Acute lung injury (ALI) is a common clinical condition that badly influences people’s health. Recent studies indicated that Aster tataricus (RA) had potential effects on ALI, but the effective components and their mechanism is not clear. In this study, we found that the Fraction-75 eluted from RA extract could significantly protect the lipopolysaccharide (LPS)-induced ALI in mice, including alleviating the severity of lung pathology, attenuating the pulmonary edema, and reducing the release of inflammatory cells. Further ingredient analyses demonstrated that there were mainly 16 components in it, among which 10 components were collected according to their relative peak area and oral bioavailability. Next, the components-disease targets network suggested that the candidate components had extensive associations with 49 known therapeutic targets of ALI, among which 31 targets could be regulated by more than one component. Herein, GO functional and pathway analysis revealed that the common targets were associated with four biological processes, including the inflammatory response to stimulus, cellular process, chemokine biosynthetic process and immune system process. Furthermore, the ELISA validation indicated that the candidate components in RA extract may protect the LPS-induced ALI mainly through inhibiting the release of inflammatory cytokines and promoting the repair of vascular endothelial.
Asthma is an airway chronic inflammatory disease with significant morbidity, mortality and huge social economic burden. Previous research demonstrated that the root of Aster tataricus (RA) may have the potential to treat asthma, but the efficacy and mechanism were not clear. In this study, preliminary results in vitro showed that Fr-75 eluted from RA extract could not only completely inhibit the tracheal ring contraction raised by KCl in 20 min, but also effectively affect the tracheal ring contraction induced by KCl-, Ach- and His in a concentration-dependent manner (3.91-250 μg/mL). Further results on cells exhibited that Fr-75 could decrease the concentration of intracellular Ca2+ as well. These results revealed the underlying mechanism in vitro that the inhibition of tracheal ring contraction might be due to the decline of the intracellular Ca2+ concentration, which caused by suppressing calcium channel, antagonizing the muscarinic and histamine receptors. Also, results in vivo exhibited that Fr-75 could distinctly ease the symptoms of ovalbumin-sensitized mice, including relieving the pathological injury, increasing the latency to preconvulsive dyspnea and to enhanced pause, reducing the inflammatory cells, chemokines and cytokines in BALF and lung tissue. In general, it could be speculated that RA fraction may attenuate asthma through dilating the tracheal ring contraction and alleviating the lung inflammation simultaneously.
An attempt was made to characterize the pharmacokinetic profiles of Qishen Keli (QSKL) that has been widely proved to be effective in clinical practice. A method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of 25 analytes in rat plasma was developed and validated. Satisfactory chromatographic separation was achieved on an ACQUITY UPLC HSS T3 column with gradient elution using mobile phase consisting of 0.02% aqueous formic acid (A) and acetonitrile fortified with 0.02% formic acid (B), and analyte detection was carried out using polarity-switching multiple reaction monitoring mode. Method validation assays in terms of selectivity, linearity, inter- and intra-day variations, matrix effect, and recovery demonstrated the newly developed method to be specific, sensitive, accurate, and precise. Following the oral administration of QSKL at a single dose, the qualified method was successfully applied for pharmacokinetic investigations in sham and model rats. Mild differences occurred for the pharmacokinetic patterns of most components between those two groups, whereas significant differences were observed for glycyrrhizic acid and glycyrrhetic acid. The obtained findings could provide meaningful information for the clarification of the effective material basis of QSKL.
Polygonum multiflorum (PM) has been used as a tonic and anti-aging remedy for centuries in Asian countries. However, its application in the clinic has been hindered by its potential to cause liver injury and the lack of investigations into this mechanism. Here, we established a strategy using a network pharmacological technique combined with integrated pharmacokinetics to provide an applicable approach for addressing this issue. A fast and sensitive HPLC-QQQ-MS method was developed for the simultaneous quantification of five effective compounds (trans-2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside, emodin-8-O-β-d-glucoside, physcion-8-O-β-d-glucoside, aloe-emodin and emodin). The method was fully validated in terms of specificity, linearity, accuracy, precision, extraction recovery, matrix effects, and stability. The lower limits of quantification were 0.125–0.500 ng/mL. This well-validated method was successfully applied to an integrated pharmacokinetic study of PM extract in rats. The network pharmacological technique was used to evaluate the potential liver injury due to the five absorbed components. Through pathway enrichment analysis, it was found that potential liver injury is primarily associated with PI3K-Akt, MAPK, Rap1, and Ras signaling pathways. In brief, the combined strategy might be valuable in revealing the mechanism of potential liver injury due to PM.
1 June 2016 in China Journal of Chinese Materia Medica
To study the absorption characteristics of Xinshao extracts in Caco-2 cells. In this paper, human colon adenocarcinoma cell line Caco-2 cell model was established, and UPLC-MS method was applied to determinate the contents of five components of Xinshao extracts(albiflorin, gallic acid, caffeic acid, scutellarin and apigenin-7-O-glucronide) in cell lysates. This model was also used to study the effect of different drug concentrations, pH, time and temperature on the absorption of five components, investigate the transport of the five components of Xinshao extracts under the conditions with or without P-glycoprotein inhibitors, and predict the absorption mechanism of these five components in Caco-2 cells. The experimental results showed that the absorption of five components of Xinshao extracts in Caco-2 cells was time-dependent at 37 ℃, and concentration-dependent in the range of 0.5-12.5 g•L⁻¹, with a passive diffusion mechanism. At the pH of 4-7.4, the absorption of caffeic acid, scutellarin and apigenin-7-O-glucronide was significantly declined with the increase of pH(P<0.05). At the temperature of 4 to 37 ℃, the absorption of caffeic acid was declined with the increase of temperature, while the absorption of other four components was increased with the increase of temperature. Compared with the control group, caffeic acid and scutellarin cell absorption was significantly higher(P<0.05) after treatment with P-glycoprotein inhibitors(verapamil and cyclosporine A). The results indicated that, the absorption mechanism of five components in Xinshao extracts may be of passive diffusion, and the caffeic acid and scutellarin may be the substrates of P-glycoprotein.