Comparative Study of Binding Behaviors of Cyanidin, Cyanidin-3-Galactoside, Peonidin with Tyrosinase.

Cyanidin, peonidin and cyanidin-3-galactoside are the common anthocyanins with a variety of biological activities. Tyrosinase is a speed-limiting enzyme associated with melanin production. The inhibition of tyrosinase activity can prevent melanin disease while contributing to whitening. The interaction behaviors of the three anthocyanins against tyrosinase have been discussed in this paper. Cyanidin has strongest inhibitory effect on tyrosinase, and then peonidin, cyanidin-3-galactoside. Furthermore, the inhibition of tyrosinase by the three anthocyanins is mixed modes. The three anthocyanins can induce the static fluorescence quenching of tyrosinase. Cyanidin exhibits strongest binding affinity on tyrosinase, and then peonidin, cyanidin-3-galactoside based on Ka values obtain by fluorescence analysis. The binding of all anthocyanin to tyrosinase induce its conformation changes. According to molecular docking and fluorescence studies, they bind to tyrosinase by hydrogen bond and van der Waals force. In addition, the optimal modes of the three anthocyanins with tyrosinase are predicated by molecular docking. This work emphasizes that cyanidin, peonidin and cyanidin-3-galactoside may be potential drugs for the treatment of diseases caused by melanin.

Interaction mechanism of pelargonidin against tyrosinase by multi-spectroscopy and molecular docking.

The interaction mechanism of pelargonidin (PG) with tyrosinase was investigated by multi-spectroscopy and molecular docking. As a result, PG had strong inhibitory activity on tyrosinase with the IC50 value of 41.94 × 10-6  mol·L-1 . The inhibition type of PG against tyrosinase was determined as a mixed-mode. Meanwhile, the fluorescence of tyrosinase was quenched statically by PG, and accompanied by non-radiative energy transfer. The three-dimensional (3-D) fluorescence, ultraviolet-visible spectroscopy (UV-Vis) and circular dichroism spectroscopies (CD) indicated that PG decreased the hydrophobicity of the micro-environment around tryptophan (Trp) and tyrosine (Tyr), which resulted in the conformational change of tyrosinase. In addition, fluorescence and molecular docking analysis indicated that PG bound to tyrosinase via hydrogen bonds (H-bonds) and van der Waals force (vdW force). We herein recommended that PG might be a potential candidate drug for the treatment of melanin-related diseases.

Spectroscopic studies and molecular docking on the interaction of delphinidin-3-O-galactoside with tyrosinase.

The inhibitory effects of delphinidin-3-O-galactoside (DG) on the activities of tyrosinase (EC 1.14.18.1) (TY) from the edible Agaricus bisporus mushroom were investigated by enzyme kinetics, multispectroscopic methods, and molecular docking. As a result, DG showed strong inhibition on TY with the IC50 of 34.14 × 10-6  mol L-1 . The inhibition mode of DG against TY was mixed type with α values of 5.09. The binding constant Ka and related thermodynamic parameters at the three different temperatures showed that the fluorescence quenching of TY by DG was static quenching. Synchronous fluorescence, three-dimensional fluorescence, ultraviolet-visible spectroscopy, and circular dichroism spectroscopies confirmed that the conformation or microenvironment of the TY protein were changed after binding with DG. Molecular docking revealed that DG had strong binding affinity to TY through hydrogen bonding and van der Waals force, and the results were consistent with the fluorescence data. Our findings suggested that DG may be potential TY inhibitor.

Inhibitory effects of astilbin, neoastilbin and isoastilbin on human cytochrome CYP3A4 and 2D6 activities.

Astilbin, neoastilbin and isoastilbin are three flavonoid isomers from Smilacis glabrae Roxb. (S. glabrae). Several studies have shown that consumption of flavonoids can increase the risk of food/drug-drug interaction by affecting the activities of human cytochrome CYP3A4 and 2D6. In the present study, an ultrahigh-performance liquid chromatography and triple quadrupole mass spectrometry method was developed for the determination of the interaction between three flavonoid isomers and two CYPs. Under the optimized reaction conditions, the Km values were 18.9 and 36.4 µM and the Vmax values were 0.02 and 0.20 µM/min for CYP3A4 and 2D6 in vitro, respectively. Astilbin showed the strongest inhibition on CYP3A4, followed by isoastilbin and neoastilbin with IC50 values of 2.63, 3.03 and 6.51 µM. Neoastilbin showed the strongest inhibition on CYP2D6, followed by isoastilbin and astilbin, with IC50 values of 1.48, 11.87 and 14.16 µM, respectively. The three isomers showed reversible inhibition on both enzymes. Neoastilbin and astilbin were noncompetitive type for CYP3A4 and 2D6, isoastilbin was a mixture and noncompetitive type for CYP3A4 and 2D6, respectively. Our study suggests that the three isomers may increase the risk of food/drug-drug interactions by affecting the activities of CYP3A4 and 2D6.

Simultaneous ultra-performance liquid chromatography-tandem mass spectrometry determination of six components in rat plasma after oral administration of Smilacis glabrae Roxb. extract.

In this study, an accurate and reliable method of ultra-performance liquid chromatography coupled with a triple-quadrupole tandem mass spectrometry was firstly developed and fully validated for the simultaneous determination of epicatechin, neoastilbin, astilbin, isoastilbin, engeletin and resveratrol in rat plasma after administration of Smilacis glabrae Roxb. extract. Naringenin was used as an internal standard (IS). The analyte and IS were separated on a C18 column by gradient elution with a mobile phase of acetonitrile-0.3% acetic acid at a flow rate of 0.25 mL/min for a total run time of 8 min. The method was validated in terms of selectivity, linearity, precision, accuracy, extraction recovery, matrix effect and stability. The developed method was successfully applied to determine the main pharmacokinetic parameters of six components in rat plasma.

Coupled effects of local movement and global interaction on contagion.

By incorporating segregated spatial domain and individual-based linkage into the SIS (susceptible-infected-susceptible) model, we propose a generalized epidemic model which can change from the territorial epidemic model to the networked epidemic model. The role of the individual-based linkage between different spatial domains is investigated. As we adjust the timescale parameter τ from 0 to unity, which represents the degree of activation of the individual-based linkage, three regions are found. Within the region of 0 < τ < 0.02 , the epidemic is determined by local movement and is sensitive to the timescale τ . Within the region of 0.02 < τ < 0.5 , the epidemic is insensitive to the timescale τ . Within the region of 0.5 < τ < 1 , the outbreak of the epidemic is determined by the structure of the individual-based linkage. As we keep an eye on the first region, the role of activating the individual-based linkage in the present model is similar to the role of the shortcuts in the two-dimensional small world network. Only activating a small number of the individual-based linkage can prompt the outbreak of the epidemic globally. The role of narrowing segregated spatial domain and reducing mobility in epidemic control is checked. These two measures are found to be conducive to curbing the spread of infectious disease only when the global interaction is suppressed. A log-log relation between the change in the number of infected individuals and the timescale τ is found. By calculating the epidemic threshold and the mean first encounter time, we heuristically analyze the microscopic characteristics of the propagation of the epidemic in the present model.

Evolutionary dynamics in financial markets with heterogeneities in investment strategies and reference points.

In nature and human societies, the effects of homogeneous and heterogeneous characteristics on the evolution of collective behaviors are quite different from each other. By incorporating pair pattern strategies and reference point strategies into an agent-based model, we have investigated the effects of homogeneous and heterogeneous investment strategies and reference points on price movement. In the market flooded with the investors with homogeneous investment strategies or homogeneous reference points, large price fluctuations occur. In the market flooded with the investors with heterogeneous investment strategies or heterogeneous reference points, moderate price fluctuations occur. The coexistence of different kinds of investment strategies can not only refrain from the occurrence of large price fluctuations but also the occurrence of no-trading states. The present model reveals that the coexistence of heterogeneous populations, whether they are the individuals with heterogeneous investment strategies or heterogeneous reference points of stock prices, is an important factor for the stability of the stock market.

Determination and Pharmacokinetics of Okanin in Rat Plasma by UltraHigh Performance Liquid Chromatography Coupled with Triple-Quadrupole Tandem Mass Spectrometry.

Okanin is a major flavonoid found in Coreopsis tinctoria Nutt., arousing huge interest recently for its considerable biological characteristics including antioxidant, antineurotoxic, and antidiabetic activities. An ultrahigh performance liquid chromatography triple-quadrupole tandem mass spectrometry (UPLC-MS) was successfully used to determine okanin in rat plasma after oral administration of okanin. Bavachalcone acted as an internal standard (IS). By gradient elution, IS and analyte were separated on a C18 column for 7 min at a flow rate of 0.25 mL/min with acetonitrile-0.1% acetic acid mobile phase. The stability, matrix effect, extraction recovery, accuracy, precision, linearity, and selectivity of the method were firstly demonstrated. The major pharmacokinetic parameters of okanin in rat plasma were then measured using the developed UPLC-MS method. An UPLC-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was finally established to obtain the specific and accurate mass of okanin in rat plasma after oral administration, and its proposed fragmentation was further elaborated.

Sec-O-glucosylhamaudol suppressed inflammatory reaction induced by LPS in RAW264.7 cells through inhibition of NF-κB and MAPKs signaling.

As a major bioactive compound from the Saposhnikovia divaricata (Turcz.) Schischk, sec-O-glucosylhamaudol (SOG), has been reported to have anti-nociceptive activity and high 5-lipoxygenase (5-LOX) activity. Nevertheless, the mechanism of the potential anti-inflammatory effects of SOG is unclear. The anti-inflammatory impacts of SOG in RAW 264.7 cell lines stimulated by LPS were explored in the present study. It was found that SOG dose-dependently reduced the emergence of inflammation cytokines, such as IL-6 and TNF-α in Raw264.7 murine macrophages stimulated by LPS. Real-time PCR assay demonstrated the SOG dose-dependently inhibited transcription of these cytokines as well. In addition, it was also found that NF-κB activation and MAPKs phosphorylation including p38, JNK and ERK1/2 induced by LPS were suppressed by SOG. Due to its anti-inflammatory activity, our results suggest that SOG might have therapeutic effects on inflammatory disease, such as acute lung injury or rheumatoid arthritis.

Curve fitting of the corporate recovery rates: the comparison of Beta distribution estimation and kernel density estimation.

Recovery rate is essential to the estimation of the portfolio's loss and economic capital. Neglecting the randomness of the distribution of recovery rate may underestimate the risk. The study introduces two kinds of models of distribution, Beta distribution estimation and kernel density distribution estimation, to simulate the distribution of recovery rates of corporate loans and bonds. As is known, models based on Beta distribution are common in daily usage, such as CreditMetrics by J.P. Morgan, Portfolio Manager by KMV and Losscalc by Moody's. However, it has a fatal defect that it can't fit the bimodal or multimodal distributions such as recovery rates of corporate loans and bonds as Moody's new data show. In order to overcome this flaw, the kernel density estimation is introduced and we compare the simulation results by histogram, Beta distribution estimation and kernel density estimation to reach the conclusion that the Gaussian kernel density distribution really better imitates the distribution of the bimodal or multimodal data samples of corporate loans and bonds. Finally, a Chi-square test of the Gaussian kernel density estimation proves that it can fit the curve of recovery rates of loans and bonds. So using the kernel density distribution to precisely delineate the bimodal recovery rates of bonds is optimal in credit risk management.