Pharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in rats.

BACKGROUND: Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. METHODS: An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods. RESULTS: Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus. CONCLUSION: The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.

Synergistic antifungal activity of berberine derivative B-7b and fluconazole.

Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells' self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections.

[Near-infrared spectroscopy technology for online monitoring of the column separation and purification process of active components of Centella asiatica L. Urban].

The present paper is to study and develop a method for online monitoring of the column separation and purification process of active components that are madecassoside and asiaticoside of Centella asiatica L. Urban using near-infrared (NIR) spectroscopy technology. After collecting 50%-ethanol eluant, we detected their NIR spectra and developed the high performance liquid chromatography (HPLC) assay method of active components. Then, partial least square (PLS) was used to develop linear correlation between their NIR spectra and contents. During modeling, correlation coefficient (R2) and root mean square errors of cross-validation (RMSECV) were regarded as the indexes to select optimal wavenumbers and preprocessing methods. The optimal wavenumbers of madecassoside and asiaticoside were in the range of 12 000.8-7 499.8 cm(-1) and 12 000.8-9 750.3 cm(-1), respectively; R2 were 96.44 and 96.07, respectively, and RMSECV were 0.084 80 and 0.000 99, respectively. The above developed model was used for online monitoring of the contents of madecassoside and asiaticoside during the column separation and purification process of Centella asiatica L. Urban. The predicted results were satisfactory. This method was proved to be fast, convenient and precise. It can be used in online monitoring and quality control of the manufacturing of madecassoside and asiaticoside.

[Establishment of the model for online monitoring of the column separation and purification process by near-infrared spectroscopy and determination of total ginsenosides in Folium Ginseng].

A method was developed for online monitoring of the constituents of ginsenoside of Folium Ginseng in the column separation and purification process using near-infrared (NIR) spectroscopy technology. Determination method of ginsenoside Rg1, Re and Rb1 was developed by high performance liquid chromatography (HPLC). After collecting 40%-ethanol eluant, their NIR spectra were detected and the contents of Rg1, Re and Rb1 were determined by the above HPLC method. The quantitative analysis models of the above three compounds and the total ginsenosides were established using partial least squares (PLS). During modeling, coefficient of determination (R2) and root mean square errors of cross-validation (RMSECV) were regarded as the indexes to select optimal wave numbers and preprocessing methods. The optimal wave numbers of ginsenoside Rg1, Re, Rb1 and total ginsenosides were all in the range of 12 000. 8 approximately 7499.8 cm-1; R2 were 0.9887, 0. 9603, 0.9905 and 0.9701, respectively; RMSECV were 0.0597, 0.0722, 0.00488 and 0.0755, respectively. A lot of samples, collected during the column separation and purification process of Folium Ginseng extract, were used to validate the predicttion effect of quantitative analysis model of total ginsenosides. As a result, the correlation coefficient of NIR predicted value and HPLC value of total ginsenosides was 0.9928 and the mean prediction recovery was 100.52%, which indicated that the prediction effect of the developed model was satisfactory. This method was proved to be fast, convenient and precise. It can be used for assaying and quality control of total ginsenosides in manufacture.

[Discriminating and quantifying potential adulteration in virgin olive oil by near infrared spectroscopy with BP-ANN and PLS].

In the present paper, the use of near infrared spectroscopy (NIR) as a rapid and cost-effective classification and quantification techniques for the authentication of virgin olive oil were preliminarily investigated. NIR spectra in the range of 12 000 - 3 700 cm(-1) were recorded for pure virgin olive oil and virgin olive oil samples adulterated with varying concentrations of sesame oil, soybean oil and sunflower oil (5%-50% adulterations in the weight of virgin olive oil). The spectral range from 12 000 to 5 390 cm(-1) was adopted to set up an analysis model. In order to handle these data efficiently, after pretreatment, firstly, principal component analysis (PCA) was used to compress thousands of spectral data into several variables and to describe the body of the spectra, and the analysis suggested that the cumulate reliabilities of the first six components was more than 99.999%. Then ANN-BP was chosen as further research method. The six components were secondly applied as ANN-BP inputs. The experiment took a total of 100 samples as original model examples and left 52 samples as unknown samples to predict. Finally, the results showed that the 52 test samples were discriminated accurately. And the calibration models of quantitative analysis were built using partial-least-square (PLS). The R values for PLS model are 98.77, 99.37 and 99.44 for sesame oil, soybean oil and sunflower oil respectively, the root mean standard errors of cross validation (RMSECV) are 1.3, 1.1 and 1.04 respectively. Overall, the near infrared spectroscopic method in the present paper played a good role in the discrimination and quantification, and offered a new approach to the rapid discrimination of pure and adulterated virgin olive oil.

[Studies on interaction of sinafloxacin with bovine serum albumin and effect of the coexistent metal ions on the reaction].

Serum albumin is the most abundant protein in plasma. It can bind with many intrinsic and extrinsic materials. The study of the interaction between serum albumin and drugs is a very important task in life science and chemistry. Quinolone drug is a kind of antibacterial drugs which have been used widely in clinical medicine, but its pharmacology and toxicology still have to be studied further. Sinafloxacin is a new quinolone antibiotics. The interaction between sinafloxacin and bovine serum albumin (BSA) at different temperatures and pH was investigated by fluorescence and UV absorption spectroscopy. The experimental results demonstrate that the fluorescence quenching of BSA by sinafloxacin is a result of the formation of sinafloxacin-BSA complex and the quenching mechanism is mainly static quenching. The interaction association constants of BSA and sinafloxacin were determined from the double reciprocal Lineweaver-Burk plot. The binding distance(r = 3.64 Rnm) and energy transfer efficiency (E = 0.163) between donor (BSA) and acceptor (sinafloxacin) were obtained based on Förster's non-radiative energy transfer theory. There is a strong interaction between sinafloxacin and BSA. From thermodynamic coordination it can be judged that the binding force between sinafloxacin and BSA is mainly electro-static force. The effect of sinafloxacin on the conformation of BSA was analyzed by synchronous fluorescence spectrometry and three-dimensional fluorescence spectrometry. The emission maximum of tyrosine residues does not show a significant shift, while the small blue shift of tryptophan residues indicates that the hydrophobicity of microenvironment was increased. In addition, in the plasma, there are some metal ions, which can participate in many important vital actions and affect the reactions of the drugs with the serum albumins. So the effect of Cu(II), Fe(III), Zn( II) and Mg(II) on the binding constant of sinafloxacin to BSA was also discussed and it was shown that the interaction between BSA and sinafloxacin was decreased. In short, the results offer a reference for the studies on the biological effects and action mechanism of sinafloxacin with albumins in vivo.