***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT Berberine , a natural plant alkaloid , is usually used as an antibiotic drug . The potential glucose-lowering effect of berberine was noted when it was used for diarrhea in diabetic patients . In vitro and in vivo studies have then showed its effects on hyperglycemia and dyslipidemia . OBJECTIVE The objective of the study was to evaluate the efficacy and safety of berberine in the treatment of type 2 diabetic patients with dyslipidemia . DESIGN One hundred sixteen patients with type 2 diabetes and dyslipidemia were r and omly allocated to receive berberine ( 1.0 g daily ) and the placebo for 3 months . The primary outcomes were changes in plasma glucose and serum lipid concentrations . Glucose disposal rate ( GDR ) was measured using a hyperinsulinemic euglycemic clamp to assess insulin sensitivity . RESULTS In the berberine group , fasting and postload plasma glucose decreased from 7.0 + /- 0.8 to 5.6 + /- 0.9 and from 12.0 + /- 2.7 to 8.9 + /- 2.8 mm/liter , HbA1c from 7.5 + /- 1.0 % to 6.6 + /- 0.7 % , triglyceride from 2.51 + /- 2.04 to 1.61 + /- 1.10 mm/liter , total cholesterol from 5.31 + /- 0.98 to 4.35 + /- 0.96 mm/liter , and low-density lipoprotein-cholesterol from 3.23 + /- 0.81 to 2.55 + /- 0.77 mm/liter , with all parameters differing from placebo significantly ( P < 0.0001 , P < 0.0001 , P < 0.0001 , P = 0.001 , P < 0.0001 , and P < 0.0001 , respectively ) . The glucose disposal rate was increased after berberine treatment ( P = 0.037 ) , although no significant change was found between berberine and placebo groups ( P = 0.063 ) . Mild to moderate constipation was observed in five participants in the berberine group . CONCLUSIONS Berberine is effective and safe in the treatment of type 2 diabetes and dyslipidemia Abstract Aims : To investigate the renoprotective roles of berberine ( BBR ) in different stages of diabetic nephropathy ( DN ) in streptozotocin (STZ)-induced diabetic rats fed a high-sugar and high-fat diet . Methods : Diabetes was induced in mice by intraperitoneal injection of STZ , and the mice were then r and omly divided into groups : normal , diabetes , high-sugar and high-fat and BBR ( high , median and low dose ) groups . The body weight ( BW ) , kidney weight to body weight ( KW/BW ) , blood urea nitrogen , urine total protein to urine creatinine ratio and serum creatinine were measured on different weeks throughout the study . The protein levels of E prostanoid receptor 4 ( EP4 ) , Gαs and content of cAMP in the kidney were , respectively , detected by western blot analysis and RIA analysis . Results : In the DN rats , there was remarkable renal damage .  BBR  restored renal functional parameters , suppressed alterations in histological and ultrastructural changes in the kidney tissues and increased EP4 , Gαs and cAMP levels compared with those of the DN model group . In addition , BBR has different therapeutic effects during the different stages of the development of DN , and it works best in the sixth week . Conclusion : These studies demonstrate , for the first time , that BBR exerts renoprotective effects in different stages of DN via EP4- Gαs- AC-cAMP signaling pathway in STZ-induced DN rats fed a high-sugar and high-fat diet AIM To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model . METHODS The 40 rats were r and omly 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 Purpose Accumulating evidence in animals suggests that leukocytes are involved in the pathogenesis of diabetic retinopathy . The present study was design ed to investigate whether leukocytes from diabetic patients could kill retinal endothelial cells and whether that cytotoxicity could be inhibited in vivo by administration of berberine . Methods Human retinal endothelial cells ( HRECs ) were cocultured ( 24 h ) with leukocytes freshly isolated from nondiabetic and diabetic patients , and leukocyte-mediated death of HRECs was analyzed with flow cytometry . HRECs or leukocytes were incubated with antibodies against intercellular adhesion molecule-1(ICAM-1 ) or integrin beta-2 , or with various concentrations of berberine . The protein expression levels of inflammatory factors were investigated using western blots , and activities of antioxidant enzymes and malondialdehyde content were examined as markers of oxidative stress . In addition , leukocytes were isolated from 28 diabetic patients with retinopathy and nondiabetic patients before and after 1 month in vivo therapy with berberine . The effects of the berberine on leukocyte-mediated killing of endothelial cells was again assessed . Results Leukocytes from diabetic patients induced more apoptosis of HRECs in a coculture system than did cells from nondiabetic patients , and this killing occurred primarily via direct cell – cell contact . Berberine inhibited the leukocyte-mediated killing of HRECs in vitro , the decrease in antioxidant enzyme activities , the nuclear translocation of nuclear factor kappa B , and the increase in intercellular adhesion molecule-1 and inducible nitric oxide synthase expression and malondialdehyde content in HRECs cultured in high glucose . Berberine also decreased integrin beta-2 expression of leukocytes in vitro and in vivo . Oral consumption of berberine for 1 month likewise inhibited the diabetes-induced increase in leukocyte-mediated killing of HRECs . Conclusions Our findings suggest that leukocytes from diabetic patients kill retinal endothelial cells , and that berberine can inhibit this leukocyte-mediated killing of vascular endothelium . Coculture of leukocytes with HRECs might serve as a biomarker to study the role of leukocytes in the development of diabetic retinopathy , and the data are consistent with berberine being a therapy against diabetic retinopathy BACKGROUND AND AIMS High-density lipoproteins ( HDLs ) may directly stimulate β-cell function and glucose metabolism . We determined the relationships of  fasting high-density lipoprotein cholesterol ( HDL-C ) , plasma apolipoprotein ( apo ) A-I and apoA-II , and HDL-C-to-apoA-I and HDL-C-to-apoA-II ratios , as estimates of HDL particle composition , with incident type 2 diabetes mellitus . METHODS A prospect i ve study was carried out in the Prevention of Renal and Vascular End-Stage Disease ( PREVEND ) cohort after exclusion of subjects with diabetes at baseline ( n = 6820 ; age , 28 - 75 years ) . The association of HDL-related variables with incident type 2 diabetes was determined by multivariate logistic regression analyses . RESULTS After a median follow-up of 7.7 years , 394 incident cases of type 2 diabetes mellitus were ascertained ( 5.8 % ) . After adjustment for age , sex , family history of diabetes , body mass index , hypertension , alcohol , and smoking , odd ratios ( ORs ) for diabetes were 0.55 ( 95 % confidence interval [ CI ] , 0.47 - 0.64 ; P < .001 ) , 0.81 ( 0.71 - 0.93 ; P = .002 ) , 0.02 ( 0.01 - 0.06 ; P < .001 ) , and 0.03 ( 0.01 - 0.060 ; P < .001 ) per 1-SD increase in HDL-C and apoA-I and in the HDL-C-to-apoA-I and the HDL-C-to-apoA-II ratios , respectively . In contrast , apoA-II was not related to incident diabetes ( OR = 1.02 ; 95 % CI , 0.90 - 1.16 ; P=0.71 ) . The relationships of HDL-C and the ratios of HDL-C to apoA-I and HDL-C to apoA-II remained significant after further adjustment for baseline glucose and triglycerides ( OR(HDL ) = 0.74 [ 95 % CI , 0.61 - 0.88 ] , OR(HDL/APO A-I ) = 0.14 [ 0.04 - 0.44 ] , and OR(HDL/APOA-II ) = 0.12 [ 0.04 - 0.36 ] ; all P ≤ .001 ) . CONCLUSIONS Higher HDL-C , as well as higher HDL-C-to-apoA-I and  HDL-C-to-apoA-II ratios are strongly and independently related to a lower risk of future type 2 diabetes The present study was design ed to eluci date the potential mechanism underlying that berberine suppressed ischemic arrhythmias  in a rat model of diabetes mellitus ( DM ) . Streptozotocin (STZ)-induced diabetic rats were subjected to ischemia by the occlusion of left anterior descending ( LAD ) coronary artery . Berberine was orally administered for 7 days before ischemic injury in diabetic rats .  Whole-cell patch-clamp was performed to measure the transient outward K⁺ current ( I(to ) ) and L-type Ca²⁺ current ( I(Ca ) ) . Results showed that oral administration of berberine ( 100 mg/kg ) attenuated ischemia-induced arrhythmias in diabetic rats . Berberine significantly shortened the prolonged QTc interval from 214 ± 6ms to 189 ± 5ms in ischemic diabetic rats , and also restored the diminished I(to ) and I(Ca ) current densities in the same animal model rats . In conclusion , the ability of berberine to protect diabetic rats against cardiac arrhythmias makes it possible to be a prospect i ve therapeutic agent in clinical management of cardiac disease secondary to diabetes BACKGROUND Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease , but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined . We aim ed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 di 
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The results demonstrate that berberine exerts beneficial effects directly in the brain : enhancing cholinergic neurotransmission , improving cerebral blood flow , protecting neurons from inflammation , limiting hyperphosphorylation of tau and facilitating β-amyloid peptide clearance .
In addition , evidence is growing that berberine is effective against diabetes and associated disorders , such as atherosclerosis , cardiomyopathy , hypertension , hepatic steatosis , diabetic nephropathy , gut dysbiosis , retinopathy and neuropathy , suggesting indirect benefits for the prevention of dementia .
Berberine could impede the development of dementia via multiple mechanisms : preventing brain damages and enhancing cognition directly in the brain , and indirectly through alleviating risk factors such as metabolic dysfunction , and cardiovascular , kidney and liver diseases .
This study provided evidence to support the value of berberine in the prevention of dementia associated with