Decreased plasma n6 : n3 polyunsaturated fatty acids ratio interacting with high C-peptide promotes non-alcoholic fatty liver disease in type 2 diabetes patients.

AIMS/INTRODUCTION: To explore relationships between polyunsaturated fatty acids (PUFA) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes, and whether insulin action has an interactive effect with PUFA on NAFLD progression. MATERIALS AND METHODS: We extracted clinical and omics data of 482 type 2 diabetes patients from a tertiary hospital consecutively from April 2018 to April 2019. NAFLD was estimated by ultrasound at admission. Plasma fasting n3 and n6 fatty acids were quantified by liquid chromatography-tandem mass spectrometry analysis. Restricted cubic spline nested in binary logistic regression was used to select the cut-off point, and estimate odds ratios and 95% confidence intervals. Additive interactions of the n6 : n3 ratio with insulin action for NAFLD were estimated using relative excess risk due to interaction, attributable proportion due to interaction and synergy index. Relative excess risk due to interaction >0, attributable proportion due to interaction >0 or synergy index >1 indicates biological interaction. Spearman correlation analysis was used to obtain partial correlation coefficients between PUFA and hallmarks of NAFLD. RESULTS: Of 482 patients, 313 were with and 169 were without NAFLD. N3 ≥800 and n6 PUFA ≥8,100 µmol/L were independently associated with increased NAFLD risk; n6 : n3 ratio ≤10 was associated with NAFLD (odds ratio 1.80, 95% confidence interval 1.20-2.71), and the effect size was amplified by high C-peptide (odds ratio 8.89, 95% confidence interval 4.48-17.7) with significant interaction. The additive interaction of the n6 : n3 ratio and fasting insulin was not significant. CONCLUSION: Decreased n6 : n3 ratio was associated with increased NAFLD risk in type 2 diabetes patients, and the effect was only significant and amplified when there was the co-presence of high C-peptide.

Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism.

OBJECTIVE: Acylcarnitine metabolism disorder contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). There are, however, few ideal medications for NAFLD, which work by targeting acylcarnitine metabolism. The aim of this study was to investigate the protective effects of theacrine, a rare purine alkaloid isolated from Camellia assamica var. kucha, against acylcarnitine metabolism disorder in NAFLD. METHODS: The pharmacological activities of theacrine were studied using high-fat diet (HFD)-fed ApoE-/- and C57BL/6J mice models. Oleate-treated HepG2 and L-02 cells were used to investigate the molecular mechanism of theacrine on acylcarnitine metabolism. The target of theacrine was confirmed in vitro as the blockade of sirtuin 3 (SIRT3) and protein kinase A. RESULTS: Theacrine inhibits hepatic steatosis and liver inflammation and improves energy expenditure in HFD-fed mice. Theacrine ameliorates acylcarnitine metabolism disorder in HFD-fed mice and oleate-treated hepatocytes by improving fatty acid oxidation. The underlying mechanism involves theacrine's activation of the mitochondrial deacetylase SIRT3 and consequently, the increased activity of long-chain acyl coenzyme A dehydrogenase (LCAD) through deacetylation. CONCLUSION: Theacrine promotes acylcarnitine metabolism in NAFLD through the SIRT3/LCAD signaling pathway. The target of theacrine's activities on NAFLD is identified as SIRT3.

Everolimus-inhibited multiple isoforms of UDP-glucuronosyltransferases (UGTs).

1. Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and has been clinically utilized to prevent the rejection of organ transplants. This study aims to determine the inhibition of everolimus on the activity of phase-II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). 2. The results showed that 100 µM of everolimus exerted more than 80% inhibition toward UGT1A1, UGT-1A3 and UGT-2B7. UGT1A3 and UGT2B7 were selected to elucidate the inhibition mechanism, and in silico docking showed that hydrogen bonds and hydrophobic interactions mainly contributed to the strong binding of everolimus toward the activity cavity of UGT1A3 and UGT2B7. Inhibition kinetic-type analysis using Lineweaver-Burk plot showed competitive inhibition toward all these UGT isoforms. The inhibition kinetic parameters (Ki) were calculated to be 2.3, 0.07 and 4.4 µM for the inhibition of everolimus toward UGT1A1, UGT-1A3 and UGT-2B7, respectively. 3. In vitro-in vivo extrapolation (IVIVE) showed that [I]/Ki value was calculated to be 0.004, 0.14 and 0.002 for UGT1A1, UGT-1A3 and UGT-2B7, respectively. Therefore, high DDI potential existed between everolimus and clinical drugs mainly undergoing UGT1A3-catalyzed glucuronidation.

Edge-selenated graphene nanoplatelets as durable metal-free catalysts for iodine reduction reaction in dye-sensitized solar cells.

Metal-free carbon-based electrocatalysts for dye-sensitized solar cells (DSSCs) are sufficiently active in Co(II)/Co(III) electrolytes but are not satisfactory in the most commonly used iodide/triiodide (I(-)/I3 (-)) electrolytes. Thus, developing active and stable metal-free electrocatalysts in both electrolytes is one of the most important issues in DSSC research. We report the synthesis of edge-selenated graphene nanoplatelets (SeGnPs) prepared by a simple mechanochemical reaction between graphite and selenium (Se) powders, and their application to the counter electrode (CE) for DSSCs in both I(-)/I3 (-) and Co(II)/Co(III) electrolytes. The edge-selective doping and the preservation of the pristine graphene basal plane in the SeGnPs were confirmed by various analytical techniques, including atomic-resolution transmission electron microscopy. Tested as the DSSC CE in both Co(bpy)3 (2+/3+) (bpy = 2,2'-bipyridine) and I(-)/I3 (-) electrolytes, the SeGnP-CEs exhibited outstanding electrocatalytic performance with ultimately high stability. The SeGnP-CE-based DSSCs displayed a higher photovoltaic performance than did the Pt-CE-based DSSCs in both SM315 sensitizer with Co(bpy)3 (2+/3+) and N719 sensitizer with I(-)/I3 (-) electrolytes. Furthermore, the I3 (-) reduction mechanism, which has not been fully understood in carbon-based CE materials to date, was clarified by an electrochemical kinetics study combined with density functional theory and nonequilibrium Green's function calculations.

Structure-inhibition relationship of podophyllotoxin (PT) analogues towards UDP-glucuronosyltransferase (UGT) isoforms.

UDP-glucuronosyltransferases (UGTs) are involved in the clearance of many important drugs and endogenous substances, and inhibition of UGTs' activity by herbal components might induce severe herb-drug interactions or metabolic disturbances of endogenous substances. The present study aims to determine the inhibition of UGTs' activity by podophyllotoxin derivatives, trying to indicate the potential herb-drug interaction or metabolic influence towards endogenous substances' metabolism. Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the podophyllotoxin derivatives' inhibition potential. Structure-dependent inhibition behavior of podophyllotoxin derivatives towards UGT isoforms was detected. Inhibition kinetic type and parameter (Ki) were determined for the inhi- bition of podophyllotoxin towards UGT1A1, and competitive inhibition of podophyllotoxin towards UGT1A1 was observed with the inhibition kinetic parameter (Ki) to be 4.0 µM. Furthermore, podophyllotoxin was demonstrated to exert medium and weak inhibition potential towards human liver microsomes (HLMs)-catalyzed SN-38 glucuronidation and estradiol-3-glucuronidation. In conclusion, podophyllotoxin inhibited UGT1A1 activity, indicating potential herb-drug interactions between podophyllotoxin-containing herbs and drugs mainly undergoing UGT1A1-mediated metabolism.

The Inhibition of the Components from Shengmai Injection towards UDP-Glucuronosyltransferase.

The mechanism of shengmai injection- (SMI-) related drug-drug interaction remains unclear. Evaluation of the inhibition potential of SMI's ingredients towards UDP-glucuronosyltransferases (UGTs) activity will provide a new insight to understand SMI-related drug-drug interaction. In vitro incubation system to model UGT reaction was used. Recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation reactions were employed to phenotype the inhibition profile of maidong's components towards the activity of UGT isoforms. Different inhibition potential of maidong's components towards various UGT isoforms was observed. Based on the inhibition kinetic investigation results, ophiopogonin D (OD) noncompetitively inhibited UGT1A6 and competitively inhibited UGT1A8, ophiopogonin D' (OD') noncompetitively inhibited UGT1A6 and UGT1A10, and ruscorectal (RU) exhibited competitive inhibition towards UGT1A4. The inhibition kinetic parameters were calculated to be 20.6, 40.1, 5.3, 9.0, and 0.02 µM, respectively. In combination with our previous results obtained for the inhibition of UGT isoforms by ginsenosides and wuweizi components, the important SMI ingredients exhibiting strong inhibition towards UGT isoforms were highlighted. All the results obtained in the present study provide a new insight to understand SMI-related drug-drug interaction.

Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7.

Herb-drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivatives towards one of the most important phase II DMEs UDP-glucuronosyltransferases (UGTs). Recombinant UGT isoforms (except UGT1A4)-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation were employed to firstly screen the andrographolide derivatives' inhibition potential. High specific inhibition of andrographolide derivatives towards UGT2B7 was observed. The inhibition type and parameters (Ki) were determined for the compounds exhibiting strong inhibition capability towards UGT2B7, and human liver microsome (HLMs)-catalyzed zidovudine (AZT) glucuronidation probe reaction was used to furtherly confirm the inhibition behavior. In combination of inhibition parameters (Ki) and in vivo concentration of andrographolide and dehydroandrographolide, the potential in vivo inhibition magnitude was predicted. Additionally, both the in vitro inhibition data and computational modeling results provide important information for the modification of andrographolide derivatives as selective inhibitors of UGT2B7. Taken together, data obtained from the present study indicated the potential herb-drug interaction between Andrographis paniculata and the drugs mainly undergoing UGT2B7-catalyzed metabolic elimination, and the andrographolide derivatives as potential candidates for the selective inhibitors of UGT2B7.

Objectifying research on special region corresponding to five internal organs in colour inspections of Chinese medicine.

OBJECTIVE: To study the differences in a special region (SR) corresponding to five internal organs between the young and the elderly and to verify the effectiveness of a developed system for objectifying research in colour inspections of Chinese medicine (CICM). METHODS: An image acquisition device imitating daylight to meet the requirement of CICM was designed. Image processing software based on CICM theory was developed. A total of 83 normal people were sampled and assigned to two groups. The first group (Group I) included 30 people with an average age of 24±2, and the second group (Group II) included 53 people with an average age of 74±4. After image processing, the chromaticity of 10 SRs corresponding to five internal organs was calculated. R, G, and B represent the chromaticity of color red, green, and blue, L indicates color brightness, whereas a and b denote red and yellow respectively. The difference between the young and the elderly was analyzed. RESULTS: (1) The chromaticity of each SR corresponding to five organs was obtained. The average R, G, B, L, a, and b of the sample were 194.4, 147.6, 119.3, 65.2, 15.5, and 22.3, respectively. (2) The R, G, B, and L of the young were greater than those of the elderly, but the a and b of the young were less than those of the elderly. (3) A statistically significant difference in each SR was found between the young and the elderly (P <0.05). The total differences for the Lung (Fei), Heart (Xin), Liver (Gan), Spleen (Pi), and Kidney (Shen) were 50% (3/6), 66.7% (4/6), 66.7% (4/6), 83.3% (5/6), and 91.7% (33/36), respectively. However, the Kidney SR had the greatest statistical discrepancy. CONCLUSION: The old Chinese saying that human Kidney deficiency worsens with age was verified by the results. The objectifying system used to examine CICM was effective. Thus, this system may be used as a basis for further research.

Comparison of inhibition capability of scutellarein and scutellarin towards important liver UDP-glucuronosyltransferase (UGT) isoforms.

Scutellarin is an important bioactive flavonoid extracted from Erigeron breviscapus (Vant.) Hand-Mazz, and scutellarein is the corresponding aglycone of scutellarin. The present study aims to compare the inhibition potential of scutellarin and scutellarein towards several important UDP-glucuronosyltransferase (UGT) isoforms, including UGT1A1, UGT1A6, UGT1A9 and UGT2B7. It was demonstrated that scutellarein exerted stronger inhibition towards the tested UGT isoforms than scutellarin. Furthermore, the inhibition kinetic type and parameters (Ki ) were determined for the scutellarein's inhibition towards these UGT isoforms. Competitive inhibition of scutellarein towards all these UGT isoforms was demonstrated, and the Ki values were calculated to be 0.02, 5.0, 5.8 and 35.9 µM for UGT1A1, 1A6, 1A9 and 2B7, respectively. Using in vivo maximum plasma concentration of scutellarein in rat, the in vitro-in vivo extrapolation was performed to predict in vivo situation, indicating the most possible in vivo adverse effects due to the inhibition of scutellarein towards UGT1A1. All these results remind us to monitor the utilization of scutellarin and scutellarein, and the herbs containing these two components.

Objectifying research on special region corresponding to five internal organs in colour inspections of Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the differences in a special region (SR) corresponding to five internal organs between the young and the elderly and to verify the effectiveness of a developed system for objectifying research in colour inspections of Chinese medicine (CICM).</p><p><b>METHODS</b>An image acquisition device imitating daylight to meet the requirement of CICM was designed. Image processing software based on CICM theory was developed. A total of 83 normal people were sampled and assigned to two groups. The first group (Group I) included 30 people with an average age of 24±2, and the second group (Group II) included 53 people with an average age of 74±4. After image processing, the chromaticity of 10 SRs corresponding to five internal organs was calculated. R, G, and B represent the chromaticity of color red, green, and blue, L indicates color brightness, whereas a and b denote red and yellow respectively. The difference between the young and the elderly was analyzed.</p><p><b>RESULTS</b>(1) The chromaticity of each SR corresponding to five organs was obtained. The average R, G, B, L, a, and b of the sample were 194.4, 147.6, 119.3, 65.2, 15.5, and 22.3, respectively. (2) The R, G, B, and L of the young were greater than those of the elderly, but the a and b of the young were less than those of the elderly. (3) A statistically significant difference in each SR was found between the young and the elderly (P <0.05). The total differences for the Lung (Fei), Heart (Xin), Liver (Gan), Spleen (Pi), and Kidney (Shen) were 50% (3/6), 66.7% (4/6), 66.7% (4/6), 83.3% (5/6), and 91.7% (33/36), respectively. However, the Kidney SR had the greatest statistical discrepancy.</p><p><b>CONCLUSION</b>The old Chinese saying that human Kidney deficiency worsens with age was verified by the results. The objectifying system used to examine CICM was effective. Thus, this system may be used as a basis for further research.</p>

Structure-inhibition relationship of ginsenosides towards UDP-glucuronosyltransferases (UGTs).

The wide utilization of ginseng provides the high risk of herb-drug interaction (HDI) with many clinical drugs. The inhibition of ginsenosides towards drug-metabolizing enzymes (DMEs) has been regarded as an important reason for herb-drug interaction (HDI). Compared with the deep studies on the ginsenosides' inhibition towards cytochrome P450 (CYP), the inhibition of ginsenosides towards the important phase II enzymes UDP-glucuronosyltransferases (UGTs) remains to be unclear. The present study aims to evaluate the inhibition behavior of ginsenosides towards important UGT isoforms located in the liver and intestine using in vitro methods. The recombinant UGT isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed as in vitro probe reaction. The results showed that structure-dependent inhibition existed for the inhibition of ginsenosides towards UGT isoforms. To clarify the possibility of in vivo herb-drug interaction induced by this kind of inhibition, the ginsenoside Rg(3) was selected as an example, and the inhibition kinetic type and parameters (K(i)) were determined. Rg(3) competitively inhibited UGT1A7, 2B7 and 2B15-catalyzed 4-MU glucuronidation reaction, and exerted noncompetitive inhibition towards UGT1A8-catalyzed 4-MU glucuronidation. The inhibition parameters (K(i) values) were calculated to be 22.6, 7.9, 1.9, and 2.0µM for UGT1A7, 1A8, 2B7 and 2B15. Using human maximum plasma concentration of Rg(3) (400ng/ml (0.5µM)) after intramuscular injection of 60mg Rg(3), the area under the plasma concentration-time curve (AUC) was extrapolated to increase by 2.2%, 6.3%, 26.3%, and 25% for the co-administered drugs completely undergoing the metabolism catalyzed by UGT1A7, 1A8, 2B7 and 2B15, respectively. All these results indicated that the ginsenosides' inhibition towards UGT isoforms might be an important reason for ginseng-drug interaction.

Deglycosylation of liquiritin strongly enhances its inhibitory potential towards UDP-glucuronosyltransferase (UGT) isoforms.

The detailed mechanisms on licorice-drug interaction remain to be unclear. The aim of the present study is to investigate the inhibition of important UGT isoforms by two important ingredients of licorice, liquiritin, and liquiritigenin. The results showed that liquiritigenin exhibited stronger inhibition towards all the tested UGT isoforms than liquiritin. Data fitting using Dixon and Lineweaver-Burk plots demonstrated the competitive inhibition of liquiritigenin towards UGT1A1 and UGT1A9-mediated 4-MU glucuronidation reaction. The inhibition kinetic parameters (Ki ) were calculated to be 9.1 and 3.2 µM for UGT1A1 and UGT1A9, respectively. Substrate-dependent inhibition behaviour was also observed for UGT1A1 in the present study. All these results will be helpful for understanding the deep mechanism of licorice-drug interaction. However, when translating these in vitro parameters into in vivo situations, more complex factors should be considered, such as substrate-dependent inhibition of UGT isoforms, the contribution of UGT1A1 and UGT1A9 towards the metabolism of drugs, and many factors affecting the abundance of ingredients in the licorice.

Investigation of the in vitro metabolism of evodiamine: characterization of metabolites and involved cytochrome p450 isoforms.

Evodiamine is the main active alkaloid of Evodia rutaecarpa (E. rutaecarpa) and has been demonstrated to exhibit many pharmacological activities including vasorelaxation, uterotonic action, anoxia and control of body temperature. The present study focused on the metabolism of evodiamine. Human and phenobarbital-induced rat liver microsomal incubation of evodiamine in the presence of NADPH resulted in the formation of five major metabolites (M-1, M-2, M-3, M-4, M-5). Four metabolites (M-1, M-2, M-3 and M-5) were identified to mono-hydroxylated evodiamine and one metabolite (M-4) was identified to be N-demethylated evodiamine. CYP3A4, CYP2C9 and CYP1A2 were identified to be the main CYP isoforms involved in the metabolism of evodiamine in human liver microsomes. Finding new metabolites can help us decipher novel substance basis of efficiency and toxicity. Elucidation of drug metabolizing enzymes will facilitate explaining the individual difference for response to the same drugs or herbs and the potential drug-drug interaction or herb-drug interaction. Taken together, these results are of significance for better understanding the pharmacokinetic behaviour of evodiamine and helpful for clinical application of evodiamine and E. rutaecarpa.

Glycyrrhetinic acid exhibits strong inhibitory effects towards UDP-glucuronosyltransferase (UGT) 1A3 and 2B7.

The aim of the present study is to evaluate the inhibitory effects of liver UDP-glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid, which are the bioactive ingredients isolated from licorice. The results showed that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT isoforms, indicating that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms. Furthermore, the inhibition kinetic type and parameters were determined for the inhibition of glycyrrhetinic acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic acid was best fit to competitive and noncompetitive type, respectively. The second plot using the slopes from Lineweaver-Burk plots versus glycyrrhetinic acid concentrations was employed to calculate the inhibition kinetic parameters (K(i)), and the values were calculated to be 0.2 and 1.7 µM for UGT1A3 and UGT2B7, respectively. All these results remind us the possibility of UGT inhibition-based herb-drug interaction. However, the explanation of these in vitro parameters should be paid more caution due to complicated factors, including the probe substrate-dependent UGT inhibition behaviour, environmental factors affecting the abundance of herbs' ingredients, and individual difference of pharmacokinetic factors.

Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation.

Isoliquiritigenin, a herbal ingredient with chalcone structure, has been speculated to be able to inhibit one of the most drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferase (UGT). Therefore, the aim of the present study was to investigate the inhibition of isoliquiritigenin towards important UGT isoforms in the liver and intestine, including UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as probe reactions. The results showed that 100µM of isoliquiritigenin inhibited the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 by 95.2%, 76.1%, 78.9%, 87.2%, 67.2%, 94.8%, and 91.7%, respectively. The data fitting using Dixon plot and Lineweaver-Burk plot showed that the inhibition of UGT1A1, UGT1A9 and UGT1A10 by isoliquiritigenin was all best fit to the competitive inhibition, and the second plot using the slopes from the Lineweaver-Burk plot versus isoliquiritigenin concentrations was used to calculate the inhibition kinetic parameter (K(i)) to be 0.7µM, 0.3µM, and 18.3µM for UGT1A1, UGT1A9, and UGT1A10, respectively. All these results indicated the risk of clinical application of isoliquiritigenin on the drug-drug interaction and other possible diseases induced by the inhibition of isoliquiritigenin towards these UGT isoforms.

Preparation and evaluation of nicotinic acid sustained-release pellets combined with immediate release simvastatin.

This study was performed to prepare high-dose nicotinic acid (NA) loaded sustained-release pellets coated with double polymer and simvastatin (SIM). The uncoated pellets were prepared by extrusion-spheronization and the double ethylcellucose (EC) films were coated in a bottom-spray fluidized bed coater. SIM was milled by wet grinding and then the milled suspension was layered on the coated pellets. Results showed that coated with 1.5% subcoating and 1% outer coating composed of EC and polyvinyl pyrrolidone K30 (PVP(K30)) in ratios of 5:1 and 2:1, NA release behavior was very similar to the reference (NER/S; SIMCOR, Abbott) in different media. And SIM was delivered more rapidly than that of the reference, while the SIM layer had no influence on NA release. During 6-month storage at 40°C/75% RH, the two drugs exhibited stable dissolution behavior. It was observed that the content uniformity of SIM was provided by the present preparation and SIM was stable if adding light magnesium oxide in the grinding procedure. Results indicated it was possible to prepare high-dose sustained-release NA pellets combined with little-dose immediate release SIM by spraying double EC polymer and SIM milled suspension on NA pellets in a bottom-spray fluidized bed coater, respectively.

Regulatory effect of Astragalus membranaceus on the immune disorder in rats with IgA nephropathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the regulattory effect of Astragalus membranaceus on immune disturbance of the rats with IgA nephropathy.</p><p><b>METHODS</b>Rats IgA nephropathy (IgAN) model was duplicated by oral feeding of bovine serum albumin (BSA), subcutaneous injection of carbon tetrachloride (CCl4) and injection of lipopolysaccharide (LSP) into vena caudalis. The rats were divided into three groups randomly for the normal, IgAN model group and the group treated with Astragalus membranaceus (treatment group). The treatment group was given the Astragalus membranaceus granules via intragastric administratsion, the normal group and the IgAN model group were given the equal amount of aqua destillata by gastric perfusion. The rats were examined for albuminuria, hematuria and pathological changes of renal tissue and the distribution of TGF-beta and interleukin-5 in renal tissue was determined by immunohistochemistry and the IFN-gamma and IL-4 of cytokine of Th1 and Th2 types were detected in rats IgA nephropathy model by sandwich enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>(1) The hematuria in rats with IgA nephropathy significantly increased compared with normal control group and Astragalus treatment group (P < 0.05). There was significant increase in albuminuria in rats with IgA nephropathy, compared with normal control group and astragalus treatment group (P < 0.01). (2) The pathological change of glomerular mesangium, renal tubules and renal interstitia became serious in rats IgA nephropathy model when compared with normal control group and astragalus treatment group. Immumofluorescence showed renal IgA density in rats IgA nephropathy model was significantly higher than that in the normal control group (P < 0.001) and astragalus treatment group (P < 0.001). (3) The result of immuno histochemistry showed that there was only weak expression of TGF-beta and interleukin 5 in normal renal tissue. The expression of TGF-beta and interleukin 5 in IgA nephropathy model was significantly stronger than those in normal control group (P < 0.05) and astragalus treatment group (P < 0.05). (4) The serum IL-4 levels were (33.74 +/- 7.52) pg/ml in rats IgA nephropathy model, significantly higher than that in normal control group (2.36 +/- 0.85) pg/ml and astragalus treatment group (3.24 +/- 1.13) pg/ml. The IFN-gamma level in serum of rats IgA nephropathy model was (18.79 +/- 3.80) pg/ml, which was significantly higher than that in normal control group (46.53 +/- 5.56) pg/ml and astragalus treatment group (41.28 +/- 2.95) pg/ml.</p><p><b>CONCLUSIONS</b>The astragalus could lower the level of hematuria and 24 hours-albuminuria of the IgAN model, and amelioratse the change of the renal pathology and reduce the deposit of IgA in glomerular mesangium. The possible mechanism of the effect is that astragalus could regulate the derangement of Th1, Th2, accordingly could improve the level of IL-4 and IFN-gamma in the serum and diminish the expression of cytokine Th2 TGF-beta1 and IL-5 of the renal tissue, and thereby could postpone the development of IgAN.</p>

[Differentiation and analysis of original meaning of classical channel theories].

OBJECTIVE: To probe into the original meanings of manifestation and root cause, root and knot, Genliu infusion, Benshu, pathway of qi, four sea, Guan-He Shu and other classical channel theories. METHODS: Based on Huangdi Neijing (The Yellow Emperor's Internal Classic) and other classical literatures, combined with medical books in bamboo slip and the silk and opinions of annotation experts of successive dynasties, deeply analyze and study. RESULTS: Classical channel theories are involved in some theories of channel structures, with 3 original meanings: expounding the origin, the end and running of channels, expounding bi-directional running of channel-qi, and expounding the affinity relation of six channels, six qi, six zang-organs and six fu-organs. CONCLUSION: Classical channel theories stress emphasize concentric running of channels, and concentric arrangement of channel acupoints, bi-directional running of channel-qi, and each affinity of six channels.

[Study on rules of distribution field of channels and collaterals].

OBJECTIVE: To study rules of distribution of channels and collaterals in external connection with orifices and limbs. METHODS: Based on classical theories in The Yellow Emperor's Internal Calssic and Classic on Medical Problem, summarization was carried out. RESULTS: There are their own steric-crossed distribution of channels and collaterals on orifices and limbs, which is called as rules of distribution field of channels and collaterals. CONCLUSION: The study on rules of distribution field of channels and collaterals can guide treatment based on syndrome differentiation, and promote development of theories of channels and collaterals.

Study on rules of distribution field of channels and collaterals / 中国针灸

<p><b>OBJECTIVE</b>To study rules of distribution of channels and collaterals in external connection with orifices and limbs.</p><p><b>METHODS</b>Based on classical theories in The Yellow Emperor's Internal Calssic and Classic on Medical Problem, summarization was carried out.</p><p><b>RESULTS</b>There are their own steric-crossed distribution of channels and collaterals on orifices and limbs, which is called as rules of distribution field of channels and collaterals.</p><p><b>CONCLUSION</b>The study on rules of distribution field of channels and collaterals can guide treatment based on syndrome differentiation, and promote development of theories of channels and collaterals.</p>