Decreased Tissue Omega-6/Omega-3 Fatty Acid Ratio Prevents Chemotherapy-Induced Gastrointestinal Toxicity Associated with Alterations of Gut Microbiome.

Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial ß-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g., Enterobacteriaceae) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g., Bifidobacterium), IMB dysfunction and systemic endotoxemia. These results uncover a host-microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.

[Discussion on research thought of dry granulation of traditional Chinese medicine: research progress at home and abroad based on dry granulation technology].

Dry granulation technology is a great innovation in granulation technology,which saves many intermediate links and reduces many intermediate costs. It is closely related to the characteristics of materials,dry granulation equipment and process. Dry granulation technology is a systematic engineering science covering many technical fields. The process of dry granulation involves complex mathematical model mechanisms of temperature field,pressure field and velocity field,closely related to the characteristics of materials and drying equipment. However,due to the late start of research on dry granulation technology of traditional Chinese medicine,basic research is still weak. The research on dry granulation technology has achieved great results in the fields of food,chemical industry,agriculture and forestry,showing great reference significance. The advantage of dry granulation of traditional Chinese medicine is that it can be directly granulated by adding an appropriate amount of auxiliary materials in the extract powder of traditional Chinese medicine,without the need of wetting,mixing,drying and other processes. The process is simple and can effectively guarantee the quality of traditional Chinese medicine. The granules obtained by the dry granulation technique are important intermediates for preparing the solid preparations of traditional Chinese medicines,which would directly affect the subsequent molding process and the quality of the preparation products. Therefore,based on the characteristics of dry granulation method in traditional Chinese medicine and by referring to the advanced research results of dry granulation technology in other fields,we would discuss the research ideas of dry granulation in traditional Chinese medicine in terms of the mechanism of dry granulation equipment,technology,on-line detection technology and mathematical model of dry granulation process,hoping to provide reference for the research of dry granulation method in traditional Chinese medicine.

Effect of combined use of a low-carbohydrate, high-protein diet with omega-3 polyunsaturated fatty acid supplementation on glycemic control in newly diagnosed type 2 diabetes: a randomized, double-blind, parallel-controlled trial.

Background: The combined effect of a low-carbohydrate, high-protein (LCHP) diet and omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on patients with type 2 diabetes (T2D) is not known. Objective: The aim of this study was to evaluate the effect of an LCHP diet combined with ω-3 (LCHP+ω-3) on glycemic control in patients with T2D. Design: In this randomized, double-blind, parallel-controlled trial, 122 newly diagnosed participants with T2D were randomly assigned to receive a high-carbohydrate, low-protein diet with low ω-3 PUFAs [control (CON)], an LCHP, ω-3, or LCHP+ω-3 diet for 12 wk. The ratio of carbohydrate to protein was 42:28 in the LCHP and LCHP+ω-3 diet and 54:17 in the CON and ω-3 diet. The participants were given 6 g fish oil/d (containing 3.65 g docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid/d) in the ω-3 and LCHP+ω-3 diet groups or 6 g corn oil/d (placebo) in the CON and LCHP diet groups. Results: Compared with the CON diet group, greater decreases in glycated hemoglobin (HbA1c) and fasting glucose were observed in all of the other 3 diet groups at 12 wk. Of note, HbA1c reduction in the LCHP+ω-3 diet group (-0.51%; 95% CI: -0.64%, -0.37%) was greater than that in the LCHP (P = 0.03) and ω-3 (P = 0.01) diet groups at 12 wk. In terms of fasting glucose, only the LCHP+ω-3 diet group showed a significant decrease at 4 wk (P = 0.03 compared with CON). Moreover, the reduction in fasting glucose in the LCHP+ω-3 diet group (-1.32 mmol/L; 95% CI: -1.72, -0.93 mmol/L) was greater than that in the LCHP (P = 0.04) and ω-3 (P = 0.03) diet groups at 12 wk. Conclusions: The LCHP+ω-3 diet provided greater effects on HbA1c and fasting glucose and faster effects on fasting glucose than both the LCHP and ω-3 diets, indicating the potential necessity of combining an LCHP diet with ω-3 PUFAs in T2D control. This trial was registered at chictr.org.cn/ as ChiCTR-TRC-14004704.

Fish Oil Supplements Lower Serum Lipids and Glucose in Correlation with a Reduction in Plasma Fibroblast Growth Factor 21 and Prostaglandin E2 in Nonalcoholic Fatty Liver Disease Associated with Hyperlipidemia: A Randomized Clinical Trial.

UNLABELLED: Fish oil has been used effectively in the treatment of cardiovascular disease via triglyceride reduction and inflammation modulation. This study aimed to assess the effects of fish oil on patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. Eighty participants with NAFLD associated with hyperlipidemia were randomly assigned to consume fish oil (n=40, 4 g/d) or corn oil capsules (n=40, 4 g/d) for 3 months in a double-blind, randomized clinical trial. Blood levels of lipids, glucose and insulin, liver enzymes, kidney parameters and cytokines at baseline and the end of the study were measured. Seventy people finished the trial. Plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid significantly increased in the fish oil group after intervention. After adjustment for age, gender and BMI, fish oil significantly decreased fasting serum concentrations of total cholesterol, triglyceride, apolipoprotein B and glucose (by (mean±SD) 0.49±0.43 mmol/L, 0.58±0.89 mmol/L, 0.28±0.33 g/L and 0.76±0.56 mmol/L, respectively, P<0.05), as well as alanine aminotransferase and γ-glutamyl transpeptidase levels (by (median (interquartile)) 9.0(0.5, 21.5) and 7.0(2.2, 20.0) IU/L, respectively, P<0.05), significantly increased serum adiponectin levels (by 1.29±0.62 µg/mL, P<0.001), and reduced serum levels of tumor necrosis factor α, leukotrienes B4, fibroblast growth factor 21 (FGF21), cytokeratin 18 fragment M30 and prostaglandin E2 (by 1.70±1.18 pg/mL, 0.59±0.28 ng/mL, 121±31 pg/mL, 83±60 IU/L and 10.9±2.3 pg/mL, respectively, P<0.001). Corn oil had no effect except for increasing serum creatinine concentrations by 7.7±8.9 µmol/L (P=0.008). The effects of fish oil on lipids, glucose and γ-glutamyl transpeptidase were positively correlated with the reductions of serum FGF21 and prostaglandin E2 concentrations after adjustment for age, gender and BMI (r = 0.275 to 0.360 and 0.261 to 0.375, respectively, P<0.05). In conclusion, our findings suggest that fish oil can benefit metabolic abnormalities associated with NAFLD treatment. TRIAL REGISTRATION: ChiCTR-TRC-12002380.

Estrogen receptor and PI3K/Akt signaling pathway involvement in S-(-)equol-induced activation of Nrf2/ARE in endothelial cells.

S-(-)equol, a natural product of the isoflavone daidzein, has been reported to offer cytoprotective effects with respect to the cardiovascular system, but how this occurs is unclear. Interestingly, S-(-)equol is produced by the human gut, suggesting a role in physiological processes. We report that treatment of human umbilical vein endothelial cells and EA.hy926 cells with S-(-)equol induces ARE-luciferase reporter gene activity that is dose and time dependent. S-(-)equol (10-250 nM) increases nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as gene products of Nrf2 target genes heme oxygenase-1 (HO-1) and NAD(P)H (nicotinamide-adenine-dinucleotide-phosphate) quinone oxidoreductase 1 (NQO1). Endothelial cells transfected with an HA-Nrf2 expression plasmid had elevated HA-Nrf2, HO-1, and NQO1 in response to S-(-)equol exposure. S-(-)equol treatment affected Nrf2 mRNA only slightly but significantly increased HO-1 and NQO1 mRNA. The pretreatment of cells with specific ER inhibitors or PI3K/Akt (ICI182,780 and LY294002) increased Nrf2, HO-1, and NQO1 protein, impaired nuclear translocation of HA-Nrf2, and decreased ARE-luciferase activity. Identical experiments were conducted with daidzein, which had effects similar to S-(-)equol. In addition, DPN treatment (an ERß agonist) induced the ARE-luciferase reporter gene, promoting Nrf2 nuclear translocation. Cell pretreatment with an ERß antagonist (PHTPP) impaired S-(-)equol-induced Nrf2 activation. Pre-incubation of cells followed by co-treatment with S-(-)equol significantly improved cell survival in response to H2O2 or tBHP and reduced apoptotic and TUNEL-positively-stained cells. Notably, the ability of S-(-)equol to protect against H2O2-induced cell apoptosis was attenuated in cells transfected with an siRNA against Nrf2. Thus, beneficial effects of S-(-)equol with respect to cytoprotective antioxidant gene activation may represent a novel strategy to prevent and treat cardiovascular diseases.

Chemometric resolution of coeluting peaks of eleven antihypertensives from multiple classes in high performance liquid chromatography: a comprehensive research in human serum, health product and Chinese patent medicine samples.

A novel chemometric-assisted high performance liquid chromatography method coupled with diode array detector (HPLC-DAD) was presented for the simultaneous determination of eleven antihypertensives from multiple classes in most concerned matrix systems. With the aid of second-order calibration which enables specific information of analytes to be well extracted, the heavily overlapping profiles between analytes and the coeluting interferences can be successfully separated and thus accurately quantified. A great advantage of the novel strategy lies in the fact that the analysis could be carried out with the same isocratic mobile phase (methanol/KH(2)PO(4): 58:42, v/v, pH 2.60) in a short time regardless of the changes of matrices, such as human serum, health product and Chinese patent medicine. Both qualitative and quantitative results indicate that the hybrid strategy that using HPLC-DAD coupled with second-order chemometric method would be a high performance approach for the purpose of simultaneously quantifying multiple classes of antihypertensives in complex systems. Additionally, the analytical strategy can potentially benefit drug monitoring in both therapeutic research and pharmaceutical quality control. Moreover, the accuracy and reliability of the proposed methodology has been evaluated using several statistical parameters such as root mean squared error of prediction (RMSEP), figures of merit (FOM) and reproducibility of inter-day analysis.

Second-order calibration applied to quantification of two active components of Schisandra chinensis in complex matrix.

The effectiveness of traditional Chinese medicine (TCM) against various diseases urges more low cost, speed and sensitive analytical methods for investigating the phamacology of TCM and providing a theoretical basis for clinical use. The potential of second-order calibration method was validated for the quantification of two effective ingredients of Schisandra chinensis in human plasma using spectrofluorimetry. The results obtained in the present study demonstrate the advantages of this strategy for multi-target determination in complex matrices. Although the spectra of the analytes are similar and a large number of interferences also exist, second-order calibration method could predict the accurate concentrations together with reasonable resolution of spectral profiles for analytes of interest owing to its 'second-order advantage'. Moreover, the method presented in this work allows one to simply experimental procedure as well as reduces the use of harmful chemical solvents.

alpha-Glucosidase inhibitors from the seeds of Syagrus romanzoffiana.

Bioassay-guided fractionation against alpha-glucosidase resulted in isolation and characterization of eight active compounds from the EtOH extract of the seeds of Syagrus romanzoffiana. Of these, seven are stilbenoids, and two of them, 13-hydroxykompasinol A (1) and scirpusin C (4), possess potent inhibitory activity against alpha-glucosidase type IV from Bacillus stearothermophilus with the IC50 value of 6.5 and 4.9 microM, respectively. The in vivo assay on normal Wistar rats using oral sucrose challenge also demonstrated that kompasinol A (2) and 3,3',4,5,5'-pentahydroxy-trans-stilbene (5) possess significant effect in reducing the postprandial blood glucose level (10.2% and 12.1% at 10mg/kg, respectively). These results suggest that stilbenoids might be explored for their therapeutic potential as hypoglycemic agents.