Study on mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy based on proteomics / 中国药理学通报

Aim To explore the mechanism of hydroxy-a-sanshool in the treatment of diabetic cardiomyopathy ( DCM) based on label-free quantitative proteomics detection technique. Methods DCM model was established by high fat diet and intraperitoneal injection of streptozotocin ( STZ) . They were divided into control group ( CON group ) , diabetic cardiomyopathy group (DCM group) and hydroxy-a-sanshool treatment group ( DCM + SAN group) . The cardiac function of mice was evaluated by echocardiography, the myocardial morphology was observed by pathology staining, the protective mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy was speculated by proteomic technique , and the expression level of cAMP/PKA signaling pathway and key proteins were verified by Western blotting. Results Cardiac ultrasound and pathology staining showed that hydroxy-a-sanshool had protective effect on the heart of DCM mice. Label-free quantitative proteomic analysis was carried out between DCM + SAN group and DCM group, and 160 differential pro-teins were identified by proteomics, in which 127 proteins were up-regulated and 33 proteins were down regulated ; GO secondary functional annotations showed the biological process, molecular function and cellular component; KEGG enrichment analysis showed that cAMP signaling pathway was the most abundant; protein interaction network showed that PKA as the central node interacted with many proteins in the cAMP signaling pathway. Western blot showed that the relative expression of с AMP, PKA protein in DCM group was significantly lower than that in CON group ( P < 0. 05 ) , while the relative expression of cAMP, PKA protein in DCM + SAN group was significantly higher than that in DCM group ( P < 0. 05 ) . Conclusions Hydroxy-a-sanshool has protective effect on heart function of mice with diabetes, which plays a role through cAMP signaling pathway.

The protective effect of naringin on cardiac injury in diabetic rats via activating Maxi K / 中国药理学通报

Aim To investigate the protective effect of naringin ( NA) on diabetic cardiomyopathy by activating the large conduction Ca2+ activated K4 channels (Maxi K ).Methods SD rats were fed with high-fat diet combined with intraperitoneal injection of strepto- zotocin (STZ) to establish a diabetic rat model.Then the rats were randomly divided into model group ( DCM) , naringin group ( NA) and naringin + Maxi K-specific inhibitor group ( NA + PAX) , with 8 rats in each group.Hats in treatment group received administration for 12 weeks and blood glucose was monitored regularly during experiments.The changes of cardiac function, morphology and fibrosis were detected after the treatment.The changes of cx and (3 subunits of Maxi K in heart were detected.Results Cardiac ultrasound results showed that NA could partially restore the cardiac function of rats.However, the cardiac protec tive function of NA was significantly reduced in diabetic rats after Maxi K was specifically blocked.Fibrosis analysis showed that the expression of collagen and fi- bronectin in rats could be decreased after NA treatment, which could be partially reversed by PAX.Western blot results showed that the expression of Maxi K a and p-subunit decreased in DCM group, but there was no significant change after NA treatment.Conclusions NA has a cardioprotective effect on diabetic rats by promoting the opening of the Maxi K channel on the membrane surface rather than increasing its expression.

Parsimonious model for blood glucose level monitoring in type 2 diabetes patients.

To establish the parsimonious model for blood glucose monitoring in patients with type 2 diabetes receiving oral hypoglycemic agent treatment. One hundred and fifty-nine adult Chinese type 2 diabetes patients were randomized to receive rapid-acting or sustained-release gliclazide therapy for 12 weeks. Their blood glucose levels were measured at 10 time points in a 24 h period before and after treatment, and the 24 h mean blood glucose levels were measured. Contribution of blood glucose levels to the mean blood glucose level and HbA1c was assessed by multiple regression analysis. The correlation coefficients of blood glucose level measured at 10 time points to the daily MBG were 0.58-0.74 and 0.59-0.79, respectively, before and after treatment (P<0.0001). The multiple stepwise regression analysis showed that the blood glucose levels measured at 6 of the 10 time points could explain 95% and 97% of the changes in MBG before and after treatment. The three blood glucose levels, which were measured at fasting, 2 h after breakfast and before dinner, of the 10 time points could explain 84% and 86% of the changes in MBG before and after treatment, but could only explain 36% and 26% of the changes in HbA1c before and after treatment, and they had a poorer correlation with the HbA1c than with the 24 h MBG. The blood glucose levels measured at fasting, 2 h after breakfast and before dinner truly reflected the change 24 h blood glucose level, suggesting that they are appropriate for the self-monitoring of blood glucose levels in diabetes patients receiving oral anti-diabetes therapy.

A review of the expression and activity of drug metabolism enzymes in tumorous cells / 药学学报

Tumorous cells are characterized by distinctive metabolic reprogramming and living conditions. Understanding drug metabolizing features in tumor cells will not only favor the estimation of metabolic rate, elimination half life and the assessment of potency, but also facilitate the optimal design of anti-tumor drugs/prodrugs. This article reviewed the expression and activity features of major drug metabolizing enzymes (DMEs) in solid tumorous tissues, such as liver, intestine, breast and lung, and the difference from the correspondingly normal tissues, exemplified by the metabolic properties of some classic antitumor-agents in tumorous tissues. In combination with the data retrieved in vitro tumor cell lines, we discussed the similarities and differences of DMEs expression and function between tumor tissues (in vivo) and tumor cells (in vitro), and proposed the possible factors that cause the differences.

Application of binding spectra in DMIs fungicide screening / 生物工程学报

In order to establish a fast and accurate method for novel DMIs fungicide screening, lanosterol 14alpha-demethylase of Magnaporthe grisea expressed in E. coli was used as target enzyme and the DMI fungicides diniconazole, tebuconazole, triadimenol and triadimefon were used as representative fungicides, the effects of enzyme activity, enzyme purity and concentration on the binding spectra were investigated. The results showed that active enzyme, elimination of interference of other P450s and proper enzyme concentration were necessary for obtaining accurate binding spectra. The Kd values of diniconazole, tebuconazole, triadimenol and triadimefon were 0.143 micromol/L, 0.24 micromol/L, 0.257 micromol/L and 0.307 micromol/L respectively, which significantly correlated to their 120h-EC50 values on the growth of Magnaporthe grisea. The results indicated that the binding spectra of fungicide and lanosterol 14alpha-demethylase can serve as a reliable and fast method for novel fungicide screening.