Antidiabetic potential of salvianolic acid B in multiple low-dose streptozotocin-induced diabetes

Abstract

Context: Salvianolic acids are the most abundant water-soluble compounds extracted from the herb Salvia miltiorrhiza L. (Lamiaceae) with antioxidant and protective effects.

Objective: This study evaluates the antidiabetic effect of salvianolic acid B (Sal B) in multiple low-dose streptozotocin (MLDS)-induced diabetes in rat.

Materials and methods: Rats were divided into control, Sal B40-treated control, diabetic, Sal B20-, and Sal B40-treated diabetic groups. Sal B was daily administered at doses of 20 or 40?mg/kg (i.p.), started on third day post-STZ injection for 3 weeks. Serum glucose and insulin level and some oxidative stress markers in pancreas were measured in addition to the oral glucose tolerance test (OGTT), histological assessment, and apoptosis determination.

Results: After 3 weeks, treatment of diabetic rats with Sal B20 and Sal B40 caused a significant decrease of the serum glucose (p?<?0.05–0.01) and improvement of OGTT. Meanwhile, serum insulin was significantly higher in Sal B20- and Sal B40-treated diabetics (p?<?0.01) and treatment of diabetics with Sal B40 significantly lowered malondialdehyde (MDA) (p?<?0.05), raised glutathione (GSH) (p?<?0.05), and activity of catalase (p?<?0.01) with no significant change of nitrite. Furthermore, the number of pancreatic islets (p?<?0.05) and their area (p?<?0.01) was significantly higher and apoptosis reactivity was significantly lower (p?<?0.05) in the Sal B40-treated diabetic group versus diabetics.

Discussion and conclusion: Three-week treatment of diabetic rats with Sal B exhibited antidiabetic activity which is partly exerted via attenuation of oxidative stress and apoptosis and augmentation of antioxidant system.     

Antidiabetic mechanism of Coptis chinensis polysaccharide through its antioxidant property involving the JNK pathway

Abstract

Context: Antidiabetic activity of Coptis chinensis Franch (Ranunculaceae) polysaccharide (CCPW) has been reported. However, its molecular mechanism remains unclear.

Objective: An attempt was made to further verify the antidiabetic activity of CCPW on type 2 diabetes mellitus (T2DM) and elucidate the mechanism of antidiabetic activity.

Materials and methods: Male Wistar rats were fed with high-fat diet (HFD) and injected with streptozotocin (STZ) to generate a T2DM model. Effects of CCPW on fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), glutathione (GSH), glutathione peroxidases (GSH-Px), superoxide dismutases (SOD), catalase (CAT), malondialdehyde (MDA), c-jun n-terminal kinase (JNK), phosphorylated insulin receptor substrate 1 (phospho-IRS1), phosphorylated phosphatidylinositol 3 kinase (phospho-PI3Kp85) and glucose transporter 4 (Glut4) were investigated.

Results: FBG level of diabetic rats could be significantly inhibited by 51.2, 42.7, and 23.3% through administration of CCPW at doses of 200, 100, and 50?mg/kg b.w., respectively (p?<?0.01). CCPW also could significantly reduce TG by 19.2, 12.1, and 7.4%, and TC by 24.2, 20.9, and 18.7%, respectively (p?<?0.05 or p?<?0.01). CCPW showed an obvious antioxidant effect through increasing GSH-Px, SOD, and CAT activities, and decreasing GSH and MDA contents (p?<?0.05 or p?<?0.01). Furthermore, CCPW could inhibit JNK and phospho-IRS1 expression and promote the expression of phospho-PI3Kp85 and Glut4 compared with those in the DM group (p?<?0.05 or p?<?0.01).

Discussion and conclusion: CCPW can produce antidiabetic activity in rats with T2DM through its antioxidative effect, which is closely related to the JNK/IRS1/PI3K pathway.     

The role of microalbuminuria and insulin resistance as significant risk factors for white matter lesions in Japanese type 2 diabetic patients

ABSTRACT

Objective: The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Microalbuminuria, which is associated with diabetes, has been flagged as a novel predictor for cerebrovascular events. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with microalbuminuria and insulin resistance in patients with type 2 diabetic mellitus (DM) not receiving insulin treatment.

Patients and methods: Based on brain magnetic resonance imaging (MRI) findings, 90 type 2 diabetic patients were divided into two groups: a WML-positive group (57?±?8 years, mean?±?SD, n?=?34) and a WML-negative group (57?±?6 years, n?=?56). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index, and hemoglobin A _1c (HbA1c).

Results: The body mass index was higher in the WML-positive group than in the WML-negative group (p?<?0.01). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol (HDL-C) was lower in the WML-positive group than in the WML-negative group (p?<?0.05 and p?<?0.0001, respectively). Fasting plasma glucose (p?<?0.005), insulin concentrations (p?<?0.0001), HOMA index (p?<?0.0001), and urinary albumin excretion (p?<?0.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the microalbuminuria and insulin resistance (p?<?0.005, p?<?0.0005, respectively).

Conclusion: The results of this preliminary study indicate that the presence of WML was associated with the microalbuminuria and insulin resistance in these Japanese patients with type 2 DM; larger cohort studies are warranted to confirm these findings.     

Metabolic effect of repaglinide or acarbose when added to a double oral antidiabetic treatment with sulphonylureas and metformin: a double-blind,cross-over,clinical trial

ABSTRACT

Objective: To compare the metabolic effects of acarbose and repaglinide in type 2 diabetic patients who are being treated with a sulphonylurea–metformin combination therapy. The primary endpoint of the study was to evaluate which add-on treatment between acarbose and repaglinide is more efficacious in reducing PPG. The second endpoint was to evaluate which of these two treatment is more efficacious in the global management of glucose homeostasis in the enrolled patients.

Research design and methods: After a 4-week run-in period with a suplonylurea–metformin combination, 103 patients were randomised to receive in addition either repaglinide, up to 6?mg/day (2?mg three times a day) or acarbose, up to 300?mg/day (100?mg three times a day) with forced titration (independently of their glycaemic control, unless side-effects developed due to the drug dosage) for 15 weeks. The treatment was then crossed-over for further 12 weeks until the 27th week. We assessed body mass index (BMI), glycosylated haemoglobin (HbA_1c), fasting plasma glucoe (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostatic model assesssment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (Tg), at baseline and at 1, 2, 15 and 27 weeks of treatment.

Results: Seven patients did not complete the study, comprising one patient who was lost to follow-up and a further six through side-effects (two in week 1, one in week 15 and three after cross-over) Side-effects were classified as nausea (one in acarbose group), gastrointestinal events (four in acarbose group), and hypoglycaemia (one in repaglinide group). After 15 weeks of therapy, the repaglinide-treated patients experienced a significant decrease in HbA_1c (?1.1%, p?<?0.05), FPG (?9.5%, p?<?0.05), and PPG (?14.9%, p?<?0.05), when compared to the baseline values. However, the same treatment was associated with a significant increase in body weight (+2.3%, p?<?0.05), BMI (+3.3%, p?<?0.05) and FPI (+22.5%, p?<?0.05); The increase was reversed during the cross-over phase. After 15 weeks of therapy, the acarbose-treated patients experienced a significant decrease in body weight (?1.9%, p?<?0.05), BMI (?4.1%, p?<?0.05), HbA_1c (?1.4%, p?<?0.05), FPG (?10.7%, p?<?0.05), PPG (?16.2%, p?<?0.05), FPI (?16.1%, p?<?0.05), PPI (?26.9%, p?<?0.05), HOMA index (?30.1%, p?<?0.05), when compared to the baseline values. All these changes were reversed during the cross-over study phase, except those relating to HbA_1c, FPG and PPG. The only changes that significantly differed when directly comparing acarbose- and repaglinide-treated patients were those relating to FPI (?16.1% vs. +22.5%, respectively, p?<?0.05) and HOMA index (?30.1% vs. +2.7%, p?<?0.05).

Conclusion: In addition from having a similar effect to repaglinide on PPG, acarbose appeared to have a more comprehensive positive effect on glucose metabolism compared to repaglinide in this relatively small sample of type 2 diabetic patients when used as add-on therapy to sulphonylureas and metformin.     

Importance of LDL/HDL cholesterol ratio as a predictor for coronary heart disease events in patients with heterozygous familial hypercholesterolaemia: a 15-year follow-up (1987-2002)

SUMMARY

This study evaluated the prognostic significance of several risk factors on the outcome of coronary heart disease (CHD) in 639 cardiovascular disease-free subjects with heterozygous familial hypercholesterolaemia (FH). During the 15-year follow-up, 53 (18%) men and 34 (9.8%) women had a CHD event (men vs women, p?<?0.001). The age-adjusted 15-year event rate was 3% (87 events/2915 person-years). Smoking increased the CHD risk (hazard ratio?=?2.45, p?<?0.001), women had a 74% lower risk of a vascular event, compared to men, after controlling for the post-menopausal status (hazard ratio?=?0.26, p?<?0.001). A one-unit difference in low density lipoprotein (LDL)/high density lipoprotein cholesterol (HDL) cholesterol ratio was associated with a 17% higher risk (hazard ratio?=?1.17, p?<?0.05); hypertension increased the risk for an adverse event (hazard ratio?=?3.02, p?<?0.05) and a 1?mg/dl increase in plasma fibrinogen level was associated with a 4% higher CHD risk (hazard ratio?=?1.04, p?<?0.05).

With the power of the 15 years of prospective evaluation, the study shows that increased smoking, hypertension and LDL cholesterol levels eight times more than HDL cholesterol predicts an adverse CHD event, in patients with FH.     

Can monocyte/HDL show inflammatory activity of isotretinoin treatment in acne patients?

Abstract

Aim: There are reports that isotretinoin causes some important diseases such as teratogenicity, inflammatory bowel disease and sacroiliitis by triggering inflammation. (Monocyte/HDL (high density lipoprotein) ratio) MHR is closely related to inflammation and is thought to be an indicator of atherosclerotic development. We aimed to investigate how isotretinoin (ISO) affects the immunoinflammatory response in acne patients.

Materials and Methods: In this study, 116 nodulocystic acne patients who received ISO treatment for at least three months were evaluated retrospectively. ISO treatment was given to patients at a dose of 0.5–1?mg/kg. Pre-treatment and post-treatment white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, mean platelet volume (MPV), platelet, plateletcrit, platelet distribution width (PDW), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), total cholesterol, LDL cholesterol, triglyceride, HDL cholesterol and MHR were evaluated.

Results: MPV and MHR values were significantly increased after 3?month treatment (p?<?0.05). There was no significant change in NLR and PLR values (p?>?0.05). There was a significant decrease in neutrophil count (p?<?0.05). There were no significant changes in WBC, lymphocyte, monocyte, platelet, plateletcrit values (p?>?0.05). Total cholesterol, LDL cholesterol and triglyceride levels were significantly increased after three months of treatment (p?<?0.05). HDL cholesterol levels decreased significantly after three months of treatment (p?<?0.05).

Conclusion: We concluded that ISO treatment may trigger inflammation due to the increase in MPV and MHR value. MHR can show inflammation after ISO treatment.     

Waist-hip ratio and low HDL predict the risk of coronary artery disease in Pakistanis

SUMMARY

Objective: To establish risk factor causal associations for coronary artery disease (CAD) in the native Pakistani population.

Methods: We conducted a hospital-based, case-control study of 200 cases with angiographically documented CAD and 200 age-and sex-matched controls without angiographic evidence of CAD. Patients on lipid lowering therapy were excluded. Lifestyle, anthropometric and biochemical risk factors were assessed in both groups.

Results: The presence of CAD was associated with current, past or passive smoking, a history of diabetes and high blood pressure, a positive family history of CAD, body fat percentage, waist-hip ratio (WHR), low apolipoprotein A1 or low HDL, lipoprotein (a), glucose, insulin, insulin resistance, C-reactive protein (CRP), total cholesterol to HDL ratio (TC/HDL) and creatinine on univariate conditional logistic regression analysis. In multiple regression analysis, significant independent

associations were found with low HDL (OR 0.11; 95% CI 0.04–0.34; p?<?0.001) positive family history (OR 1.79; 95% CI 1.09-2.93; p?=?0.02), CRP (OR 1.45; 95% CI 1.19–1.75; p?<?0.001) and WHR (OR 1.04; 95% CI 1.01-1.08; p?=?0.01). Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. Quantitative angiographic data showed associations with age (p?=?0.01), the duration of diabetes (p?=?0.04), WHR (p?=?0.06), low HDL (p?<?0.001), lipoprotein (a) (p?=?0.001), creatinine (p?<?0.001) and CRP (p?=?0.007). Results indicate that total and LDL cholesterol were not significant risk factors in this study; levels were below currently accepted thresholds for treatment.

Conclusions: The cardiovascular risk profile in this population is consistent with metabolic syndrome where low HDL and WHR can be used to predict the risk of CAD. Results suggest the need to redefine the currently practised approach to CAD management in this population to fit local needs.     

Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes

ABSTRACT

Objective: Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.

Research design and methods: This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N?=?211) using insulin glargine (without mealtime insulin)?±?oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120?µg with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of ≥70 to <100?mg/dL.

Main outcome measures: Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.

Results: Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (?1.6?±?0.3?kg vs. +0.7?±?0.3?kg, p?<?0.001; mean?±?SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (?0.8?±?0.2?mg/L vs. 0.1?±?0.2?mg/L, p?<?0.01; mean?±?SE). Patients with baseline hsCRP?>?3?mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p?<?0.05). Patients with baseline triglycerides ≥150?mg/dL or ≥200?mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (?43?±?14?mg/dL or ?59?±?19?mg/dL; p?<?0.05; mean?±?SE) but not with placebo (1?±?29?mg/dLor ?3?±?54?mg/dL; mean?±?SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.

Conclusions: Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.     

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines

Abstract

Context: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment.

Objective: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action.

Materials and methods: Mice treated acutely with PC (25, 50, or 100?mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30–180?min), carrageenan-induced pleurisy (4?h), and tail-flick test (1–8?h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence.

Results: PC reduced (p?<?0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE₂. PC decrease total leukocyte migration (100?mg/kg: p?<?0.01), neutrophils (50 and 100?mg/kg: p?<?0.05 and 0.001), and TNF-α (25, 50, and 100?mg/kg: p?<?0.01, 0.05, and 0.001, respectively), besides reducing NO production (p?<?0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p?<?0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p?<?0.001) the number of c-Fos-immunoreactive neurons in PAG.

Discussion and conclusion: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.     

Prevention of arsenic-mediated reproductive toxicity in adult female rats by high protein diet

Abstract

Context: The detrimental effects of arsenic on female reproductive functions may involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)] proteins have antioxidant properties.

Objective: To investigate the role of casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection from arsenic toxicity.

Materials and methods: Adult female Wistar rats were orally gavaged with vehicle (Gr-I) or arsenic at 3?ppm/rat/d (Gr-II and Gr-III) for 30 consecutive days, when they were maintained on either regular diet containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated using a battery of biochemical and histological techniques.

Results: As compared to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in weight (mg/100?g body weight) of ovary (Gr-I: 54.3?±?4.2 versus Gr-II: 35.8?±?1.6; p?<?0.001) and uterus (Gr-I: 161.7?±?24.6 versus Gr-II: 94.44?±?13.2; p?<?0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg tissue/h) of Δ⁵, 3β-hydroxysteroid dehydrogenase (Gr-I: 3.41?±?0.12 versus Gr-II: 2.31?±?0.09; p?<?0.01) and 17β-hydroxysteroid dehydrogenase (Gr-I: 3.82?±?0.57 versus Gr-II: 1.24?±?0.19; p?<?0.001), and decreased serum estradiol level (pg/ml) (Gr-I: 61.5?±?2.06 versus 34.1?±?2.34; p?<?0.001). Ovarian DNA damage was preponderant with blatant generation of malondialdehyde (nM/mg tissue; Gr-I: 15.10?±?2.45 versus Gr-II: 29.51?±?3.44; p?<?0.01) and attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18?±?0.19 versus Gr-II: 1.33?±?0.18; p?<?0.05). The Gr-III rats were significantly protected from these ill effects of arsenic.

Discussion and conclusion: HPD, by way of antioxidant properties, may find prospective role in the protection of reproductive damage caused by arsenic.     

Efficacy of Aloe vera/olive oil cream versus betamethasone cream for chronic skin lesions following sulfur mustard exposure: a randomized double-blind clinical trial

Background: Chronic pruritic skin lesions are among the common late complications of sulfur mustard intoxication. In the present randomized double-blind clinical trial, therapeutic efficacy of Aloe vera/olive oil combination cream in the alleviation of these lesions was evaluated and compared to that of betamethasone 0.1% cream.

Methods: Sixty-seven Iranian chemical warfare-injured veterans were randomized to apply A. vera/olive oil (n?=?34, completers?=?31) or betamethasone 0.1% (n?=?33, completers?=?32) cream twice daily for 6 weeks. Evaluation of pruritus severity was performed using a pruritic score questionnaire and visual analogue scale (VAS).

Results: Both treatments were associated with significant reductions in the frequency of pruritus (p?<?0.05), burning sensation (p?<?0.01 and p?<?0.001 in A. vera/olive oil and betamethasone group, respectively), scaling (p?<?0.01 and p?<?0.05) and dry skin (p?<?0.001) at the end of trial. Fissure and excoriation were only reduced in the A. vera group (p?<?0.05). The change in the frequency of hyper- and hypopigmentation lesions, blisters, erythema and lichenification did not reach statistical significance in any of the groups (p?>?0.05). Mean pruritus (p?<?0.05) and VAS scores (p?<?0.01 and p?<?0.05) were significantly decreased by the end of trial in both groups. The rate of improvement in the pruritus severity [defined as being classified in a less severe category (mild, moderate and severe)] was found to be comparable between the groups (p?>?0.05).

Conclusion: A. vera/olive oil cream was at least as effective as betamethasone 0.1% in the treatment of sulfur mustard-induced chronic skin complications and might serve as a promising therapeutic option for the alleviation of symptoms in mustard gas-exposed patients.     

Antihyperlipidemic activity of adenosine triphosphate in rabbits fed a high-fat diet and hyperlipidemic patients

Context Recently, adenosine triphosphate (ATP) was occasionally found to decrease the triglyceride (TG) levels in several hyperlipidemic patients in our clinical practice.

Objective The study investigates the anti-hyperlipidemic effects of ATP in a high-fat fed rabbit model and hyperlipidemic patients.

Materials and methods Twenty-four rabbits were randomly divided into three groups of eight animals each as follows: normal diet, high-fat diet and high-fat diet?+?ATP group. ATP supplementation (40?mg/day) was started at the 20th day and lasted for 10 days. Serum concentrations of total cholesterol (TC), TG, LDL-C, HDL-C were measured on the 20th day and 30th day. Heart, liver and aorta were subjected histopathological examination. Twenty outpatients diagnosed primary hyperlipidemia took ATP at a dose of 60?mg twice a day for 1 week.

Results Feeding rabbits with a high-fat diet resulted in a significant elevation of lipid parameters including TC, TG, LDL-C, VLDL-C compared to the normal diet group (p?<?0.01). ATP treatment significantly decreased serum TG level (p?<?0.01), whilst other parameters remained statistically unaltered. Meanwhile, ATP significantly reduced the thickness of fat layer in cardiac epicardium (p?<?0.05) and pathological gradation of ballooning degeneration in hepatocytes (p?<?0.05). After taking ATP for 1 week, hyperlipidemia patients exhibited a significant decrease of TG (p?<?0.01), but other lipid parameters had no significant change.

Discussion and conclusion The study indicates that ATP selectively decreases serum TG levels in high-fat diet rabbits and hyperlipidemic patients. Therefore, ATP supplementation may provide an effective approach to control TG level.     

Artemisia pallens alleviates acetaminophen induced toxicity via modulation of endogenous biomarkers

Abstract

Context: Acetaminophen (APAP) leads to severe hepatic and renal necrosis and thus causes significant clinical problems. Artemisia pallens Walls ex D.C. (Asteraceae) possesses various pharmacological properties such as antidiabetic, antioxidant, analgesic, and anti-inflammatory activity.

Objective: The objective was to evaluate the protective effects of Artemisia pallens methanol extract (APME) in APAP-induced hepatic and nephro-toxicity.

Materials and methods: The methanolic extract of aerial parts of Artemisia pallens (APME) was prepared. Toxicity was induced in male Wistar rats (180–220?g) by administration of APAP (700?mg/kg, p.o., 14?d). APME (100, 200, and 400?mg/kg, p.o.) was administered to rats 2?h before APAP oral administration. Various biochemical and molecular parameters along with histopathological aberration were studied in the kidney and liver of rats.

Results: Pretreatment with APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) decreased aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, blood urea nitrogen (BUN), and serum creatinine as compared with APAP-treated rat. Decreased level of serum albumin, serum uric acid, and HDL were significantly (p?<?0.01 and p?<?0.001) restored by APME (200 and 400?mg/kg, p.o.) pre-treatment. Administration of APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) reduced the elevated level of cholesterol, LDL, LDH, triglyceride, and VLDL. It also significantly (p?<?0.01 and p?<?0.001) restored the altered level of hepatic and renal antioxidant enzymes (superoxide dismutase (SOD) and glutathione (GSH)). The increased level of malondialdehyde (MDA) and nitric oxide (NO) in hepatic as well as renal tissue was significantly (p?<?0.01 and p?<?0.001) decreased by APME (200 and 400?mg/kg, p.o.) administration. Histological alternation induced by APAP in liver and kidney was also reduced by the APME (200 and 400?mg/kg, p.o.) pre-treatment.

Conclusion: It is concluded that the methanol extract of Artemisia pallens alleviates APAP induced in rats toxicity through its antioxidative and anti-inflammatory actions.     

Inhibitory effect of TGF-β peptide antagonist on the fibrotic phenotype of human hypertrophic scar fibroblasts

Context: TGF-β plays a central role in hypertrophic scar (HS) formation and development.

Objective: This study investigated the role of a TGF-β antagonist peptide in inhibiting fibrotic behavior of human HS-derived fibroblasts (HSFs).

Materials and methods: HSFs were seeded at a density of 3.1?×?10⁴/cm² and were subjected to treatment of peptide antagonist (30?μM) or TGF-β receptor inhibitor LY2109761 (10?μM) or without treatment followed by the analyses of quantitative PCR, Elisa, in vitro wounding and fibroblast-populated collagen lattice (FPCL) assays.

Results: qPCR and Elisa analyses showed that the peptide could, respectively, reduce the gene (at 48?h) and protein (at 72?h) expression levels of collagen I (86?±?4.8%; 56.6?±?7.3%), collagen III (73?±?10.7%; 43.7?±?7.2%), fibronectin (90?±?8.9%; 21.1?±?2.8%), and TGF-β1 (85?±?9.3%; 25.0?±?9.4%) as opposed to the non-treated group (p?<?0.05), as the LY2109761 group similarly did. Cell proliferation was also significantly inhibited at day 5 (CCK-8 assay) by both peptide and LY2109761 treatments compared with the non-treated group (p?<?0.05). The peptide also significantly inhibited cell migration as opposed to blank control at 24?h (43?±?6.7% versus 60?±?2.1%, p?<?0.05) and at 48?h (63.9?±?3.1% versus 95?±?4.1%, p?<?0.05). Similar to LY2109761, the peptide antagonist significantly reduced HS FPCL contraction compared with the non-treated group with significant differences in surface area at 48?h (0.71?±?0.06?cm² versus 0.51?±?0.06?cm², p?<?0.05) and at 72?h (0.65?±?0.02?cm² versus 0.42?±?0.01?cm², p?<?0.05).

Conclusion: The TGF-β antagonist peptide may serve as an important drug for HS prevention and reduction given the obvious benefits of good biosafety, low cost, and easy manufacture and delivery.     

Proulcerogenic effect of water extract of Boswellia sacra oleo gum resin in rats

Context: The water extract of Boswellia sacra Flueck. (Burseraceae) is used in the treatment of gastric and hepatic disorders in the Arab countries.

Objective: The effect of Boswellia sacra water extract on gastric secretion and experimentally induced gastric ulcers in rats was studied.

Materials and methods: Acetic acid-induced chronic gastric ulcers, pylorus ligation, aspirin-induced, ethanol-induced, and restraint plus cold stress-induced gastric ulcer models were employed. The effect on normal rats was also studied. The water extract of B. sacra was administered orally at doses of 2 and 5?ml/kg once daily ranging from single dose to 30?d treatment depending on the model. The extract was subjected to GC-MS analysis to determine the presence of various phytoconstituents.

Results: Boswellia sacra water extract (5?ml/kg, p.o (per os)) aggravated acetic acid-induced chronic ulcers, wherein an increase in ulcer index (p?<?0.01) and ulcer score (p?<?0.05) was observed. In pylorus-ligated rats, the extract increased gastric content volume (p?<?0.01), free acidity (p?<?0.01), total acidity (p?<?0.01), ulcer index (p?<?0.01), and pepsin activity (p?<?0.05). There was no significant effect on the development of ethanol-induced and aspirin-induced ulcers while an increase in the development of stress-induced ulcers was observed (p?<?0.01). The extract did not produce any ulcers when administered to normal rats. The dose of 2?ml/kg was less proulcerogenic compared with 5?ml/kg. The GC-MS analysis revealed the presence of several phytoconstituents that included menthol, 3-cyclohexen-1-ol, and octanoic acid.

Conclusion: Boswellia sacra water extract has proulcerogenic activity due to its gastric hypersecretory effect.     

The ginsenoside metabolite compound K exerts its anti-inflammatory activity by downregulating memory B cell in adjuvant-induced arthritis

Context: Compound K (CK, 20-O-d-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, is structurally a member of the dammarane-type triterpene saponins. Several studies have identified the anti-inflammatory activity of CK. Our previous study demonstrated that CK exerted its anti-inflammatory effect via inhibition of abnormal activation and differentiation of T cells. However, its mechanism of action on B cells remains unclear.

Objective: The objective of this study is to investigate the effect and underlying mechanisms of CK’s effects on memory B cells in the setting of adjuvant-arthritis (AA).

Materials and methods: Complete Freund’s adjuvant was used to induce AA in rats. Rats were administered, either CK (10, 40, and 160?mg/kg), once daily for 15?d, or methotrexate (MTX; 0.5?mg/kg) once every 3?d, for a total of six times. To evaluate the anti-inflammatory effect of CK, a global assessment and a swollen joint count of AA rats were performed every 3?d. Spleen index and histopathology were examined. Subsets of B cells including CD45R⁺IgM⁺ (total B cells) and CD45R⁺CD27⁺ (memory B cells) and expression of CD40 and CD40L were assayed by flow cytometry.

Results: Compared with the AA rats, global assessment scores and swollen joint counts were significantly lower in the treated groups received CK (40 and 160?mg/kg; p?<?0.05 and p?<?0.01, respectively). CK (40 and 160?mg/kg) decreased the spleen index (p?<?0.01), and alleviated hyperplasia of lymph nodes (p?<?0.05 and p?<?0.01, respectively) and marginal zone (p?<?0.05) in the spleen. In addition, CK (40 and 160?mg/kg) suppressed memory B cell subsets (p?<?0.05), and suppressed CD40L expression on T cells and CD40 expression on B cells (p?<?0.05 and p?<?0.01, respectively).

Discussion and conclusion: This study demonstrated that CK downregulated memory B cells in AA rats, and this down-regulation may be T-cell dependent.     

Comparison of self-reported survey (SHIELD) versus NHANES data in estimating prevalence of dyslipidemia

ABSTRACT

Objectives: The study purpose was to compare the prevalence of dyslipidemia between a self-reported survey, Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD), and survey and laboratory data from National Health and Nutrition Examination Survey (NHANES 1999–2002).

Methods: A SHIELD questionnaire was mailed to 200?000 households representative of US adult population (64% response, n = 211?097 individuals) and included if ever diagnosed with diabetes, high blood pressure or cholesterol problems, high total cholesterol (TC), high bad cholesterol (LDL-C), low good cholesterol (HDL-C), or high triglycerides (TG). In NHANES using a combination of interviewer-administered survey and clinical and laboratory data, dyslipidemia was defined as any one of: TC ≥?240?mg/dL or diagnosis of high cholesterol; TG >?200?mg/dL;LDL-C ≥?160?mg/dL; or HDL-C <?40?mg/dL. NHANES diabetes mellitus definition was doctor diagnosis or fasting glucose >?125?mg/dL and hypertension was elevated blood pressure or taking anti-hypertensive medication. Prevalence of dyslipidemia was determined for SHIELD in 2004 and compared to NHANES 1999–2002. Prevalence of diabetes and hypertension was estimated for broader contextual comparison within cardiometabolic diseases.

Results: In contrast to the prevalence of diabetes (8% in SHIELD and 9% in NHANES, p < 0.01) and hypertension (23% in SHIELD and 29% in NHANES, p < 0.01), dyslipidemia was reported only half as frequently in SHIELD (26%) as in NHANES (53%), p < 0.01. Com­ponents of dyslipidemia were uniformly less in SHIELD than NHANES: high TC = 17 vs. 35%, high LDL-C = 10 vs. 14%, high TG = 7 vs. 17% and low HDL-C = 5 vs. 24%; all comparisons p < 0.01.

Limitations: Differences in survey methodology, non-response and timing may have impacted the comparison of SHIELD to NHANES.

Conclusions: Dyslipidemia prevalence was lower in self-reported SHIELD than the objectively assessed NHANES, with especially low self-report of high TG and low HDL-C. Self-reported prevalence of dyslipidemia may under-report the prevalence based on laboratory data.     

Once-daily insulin detemir in a cohort of insulin-naïve patients with type 2 diabetes: a sub-analysis from the PREDICTIVE study

ABSTRACT

Objective: PREDICTIVE^* is a large, observational study of the empirical use of insulin detemir in patients with type 1 or type 2 diabetes (T1DM/T2DM). This post hoc analysis evaluates insulin-naïve patients with T2DM uncontrolled on oral antidiabetic drugs (OADs) who were initiated and remained on once-daily insulin detemir for 12 weeks.

Research design and methods: This observational, multinational, multi-center, open-label prospective study evaluated the efficacy and safety of insulin detemir in 1653 insulin-naïve patients with T2DM (mean age 60.8?±?10.9 years, BMI 29.8?±?4.8?kg/m², and HbA_1C 8.82?±?1.50%). Statistical comparisons were made between baseline and 12-week follow up data. Our study was subject to the usual limitations of observational studies.

Main outcome measures: Endpoints were: incidence of serious adverse drug reactions, including number of hypoglycemic events (total, major, and nocturnal), glycemic parameters, and weight change.

Results: Following insulin initiation, no significant change occurred in the number of nocturnal hypoglycemic events or total hypoglycemic events (p?=?0.4513), and no serious adverse drug reactions were observed during the 12 weeks of treatment. HbA_1C decreased by a mean 1.25% (SD?±?1.25%; p?<?0.0001), with 30% of patients (n?=?383) achieving HbA_1C <7% at 12 weeks. Mean changes in fasting blood glucose and fasting blood glucose variability were –3.62?mmol/L (SD?±?2.93; p?<?0.0001) and ?0.48?mmol/L (SD?±?1.03; p?<?0.0001), respectively. Body weight decreased by a mean 0.5?kg (SD?±?3.3; p?<?0.0001), with weight loss or no weight change occurring in a substantial percentage of patients in each BMI category (<25, 25–30, 30–35, and >35?kg/m²). Patients with higher baseline BMI lost the most weight, with the greatest weight loss (–1.20?kg) reported in those with BMI >35?kg/m².

Conclusions: Empirical use of insulin detemir as an insulin initiation strategy can improve glycemic control with good tolerability, including a low risk of hypoglycemia and a weight benefit, in a majority of insulin-naïve patients uncontrolled on OADs.     

Effects of Piper nigrum extracts: Restorative perspectives of high-fat diet-induced changes on lipid profile,body composition,and hormones in Sprague–Dawley rats

Abstract

Context: Piper nigrum Linn (Piperaceae) (PnL) is used in traditional medicine to treat gastric ailments, dyslipidemia, diabetes, and hypertension.

Objective: The present study explores the possible protective effects of P. nigrum extracts on high-fat diet-induced obesity in rats.

Materials and methods: High-fat diet-induced obese rats were treated orally with 200?mg/kg bw of different extracts (hexane, ethylacetate, ethanol, and aqueous extracts) of PnL for 42?d. The effects of PnL extracts on body composition, insulin resistance, biochemical parameters, leptin, adiponectin, lipid profile, liver marker enzymes, and antioxidants were studied.

Results and discussion: The HFD control group rats showed a substantial raise in body weight (472.8?±?9.3?g), fat% (20.8?±?0.6%), and fat-free mass (165.9?±?2.4?g) when compared with normal control rats whose body weight, fat%, and fat-free mass were 314.3?±?4.4?g, 6.4?±?1.4%, and 133.8?±?2.2?g, respectively. Oral administration of ethyl acetate or aqueous extracts of PnL markedly reduced the body weight, fat%, and fat-free mass of HFD-fed rats. In contrast to the normal control group, a profound increase in plasma glucose, insulin resistance, lipid profile, leptin, thiobarbituric acid reactive substance (TBARS), and the activities of lipase and liver marker enzymes, and a decrease in adiponectin and antioxidant enzymes were noted in HFD control rats. Administration of PnL extracts to HFD-induced obese rats significantly (p?<?0.05) restored the above profiles.

Conclusion: PnL extracts significantly reduced the body weight, fat%, and ameliorated HFD-induced hyperlipidemia and its constituents.     

Effects of the hydroalcoholic extract of Rosa damascena on learning and memory in male rats consuming a high-fat diet

Context: High-fat diet (HFD) can cause deficits in learning and memory through oxidative stress and increase Alzheimer disease risk. Rosa damascena Mill. (Rosaceae) extract possesses potent antioxidant properties.

Objective: This study investigated the effects of the hydroalcoholic extracts of petals of R. damascena on learning and memory in male rats consuming an HFD.

Materials and methods: Forty male Wistar rats (200–250?g) were randomly assigned to four groups: control, R. damascena extract, HFD and HFD?+?extract. The extract (1?g/kg bw daily) was administered by oral gavage for 1?month. Animals were allowed free access to high-fat chow for 3?months. The Morris water maze and the passive avoidance learning tests were used to assess learning and memory.

Results: In the passive avoidance learning test, the step-through latencies in the retention test (STLr) of the extract (147.4?±?23.3) and HFD (150.3?±?25.2) groups were significantly lower than those of the control group (270.4?±?10.5) (respectively, p?p?p?p?Discussion and conclusion: Our results indicate that, while HFD or R. damascena extract alone leads to memory deficits, R. damascena extract exerted a positive effect on HFD-induced memory deficits. We hypothesize that the observed effects of R. damascena extract are likely due to its strong antioxidant properties.