Salty taste thresholds and preference in patients with chronic kidney disease according to disease stage: A cross‐sectional study

Aim

The present study was performed to evaluate the differences in salty taste thresholds among normal controls and non‐dialysis chronic kidney disease (CKD) patients according to disease stage and to evaluate the relationship between salty taste thresholds or preferences and mean spot urine sodium concentrations.

Methods

This cross‐sectional study enrolled 436 patients with non‐dialysis CKD and 74 normal controls. We evaluated detection and recognition thresholds, salty taste preferences and salt usage behaviours (through a questionnaire) in CKD patients and normal controls. We averaged the three most recent spot urine sodium concentrations and used this ‘mean spot urine sodium’ value to estimate sodium intake in CKD patients.

Results

Detection thresholds of stages 3 and 5 and recognition thresholds of stage 3 CKD patients were higher than those of normal controls. Salty taste preferences of stage 5 and salt usage behaviour scores of stages 4 and 5 CKD patients were lower than those of normal controls. Univariate analysis showed that estimated glomerular filtration rate (eGFR), salt usage behaviour score, salty taste preference, smoking, gender and zinc level were significantly associated with mean spot urine sodium in CKD patients. Multiple regression analysis showed that the eGFR and salty taste preference were independently correlated with mean spot urine sodium.

Conclusions

Education to change salty taste preferences and regular follow up are necessary to decrease salt intake in CKD patients.     

Molecular mechanism of capillarisin-mediated inhibition of MyD88/TIRAP inflammatory signaling in in vitro and in vivo experimental models

Ethnopharmacological relevance

Artemisia capillaris Thunberg (Compositae) have been used as traditional medicine as a diuretic, liver protective agent, and for amelioration of inflammatory and analgesic disorders. The present study was carried out to establish the scientific rationale for treating inflammation and to find active principles from A. capillaris.The aim of the present study is to investigate the possible anti-inflammatory mechanism of the major component (capillarisin) isolated from A. capillaris via inhibition of MyD88/TIRAP inflammatory signaling both in vitro and in vivo models.

Materials and methods

The nitrite, PGE₂, and TNF-α productions were evaluated by Griess reagent and ELISA kits. The protein and mRNA expression levels were investigated by Western blot and RT-PCR. The NF-κB and AP-1 DNA-binding was performed by electrophoretic mobility shift assay. The CFA- and carrageenan-induced paw edema was performed in ICR mice in which 20 and 80 mg/kg body weight of capillarisin was administered intraperitoneally (i.p.).

Results

The results demonstrated that pretreatment with capillarisin effectively inhibited the LPS-induced activation of NF-κB, Akt, and MAP kinase-activated inflammatory genes, which is mediated by MyD88 and TIRAP. Treatment with capillarisin reduced the mRNA and protein levels of iNOS and COX-2 in RAW 264.7 cells as assessed by RT-PCR and Western blot. Capillarisin suppressed LPS-induced inhibitory kappa kinase (IKK) phosphorylation and the degradation of inhibitory kappa B (IκBα) and prevented the nuclear translocation of p65 and p50. Capillarisin also exhibited a promising inhibitory effect on the LPS-induced NF-κB and AP-1 DNA binding activity based on an electrophoretic mobility shift assay. The LPS-induced activation of p-JNK, p-p38, p-ERK, and p-Akt was significantly inhibited. In addition, the TNF-α level in the media was effectively reduced by capillarisin. In vivo experimental analysis revealed that capillarisin (20 and 80 mg/kg, i.p.) inhibited complete Freund's adjuvant (CFA)-and carrageenan-induced paw edema, nitrite production in plasma, and TNF-α, a pro-inflammatory cytokine production.

Conclusion

The results presented here demonstrate that capillarisin has consistent anti-inflammatory properties and acts by inhibiting inflammatory mediators in in vitro and in vivo experimental models, and suggest its potential utility in the control of inflammatory disorders.     

2-methoxycinnamaldehyde from Cinnamomum cassia reduces rat myocardial ischemia and reperfusion injury in vivo due to HO-1 induction

Ethnopharmacological relevance

Cinnamomum cassia Blume has been used as a traditional Chinese herbal medicine for alleviation of fever, inflammation, chronic bronchitis, and to improve blood circulation.

Aim of the study

We addressed whether 2-methoxycinnamaldehyde (2-MCA), one of active ingredients of Cinnamomum cassia, reduces vascular cell adhesion molecule-1 (VCAM-1) expression in tumor necrosis factor-alpha (TNF-α)-activated endothelial cells and protects ischemia/reperfusion (I/R)-injury due to heme oxygenase (HO)-1 induction.

Materials and methods

Adult male rats were subjected to 30 min of ischemia by occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion. Rats were randomized to receive vehicle or 2-MCA (i.v.) 10 min before reperfusion.

Results

Administration of 2-MCA significantly improved I/R-induced myocardial dysfunction by increasing the values of the first derivative (±dp/dt) of left ventricular pressure and decreased infarct size. In addition, 2-MCA reduced the expression of high mobility group box 1 (HMGB1), an activator of the inflammatory cascade when released into the extracellular space, and VCAM-1 in I/R myocardium along with increase of HO-1 induction. The reduced injury was accompanied by significantly reduction of neutrophils infiltration and increased SOD activity in ischemic tissues and reduced serum level of cardiac troponin I (cTnI). Furthermore, 2-MCA significantly increased HO-1 induction by translocation of Nrf-2 from cytosol to nucleus in endothelial cells. Inhibition of VCAM-1 expression by 2-MCA was reversed both by SnPPIX, a HO-1 inhibitor and siHO-1 RNA trasfection in TNF-α-activated cells. In addition, 2-MCA significantly inhibited NF-κB luciferase activity in TNF-α-activated endothelial cells. As expected, 2-MCA significantly inhibited monocyte (U937) adhesion to endothelial cells.

Conclusion

We concluded that 2-MCA protects of myocardial I/R-injury due to antioxidant and anti-inflammatory action possibly by HO-1 induction which can be explained why Cinnamomum cassia has been used in inflammatory disorders.     

Momilactone B,an Allelochemical of Rice Hulls,Induces Apoptosis on Human Lymphoma Cells (Jurkat) in a Micromolar Concentration

Although momilactone B has been studied as an allelochemical of rice (Oryza sativa L.), to date we have no report showing the effect of momilactone B on mammalian cells. This study was undertaken to examine whether this allelochemical has anticancer activity on cancer cells. We show here that momilactone B at micromolar doses has antitumor efficacy by inducing apoptosis in several blood cancer cells including human leukemic T cells. In addition, our study elucidated that anticancer activity of momilactone B on human leukemic T cells resulted from the induction of apoptosis via caspase and mitochondria. From these results, momilactone B can be considered as a novel therapeutic strategy for human leukemic T cells from its direct apoptosis-inducing activity.     

Isoflavonoids from the rhizomes of Belamcanda chinensis and their effects on aldose reductase and sorbitol accumulation in streptozotocin induced diabetic rat tissues

Aldose reductase, the key enzyme of the polyol pathway, is known to play important roles in the diabetic complication. The inhibitors of aldose reductase, therefore, would be potential agents for the prevention of diabetic complications. To evaluate active principles for the inhibition of aldose reductase from the rhizomes of Belamcanda chinensis, twelve phenolic compounds were isolated and tested for their effects on rat lens aldose reductase. As a result, isoflavones such as tectorigenin, irigenin and their glucosides were found to show a strong aldose reductase inhibition. Tectoridin and tectorigenin, exhibited the highest aldose reductase inhibitory potency, their IC50 values, being 1.08 x 10(-6) M and 1.12 x 10(-6) M, respectively, for DL-glyceraldehyde as a substrate. Both compounds, when administered orally at 100 mg/kg for 10 consecutive days to streptozotocin-induced diabetic rats, caused a significant inhibition of sorbitol accumulation in the tissues such as lens, sciatic nerves and red blood cells. Tectorigenin showed a stronger inhibitory activity than tectoridin. From these results, it is suggested that tectorigenin is attributed to be a promising compound for the prevention and/or treatment of diabetic complications.     

Inhibition by acharan sulphate of angiogenesis in experimental inflammation models

1. The effects of acharan sulphate, a glycosaminoglycan isolated from the giant African snail Achatina fulica, on angiogenesis in the granulation tissue were analysed using an air pouch-type carrageenin-induced inflammation model in rats and a cotton thread-induced inflammation model in mice. 2. In the carrageenin-induced inflammation model in rats, intra-pouch injections of acharan sulphate (5 and 50 micro g) inhibited the pouch fluid accumulation and the granulation tissue formation as well as the angiogenesis in the granulation tissue at day 6 in a dose-dependent manner. 3. The inhibitory effects of acharan sulphate at 50 micro g on the pouch fluid accumulation and the leucocyte infiltration into the pouch fluid was not so effective as that of the cyclo-oxygenase inhibitor indomethacin at 100 micro g, but the inhibitory effects of acharan sulphate at 50 micro g on the granulation tissue formation and angiogenesis in the granulation tissue were almost the same as those of indomethacin at 100 micro g. 4. Acharan sulphate did not affect levels of vascular endothelial growth factor (VEGF) in the granulation tissue and in the pouch fluid at day 6, but indomethacin significantly lowered them. 5. In the cotton thread-induced inflammation model in mice, injections of acharan sulphate (10 micro g) at the site of the cotton thread implantation inhibited the granulation tissue formation and angiogenesis as indomethacin (20 micro g) did. Acharan sulphate (10 micro g) did not affect levels of VEGF in the cotton thread-induced granulation tissue at day 5, but indomethacin (20 micro g) significantly lowered them. 6. In culture of human vascular endothelial cells, acharan sulphate at 10 and 100 micro g ml(-1) inhibited VEGF-induced capillary tube formation. 7. These findings suggest that the inhibitory effect of acharan sulphate on angiogenesis in carrageenin- and cotton thread-induced granulation tissues is not due to the inhibition of VEGF protein induction, but is due to the inhibition of VEGF-induced vascular tube formation.     

Pharmacological activities of a new glycosaminoglycan,acharan sulfate isolated from the giant African snail Achatina fulica

Acharan sulfate (AS) is a glycosaminoglycan (GAG) prepared from the giant African snail, Achatina fulica. In this study, some biological activities of AS were evaluated on the basis of structural similarities to heparin/heparan sulfate and the biological functions of GAGs. We demonstrated that it exhibited strong immunostimulating activities as measured by carbon clearance test in mice and in vivo phagocytosis. It also exhibited a significant hypoglycemic activity in epinephrine (EP)-induced hyperglycemia as well as antifatigue effects by weight-loaded forced swimming test. And it showed hypolipidemic activities in cholesterol-rich mixture induced hyperlipidemia in rats. The above results indicate that AS has diverse biological activities and suggest therapeutically important target molecules.     

Increased antibacterial activity of DW286, a novel fluoronaphthyridone antibiotic, against Staphylococcus aureus strains with defined mutations in DNA gyrase and topoisomerase IV

To investigate the activity of DW286, a new fluoronaphthyridone, the quinolone resistance determining regions (QRDRs) of gyrA, gyrB, grlA and grlB genes in 64 Staphylococcus aureus clinical isolates were analyzed and the MICs of DW286 and comparator quinolones determined. Double and triple mutants in gyrA and grlA were resistant to ciprofloxacin, sparfloxacin, trovafloxacin and gemifloxacin but susceptible to DW286 (MIC 0.25-0.5 mg/l). The fourth alteration, Ser85Pro of GyrA was required to make a strain resistant to DW286 (MIC 4-32 mg/l). For a strain with the mutations at GyrA Ser84Leu and GrlA Ser80Phe, the MBC of DW286 was two-fold higher than its corresponding MIC, in contrast to ciprofloxacin which was not bactericidal.