Suppressive effect of coffee on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats

A coffee extract significantly suppressed lipopolysaccharide (LPS)-induced hepatitis in D-galactosamine-sensitized rats, as assessed by the plasma alanine and aspartate aminotransferase activities, when it was added to the diet (30 g/kg) and fed to rats for 14 days. Its effect was as strong as that of a green tea extract. The coffee extract suppressed LPS-induced hepatitis when singly force-fed (1.2 g/kg) 1.5 h prior to the injection of the drugs, whereas a decaffeinated coffee extract had no significant effect. The hepatoprotective effect of caffeine was stronger than that of theobromine. These results indicate that coffee can protect animals from LPS-induced hepatitis, and that the effect of coffee might be mainly due to caffeine.     

Suppression of lipopolysaccharide-induced liver injury by various types of tea and coffee in D-galactosamine-sensitized rats

Extracts of various types of tea and coffee significantly suppressed lipopolysaccharide (LPS)-induced liver injury, as assessed by the plasma enzyme activities, in D-galactosamine-sensitized rats when administered orally once before injecting the drugs. There was a significant negative correlation between the caffeine levels of these extracts and liver injury. Authentic caffeine also had a hepatoprotective effect. These results suggest that caffeine-containing beverages generally suppress LPS-induced liver injury according to their caffeine content.     

Chromosome aberrations induced by aflatoxin B1 in rat bone marrow cells in vivo and their suppression by green tea

Aflatoxin B1 (AFB1)-induced chromosome aberrations (CA) in rat bone marrow cells consisted mainly of gaps and breaks. Cells with exchanges and multiple CA were observed infrequently. The incidence of aberrant cells and the number of aberrations per cell were at their maximum levels 18 h after the AFB1 injection. They were dependent on the administered dose of AFB1. Rats given the hot water extract from green tea (GTE) 24 h before they were injected with AFB1 displayed considerably suppressed AFB1-induced CA in their bone marrow cells. Rats administered GTE 2 h before or after the AFB1 injection showed no suppressive effect. The suppressive effect of GTE on AFB1-induced CA paralleled the dose of GTE when given in the range between 0.1 and 2 g/kg body weight; higher doses produced no additional suppression. On the other hand, rats given the hot water extract from black tea or coffee 24 or 2 h before the AFB1 injection showed no suppressive effect. The administration of caffeine 24 h before the AFB1 injection suppressed AFB1-induced CA as well as the administration of caffeine 2 h before the AFB1 injection. However, the suppression rate with 2 h was larger than with 24 h. The suppression by ellagic acid was found only when it was given 2 h before the AFB1 injection. The administration of ascorbic acid or tannic acid did not significantly suppress AFB1-induced CA. The tannin mixture extracted from green tea (GTTM) showed a similar tendency to GTE, that is, the administration of GTTM 24 h before the AFB1 injection potently suppressed AFB1-induced CA, while the administration of GTTM 2 h before the AFB1 injection did not suppress them significantly. The suppressive effect of GTTM on AFB1-induced CA paralleled the dose of GTTM when given in the range of 75-450 mg/kg body weight.     

Effect of Tridax procumbens on liver antioxidant defense system during lipopolysaccharide-induced hepatitis in D-galactosamine sensitised rats

The present study was carried out to assess the effect of chloroform insoluble fraction of ethanolic extract of Tridax procumbens (TP) against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced hepatitis in rats. Induction of rats with D-GalN/LPS (300 mg/kg body weight/30 microg/kg body weight) led to a marked increase in lipid peroxidation as measured by thiobarbituric acid reactive substances (TBARS) in liver. Further there was a decline in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferase and the levels of non-enzymic antioxidants namely reduced glutathione, vitamin C and vitamin E. These biochemical alterations were normalised upon pretreatment with TP extract. Thus, the above results suggest that TP (300 mg/kg body weight orally for 10 days) is very effective in allievating the D-GalN/LPS-induced oxidative stress suggesting its antioxidant property.     

Suppressive effect of caffeine on hepatitis and apoptosis induced by tumor necrosis factor-alpha, but not by the anti-Fas antibody, in mice

Tumor necrosis factor (TNF)-alpha-induced hepatitis and apoptosis, as respectively assessed by serum enzyme activities and hepatic DNA fragmentation were effectively suppressed by a single force-feeding of caffeine (100 mg/kg) 1.5 h before injecting the drug. In contrast, caffeine had no significant effect on anti-Fas antibody-induced hepatitis and apoptosis. These results suggest that caffeine differentially affected TNF-alpha receptor- and Fas-mediated hepatitis and apoptosis.     

Suppressive Effect of Caffeine on Hepatitis and Apoptosis Induced by Tumor Necrosis Factor-α, but Not by the Anti-Fas Antibody,in Mice

Tumor necrosis factor (TNF)-α-induced hepatitis and apoptosis, as respectively assessed by serum enzyme activities and hepatic DNA fragmentation were effectively suppressed by a single force-feeding of caffeine (100 mg/kg) 1.5 h before injecting the drug. In contrast, caffeine had no significant effect on anti-Fas antibody-induced hepatitis and apoptosis. These results suggest that caffeine differentially affected TNF-α receptor- and Fas-mediated hepatitis and apoptosis.     

Effect of <Emphasis Type="Italic">Tridax procumbens</Emphasis> on liver antioxidant defense system during lipopolysaccharide-induced hepatitis in D-galactosamine sensitised rats

The present study was carried out to assess the effect of chloroform insoluble fraction of ethanolic extract of Tridax procumbens (TP) against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced hepatitis in rats. Induction of rats with D-GalN/LPS (300 mg/kg body weight/30 g/kg body weight) led to a marked increase in lipid peroxidation as measured by thiobarbituric acid reactive substances (TBARS) in liver. Further there was a decline in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferase and the levels of non-enzymic antioxidants namely reduced glutathione, vitamin C and vitamin E. These biochemical alterations were normalised upon pretreatment with TP extract. Thus, the above results suggest that TP (300 mg/kg body weight orally for 10 days) is very effective in allievating the D-GalN/LPS-induced oxidative stress suggesting its antioxidant property. (Mol Cell Biochem 269: 131–136, 2005)     

Effects of chronic coffee consumption on glucose kinetics in the conscious rat

Epidemiological studies indicate that regular coffee consumption reduces the risk of developing type 2 diabetes. Despite these findings, the biological mechanisms by which coffee consumption exerts these effects are unknown. The aim of this study was twofold: to develop a rat model that would further delineate the effects of regular coffee consumption on glucose kinetics, and to determine whether coffee, with or without caffeine, alters the actions of insulin on glucose kinetics in vivo. Male Sprague-Dawley rats were fed a high-fat diet for 4 weeks in combination with one of the following: (i) drinking water as placebo (PL), (ii) decaffeinated coffee (2 g/100 mL) (DC), or (iii) alkaloid caffeine (20 mg/100 mL) added to decaffeinated coffee (2 g/100 mL) (CAF). Catheters were chronically implanted in a carotid artery and jugular vein for sampling and infusions, respectively. Recovered animals (5 days postoperative) were fasted for 5 h before hyperinsulinemic-euglycemic clamps (2 mU x kg(-1) x min(-1)). Glucose was clamped at 6 mmol/L and isotopes (2-deoxy-[(14)C]glucose and [3-(3)H]glucose) were administered to obtain indices of whole-body and tissue-specific glucose kinetics. Glucose infusion rates and measures of whole-body metabolic clearance were greater in DC than in PL or CAF, indicating increased whole-body insulin sensitivity. As the only difference between DC and CAF was the addition of alkaloid caffeine, it can be concluded that caffeine antagonizes the beneficial effects of DC. Given these findings, decaffeinated coffee may represent a nutritional means of combating insulin resistance.     

Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

SOS-inducing activity of UV or chemical mutagens (AF-2, 4NQO and MNNG) was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans.     

Time effect of rutaecarpine on caffeine pharmacokinetics in rats

Rutaecarpine is reported as a potent inducer of CYP1A2 enzyme in rats. There are natural herbal supplements containing rutaecarpine that are designed to enhance the CYP1A2-dependent removal of caffeine from blood so that people can have coffee later in the day without causing sleep interference. This study aimed to determine the minimum amount of time needed from oral rutaecarpine administration until the observed effect of rutaecarpine on caffeine pharmacokinetics (PK) in 15 male Sprague-Dawley rats. PK parameters for caffeine and its metabolites in the control and rutaecarpine groups were calculated using WinNonlin®. Results showed that orally administered rutaecarpine at 100 mg/kg dose as early as 3 h before oral caffeine administration significantly decreased the oral systemic exposure and mean residence time of caffeine and its metabolites due to decreased caffeine bioavailability (by up to 75%) and increased clearance. The systemic exposure of caffeine and its metabolites were also decreased when caffeine was given intravenously, though this effect was less pronounced than when caffeine was given orally. Although plasma level of rutaecarpine was undetectable (less than 10 ng/mL), rutaecarpine still induced hepatic CYP1A2 activity. Results from 7-methoxyresorufin O-demethylation activity, which is specific to CYP1A2, showed that 3 h after one rutaecarpine oral dose, CYP1A2 activity in rat liver tissue was increased by 3- fold. This finding suggested that rutaecarpine effectively induced CYP1A2 activity in the liver.     

Effects of chlorogenic acid,caffeine and coffee on components of the purinergic system of streptozotocin-induced diabetic rats

We evaluated the effect of chlorogenic acid (CGA), caffeine (CA) and coffee (CF) on components of the purinergic system from the cerebral cortex and platelets of streptozotocin-induced diabetic rats. Animals were divided into eight groups: control animals treated with (I) water (WT), (II) CGA (5 mg/kg), (III) CA (15 mg/kg) and (IV) CF (0.5 g/kg), and diabetic animals treated with (V) WT, (VI) CGA (5 mg/kg), (VII) CA (15 mg/kg) and (VIII) CF (0.5 g/kg). Our results showed an increase (173%) in adenosine monophosphate (AMP) hydrolysis in the cerebral cortex of diabetic rats. In addition, CF treatment increased adenosine diphosphate (ADP) and AMP hydrolysis in group VIII synaptosomes. Platelets showed an increase in ectonucleotidase activity in group V, and all treatments reduced the increase in adenosine triphosphate and ADP hydrolysis. Furthermore, there was an increase in platelet aggregation of 72% in the diabetic rats, and CGA and CF treatment reduced platelet aggregation by nearly 60% when compared to diabetic rats. In this context, we can suggest that CGA and CF treatment should be considered a therapeutic and scientific target to be investigated in diseases associated with hyperglycemia.     

Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-alpha.

Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two different models of septic shock. Intravenous injection of 250 micrograms/kg G-CSF to mice prevented lethality induced by 5 mg/kg LPS. Injection of 50 micrograms/kg G-CSF protected galactosamine-sensitized mice against LPS-induced hepatitis. In either case, this protection was accompanied by a suppression of LPS-induced serum TNF activity. In contrast, when galactosamine-sensitized mice were pretreated with 50 micrograms/kg murine recombinant granulocyte/macrophage CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was significantly enhanced and mortality was increased. The suppressive effect of G-CSF on LPS-induced TNF production was also demonstrated in rats. In vivo, no TNF was detectable in the blood of LPS-treated rats, which had been pretreated with G-CSF. Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or peritoneal macrophages prepared from G-CSF-treated rats produced significantly less TNF upon stimulation with LPS than corresponding populations from control rats. However, when these macrophage populations were incubated with G-CSF in vitro, LPS-induced TNF production was unaffected. These data suggest that the G-CSF-mediated suppression of TNF production is not a direct effect of G-CSF on macrophages. To examine whether, independent of the protection against LPS, G-CSF treatment still activated neutrophils, it was demonstrated that granulocytes from G-CSF-treated rats were primed for PMA-induced oxidative burst and for ionophore/arachidonic acid-stimulated lipoxygenase product formation. The experiments of this study support the notion that G-CSF is a negative feedback signal for macrophage-derived TNF-alpha production during Gram-negative sepsis.     

The Metabolic and Performance Effects of Caffeine Compared to Coffee during Endurance Exercise

There is consistent evidence supporting the ergogenic effects of caffeine for endurance based exercise. However, whether caffeine ingested through coffee has the same effects is still subject to debate. The primary aim of the study was to investigate the performance enhancing effects of caffeine and coffee using a time trial performance test, while also investigating the metabolic effects of caffeine and coffee. In a single-blind, crossover, randomised counter-balanced study design, eight trained male cyclists/triathletes (Mean±SD: Age 41±7y, Height 1.80±0.04 m, Weight 78.9±4.1 kg, VO₂ max 58±3 ml•kg⁻¹•min⁻¹) completed 30 min of steady-state (SS) cycling at approximately 55% VO₂max followed by a 45 min energy based target time trial (TT). One hour prior to exercise each athlete consumed drinks consisting of caffeine (5 mg CAF/kg BW), instant coffee (5 mg CAF/kg BW), instant decaffeinated coffee or placebo. The set workloads produced similar relative exercise intensities during the SS for all drinks, with no observed difference in carbohydrate or fat oxidation. Performance times during the TT were significantly faster (∼5.0%) for both caffeine and coffee when compared to placebo and decaf (38.35±1.53, 38.27±1.80, 40.23±1.98, 40.31±1.22 min respectively, p<0.05). The significantly faster performance times were similar for both caffeine and coffee. Average power for caffeine and coffee during the TT was significantly greater when compared to placebo and decaf (294±21 W, 291±22 W, 277±14 W, 276±23 W respectively, p<0.05). No significant differences were observed between placebo and decaf during the TT. The present study illustrates that both caffeine (5 mg/kg/BW) and coffee (5 mg/kg/BW) consumed 1 h prior to exercise can improve endurance exercise performance.     

Coffee and caffeine improve insulin sensitivity and glucose tolerance in C57BL/6J mice fed a high-fat diet

We have previously demonstrated that coffee and caffeine ameliorated hyperglycemia in spontaneously diabetic KK-A(y) mice. This present study evaluates the antidiabetic effects of coffee and caffeine on high-fat-diet-induced impaired glucose tolerance in C57BL/6J mice. C57BL/6J mice fed a high-fat diet were given regular drinking water (control group), or a 2.5-fold-diluted coffee or caffeine solution (200 mg/L) for 17 weeks. The ingestion of coffee or caffeine improved glucose tolerance, insulin sensitivity, and hyperinsulinemia when compared with mice in the control group. The adipose tissue mRNA levels of inflammatory adipocytokines (MCP-1 and IL-6) and the liver mRNA levels of genes related to fatty acid synthesis were lower in the coffee and caffeine groups than those in the control group. These results suggest that coffee and caffeine exerted an ameliorative effect on high-fat-diet-induced impaired glucose tolerance by improving insulin sensitivity. This effect might be attributable in part to the reduction of inflammatory adipocytokine expression.     

Caffeine adsorption of montmorillonite in coffee extracts

The growth in health-conscious consumers continues to drive the demand for a wide variety of decaffeinated beverages. We previously developed a new technology using montmorillonite (MMT) in selective decaffeination of tea extract. This study evaluated and compared decaffeination of coffee extract using MMT and activated carbon (AC). MMT adsorbed caffeine without significant adsorption of caffeoylquinic acids (CQAs), feruloylquinic acids (FQAs), dicaffeoylquinic acids (di-CQAs), or caffeoylquinic lactones (CQLs). AC adsorbed caffeine, chlorogenic acids (CGAs) and CQLs simultaneously. The results suggested that the adsorption selectivity for caffeine in coffee extract is higher in MMT than AC. The caffeine adsorption isotherms of MMT in coffee extract fitted well to the Langmuir adsorption model. The adsorption properties in coffee extracts from the same species were comparable, regardless of roasting level and locality of growth. Our findings suggest that MMT is a useful adsorbent in the decaffeination of a wide range of coffee extracts.     

Anti-inflammatory and anti-arthritic effects of new synthetic 3-(4-hydroxyphenyl)-4-(4-thiomethoxyphenyl)-1H-pyrrole-2,5-dione

We previously reported that 3-(4-hydroxyphenyl)-4-(4-thiomethoxyphenyl)-1H-pyrrole-2,5-dione (1, HMP) has a strong inhibitory effect on prostaglandin E(2) (PGE(2)) production. In this study, the anti-inflammatory and anti-arthritic effects of HMP were evaluated on LPS-induced RAW 264.7 macrophages and rats with carrageenan-induced paw edema and adjuvant-induced arthritis (AIA). The attenuation of PGE(2) production by HMP was found to be caused by the inhibition of cyclooxygenase-2 (COX-2) activity, but not COX-1 activity. However, HMP did not affect COX-2 at the protein or mRNA levels, whereas it suppressed the releases and expressions of inflammatory cytokines, such as, interleukin-1β (IL-1β) and IL-6 in LPS-induced macrophages. Furthermore, HMP suppressed LPS-induced nitric oxide (NO) production by down regulating the protein and mRNA expressions of inducible nitric oxide synthase (iNOS). In rats with carrageenan-injected acute inflammation, oral administration of HMP (25 or 50mg/kg, po) reduced paw swelling, and PGE(2) release and myeloperoxidase (MPO) activity in tissue. Furthermore, HMP (25 or 50mg/kg, po) significantly reduced paw swelling, arthritic indices and plasma PGE(2) concentrations in rat with AIA. These results show that HMP reduces swelling in a model acute inflammation and inhibits arthritic responses in a model of chronic inflammation via the inhibition of PGE(2) production. These results suggest that HMP is a potential therapeutic agent for the treatment of arthritis and associated disorders.     

Interactions in caffeine-sucrose and coffee-sucrose mixtures: evidence of taste and flavor suppression

Taste–taste and flavor–taste interactions (suppression)in caffeine–sucrose and coffee–sucrose mixtureswere determined. Similar interactions for both types of mixturesshowed an extended hypoadditivity effect for overall taste orflavor intensity (percentage of suppression about 30–40%).Futhermore, mutual suppression among the components has beendetermined. Firstly, the physical intensity of the suppressivecomponent controls the amount of suppression of the other component.Thus, the suppression of bitterness and coffee flavor qualitiesincrease when sucrose levels increase, and similarly, the suppressionof sweetness increases when caffeine or coffee levels rise.Secondly, the magnitude of suppression depends upon the qualityof the suppressive component. Comparisons of the reciprocalactions were made at similar subjective intensities of the mixture'sconstituents in isolation. The results showed that, at similarperceived intensities, caffeine bitterness or coffee flavorwere suppressed by sucrose but sweetness was not affected bycaffeine or coffee.     

Y-40138, a multiple cytokine production modulator, protects against D-galactosamine and lipopolysaccharide-induced hepatitis

Acute and fulminant liver failure induced by viral hepatitis, alcohol or other hepatotoxic drugs are associated with tumor necrosis factor (TNF) production. D-Galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure. In this model, TNF-alpha plays a central role in the pathogenesis of D-GalN/LPS-induced liver injury in mice. Y-40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl inhibits TNF-alpha and augments interleukin (IL)-10 production in LPS-injected mice in plasma. In the present study, we examined the effect of Y-40138 on D-GalN/LPS-induced hepatitis. Y-40138 (10mg/kg, i.v.) significantly suppressed TNF-alpha and monocyte chemoattractant protein-1 (MCP-1) production and augmented IL-10 production in plasma. In addition, Y-40138 significantly inhibited TNF-alpha production induced by direct interaction between human T lymphocytes and macrophages. Y-40138 suppressed plasma alanine transaminase (ALT) elevation and improved survival rate in D-GalN/LPS-injected mice, and it is suggested that the protective effect of Y-40138 on hepatitis may be mediated by inhibition of TNF-alpha and MCP-1, and/or augmentation of IL-10. This compound is expected to be a new candidate for treatment of cytokine and/or chemokine-related liver diseases such as alcoholic hepatitis.     

Effect of the nitrogen source on caffeine degradation by Aspergillus tamarii

AIMS: To evaluate caffeine degradation and nitrogen requirements during Aspergillus tamarii growth in submerged culture. METHODS AND RESULTS: Aspergillus tamarii spores produced on a coffee infusion agar medium added with sucrose were used. Several caffeine and ammonium sulphate concentrations (0-1 and 0-1.36 g l-1, respectively) were tested simultaneously on fungal biomass production and caffeine degradation. An additional caffeine pulse (4 g l-1) was added for all experiments after 48 h of fermentation. Results revealed that when using 0.90 g l-1 of caffeine and 0.14 g l-1 of ammonium sulphate, biomass production and caffeine degradation were enhanced. Highest biomass production (Xmax = 9.87 g l-1) with a specific growth rate (micro) of 0.073 h-1 and caffeine degradation rate of 0.033 g l-1 h-1, was observed under these conditions. CONCLUSIONS: Caffeine degradation as well as biomass production were characterized. SIGNIFICANCE AND IMPACT OF THE STUDY: These studies set the stage for future characterization studies of intracellular enzymes involved in caffeine degradation. Moreover, results observed may help in the biotreatment of residues from the coffee agroindustry.     

Effect of Indigofera tinctoria Linn on liver antioxidant defense system during D-galactosamine/endotoxin-induced acute hepatitis in rodents

Effects of pre-treatment with the alcoholic extract of I. tinctoria (500 mg/kg body wt/day, p.o. for 21 days) on liver antioxidant defense system during acute hepatitis induced by D-galactosamine (D-GalN)/endotoxin (LPS extracted by phenol water method from E. coli serotype 0111.B4; 300 mg and 30 micrograms/kg body wt/day, i.p., 18 hr before the assay) were investigated on the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase, and levels of total reduced glutathione in the liver of normal and experimental groups of male albino rats. Since lipid peroxidation and associated membrane damage is a key feature of D-galN/LPS-induced liver injury, the levels of lipid peroxides, was estimated and used as an index of oxidative stress. D-GalN/endotoxin-induced hepatic damage was manifested by a significant decrease in the activities of antioxidant enzymes, decreased glutathione levels and increased levels of lipid peroxides. I. tinctoria pre-treated rats showed considerable protection against D-galN/endotoxin, induced oxidative stress as evidenced by a significant increase in the activities of all the antioxidant enzymes studied and significant decrease in the levels of lipid peroxides. Results indicate that pretreatment with I. tinctoria extract in rats is very effective in reducing D-GalN/endotoxin-induced oxidative stress suggesting an antioxidant effect.