Induction of Precocious Metamorphosis by 1,5-Disubstituted Imidazoles with a Non-terpene Chain

The effects of blueberry leaf (BBL) on lipid metabolism were studied in obese rats. Feeding of BBL lowered levels of serum lipids and C-reactive protein and alleviated hepatic triglyceride accumulation in the rats. The hypolipidemic effect might be attributable to a reduction of lipogenesis and enhancement of lipolysis in the liver. These results suggest the use of blueberry leaf as a dietary hypolipidemic component.     

Effect of Vaccinium ashei reade Leaf Extracts on Lipid Metabolism in Obese OLETF Rats

The effects of a hot water extract and fractional extracts from rabbiteye blueberry (Vaccinium ashei reade) leaves (BBL) on lipid metabolism were studied in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Feeding the hot water extract and fractional extracts from BBL alleviated hepatic triglyceride accumulation in the rats. Additionally, feeding with the flavonol glycoside (FG) and proanthocyanidin (PA) fractions lowered serum cholesterol levels in the obese rats. The results from measurements of the hepatic enzyme activity indicate that the hypolipidemic effects of the hot water extract and the PA fraction might be attributable to enhanced lipolysis in the liver. The reduced serum levels of C-reactive protein, an inflammatory cytokine, by the chlorogenic acid + rutin fraction and FG fraction might be associated with alleviating the metabolic abnormalities in obese rats. These results indicate that the BBL extracts, and especially FG and PA, exerted hypolipidemic effects on obese OLETF rats and suggest that an infusion of BBL can be useful as a dietary hypolipidemic component.     

Effect of Vaccinium ashei reade leaf extracts on lipid metabolism in obese OLETF rats

The effects of a hot water extract and fractional extracts from rabbiteye blueberry (Vaccinium ashei reade) leaves (BBL) on lipid metabolism were studied in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Feeding the hot water extract and fractional extracts from BBL alleviated hepatic triglyceride accumulation in the rats. Additionally, feeding with the flavonol glycoside (FG) and proanthocyanidin (PA) fractions lowered serum cholesterol levels in the obese rats. The results from measurements of the hepatic enzyme activity indicate that the hypolipidemic effects of the hot water extract and the PA fraction might be attributable to enhanced lipolysis in the liver. The reduced serum levels of C-reactive protein, an inflammatory cytokine, by the chlorogenic acid + rutin fraction and FG fraction might be associated with alleviating the metabolic abnormalities in obese rats. These results indicate that the BBL extracts, and especially FG and PA, exerted hypolipidemic effects on obese OLETF rats and suggest that an infusion of BBL can be useful as a dietary hypolipidemic component.     

Effect of Vaccinium ashei reade leaves on angiotensin converting enzyme activity in vitro and on systolic blood pressure of spontaneously hypertensive rats in vivo

The hypotensive effects of Vaccinium ashei reade (blueberry) leaves were studied in vitro and in vivo. Blueberry leaf showed a strong inhibitory effect on angiotensin-converting enzyme activity in vitro. Additionally, feeding of blueberry leaf suppressed the development of essential hypertension in spontaneously hypertensive rats in vivo. These results promise the use of blueberry leaf as a source of dietary hypotensive components.     

Hypolipidemic activity of Eclipta prostrata (L.) L. leaf extract in atherogenic diet induced hyperlipidemic rats

In atherogenic diet induced hyperlipidemic model, the rats receiving treatment with the aqueous extract of the leaves of E. prostrata showed significant reduction in total cholesterol, triglyceride, total protein and elevation in high density lipoprotein cholesterol.The aqueous extract of E. prostrata was found to possess significant hypolipidemic activity. The results also suggest that E. prostrata leaf extract at 100 and 200 mg/kg b.wt. concentrations is an excellent lipid-lowering agent.     

Di-(2-ethylhexyl)phthalate: an industrial plasticizer induces hypolipidemia and enhances hepatic catalase and carnitine acetyltransferase activities in rat and mice.

Di-(2-ethylhexyl)phthalate (DOP), a plasticizer, when administered to rats and mice at a dietary concentration of 0.5 percent, 2 percent or 4 percent, caused a substantial reduction in serum cholesterol and triglyceride levels. The hypocholesterolemic and hypotriglyceridemic effects were more pronounced in rats fed DOP at 2 and 4 percent level than in mice. The hypolipidemic effect of this compound is associated with marked hepatomegaly in both species. The liver cells of both rats and mice fed this plasticizer for 1–4 weeks, revealed a considerable increase in peroxisome population. The elevations of hepatic catalase and carnitine acetyltransferase activities appeared to parallel the peroxisome proliferation induced by this compound. The hypolipidemic and peroxisome proliferative effects of this compound strongly suggest that all peroxisome proliferators possess hypolipidemic properties.     

Purification and partial characterization of a new pro-inflammatory lectin from Bauhinia bauhinioides Mart (Caesalpinoideae) seeds

A new galactose-specific lectin, named BBL, was purified from seeds of Bauhinia bauhinioides by precipitation with ammonium sulfate, followed by two steps of ion exchange chromatography. BBL haemagglutinated rabbit erythrocytes (native and treated with proteolytic enzymes) showing stability even after exposure to 60 °C for an hour. The lectin haemagglutinating activity was optimum between pH 8.0 and 9.0 and inhibited after incubation with D-galactose and its derivatives, especially α-methyl-D-galactopyranoside. The pure protein possessed a molecular mass of 31 kDa by SDS-PAGE and 28.310 Da by mass spectrometry. The lectin pro-inflammatory activity was also evaluated. The s.c. injection of BBL into rats induced a dose-dependent paw edema, an effect that occurred via carbohydrate site interaction and was significantly reduced by L-NAME, suggesting an important participation of nitric oxide in the late phase of the edema. These findings indicate that BBL can be used as a tool to better understand the mechanisms involved in inflammatory responses.     

Recombinant salmonella-based 4-1BBL vaccine enhances T cell immunity and inhibits the development of colorectal cancer in rats: in vivo effects of vaccine containing 4-1BBL

Background

Immunotherapy with vaccines is attractive for the treatment of cancer. This study is aimed at determining the effect of recombinant Salmonella (SL3261)-based 4-1BB ligand (4-1BBL) vaccine on the development of colorectal cancers and the potential immune mechanisms in rats.

Results

In comparison with that in the PBS group, similar levels of 4-1BBL expression, the frequency of T cells, IFN-γ responses, and comparable numbers of tumors were detected in the SL3261 and SL3261C groups of rats. In contrast, significantly fewer numbers of tumors, increased levels of 4-1BBL expression in the spleens and colorectal tissues, higher frequency of peripheral blood and splenic CD3⁺CD25⁺ T cells, and stronger splenic T cell IFN-γ responses were detected in the SL3261R group of rats.

Conclusion

Our results indicated that vaccination with recombinant attenuated Salmonella harboring the 4-1BBL gene efficiently enhanced T cell immunity and inhibited the development of carcinogen-induced colorectal cancers in rats.     

The galactose‐binding lectin isolated from Bauhinia bauhinioides Mart seeds inhibits neutrophil rolling and adhesion via primary cytokines

In this study, the amino acid sequence and anti‐inflammatory effect of Bauhinia bauhinioides (BBL) lectin were evaluated. Tandem mass spectrometry revealed that BBL possesses 86 amino acid residues. BBL (1 mg/kg) intravenously injected in rats 30 min prior to inflammatory stimuli inhibited the cellular edema induced by carrageenan in only the second phase (21% – 3 h, 19% – 4 h) and did not alter the osmotic edema induced by dextran. BBL also inhibited carrageenan peritoneal neutrophil migration (51%), leukocyte rolling (58%) and adhesion (68%) and the neutrophil migration induced by TNF‐α (64%). These effects were reversed by the association of BBL with galactose, demonstrating that the carbohydrate‐binding domain is essential for lectin activity. In addition, BBL reduced myeloperoxidase activity (84%) and TNF‐α (68%) and IL1‐β (47%) levels. In conclusion, the present investigation demonstrated that BBL contains highly homologous isolectins, resulting in a total of 86 amino acid residues, and exhibits anti‐inflammatory activity by inhibiting neutrophil migration by reducing TNF‐α and IL1‐β levels via the lectin domain. Copyright © 2015 John Wiley & Sons, Ltd.     

Age-related toxicity of amyloid-beta associated with increased pERK and pCREB in primary hippocampal neurons: reversal by blueberry extract

Further clarification is needed to address the paradox that memory formation, aging and neurodegeneration all involve calcium influx, oxyradical production (ROS) and activation of certain signaling pathways. In aged rats and in APP/PS-1 mice, cognitive and hippocampal Ca²⁺ dysregulation was reversed by food supplementation with a high antioxidant blueberry extract. Here, we studied whether neurons were an important target of blueberry extract and whether the mechanism involved altered ROS signaling through MAP kinase and cyclic-AMP response element binding protein (CREB), pathways known to be activated in response to amyloid-beta (Aβ). Primary hippocampal neurons were isolated and cultured from embryonic, middle-age or old-age (24 months) rats. Blueberry extract was found to be equally neuroprotective against Aβ neurotoxicity at all ages. Increases in Aβ toxicity with age were associated with age-related increases in immunoreactivity of neurons to pERK and an age-independent increase in pCREB. Treatment with blueberry extract strongly inhibited these increases in parallel with neuroprotection. Simultaneous labeling for ROS and for glutathione with dichlorofluorescein and monochlorobimane showed a mechanism of action of blueberry extract to involve transient ROS generation with an increase in the redox buffer glutathione. We conclude that the increased age-related susceptibility of old-age neurons to Aβ toxicity may be due to higher levels of activation of pERK and pCREB pathways that can be protected by blueberry extract through inhibition of both these pathways through an ROS stress response. These results suggest that the beneficial effects of blueberry extract may involve transient stress signaling and ROS protection that may translate into improved cognition in aging rats and APP/PS1 mice given blueberry extract.     

Sucrose level influences micropropagation and gene delivery into leaves from in vitro propagated highbush blueberry shoots

In an effort to increase in vitro blueberry (Vaccinium corymbosum L.) shoot production without negatively impacting subsequent genetic engineering experiments, studies were conducted to examine the effects of sucrose concentration in the propagation medium on shoot proliferation and on the transfer of an intron-containing -glucuronidase (GUS) gene into leaf explants from the propagated shoots. Numbers of axillary shoots >0.5 cm in length did not significantly increase for `Bluecrop' when sucrose levels were increased from 15 mM to either 29, 44 or 58 mM. The number of axillary shoots increased significantly for Duke ' and `Georgiagem' when sucrose concentrations were increased from 15 to 44 mM, and from 15 to 58 mM, respectively. Four-days of cocultivation with Agrobacterium tumefaciens strain EHA105 yielded highest GUS-expressing leaf zones on leaf explants from shoots cultured on either 15 or 29 mM sucrose. The number of GUS-expressing leaf zones was significantly lower on leaf explants derived from shoots grown on 58 mM sucrose than from those grown on 15 mM sucrose for all three cultivars, and was significantly lower on 44 mM compared to 15 mM for cultivars Duke and Georgiagem. These studies indicate shoot pretreatment conditions for optimizing subsequent blueberry genetic engineering experiments. Thus, a blueberry shoot proliferation medium containing 15–29 mM sucrose is recommended for explants later used for genetic transformation.     

Synthesis and pharmacological evaluation of substituted 5-[4-[2-(6,7-dimethyl-1,2,3,4-tetrahydro-2-oxo-4-quinoxalinyl)ethoxy]phenyl]methylene]thiazolidine-2,4-dione derivatives as potent euglycemic and hypolipidemic agents

A series of substituted 5-[4-[2-(6,7-dimethyl-1,2,3,4-tetrahydro-2-oxo-4-quinoxalinyl)ethoxy]phenyl]methylene]thiazolidine-2,4-diones were synthesized and their euglycemic and hypolipidemic activities were investigated in Wistar male rats. Based on the in vivo data in rats, compound 4a was identified as a potent euglycemic and hypolipidemic agent.     

Lethal and sublethal activities of imidacloprid contribute to control of adult Japanese beetle in blueberries

Field-based bioassays and residue profile analysis were used to determine the relative importance of lethal and sublethal effects of imidacloprid on adult Japanese beetle, Popillia japonica Newman, in blueberries, Vaccinium corymbosum L. Field-based bioassays assessed adult mortality and knockdown, and fruit and leaf injury from Japanese beetles exposed to 4-h and 7-d field-aged residues of imidacloprid, and the conventional insecticides azinphosmethyl and esfenvalerate. Azinphosmethyl and imidacloprid caused high levels of mortality when beetles were exposed to blueberry shoots with ripe fruit 4 h postapplication, and all compounds protected blueberry fruit and foliage from beetle feeding. Azinphosmethyl and esfenvalerate caused significant Japanese beetle mortality when adults were exposed to blueberry shoots 7 d postapplication, whereas imidacloprid residues caused effects that protected leaves, although not of ripe fruit. When beetles were exposed to shoots with immature green fruit, relatively more leaf feeding and mortality were observed, suggesting that earlier treatment timings may be most effective for systemic neonicotinoids. Japanese beetle mortality was highly correlated with imidacloprid fruit and leaf surface residues, whereas sublethal feeding deterrent effects were observed after the surface residues diminished. The value of the plant-insect-chemistry model for describing the spatial and temporal dimensions of insecticide modes of activity is discussed in terms of optimizing crop protection.     

Biochemical effects of garlic protein on lipid metabolism in alcohol fed rats

Garlic protein is a very good hypolipidemic agent. In the present study the water soluble protein fraction of garlic was investigated for its effect on hyperlipidemia induced by alcohol (3.76 g/kg. body wt./day). The hypolipidemic action is mainly due to an increase in cholesterol degradation to bile acids and neutral sterols and mobilization of triacyl glycerols in treated rats. Garlic protein (500 mg./kg body wt./day) showed significant hypolipidemic action comparable with a standard dose of gugu-lipid (50 mg./kg. body wt./day).     

Isolation and identification of a novel endophytic bacterial strain with antifungal activity from wild blueberryVaccinium uliginosum

A strain of endophytic bacterium with a good anti-fungal ability was first isolated fromVaccinium uliginosum. It was identified asSerratia marcescens using the 16s rDNA sequence homology and through its physiological and biochemical characteristics. Through the alignment and cladistic analysis of homologous nucleotide sequences of knownSerratia marcescens, it was found to be a novel subspecies ofS. marcescens. An extensive suppressive spectrum of this endophytic strain ofS. marcescens against plant pathogenic fungi was observed. In particular, it inhibited the growth of the causal agents of blueberry leaf spot and of other ten plant fungal pathogens. The inhibition rate, among the different fungi, ranged from 22.7–70.5%. The study indicated the potential use of thisS. marcescens endophytic strain in the biological control of blueberry’s leaf spot as well as many other plant diseases. To our knowledge, this was the first time that an endophyticS. marcescens was isolated from a wild blueberry in China, and may also represent a novel introduction to the world.     

Detection of DNA methylation pattern in thidiazuron-induced blueberry callus using methylation-sensitive amplification polymorphism

During the normal developmental process, programmed gene expression is an essential phenomenon in all organisms. In eukaryotes, DNA methylation plays an important role in the regulation of gene expression. The extent of cytosine methylation polymorphism was evaluated in leaf tissues collected from the greenhouse grown plants and in in vitro-derived callus of three lowbush and one hybrid blueberry genotypes, using methylation-sensitive amplification polymorphism (MSAP) technique. Callus formation started from the leaf segments after 4 weeks of culture on a thidiazuron (TDZ) containing medium. Maximum callus formation (98 %) was observed in the hybrid blueberry at 1.0 mg dm^-3 TDZ. Although noticeable changes in cytosine methylation pattern were detected within the MSAP profiles of both leaf and callus tissues, methylation events were more polymorphic in calli than in leaf tissues. The number of methylated CCGG sites varied significantly within the genotypes ranging from 75 to 100 in leaf tissues and from 215 to 258 in callus tissues. Differences in the methylation pattern were observed not only in a tissue-specific manner but also within the genotype in a treatment specific manner. These results demonstrated the unique effect of TDZ and the tissue culture process on DNA methylation during callus development.     

Blueberry extract attenuates γ-radiation-induced hepatocyte damage by modulating oxidative stress and suppressing NF-κB in male rats

Radiation exposure is known to produce many harmful effects in biological systems, and these effects are often mediated by oxygen free radicals. Because blueberries are rich in antioxidant compounds such as anthocyanins and phenolic acids, we divided forty adult rats into four treatment groups of 10 (G1–4) as follows: G1 rats were used as a control, G2 rats were irradiated with 8?Gy at 2?Gy/week at a dose rate of 0.5?Gy/min, G3 rats were administered blueberry extract (200?mg/kg) and G4 rats were administered blueberry extract during the same irradiation period. In subsequent determinations, γ-irradiated rats had increased levels of cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL), and significantly elevated liver enzyme activities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and total bilirubin. In contrast, significant reductions in albumin, total protein and globulin were observed, whereas gamma irradiation decreased activities of the antioxidant enzymes glutathione (GSH), catalase (CAT), xanthine dehydrogenase (XDH) and superoxide dismutase (SOD). We also observed incremental increases in DNA fragmentation percentages and histopathological changes in liver tissues. Serum pro-inflammatory cytokine levels (IL-6, IL-10 and TNF-α) were significantly elevated and hepatic NF-кB was upregulated. In G4 rats, treatments with blueberry extract restored liver pro-oxidant status, reduced cytokine levels, ameliorated histopathological parameters and reduced DNA damage. In conclusion, γ-radiation exerts toxic effects in the rat livers, and blueberry extract is protective against these.     

Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis

The objective of the present study was to explore the bone protective role of blueberry in an ovariectomized rat model. Thirty 6-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided into three groups: Sham, Ovx (control), Ovx+blueberry (5% blueberry w/w). After 100 days of treatment, rats were euthanized, and blood and tissues were collected. Bone mineral density (BMD) and content of whole body, right tibia, right femur and fourth lumbar vertebra were assessed via dual-energy X-ray absorptiometry. As expected, Ovx resulted in loss of whole-body, tibial, femoral, and 4th lumbar BMD by approximately 6%. Blueberry treatment was able to prevent the loss of whole-body BMD and had an intermediary effect on prevention of tibial and femoral BMD when compared to either Sham or Ovx controls. The bone-protective effects of blueberry may be due to suppression of Ovx-induced increase in bone turnover, as evident by lowered femoral mRNA levels of alkaline phosphatase, collagen type I and tartrate-resistant acid phosphatase to the Sham levels. Similarly, serum osteocalcein levels were also lower in the blueberry group when compared to the Ovx control group, albeit not significantly. In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in BMD and favorable changes in biomarkers of bone metabolism.     

Bis[3-(4'-substituted phenyl)prop-2-ene]disulfides as a new class of antihyperlipidemic compounds

A series of bis[3-(4'-substituted phenyl)prop-2-ene]disulfides were prepared and their hypolipidemic activities were examined in hypercholesterolemic Wistar rats. Introduction of an electron withdrawing group to the phenyl ring in the parent compound led to the identification of compound 8 as a potent and efficacious hypolipidemic agent.     

Hypolipidemic effect of beta, beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) in normal and nephrotic rats

Treatment of normal or puromycin aminonucleoside-nephrotic rats, kept on a balanced Purina chow diet, with beta, beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) (Bar-Tana, J., G. Rose-Kahn, and M. Srebnik. 1985. J. Biol. Chem. 260: 8404-8410) resulted in an acute reversible inhibition of liver lipogenesis and cholesterogenesis with a concomitant hypolipidemic effect which was sustained as long as the drug was administered. The hypolipidemic effect in normal and nephrotic rats consisted of 70-80% and 40-60% reduction in plasma VLDL-triacylglycerols and cholesterol, respectively, with a respective increase in the HDL-cholesterol/(VLDL + LDL)-cholesterol ratio. The observed hypolipidemic effect was accompanied by a 10-fold decrease in VLDL-apoC-III content with a concomitant enrichment of the VLDL fraction by VLDL remnants having an increased apoB-100/apoB-48 ratio. The pharmacological reduction of VLDL by MEDICA 16 may offer a treatment mode of choice for selected hyperlipidemic states.