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OBJECTIVE@#To explore the protective effect and the underlying mechanism of Hu-Lu-Ba-Wan (, HLBW) on the testis of diabetic rats.@*METHODS@#Twenty-four male Wistar rats (160-180 g) were randomly divided into 3 groups according to a random number table, including a control group (n=8), diabetic group (n=8), and HLBW group (n=8). Diabetic rat model was established by high-fat-diet administration and single intravenous injection of streptozotocin (26 mg/kg). Then HLBW granule was administrated for 12 weeks. Fasting blood glucose and insulin levels as well as serum total testosterone level and testicular testosterone content were examined. Oxidative stress markers in both serum and testis were tested. Meanwhile, testicular morphology was observed under hematoxylin and eosin (HE) and the ultrastructure of Leydig cell was observed by electron microscope. The superoxide anion level was detected by DHE, and TUNEL-positive cells of testis was evaluated by TUNEL assay. The gene and protein expression of protein kinase C (PKCα), phosphorylated PKCα (P-PKCα) and P47phox in testicular tissues were determined by quantitative RT-PCR analysis and Western bolt analysis.@*RESULTS@#Compared with the diabetic group, HLBW treatment significantly reduced the fasting glucose levels and increased the levels of fasting insulin and testosterone in serum (P<0.01). HLBW administration also reduced the levels of reactive oxygen species (ROS) in plasma and alleviated the damage of oxidative stress in the testis of diabetic rats. Additionally, HLBW down-regulated the protein and mRNA levels of PKCα, P-PKCα and P47phox in testicular tissues.@*CONCLUSION@#HLBW may attenuate the oxidative stress in the testis of diabetic rats via PKCα /NAPDH oxidase signaling pathway.
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This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR)rats with chronic partial sleep deprivation (PSD).OR rats with PSD were orally given JTW and Estazolam for 4 weeks.The amount of food intake and metabolic parameters such as body weight increase rate,fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured.The expression levels of circadian proteins cryptochrome 1 (Cry1)and cryptochrome 2 (Cry2) in hypothalamus,adipose and liver tissues were also determined.Meanwhile,the mRNA expression of inflammatory markers,activity of nuclear factor kappa B (NF-κB) p65 protein,as well as the expression levels of insulin signaling pathway proteins in hypothalamus,adipose and liver tissues were measured.Additionally,cyclic adenosine 3',5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP)in hypothalamus tissue were measured.JTW significantly decreased the body weight increase rate and food intake,ameliorated systemic inflammation and insulin resistance.JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus,adipose and liver.Interestingly,all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression.We also found that in hypothalamus tissue of P SD rats,down-regulation of Cry 1 and Cry2 activated cAMP/PKA signaling and then led to inflammation,while JTW inhibited this signaling.These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.
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This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR)rats with chronic partial sleep deprivation (PSD).OR rats with PSD were orally given JTW and Estazolam for 4 weeks.The amount of food intake and metabolic parameters such as body weight increase rate,fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured.The expression levels of circadian proteins cryptochrome 1 (Cry1)and cryptochrome 2 (Cry2) in hypothalamus,adipose and liver tissues were also determined.Meanwhile,the mRNA expression of inflammatory markers,activity of nuclear factor kappa B (NF-κB) p65 protein,as well as the expression levels of insulin signaling pathway proteins in hypothalamus,adipose and liver tissues were measured.Additionally,cyclic adenosine 3',5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP)in hypothalamus tissue were measured.JTW significantly decreased the body weight increase rate and food intake,ameliorated systemic inflammation and insulin resistance.JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus,adipose and liver.Interestingly,all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression.We also found that in hypothalamus tissue of P SD rats,down-regulation of Cry 1 and Cry2 activated cAMP/PKA signaling and then led to inflammation,while JTW inhibited this signaling.These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.
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Diabetic kidney disease (DKD) is a chronic renal microvascular complication associated with abnormal glucose metabolism, which is an important cause of end stage renal disease. Diabetes can damage the kidney through many ways, including renal vascular, glomerular, tubular, and renal interstitial damages. Therefore, a comprehensive treatment process must be taken for the treatment of DKD, and the selection of appropriate drugs has important significance in the treatment of DKD. Berberine has significant curative effect in the treatment of DKD, and the mechanism is related to the reduction of blood sugar, improvement of renal hemodynamics abnormality, regulation of blood lipid profile and the attenuation of systemic and local inflammation.
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<p><b>OBJECTIVE</b>To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD).</p><p><b>METHODS</b>Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined.</p><p><b>RESULTS</b>The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine.</p><p><b>CONCLUSIONS</b>JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.</p>
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Intestinal tight junction is an important part of the small intestinal mucosa barrier. It plays a very significant role in maintaining the intestinal mucosal permeability and integrity, preventing the bacterial endotoxin and toxic macromolecular substances into the body so as to keep a stable internal environment. Numerous studies have shown that intestinal mucosal barrier dysfunction is closely related to the development of diabetes. Therefore, protecting intestinal tight junction and maintaining the mucosal barrier have great significance in the prevention and treatment of diabetes. The effect of berberine in diabetes treatment is obvious. However, the pharmacological study found that the bioavailability of berberine is extremely low. Some scholars put forward that the major site of pharmaceutical action of berberine might be in the gut. Studies have shown that berberine could regulate the intestinal flora and intestinal hormone secretion, protect the intestinal barrier, inhibit the absorption of glucose, eliminate the intestinal inflammation and so on. Recently studies have found that the hypoglycemic effect of berberine is likely to relate with the influence on intestinal tight junction and the protection of mucosal barrier. Here is the review about the association between intestinal tight junction barrier dysfunction and diabetes, and the related hypoglycemic mechanism of berberine.
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The polymorphisms of thyroid stimulating hormone receptor (TSHR) intron 1 rs179247 and rs12101255 have been found to be associated with Graves' disease (GD) in genetic studies. In the present study, we conducted a meta-analysis to examine this association. Two reviewers systematically searched eligible studies in PubMed, Web of Science, Embase and China Biomedical Literature Database (CBM). A meta-analysis on the association between GD and TSHR intron 1 rs179247 or rs12101255 was performed. The odd ratios (OR) were estimated with 95% confidence interval (CI). Meta package in R was used for the analyses. Seven articles (13 studies) published between 2009 and 2014, involving 5754 GD patients and 5768 controls, were analyzed. The polymorphism of rs179247 was found to be associated with an increased GD risk in the allele analysis (A vs. G: OR=1.40, 95% CI=1.33-1.48) and all genetic models (AA vs. GG: OR=1.94, 95% CI=1.73-2.19; AA+AG vs. GG: OR=1.57, 95% CI=1.41-1.74; AA vs. AG+GG: OR=1.54, 95% CI=1.43-1.66). The site rs12101255 also conferred a risk of GD in the allele analysis (T vs. C: OR=1.50, 95% CI=1.40-1.60) and all genetic models (TT vs. CC: OR=2.22, 95% CI=1.92-2.57; TT+TC vs. CC: OR=1.66, 95% CI=1.50-1.83; TT vs. TC+CC: OR=1.74, 95% CI=1.53-1.98). Analysis of the relationship between rs179247 and Graves' ophthalmopathy (GO) showed no statistically significant correlation (A vs. G: OR=1.02, 95% CI=0.97-1.07). Publication bias was not significant. In conclusion, GD is associated with polymorphisms of TSHR intron 1 rs179247 and rs12101255. There is no association between rs179247 SNPs and GO.
Subject(s)
Female , Humans , Male , China , Genetic Association Studies , Genetic Predisposition to Disease , Graves Disease , Genetics , Pathology , Graves Ophthalmopathy , Genetics , Pathology , Introns , Genetics , Polymorphism, Single Nucleotide , Receptors, Thyrotropin , Genetics , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells.</p><p><b>METHODS</b>Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction.</p><p><b>RESULTS</b>PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study.</p><p><b>CONCLUSION</b>It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.</p>
Subject(s)
Animals , Mice , AMP-Activated Protein Kinases , Metabolism , Berberine , Chemistry , Pharmacology , Cell Line , Cinnamates , Chemistry , Pharmacology , Fatty Acids , Metabolism , Gene Expression Regulation , Insulin-Secreting Cells , Metabolism , Intracellular Space , Metabolism , Lipogenesis , Genetics , Oxidation-Reduction , Palmitic Acid , Toxicity , Triglycerides , MetabolismABSTRACT
Diabetes is seriously hazards to human health and its pathogeneses are not clear. Recent studies show that the imbalance of intestinal flora and the development of diabetes are closely related. Appropriate bacteria can improve blood sugar disorder. Treating diabetes from the theory of Pi-Wei is effective. Regulating intestinal flora has become a new pathway for treating diabetes from the theory of Pi-Wei. On the basis of intestinal flora, authors discussed the treatment of diabetes from Pi and Wei.
Subject(s)
Humans , Bacteria , Blood Glucose , Diabetes Mellitus , Microbiology , Therapeutics , Gastrointestinal MicrobiomeABSTRACT
This article focused on a comparative analysis on the pharmacokinetic and pharmacodynamic characteristics of berberine (BER) and jateorhizine(JAT) in Coptidis Rhizoma powder (HL-P) and their monomeric compounds (BER + JAT, BJ) in type 2 diabetic (T2D) rats to explore the beneficial. effect of HL-P in the treatment of T2D. The T2D rats were treated with HL-P, BER, JAT and BJ, respectively for 63 d. The pharmacokinetic parameters, dynamic changes in blood glucose level and blood lipid values were measured. The results showed that, compared with other corresponding group, t(max), T(½ka) of BER and JAT in HL-P group were reduced, while C(max), AUC(inf), AUC(last), V(L)/F were significantly increased; compared with model group, blood glucose levels were decreased significantly in HL-P group since the 18th day, while those in BER or BJ group were reduced since the 36th day, however, blood glucose levels showed no obvious changes in JAT group; compared with model group, FFA values in all treatment group were decreased significantly. Moreover, TG, HDL and LDL value in HL-P group, LDL value in BER group and HDL value in BJ group were improved significantly. The above results showed that Coptidis Rhizoma powder showed excellent pharmacokinetic characteristics and excellent activity of lowering blood glucose and lipid. It provided a scientific basis for oral application of Coptidis Rhizoma powder in the treatment of T2D.
Subject(s)
Animals , Humans , Male , Rats , Berberine , Pharmacokinetics , Blood Glucose , Metabolism , Coptis , Chemistry , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacokinetics , Powders , Pharmacokinetics , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in rats.</p><p><b>METHODS</b>A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly selected as control group. The hyperlipidemic rats were then randomly divided into the following groups: a model group (MOD); a berberine group [BBR, 156 mg/(kg day)]; Hdber groups, which were treated with different doses of Hdber [78, 39 and 19.5 mg/(kg day)]; and a simvastatin group [SIM, 4 mg/(kg day)]. The corresponding therapy was administered to the rats of each treatment via gastric tubes. Normal animals were used as a control group. The blood levels of various lipids, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acid (FFA), apolipoprotein AI(Apo-AI) and apolipoprotein B (Apo-B) were examined. The protein expressions of low-density lipoprotein receptor (LDL-R), sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and proprotein convertase subtilisin/kexin type 9 (PCSK-9) in liver tissues were determined by Western blot analysis.</p><p><b>RESULTS</b>Compared with the control group of rats, the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9 protein in their liver tissues (P<0.01). In addition, the high-fat diet decreased the expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues. However, the addition of berberine or Hdber reversed the blood lipid profile changes (P<0.05 or P<0.01), decreased the expression levels of PCSK-9 proteins (P<0.01), and increased the expression levels of LDL-R proteins in the hyperlipidemic rats (P<0.01). These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats.</p><p><b>CONCLUSIONS</b>Hdber is effective in the treatment of hyperlipidemia in rats. The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.</p>
Subject(s)
Animals , Male , Apolipoprotein A-I , Blood , Apolipoproteins B , Blood , Berberine , Pharmacology , Therapeutic Uses , Hydroxymethylglutaryl CoA Reductases , Metabolism , Hyperlipidemias , Blood , Drug Therapy , Lipids , Blood , Liver , Metabolism , Proprotein Convertase 9 , Rats, Wistar , Receptors, LDL , Metabolism , Serine Endopeptidases , Metabolism , Sterol Regulatory Element Binding Protein 2 , MetabolismABSTRACT
In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.
Subject(s)
Animals , Humans , Male , Rats , Apoptosis , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Fats , Metabolism , Glucose Tolerance Test , Islets of Langerhans , Cell Biology , Pancreas , Metabolism , Rats, WistarABSTRACT
This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy (DN). The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin (STZ). Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Captopril group. Oral glucose tolerance test (OGTT) was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), creatinine clearance rate (Ccr), 24-h urinary albumin (UA), the ratio of kidney mass/body weight (renal index) and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor (TGF)-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of control group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.
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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.
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This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy (DN). The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin (STZ). Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Captopril group. Oral glucose tolerance test (OGTT) was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), creatinine clearance rate (Ccr), 24-h urinary albumin (UA), the ratio of kidney mass/body weight (renal index) and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor (TGF)-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of control group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.
Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Type 2 , Drug Therapy , Pathology , Diabetic Nephropathies , Drug Therapy , Pathology , Drugs, Chinese Herbal , Ethanol , Chemistry , Glomerular Filtration Rate , Plant Extracts , Chemistry , Rats, Wistar , Rhodiola , Chemistry , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Jiaotai Pill (, JTP) at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase (PI3K) pathway in the skeletal muscle of diabetic rats.</p><p><b>METHODS</b>The rat model of type 2 diabetes mellitus (T2DM) was established by intravenous injection of a small dose of streptozotoein plus high fat diet feeding. JTP at the same dosage of cinnamon and the increasing dosage of Coptis chinensis was administered to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels were assayed. The expressions of proteins were determined by Western blot method.</p><p><b>RESULTS</b>All the three formulations of JTP decreased plasma glucose and fasting insulin levels as well as increased the protein expressions of insulin receptor β (InsRβ) subunit, insulin receptor substrate-1 (IRS-1), PI3K p85 subunit and glucose transporter 4 (GLUT4) in skeletal muscle. Meanwhile, JTP increased the tyrosine phosphorylation of InsRβ subunit and IRS-1, and reduced the serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP containing the least amount of Coptis chinensis exhibited the best effect.</p><p><b>CONCLUSION</b>JTP at different constitutional proportions attenuates the development of diabetes in a rat model of T2DM. The mechanism might be associated with enhancing insulin signaling through PI3K pathway in the skeletal muscle.</p>
Subject(s)
Animals , Male , Rats , Body Weight , Diabetes Mellitus, Experimental , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Glucose Tolerance Test , Glucose Transporter Type 4 , Metabolism , Homeostasis , Insulin , Metabolism , Insulin Receptor Substrate Proteins , Metabolism , Insulin Resistance , Muscle, Skeletal , Metabolism , Pathology , Phosphatidylinositol 3-Kinases , Metabolism , Phosphorylation , Phosphotyrosine , Metabolism , Protein Subunits , Metabolism , Rats, Wistar , Receptor, Insulin , Metabolism , Signal TransductionABSTRACT
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.
Subject(s)
Animals , Male , Rats , Adipose Tissue , Metabolism , Arrestins , Genetics , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Glucose Intolerance , Drug Therapy , Glucose Transporter Type 4 , Genetics , Metabolism , Hypoglycemic Agents , Pharmacology , Therapeutic Uses , Insulin Receptor Substrate Proteins , Genetics , Metabolism , Insulin Resistance , Liver , Metabolism , Muscle, Skeletal , Metabolism , RNA, Messenger , Genetics , Metabolism , Rats, Wistar , Receptor, Insulin , Genetics , Metabolism , beta-Arrestin 2 , beta-ArrestinsABSTRACT
Chinese herbal medicine has developed new therapies for nonalcoholic fatty liver disease (NAFLD) based on its unique theory system and substantial herb remedies. In this review, 21 traditional Chinese herbs were introduced for their potential benefit in the treatment of NAFLD. Majority of them are evaluated by experimental studies and few by multicenter clinical trials. Herbal monomers as berberine and resveratrol, extracts from Polygonum hypoleucum Ohwi, and Artemisia sacrorum Ledeb., and formulae including Yinchenhao Decoction (, YCHD), Qushi Huayu Decoction (, QSHYD), and Danning Tablet () were discussed in detail on their therapeutic potentials. Most of these herbal medicines were proved to improve biochemical and histological changes of NAFLD both in vitro and in vivo. Also, their therapeutic activities were associated with inhibiting lipid accumulation through adenosine monophosphate-activated protein kinase activation or upregulating low-density lipoprotein receptor (LDLR) expression, alleviating lipid peroxidation, and reducing the production of inflammatory cytokines. Although the efficacy and safety of these herbal medicines needed to be evaluated in multicenter large-scale clinical trials, Chinese medicine is promising and effective for preventing and treating NAFLD disease.
Subject(s)
Animals , Humans , Drugs, Chinese Herbal , Chemistry , Therapeutic Uses , Fatty Liver , Drug Therapy , Non-alcoholic Fatty Liver Disease , Plant Extracts , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of berberine on the pancreatic 13 cell apoptosis in rats with insulin resistance (IR).</p><p><b>METHODS</b>IR Wistar rat model was established by feeding with high fructose diet. After 6-week treatment of berberine, oral glucose tolerance test (OGTT) was performed. Then fasting insulin level (Fins) was detected and insulin sensitivity index (ISI) calculated. The islet was isolated and purified. The pancreatic p3 cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The apoptosis-related protein ASK1 and Caspase-12 expressions were examined by immunohistochemical assay.</p><p><b>RESULTS</b>Compared with the normal group, the blood glucose at 0 and 1 h increased, the Fins increased and ISI decreased, the blood lipids were disarranged, the pancreatic beta cell apoptosis increased, and ASK1 and Caspase-12 protein expressions increased in IR rats. Compared with the model group, the blood glucose at 0 and 1 h and the Fins decreased, ISI increased, the disarranged blood lipids were improved, the pancreatic beta cell apoptosis decreased, and the ASK1 expression decreased, but with no obvious change in the Caspase-12 expressions in the berberine group.</p><p><b>CONCLUSIONS</b>Berberine could alleviate IR state in IR rats and inhibit pancreatic 13 cell apoptosis. Its mechanism might be correlated with the inhibition of ASK1 protein expressions.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Berberine , Pharmacology , Blood Glucose , Caspase 12 , Metabolism , Cell Line , Insulin Resistance , Insulin-Secreting Cells , Cell Biology , MAP Kinase Kinase Kinase 5 , Metabolism , Rats, WistarABSTRACT
Acupuncture has been used to treat infertility extensively, including ovulatory dysfunction, in vitro fertilization and embryo transfer (IVF-ET), and male infertility. This review summarizes the recent studies which investigated the role of acupuncture in infertility. In conclusion, most of the existing studies suggest a positive effect of acupuncture in infertility treatment. Firstly, acupuncture may improve ovulation by modulating the central and peripheral nervous systems, the neuroendocrine and endocrine systems, the ovarian blood flow, and metabolism. Secondly, acupuncture can improve the outcome of IVF-ET, and the mechanisms may be related to the increased uterine blood flow, inhibited uterine motility, and the anesis of depression, anxiety and stress. Its effect on modulating immune function also suggests helpfulness in improving the outcome of IVF-ET. Finally, the studies suggest that acupuncture plays a positive role in male infertility, the mechanism of which is not yet clear. Even though a positive effect of acupuncture in infertility has been found, well-designed multi-center, prospective randomized controlled studies are still needed to provide more reliable and valid scientific evidence. Furthermore, it is urgent and necessary to clarify the mechanism of acupuncture for infertility.