Antimicrobial Activity of Kumazasa (Sasa albo-marginata)

The organic solvent extract of Kumazasa leaves (Sasa albo-marginata) showed antimicrobial activity against bacteria, fungi and yeast. Kumazasa at a concentration of 0.2-1.0% showed stronger antimicrobial activity than potassium sorbate or sodium benzoate at the same concentration. Both acidic and phenolic fractions of the extract showed strong antimicrobial activity. Thirty acidic and phenolic compounds were identified by GC and GC-MS analysis. Acetic, propionic, benzoic, phenylacetic, salicylic, 3-hydroxybenzoic and o-anisic acids, and guaiacol, phenol, 4-ethylphenol, xylenol and 4-vinylphenol were the main components. It was estimated that these components play an important role in the formation of the antimicrobial activity of Kumazasa extract.     

Lowering Effect of Phenolic Glycosides on the Rise in Postprandial Glucose in Mice

Glycosides were screened for their lowering effect on the postprandial blood glucose rise in vivo. The effect of phlorizin and other phenolic glycosides on the postprandial blood glucose response to glucose ingestion was evaluated in Std ddY mice. When phlorizin was simultaneously added, the peak blood glucose level was significantly decreased by 51% (p < 0.01) compared to vehicles following glucose ingestion by mice, while the blood insulin responses were generally similar. Screening experiments were conducted with different classes of phenolic glycosides added to a glucose solution. Reductions of 40–52% (p < 0.05) were observed in vehicles containing arbutin, 4-hydroxyphenyl-α-d-glucopyranoside (hydroquinone-α-glucoside) or glycyrrhizin, and of only 15–31% (not significant) in vehicles containing neohesperidin dihydrochalcone, glycyrrhetinic acid monoglucuronide, or 3,4-dimethoxyphenyl-β-d-glucopyranoside. No lowering effect was observed in vehicles containing salicin. Since glycyrrhizin, arbutin, and hydroquinone-α-glucoside blunted to varying degrees the postprandial blood glucose rise following glucose ingestion, they may be useful adjuvants for the treatment of diabetic subjects.     

Dose-Dependent Suppression of Tea Catechins with a Galloyl Moiety on Postprandial Hypertriglyceridemia in Rats

Tea has long been believed to be a healthy beverage, and its beneficial effects are almost all attributed to catechins. The effect of catechins on postprandial hypertriglyceridemia in rats was investigated in this study. A lipid emulsion administered orally to rats with (?)-epigallocatechin gallate at a dose of 100 mg/kg resulted in the increase in plasma triacylglycerol being significantly inhibited after 1 and 2 h compared to the case without (?)-epigallocatechin gallate. The effect of (?)-epigallocatechin was weaker than that of (?)-epigallocatechin gallate. A tea extract (THEA-FLAN 90S), mainly composed of catechins with a galloyl moiety, dose-dependently suppressed postprandial triacylglycerol after the administration of a lipid emulsion at doses of 50–200 mg/kg. The administration of the tea extract alone at a dose of 200 mg/kg had no effect on the plasma triacylglycerol level. These results strongly suggest that catechins with a galloyl moiety would be promising agents for suppressing dietary fat absorption through the small intestine.     

Focus: The Aging Brain: Neurocardiovascular Instability and Cognition

Neurocardiovascular instability (NCVI) refers to abnormal neural control of the cardiovascular system affecting blood pressure and heart rate behavior. Autonomic dysfunction and impaired cerebral autoregulation in aging contribute to this phenomenon characterized by hypotension and bradyarrhythmia. Ultimately, this increases the risk of falls and syncope in older people. NCVI is common in patients with neurodegenerative disorders including dementia. This review discusses the various syndromes that characterize NCVI icluding hypotension, carotid sinus hypersensitivity, postprandial hypotension and vasovagal syncope and how they may contribute to the aetiology of cognitive decline. Conversely, they may also be a consequence of a common neurodegenerative process. Regardless, recognition of their association is paramount in optimizing management of these patients.     

Ultrasonic synthesis of tyramine derivatives as novel inhibitors of α-glucosidase in vitro

Tyramine derivatives 3–27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC₅₀?=?49.7?±?0.4, 318.8?±?3.7, 23.5?±?0.9, 302.0?±?7.3 and 230.7?±?4.0?μM, respectively) than the standard drug, acarbose (IC₅₀?=?840.0?±?1.73?μM (observed) and 780?±?0.028?μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC₅₀ values 505.27?±?5.95, 581.87?±?5.50 and 440.58?±?2.74?μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3–27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents.     

CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance

CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient (cd36(-)(/)(-)) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36(-)(/)(-) mice. cd36(-)(/)(-) mice showed no differences in hepatic VLDL-TG production or intestinal [(3)H]TG uptake compared with wild-type littermates. cd36(-)(/)(-) mice showed a 2-fold enhanced postprandial TG response upon an intragastric fat load (P < 0.05), with a concomitant 2.5-fold increased FFA response (P < 0.05), suggesting that the increased FFA in cd36(-/-) mice may impair LPL-mediated TG hydrolysis. Postheparin LPL levels were not affected. However, the in vitro LPL-mediated TG hydrolysis rate as induced by postheparin plasma of cd36(-)(/)(-) mice in the absence of excess FFA-free BSA was reduced 2-fold compared with wild-type plasma (P < 0.05). This inhibition was relieved upon the addition of excess FFA-free BSA. Likewise, increasing plasma FFA in wild-type mice to the levels observed in cd36(-)(/)(-) mice by infusion prolonged the plasma half-life of glycerol tri[(3)H]oleate-labeled VLDL-like emulsion particles by 2.5-fold (P < 0.05). We conclude that the increased plasma TG levels observed in cd36(-)(/)(-) mice are caused by decreased LPL-mediated hydrolysis of TG-rich lipoproteins resulting from FFA-induced product inhibition of LPL.     

Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice

The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of HDL cholesteryl esters is well established. In SR-BI-deficient mice, we recently observed a delayed postprandial triglyceride (TG) response, suggesting an additional role for SR-BI in facilitating chylomicron (CM) metabolism. Here, we assessed the effect of adenovirus-mediated hepatic overexpression of SR-BI (Ad.SR-BI) in C57BL/6J mice on serum lipids and CM metabolism. Infection of 5 x 10(8) plaque-forming units per mouse of Ad.SR-BI significantly decreases serum cholesterol (>90%), phospholipids (>90%), and TG levels (50%), accompanied by a 41.4% reduction (P < 0.01) in apolipoprotein B-100 levels. The postprandial TG response is 2-fold lower in mice treated with Ad.SR-BI compared with control mice (area under the curve = 31.4 +/- 2.4 versus 17.7 +/- 3.2; P < 0.05). Hepatic mRNA expression levels of genes known to be involved in serum cholesterol and TG clearance are unchanged and thus could not account for the decreased plasma TG levels and the change in postprandial response. We conclude that overexpression of SR-BI accelerates CM metabolism, possibly by mediating the initial capture of CM remnants by the liver, whereby the subsequent internalization can be exerted by additional receptor systems such as the LDL receptor (LDLr) and LDLr-related protein 1.     

Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia

HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL. These effects were associated with reduced production of LDL-apoB, mainly as a result of reduced secretion of apoB-lipoproteins directly into the LDL density range. Statin therapy also reduced hepatic production of VLDL-TG. There were no effects of simvastatin on the fractional catabolic rates of VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion during simvastatin treatment is not clear, but recent studies suggest that statins may activate peroxisomal proliferator-activated receptor alpha (PPARalpha). Activation of PPARalpha could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.     

Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men

The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism, we studied the effects of nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism. Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 -2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886 (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples were extracted for 11 h after the meal. Total cholesterol and fractions [HDL-cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma concentration during this state. APOC3 -640 was associated with altered TG kinetics but not its magnitude. We have identified new associations between SNPs in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.     

Constitutive inhibition of plasma CETP by apolipoprotein C1 is blunted in dyslipidemic patients with coronary artery disease

Plasma cholesteryl ester transfer protein (CETP) promotes the cholesterol enrichment of apoB-containing lipoproteins (VLDL and LDL) at the expense of HDL. Recent studies demonstrated that apoC1 is a potent CETP inhibitor in plasma of healthy, normolipidemic subjects. Our goal was to establish whether the modulation of CETP activity by apoC1 is influenced by dyslipidemia in patients with documented coronary artery disease (CAD). In the total CAD population studied (n = 240), apoC1 levels correlated negatively with CETP activity, independently of apoE-epsilon, CETP-Taq1B, and apoC1-Hpa1 genotypes. In multivariate analysis, the negative relationship was observed only in normolipidemic patients, not in those with hypercholesterolemia, hypertriglyceridemia, or combined hyperlipidemia. In the normolipidemic subjects, apoC1 levels were positively associated with higher HDL- to LDL-cholesterol ratio (r = 0.359, P < 0.001). It is concluded that apoC1 as a CETP inhibitor no longer operates on cholesterol redistribution in high-risk patients with dyslipidemia, probably due to increasing amounts of VLDL-bound apoC1, which is inactive as a CETP inhibitor. Patients with dyslipidemia could experience major benefits from treatment with pharmacological CETP inhibitors, which might compensate for blunted endogenous inhibition.