Uncovering the anti-proliferation mechanism and bioactive compounds in red kidney bean coat against B16-F10 melanoma cells by metabolomics and network pharmacology analysis.

In this study, coat (RKBC) and kernel (RKBK) extracts of red kidney bean were prepared, and their chemical compositions and potential anti-cancer activity against B16-F10 cells were evaluated. Then the anti-proliferation mechanisms of the active RKBC extract were investigated by flow cytometry analysis, cellular metabolomics, network pharmacology and western blotting. The RKBC extract inhibited B16-F10 cell proliferation and migration in a dose-dependent manner. Further analysis showed that RKBC induced G1 and G2/M phase arrest, and triggered apoptosis and vacuolization. Mechanistically, RKBC significantly increased the cellular content of cGMP, decreased the levels of AKT1/2/3 and cleaved-MMP2, and up-regulated the expression of Bcl-xl. Besides, network pharmacology revealed that RKBC potentially influenced the cell cycle via the regulation of CDK2 and CDK4. Finally, quercetin might serve as the major active component in the RKBC extract. In conclusion, our study showed the potential of the RKBC extract for the prevention or treatment of melanoma.

Quantitative structure-hydrophobicity relationships of molecular fragments and beyond.

Quantitative structure-property relationship (QSPR) models were firstly established for the hydrophobic substituent constant (πX) using the theoretical descriptors derived solely from electrostatic potentials (EPSs) at the substituent atoms. The descriptors introduced are found to be related to hydrogen-bond basicity, hydrogen-bond acidity, cavity, or dipolarity/polarizability terms in linear solvation energy relationship, which endows the models good interpretability. The predictive capabilities of the models constructed were also verified by rigorous Monte Carlo cross-validation. Then, eight groups of meta- or para-disubstituted benzenes and one group of substituted pyridines were investigated. QSPR models for individual systems were achieved with the ESP-derived descriptors. Additionally, two QSPR models were also established for Rekker's fragment constants (foct), which is a secondary-treatment quantity and reflects average contribution of the fragment to logP. It has been demonstrated that the descriptors derived from ESPs at the fragments, can be well used to quantitatively express the relationship between fragment structures and their hydrophobic properties, regardless of the attached parent structure or the valence state. Finally, the relations of Hammett σ constant and ESP quantities were explored. It implies that σ and π, which are essential in classic QSAR and represent different type of contributions to biological activities, are also complementary in interaction site.

Residue behavior and risk assessment of mixed formulation of imidacloprid and chlorfenapyr in chieh-qua under field conditions.

A simple and rapid method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for the simultaneous determination of imidacloprid and chlorfenapyr residues in chieh-qua. Field trials were designed to investigate the dissipation and terminal residue behavior of the mixed formulation of imidacloprid and chlorfenapyr in chieh-qua in Guangzhou and Nanning areas. Risk assessment was performed by calculating the risk quotient (RQ) values. The developed analytical method exhibited recoveries of 89.9-110.3% with relative standard deviations (RSDs) of 2.8-12.5% at the spiked levels of 0.01, 0.10, and 1.00 mg/kg. The limit of detection (LOD) was 0.003 mg/kg, and the limit of quantification (LOQ) was 0.01 mg/kg for both imidacloprid and chlorfenapyr. It was found that the half-lives of imidacloprid in chieh-qua under field conditions were 3.3 and 3.5 days in Guangzhou and Nanning at a dose of 180 g ai/ha, while the half-lives of chlorfenapyr were 3.3 and 2.6 days, respectively. The terminal residues of imidacloprid and chlorfenapyr were from 0.01 to 0.21 mg/kg and from 0.01 to 0.46 mg/kg, respectively. Results of dietary exposure assessment showed that the RQ values were much lower than 1, indicating that the risk of imidacloprid and chlorfenapyr applied in chieh-qua was negligible to human health under recommended dosage and good agricultural practices. The proposed study would provide guidance for safe and reasonable use of imidacloprid and chlorfenapyr in chieh-qua cultivation in China.