Integrated metabolomics and network pharmacology study on the mechanism of herbal pair of danggui-kushen for treating ischemia heart disease.

DangGui-KuShen (DK) is a well-known classic traditional Chinese medicine recipe that improves blood circulation, eliminates moisture, and detoxifies, and is frequently used in the treatment of cardiovascular problems. Some protective effects of DK on cardiovascular disease have previously been identified, but its precise mechanism remains unknown. The goal of this study is to combine metabolomics and network pharmacology to investigate DK's protective mechanism in Ischemic Heart Disease(IHD) rat models. A combination of metabolomics and network pharmacology based on UPLC-Q-TOF/MS technology was used in this study to verify the effect of DK on IHD through enzyme-linked immunosorbent assay, HE staining, and electrocardiogram, and it was determined that DK improves the synergistic mechanism of IHD. In total, 22 serum differential metabolites and 26 urine differential metabolites were discovered, with the majority of them involved in phenylalanine, tyrosine, and tryptophan biosynthesis, glycine, serine, and threonine metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, purine metabolism, and other metabolic pathways. Furthermore, using network pharmacology, a composite target pathway network of DangGui and KuShen for treating IHD was created, which is primarily associated to the tumor necrosis factor (TNF) signaling pathway, P53 signaling, and HIF-1 signaling pathways. The combined research indicated that the NF-B signaling pathway and the HIF-1 signaling pathway are critical in DK treatment of IHD. This study clearly confirms and expands on current knowledge of the synergistic effects of DG and KS in IHD.

Characterization of chemical constituents and metabolites in vivo and in vitro after oral administration of Wuteng tablets in rats by UHPLC-Q/TOF-MS.

Waste medicinal plants are widely used in drug production. With the increasing demand for botanical drugs, there is an urgent need to identify new and effective drugs and improve the utilization of medicinal plant resources. Wuteng tablets (WTP) are extracted from the stem of Schisandra chinensis and have a good therapeutic effect on Alzheimer's disease. In this study, a holistic identification strategy based on UHPLC-Q/TOF-MS was developed for the first time to investigate the metabolites and metabolic pathways involved in the in vitro metabolism and liver microsomal incubation and in the in vivo metabolic system of rats after WTP administration. After the oral administration of WTP, 21 metabolites were identified in the serum and 25 metabolites were identified in the urine, of which six were new metabolites; 33 metabolites were inferred from the microsomal metabolites in vitro. The metabolic pathways related to WTP mainly involve demethylation, hydroxylation, dehydroxylation and dehydrogenation. In this study, the metabolites and metabolic pathways of WTP were elucidated via UHPLC-Q/TOF-MS, which provided a basis for an in-depth study of the pharmacodynamic and pharmacotoxicological effects of WTP.

Novel Approach for Rate Transient Analysis of Fractured Wells from Carbonate Reservoirs with Heterogeneous Natural Fractures.

This paper developed a new methodology for rate transient analysis of fractured wells in carbonate reservoirs. Both the heterogeneity and dual-permeability flow behavior are incorporated into the proposed model, and the fractured carbonate reservoir was simulated with a two-zone composite model. In each zone, a traditional dual-porosity model was applied to describe the characteristics of the natural fractures and matrix. With the Laplace transform, we derived the solution of the mathematical model and plotted new type curves for transient rate decline analysis. Then, the flow regimes were divided and analyzed based on the new type curves. The influences of several critical parameters on transient rate response were also examined. A field case was studied further to demonstrate the precision and application of the proposed method. The results show that the new type curves are mainly composed of eight flow stages. The difference in physical properties (k 2,1, η2,1) between the two zones significantly impacts the transition and boundary-dominated flow regimes. When the values of k 2,1 and η2,1 are smaller, the derivative curve of the transition flow stage will move down, and the duration of this stage on the derivative curve is longer, while the duration of the boundary dominant flow stage will decrease. The dimensionless radial radius of the inner zone (r 1D) can significantly influence the transition flow regime. When r 1D is larger, the production rate and its derivative curve of the transition flow stage will move up, and the duration of this stage will be longer. The results also show that the proposed methodology can effectively fit the field production data. This method can be applied in well productivity evaluation for fractured carbonate reservoirs.