ABSTRACT: BACKGROUND Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). MATERIAL AND METHODS We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. RESULTS Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. CONCLUSIONS Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma.
Medical science monitor: international medical journal of experimental and clinical research 09/2015; 21:2613-20. DOI:10.12659/MSM.895075 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Jinlida granule (JLDG), composed of seventeen Chinese medical herbs, is a widely used Chinese herbal prescription for treating diabetes mellitus. However, the mechanism underlying this effect remains unclear.Aim of the studyTo determine the main components in JLDG and to explore the effect of JLDG on autophagy and lipid accumulation in NIT-1 pancreatic β cells exposed to politic acid (PA) through AMP activated protein kinase (AMPK) signaling pathway.Materials and methodsJLDG was prepared and the main components contained in the granules were identified by ultra performance liquid chromatography (UPLC) fingerprint. Intracellular lipid accumulation in NIT-1 cells was induced by culturing with medium containing PA. Intracellular lipid droplets were observed by Oil Red O staining and triglyceride (TG) content was measured by colorimetric assay. The formation of autophagosomes was observed under transmission electron microscope. The expression of AMPK and phospho-AMPK (pAMPK) proteins as well as its downstream fatty acid metabolism-related proteins (fatty acid synthase, FAS; acetyl-coA carboxylase, ACC; carnitine acyltransferase 1, CPT-1) and autophagy-related genes (mammal target of rapamycin, mTOR; tuberous sclerosis complex 1, TSC1; microtubule-associated protein 1 1ight chain 3, LC3-II) were determined by western blot. The expression of sterol regulating element binding protein 1c (SREBP-1c) mRNA was examined by real time PCR (RT-PCR).ResultsOur data showed that JLDG could significantly reduce PA-induced intracellular lipid accumulation in NIT-1 pancreatic β cells. This effect was associated with increased protein expression of pAMPK and AMPK in NIT-1 cells. Treatment with JLDG also decreased the expression of AMPK downstream lipogenic genes (SREBP-1c mRNA, FAS and ACC proteins) where as increased the expression of fatty acid oxidation gene (CPT-1 protein). Additionally, JLDG-treated cells displayed a markedly increase in the number of autophagosomes which was accompanied by the down-regulation of mTOR and the up-regulation of TSC1 and LC3-II proteins expression. However, when AMPK phosphorylation was inhibited by Compound C, JLDG supplementation did not exhibit any effect on the expression of these AMPK downstream molecules in NIT-1 cells.Conclusions
The results suggest that JLDG could reduce intracellular lipid accumulation and enhance the autophagy in NIT-1 pancreatic β cells cultured with PA. The mechanism is possibly mediated by AMPK activation.Graphical abstractAbbreviationsJLDG, Jinlida granuleTCM, traditional Chinese medicineACC, acetyl-coA carboxylaseFAS, fatty acid synthaseCPT-1, carnitine acyl transferase 1AMPK, AMP activated protein kinasepAMPK, phospho-AMP activated protein kinaseSREBP-1c, sterol regulating element binding protein 1cmTOR, mammal target of rapamycinTSC1, tuberous sclerosis complex 1LC3-II, microtubule-associated protein 1 1ight chain 3PA, palmitateT2DM, type 2 diabetes mellitusRT-PCR, real time PCRTG, triglycerideUPLC, ultra performance liquid chromatographyAICAR, 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranosideKeywordsJinlida granuleType 2 diabetesLipid metabolismAutophagyAMP activated protein kinaseNIT-1 cells
Journal of Ethnopharmacology 12/2014; 161. DOI:10.1016/j.jep.2014.12.005 · 3.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estrogens are key signaling molecules that regulate various physiological processes such as cell growth, development, and differentiation. They also play a major role in many pathological conditions, such as hormone-dependent cancer. The importance of inhibiting estrogen receptor signaling
in diseases of estrogen target tissues, such as breast cancer, is well documented. However, the role of estrogen signaling in diseases of nontarget tissues, such as lung cancer, is not well characterized. The aim of the current study is to examine the expression of estrogen receptor β
(ERβ) and the roles of estradiol (E2) and fulvestrant on the progression of lung cancer. Tissue microarray (TMA) and immunohistochemistry (IHC) analyses were used to detect the expression of aromatase, ERα, and ERβ in 198 patients. We performed analyses to determine if there
was any correlation among these three proteins. A mouse model of urethane-induced lung adenocarcinoma was used in the study. Mice were divided into three treatment groups: blank control, E2 alone, and E2 + fulvestrant (ERβ antagonist). Western blot analysis and fluorescence quantitative
PCR (FQ-PCR) were used to measure expression of ERβ protein and mRNA levels, respectively. ERβ, but not ERα, was overexpressed in NSCLC samples. Lung cancer progression in mice treated with E2 was significantly increased compared to either the control group or the E2 + fulvestrant
group. Mice in the E2 treatment group had significantly increased expression of ERβ at both the mRNA and protein levels compared to mice treated with E2 + fulvestrant or control. Our data suggest that ERβ promotes lung cancer progression in mice and that this progression can be inhibited
with fulvestrant. These findings may help elucidate the role of ERβ in lung cancer and suggest that estrogen receptor antagonists, such as fulvestrant, may be therapeutically beneficial for the treatment of the disease.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 10/2014; 22(1). DOI:10.3727/096504014X14077751730315 · 1.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism.
Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined.
(a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05).
(a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.
Alcohol and Alcoholism 03/2014; 49(3). DOI:10.1093/alcalc/agu009 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effect of Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feeding on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of streptozotocin. Rats in treatment groups, including the Fructus Mume formula treatment group (FM), the cold property herbs of Fructus Mume formula treatment group (CFM), the warm property herbs of Fructus Mume formula treatment group (WFM), were administrated with Fructus Mume formula and its separated prescription extract by gavage, while the rats in diabetic model group (DM) and metformin group (MET) were given by gavage with normal saline and metformin correspondingly. The body weight before and after treatment was measured, and the oral glucose tolerance test (OGTT) and the insulin release test (IRT) were performed. The homeostasis model assessment-insulin resistance index (HOMA-IR) was calculated. The protein and mRNA expression levels of Insr, β-arrestin-2, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT (0 h, 1 h) levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of β-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and β-arrestin-2 in the liver and skeletal muscle tissues.
Journal of Huazhong University of Science and Technology 12/2013; 33(6):877-885. DOI:10.1007/s11596-013-1215-7 · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Jiao Tai Wan (JTW), a Chinese herbal formula containing Rhizoma Coptidis and Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of this study was to determine the main components in JTW and to investigate the effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW extract was prepared and the main components were assayed by HPLC. An animal model of diabetes mellitus was established and JTW was administered intragastrically. In the clinical study, diabetic patients with poor glycemic control were treated with JTW. Blood glucose and lipid parameters, liver histology, hepatic triglyceride content and lipogenic gene expression were examined. Our data demonstrated that JTW significantly improved hyperglycemia, hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) protein expressions, and the up-regulation of AMP-activated protein kinase (AMPK) and phosphorylated-ACC (pACC) protein expressions in the liver tissues. Diabetic patients also exhibited decreases in their hepatic triglyceride content. The results suggest that JTW attenuates hepatic lipid accumulation in diabetic rats and humans. These beneficial effects are possibly associated with the inhibition of lipogenic gene expression in the liver.
Evidence-based Complementary and Alternative Medicine 11/2013; 2013(4):567045. DOI:10.1155/2013/567045 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and protein kinase C-alpha (PKC-
) related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47
, and the protein expression of phosphorylated PKC-
in renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-
/NADPH oxidase signaling pathway.
Evidence-based Complementary and Alternative Medicine 06/2013; 2013(2):504642. DOI:10.1155/2013/504642 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Jiao-Tai-Wan (JTW), a classical Chinese prescription, has been clinically employed to treat diabetes mellitus in recent years. To investigate the comparative evaluations on anti-diabetic effects and pharmacokinetics of the active ingredient berberine in mice treated with JTW in various combinations of its constituent herbs. In our study, the anti-diabetic study was carried out in diabetic mice induced by intraperitoneal injection of streptozotocin. The diabetic mice were randomly assigned to three therapy groups and orally administered with different prescription proportions of Rhizoma Coptidis and Cinnamomum cassia respectively. The level of plasma glucose, lipid profile and parameters related to oxidative stress were determined. The concentrations of berberine in non-diabetic mice plasma were determined using HPLC, and main pharmacokinetic parameters were investigated. The results indicated that the compatibility effects of ingredients present in Cinnamomum cassia could affect the anti-diabetic ability and pharmacokinetics of berberine in JTW.
Phytomedicine: international journal of phytotherapy and phytopharmacology 04/2013; 20(10). DOI:10.1016/j.phymed.2013.03.004 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estrogens play a pivotal role in the development and progression of non-small lung cancer (NSCLC). With the discovery of estrogen receptor β (ERβ) isoforms, some controversial roles of ERβ were explained adequately in NSCLC. In this study, our aim is to elucidate expression, distribution, and prognostic significance of ERβ 1, 2, 5 in NSCLC. Estrogen receptors β1, 2, 5 protein expression were confirmed by Western-blot analysis in all frozen tissues, and immunohistochemistry (IHC). Nuclear and cytoplasmic staining was evaluated and correlated with histopathologic characteristics, overall survival (OS) and disease-free survival (DFS) via Pearson χ 2 square, Kaplan-Meier plots and Cox proportional hazard models. ERβ1 was commonly found in the cytoplasm and was the most abundant isofroms followed by ERβ2 and ERβ5 which were localized in the cytoplasm and nucleus. In contrast to BPL, both in nucleus and cytoplasm, ERβ1, ERβ2, and ERβ5 were over expressed all in NSCLC (P < 0.05). IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ERβ1, ERβ2, and ERβ5 in NSCLC. nERβ1 "nuclear", cERβ2 and cERβ5 "cytoplasm" were in a negative correlation with the pathological stage and lymph node metastasis. In a Kaplan-Meier analysis, the expression cERβ2 and cERβ5 identified a group of patients with the longest DFS and OS. Cox proportional hazard models revealed that cERβ2 and cERβ5 predicted long time to DFS and OS. This is the first study to uncover the expression of ERβ1, ERβ2, and ERβ5, and show that they were over expressed in NSCLC. Meantime, we find that positive expression of cERβ2 and cERβ5 were in a positive correlation with DFS, and have prognostic values for the progression of NSCLC.
[Show abstract][Hide abstract] ABSTRACT: The estrogen receptor (ER) signaling and the insulin-like growth factor-1 receptor (IGF-1R) signaling are implicated in lung cancer progression. Here, we sought to investigate whether estrogen regulated the IGF-1R signaling in non-small cell lung cancer (NSCLC) and the underlying mechanisms. We examined and analyzed the correlation of the expression of aromatase (Arom), ERβ, ERα, insulin-like growth factor-1 (IGF-1), and IGF-1R in NSCLC. Tissue-microarray and immunohistochemistry analysis of tissue specimens from 162 NSCLC patients and 38 patients with benign pulmonary lesions showed that Arom, ERβ, IGF-1, and IGF-1R were overexpressed while ERα was not expressed in NSCLC. Furthermore, ERβ expression was positively correlated with that of Arom, IGF-1, and IGF-1R (r = 0.554, 0.649, 0.496, respectively, P values are equal to 0.000), while Arom expression was positively associated with that of IGF-1 and IGF-1R (r = 0.657, 0.714, respectively, P values are equal to 0.000). Additionally, ERβ, IGF-1, and phospho-IGF-1R, but not ERα, were expressed in A549 cells. Immunoblotting assays showed that A549 cells treated with E2 showed significantly higher IGF-1 and p-IGF-1R levels than those receiving the combination treatment of 17β-estradiol (E2) and fulvestrant (Ful, ER antagonist) (P = 0.042, 0.002, respectively) or controls (P values are equal to 0.000). The MTT assays further revealed that E2 and IGF-1 synergistically promoted A549 cell proliferation. Together, our study provides the first direct evidence for an interaction between ER and IGF-1R in lung cancer. We showed that estrogen upregulated the IGF-1R signaling through ERβ in lung cancer tissues and A549 cells. These findings shed further light on the mechanisms whereby estrogen promotes lung cancer and highlight the ER and IGF-1R signaling pathways as promising targets for combinational therapy for lung cancer.
Medical Oncology 03/2012; 29(4):2640-8. DOI:10.1007/s12032-012-0198-8 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the effects of different compatibility proportion of Jiaotai pills on treating type 2 diabetes mellitus (T2DM) in rats.
The model of type 2 diabetes mellitus in rats was established by injecting streptozotocin from tail vein and feeding with high fat and high caloric diet. Diabetic rats were randomly divided into model group, Jiaotai pill 1 group (Coptidis Rhizoma-cinnamon 2: 1), Jiaotai pill 2 group (Coptidis Rhizoma-cinnamon 4: 1), Jiaotai pill 3 group (Coptidis Rhizoma-cinnamon 10: 1) and metformin group. Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile normal control group was another set. Body weight, oral glucose tolerance test (OGTT), blood lipid level including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), plasma levels of free fatty acid (FFA) and adiponectin, plasma liver enzymes activity(ALT, AST, AKP, gamma-GT) and pathological results of liver tissue were determined after eight weeks.
Body weight, fasting plasma glucose (FPG), postpradial plasma glucose at one hour (PG-1 h), postpradial blood glucose at two hour (PG-2 h), plasma levels of TC, TG, LDL-C, FFA and liver enzymes activity were all increased in rats of model group compared with those in normal control group. Plasma levels of HDL-C and adiponectin were decreased in model group (P < 0.01). Fatty degeneration of hepatocytes was apparent in liver tissues in rats of model group. Compared with model group results of OGTT, blood lipid levels and liver enzymes activity were improved while levels of HDL-C and adiponectin were increased in rats of different treatment groups (P < 0.05 or P < 0.01). Meanwhile fatty degeneration of hepatocytes was improved in liver tissues in rats of different treatment groups. Compared with metformin group, plasma level of HDL-C was elevated while AKP and gamma-GT were decreased significantly in rats of Jiaotai pill 1 group (P < 0.05), gamma-GT level was decreased significantly in rats of Jiaotai pill 2 group (P < 0.05), AST, AKP and gamma-GT levels were decreased significantly in rats of Jiaotai pill 3 group (P < 0.05). Compared with Jiaotai Pill 1 group, plasma levels of HDL-C was decreased while AKP levels was elevated significantly in rats of Jiaotai pill 2 group, but HDL-C was decreased in rats of Jiaotai pill 3 group (P < 0.05).
It is suggested that different compatibility proportion of Jiaotai pills are effective on treating type 2 diabetes mellitus in rats. The effect of Jiaotai pill 1 group is better than that of other therapy groups.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 08/2011; 36(16):2271-6.
[Show abstract][Hide abstract] ABSTRACT: Lung cancer has been viewed as the most common malignant cancer with high incidence, mortality and poor survival all over the world. A lot of investigations indicated there are significant gender-associated differences in lung cancer in several characteristics such as epidemiology, pathology, clinical outcome and prognosis. The insight into these differences may help to clarify the gender-associated characteristics of lung cancer, and to drawn out new approach for treatment and prevent of lung cancer depending on gender-associated characteristics. Furthermore, study on mechanism of gender-associated characteristics may even help to illuminate the pathogenesis of lung cancer.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 07/2011; 14(7):625-30. DOI:10.3779/j.issn.1009-3419.2011.07.12
[Show abstract][Hide abstract] ABSTRACT: The effects of Cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers,
and the compatibility mechanism of Jiao-Tai-Wan (JTW) composed of Rhizoma Coptidis granules and Cinnamon granules were investigated.
The concentration of berberine in plasma of healthy male volunteers was determined directly by high performance liquid chromatography
(HPLC) after an oral administration of Rhizoma Coptidis granules alone or combined with Cinnamon granules (JTW). The plasma
concentration-time curves of berberine were plotted. The data were analyzed with Drug and Statistics (DAS) 2.0 pharmacokinetic
program (Chinese Pharmacology Society) to obtain the main pharmacokinetic parameters. The results showed that the plasma concentration-time
curve of berberine was described by a two-compartment model. The Cmax, Tmax, t1/2 and CLz/F of berberine in Rhizoma Coptidis granules were 360.883 μg/L, 2.0 h, 3.882 h, 119.320 L·h−1·kg−1 respectively, and those of berberine in JTW were 396.124 μg/L, 1.5 h, 4.727 h, 57.709 L·h−1·kg−1 respectively. It was suggested that Rhizoma Coptidis granules combined with Cinnamon granules could increase the plasma concentration
of berberine, promote berberine absorption and lengthen the detention time of berberine in healthy male volunteers.
Key wordsRhizoma Coptidis–Cinnamon cassia–Jiao-Tai-Wan–berberine–pharmacokinetics
Journal of Huazhong University of Science and Technology 06/2011; 31(3):379-383. DOI:10.1007/s11596-011-0385-4 · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study is to investigate the effect of 8-hydroxy-dihydroberberine on insulin resistance induced by high free fatty acid (FFA) and high glucose in 3T3-L1 adipocytes and its possible molecular mechanism. Palmic acid or glucose in combination with insulin was used to induce insulin resistance in 3T3-L1 adipocytes. 8-Hydroxy-dihydroberberine and berberine were added to the cultured medium separately, which were considered as treated group and positive control group. The rate of glucose uptake was determined by 2-deoxy-[3H]-D-glucose method. The amount of glucose consumption in the medium was measured by glucose oxidase method. Cell growth and proliferation of 3T3-L1 adipocytes were detected with Cell Counting Kit-8 (CCK-8) assay. After incubated with palmic acid for 24 hours or glucose with insulin for 18 hours, the rate of glucose transport in 3T3-L1 adipocytes was inhibited by 67% and 58%, respectively. The amount of glucose consumption in 3T3-L1 adipose cells was decreased by 41% after cells were incubated with palmic acid for 24 h. However, the above changes were reversed by pretreatment with 8-hydroxy-dihydroberberine for 24 and 48 h. Significant difference existed between groups. Insulin resistance in 3T3-L1 adipocytes, which is induced by high FFA and high glucose, could be ameliorated by 8-hydroxy-dihydroberberine.
Yao xue xue bao = Acta pharmaceutica Sinica 11/2009; 44(11):1304-8.
[Show abstract][Hide abstract] ABSTRACT: To observe the effect of berberine on insulin secretion in rat pancreatic islets and to explore its possible molecular mechanism.
Primary rat islets were isolated from male Sprague-Dawley rats by collagenase digestion and treated with different concentrations (1, 3, 10 and 30 micromol/L) of berberine or 1 micromol/L Glibenclamide (GB) for 24 h. Glucose-stimulated insulin secretion (GSIS) assay was conducted and insulin was determined by radioimmunoassay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate cytotoxicity. The mRNA level of hepatic nuclear factor 4 alpha (HNF4alpha) was determined by reverse transcription polymerase chain reaction (RT-PCR). Indirect immunofluorescence staining and Western blot analysis were employed to detect protein expression of HNF4alpha in the islets. Glucokinase (GK) activity was measured by spectrophotometric method.
Berberine enhanced GSIS rather than basal insulin secretion dose-dependently in rat islets and showed no significant cytotoxicity on islet cells at the concentration of 10 mumol/L. Both mRNA and protein expressions of HNF4alpha were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly. However, GB demonstrated no regulatory effects on HNF4alpha expression or GK activity.
Berberine can enhance GSIS in rat islets, and probably exerts the insulinotropic effect via a pathway involving HNF4alpha and GK, which is distinct from sulphonylureas (SUs).
World Journal of Gastroenterology 11/2008; 14(39):6004-11. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes.
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-[(3)H]-D-glucose method. The levels of IkB kinase beta (IKKbeta) Ser(181) phosphorylation, insulin receptor substrate-1(IRS-1) Ser(307) phosphorylation, expression of IKKbeta, IRS-1, nuclear transcription factor kappaB p65 (NF-kappaB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-kappaB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy (CLSM).
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 IKKbeta Ser(181) and IRS-1 Ser(307) phosphorylation, and nuclear translocation of NF-kappaB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKbeta and total NF-kappaB p65 protein were not changed during this study.
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 IKKbeta.
World Journal of Gastroenterology 03/2008; 14(6):876-83. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of berberine on nuclear transcription factor kappaB (NF-kappaB p65) expression and translocation in insulin resistant 3T3-L1 adipocytes induced by free fatty acid (FFA) and its possible molecular mechanism.
3T3-L1 adipocytes were treated with palmic acid (0.5 mmol/L) to induce insulin resistance and intervened with berberine. Controlled with aspirin, the glucose consumption in the medium was determined by glucose oxidase method; glucose transportation by 2-deoxy-[3H]-D-glucose method; protein expression of NF-kappaB p65 in adopocytes by Western blot; and the distribution of NF-kappaB p65 was displayed by confocal laser scanning microscope (CLSM).
Treatment with 0.5 mmol/L of palmic acid for 24 h made glucose consumption of 3T3-L1 adipocytes decrease by 41%; the insulin-stimulated glucose transportation inhibited by 67%; nuclear NF-kappaB p65 protein expression and nuclear translocation of NF-kappaB p65 significantly increased. These changes were reversed by prior treatment with berberine or aspirin. But total NF-kappaB p65 protein expression was not responded to palmic acid, berberine and aspirin.
Berberine significantly improve the insulin resistance induced by FFA in 3T3-L1 adipocytes, its molecular mechanism might through inhibiting the activation and translocation related gene expression of NF-kappaB.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 01/2008; 27(12):1099-104.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of berberine on insulin secretion of NIT-1 cells stimulated by glucose and the possible molecular mechanism, we used radioimmunoassay, scintillation counting technique, enzymatic method and Western blotting to measure the effects of berberine on insulin secretion, glucose utilization, the activity of glucokinase (GK) and protein level of GK and GK regulation protein (GKRP). Compared with untreated group, insulin secretion level, glucose utilization, the activity and protein level of GK in NIT-1 cells stimulated by high concentration of glucose were increased significantly in berberine group (P < 0.05), while the protein level of GKRP in berberine group decreased markedly. In conclusion, berberine can promote insulin secretion of NIT-1 cells induced by high concentration of glucose. The possible molecular mechanism may be associated with berberine acting as a GK activator, improving glucose utilization, enhancing the activity and protein expression level of GK, as well as decreased the protein level of GKRP.
Yao xue xue bao = Acta pharmaceutica Sinica 11/2007; 42(10):1045-9.
[Show abstract][Hide abstract] ABSTRACT: To observe the effects of Huanglian Jiedu Decoction (HLJDD), a traditional Chinese compound herbal medicine, on p85 mRNA and protein expressions of phosphatidylinositol-3-kinase (PI-3K) in target tissues (skeletal muscular and adipose tissues) in rats with type 2 diabetes mellitus (T2DM) and to investigate the molecular mechanism of HLJDD in treating T2DM.
The male Wistar rats were injected with streptozotocin (STZ) 30 mg/kg through tail vein, and fed with high-fat and high-caloric diets to induce T2DM. Then the rats were randomly divided into untreated group, aspirin-treated group and HLJDD group, and treated correspondingly. Meanwhile, a group of normal animals without any treatment was set up for normal control group. Ten weeks later, serum fasting blood glucose (FBG), serum fasting insulin (FINS) and oral glucose tolerance test (OGTT) were routinely determined. The expressions of PI-3K p85 mRNA and protein in skeletal muscle and adipose tissue were determined with RT-PCR and Western blotting before and after insulin treatment.
Compared with the untreated group, the FBG and OGTT levels in T2DM rats treated with HLJDD decreased significantly (P<0.05). The FINS in HLJDD group was lower than that in the normal control group (P<0.05), but was not significantly different from that in the untreated group. The PI-3K p85 mRNA and protein expressions in HLJDD group obviously increased, as compared with those in the untreated group.
The effect of HLJDD in treating T2DM was probably associated with its improvement of PI-3K p85 mRNA and protein expressions in skeletal muscle and adipose tissue of the T2DM rats.
Journal of Chinese Integrative Medicine 10/2007; 5(5):541-5.