α-Glucosidase inhibitory effect of anthocyanins from Cinnamomum camphora fruit: Inhibition kinetics and mechanistic insights through in vitro and in silico studies.

α-Glucosidase inhibitors are widely used to suppress postprandial glycemia in the treatment of type 2 diabetes mellitus. The present study evaluated the in vitro α-glucosidase inhibitory activity of three major pigment constituents of Cinnamomum camphora fruit, namely cyanidin, cyanidin 3-rutinoside, and cyanidin-3-O-glucoside. We found that cyanidin exerted strong inhibitory activity on α-glucosidase, with IC50 of 5.293 × 10-3 mM, whereas cyanidin 3-rutinoside and cyanidin-3-O-glucoside did not show inhibitory activity on α-glucosidase. The inhibitory activity of cyanidin was stronger than that of acarbose (IC50 1.644 mM), the current most commonly used drug for postprandial glycemia. Kinetic analysis indicated that cyanidin inhibited α-glucosidase through competition, with a Ki value of 0.0183 mM. Fluorescence spectrum titration showed only one binding site between cyanidin and α-glucosidase, and the binding constant was calculated. Further, molecular docking was conducted to simulate the binding interactions between cyanidin and α-glucosidase. Cyanidin was found to interact with several residues close to the catalytic site of α-glucosidase through π-π stack interaction and hydrogen bonds. The calculated binding energy of the cyanidin and enzyme complex was -105.031 kJ/mol. Molecular simulation and calculation showed that the van der Waals force played an essential role in the binding of α-glucosidase and cyanidin.

The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells.

Abnormalities in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway are commonly observed in human cancers and contribute to chemotherapy resistance. Combination therapy, involving the use of molecular targeted agents and traditional cytotoxic drugs, may represent a promising strategy to lower resistance and enhance cytotoxicity. Here, we demonstrate the efficacy of an Akt inhibitor, MK-2206, in increasing the cytotoxic effect of either paclitaxel (Taxol) or cisplatin against the ovarian cancer cell lines SKOV3 (with constitutively active Akt) and ES2 (with inactive Akt). Sequential treatment of Taxol or cisplatin, followed by MK-2206, induced a synergistic inhibition of cell proliferation and effectively promoted cell death, either by inhibiting the phosphorylation of Akt and its downstream effectors 4E-BP1 and p70S6K in SKOV3 cells or by restoring p53 levels, which were downregulated after Taxol or cisplatin treatment, in ES2 cells. Combination treatment also downregulated the pro-survival protein Bcl-2 in both SKOV3 and ES2 cells, which may have contributed to cell death. In addition, we discovered that Taxol/MK-2206 or cisplatin/MK-2206 combination treatment resulted in significant enhancement of intracellular reactive oxygen species (ROS) induced by MK-2206, in both SKOV3 and ES2 cells; however, MK-2206-induced growth inhibition was reversed by a ROS scavenger only in ES2 cells. MK-2206 also suppressed DNA repair, particularly in SKOV3 cells. Taken together, our results demonstrate that the Akt inhibitor MK-2206 enhances the efficacy of cytotoxic agents in both Akt-active and Akt-inactive ovarian cancer cells but through different mechanisms.

Effects of a new nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) on nitrate and potassium leaching in two soils.

In this study, soil column was used to study the new nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) on nitrate (NO3(-)-N) and potassium (K) leaching in the sandy loam soil and clay loam soil. The results showed that DMPP with ammonium sulphate nitrate (ASN) ((NH4)2SO4 and NH4NO3) or urea could reduce NO3(-)-N leaching significantly, whereas ammonium (NH4(+)-N) leaching increased slightly. In case of total N (NO3(-)-N+NH4(+)-N), losses by leaching during the experimental period (40 d) were 37.93 mg (urea), 31.61 mg (urea+DMPP), 108.10 mg (ASN), 60.70 mg (ASN+DMPP) in the sandy loam soil, and 30.54 mg (urea), 21.05 mg (urea+DMPP), 37.86 mg (ASN), 31.09 mg (ASN+DMPP) in the clay loam soil, respectively. DMPP-amended soil led to the maintenance of relatively high levels of NH4(+)-N and low levels of NO3(-)-N in soil, and nitrification was slower. DMPP supplementation also resulted in less potassium leached, but the difference was not significant except the treatment of ASN and ASN+DMPP in the sandy loam soil. Above results indicate that DMPP is a good nitrification inhibitor, the efficiency of DMPP seems better in the sandy loam soil than in the clay loam soil and lasts longer.

[Effects of DMPP-compound fertilizer on greenhouse celery growth and nutritional quality].

A field study with greenhouse celery (Apium graveolens L. ) showed that compared with basal application of ordinary compound fertilizer, one-time basal application of DMPP-compound fertilizer ( ENTEC , 12-12-17) at the rates of 67. 5 kg N x hm(-2) and 54. 0 kg N x hm(-2) increased the yield by 5. 78% and 10. 14% , respectively. The application of ENTEC also improved the nutritional quality of edible parts, e. g. , the Vc, amino acid, soluble sugar, N and P contents increased, while nitrate content decreased. Compared with basal plus side dressing applications, appropriately reducing the application rate and times of ENTEChad more beneficial effects on celery yield and quality, and reduced the production costs. ENTEC could suppress the transformation of soil NH4+ -N to NO3 - -N effectively, and thus, its application could retain soil residual N more in NH4+ -N than in NO3- -N form after celery harvested, resulting in a reduction of nitrate leaching.