The potential mechanism of Astragali Radix in the treatment of children with nephrotic syndrome.

BACKGROUND: The molecular mechanism of Astragali Radix in the treatment of children with nephrotic syndrome (NS) is unclear. This study aimed to use network pharmacology to explore this potential mechanism. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to identify the main active ingredients of Astragali Radix. The PharmMapper, Online Mendelian Inheritance in Man (OMIM), and GeneCards databases were then used to identify the active ingredients of Astragali Radix. The String database and Cytoscape software were used to construct the protein-protein network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID Database. RESULTS: In the TCMSP Database, a total of 20 chemical constituents of Astragali Radix were screened. After removing the duplicates and false positive genes, 394 targets of these active ingredients were obtained from PharmMapper. By comparing the NS-related genes in the GeneCards and OMIM Databases, a total of 39 potential NS-related targets were ultimately identified. The protein-protein-interaction network included 39 nodes and 366 edges. The top 5 proteins were albumin (ALB), serine/threonine kinase (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), and matrix metallopeptidase 9 (MMP9). The GO analysis showed that the target genes were mainly involved in biological processes (e.g., signal transduction, the positive regulation of cell proliferation, and the positive regulation of migration). The cellular components included a plasma membrane, extracellular exosome, and extracellular space. The molecular functions included protein binding, zinc-ion binding, protein tyrosine kinase activity, and enzyme binding. The KEGG analysis showed that the treatment of NS by Astragali Radix mainly involved pathways in cancer, proteoglycans in cancer, the phosphatidylinositol 3-kinase and protein kinase B (PI3K-Akt) signaling pathway, the rennin-angiotensin-system (Ras) signaling pathways, and Forkhead box protein O1 (FoxO) signaling pathways. CONCLUSIONS: In the present study, the network pharmacology method was used to explore the potential targets and pathways of Astragali Radix in the treatment of NS. We also provided future research directions for the treatment of NS with a complex pathogenesis.

Steroidal constituents from Helleborus thibetanus and their cytotoxicities.

Thibetanosides E-H (1-4), four new steroidal constituents including three rare sulfonates (2-4), were isolated from the roots and rhizomes of Helleborus thibetanus, together with nine known steroidal compounds (5-13). Their structures were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical evidence. In this study, compounds 2-13 were evaluated for their cytotoxic activities against HCT116, A549 and HepG2 tumor cell lines in vitro. Among them, compound 8 (thibetanoside C) showed cytotoxicities against A549 cells(IC50 39.6 ± 1.9 µmol·L-1) and HepG2 cells(IC50 41.5 ± 1.1 µmol·L-1), respectively. Compound 9 (23S, 24S)-24-[(O-ß-D-fucopyranosyl)oxy]-3ß, 23-dihydroxy-spirosta-5, 25(27)-diene-1ß-ylO-(4-O-acetyl- α-L-rhamnopyranosyl)-(1→2)-O-[ß-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside) showed cytotoxicity against HCT116 cells(IC50 33.6 ± 2.1 µmol·L-1).

Five new polyhydroxylated furostanol saponins from the rhizomes of Tupistra chinensis.

Five new polyhydroxylated furostanol saponins were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as tupistrosides J-N (1-5), together with four known furostanol saponins (6-9), on the basis of physico-chemical properties and spectral analysis. Among them, compounds 3 and 5 showed cytotoxicity against human cancer cell lines SW620 with IC50 values of 72.5 ± 2.4 and 77.3 ± 2.5 µmol·L-1, respectively. Compound 4 showed cytotoxicity against human cancer cell line HepG2 with IC50 value of 88.6 ± 2.1 µmol·L-1.

[Efficient method for analyzing absorbed ingredients of traditional Chinese medicine genitana macrophyllae radix].

In present study, a method for analyzing the absorbed ingredients of traditional Chinese medicine QinJiao has been developed. A rat everted gut sac (EGS) model has been established, and the transporting capacity of gut sacs was identified by histological examinations. The ingredients including loganic acid, sweroside, gentiopicroside, and swertiamarian in serosal solution absorbed by active transport of rat everted ileum and jejunum from Qinjiao extraction were determined using an HPLC method. Histological integrality of the gut sacs remains perfect and the active transport activity of them is normal within 45 min of the experiment. The HPLC method employed in this study presents high specificity and good correlation. The relative standard deviation of precision of this method is less than 5.5%. Extraction recovery of samples is more than 90%. And stability of the samples in room temperature is perfect. Eight ingredients of Qinjiao absorbed in serosal solution are identified. Furthermore, concentration of Qinjiao extraction significantly affects accumulated absorption and absorption coefficient of the ingredients. However, there is no significant impact on the accumulated absorption and absorption coefficient by diverse of everted gut sections. From above, the EGS techniques might be an efficient method, which can be employed for investigation of absorbed ingredients of Traditional Chinese Medicines.

[Quickly investigating the absorption ingredients of Gentianae Radix et Rhizoma by SEMAC].

OBJECTIVE: To establish a method for quickly investigating the absorption ingredients which could be used as the index of quality control of Gentianae Radix et Rhizoma. METHOD: The absorption ingredients of Gentianae Radix et Rhizoma were investigated by using the model of in vitro everted intestinal sac (VEIS). The intestinal sac liquors of jejunum and ileum were collected at 6 intervals (15, 30, 45, 60, 90, 120 min) and gentiopicroside, loganin acid, swertiamarin and sweroside were detected by HPLC as the representative marker. The accumulative absorption quantity of gentiopicroside, loganin acid, swertiamarin and sweroside were calculated, respectively. RESULT: Six components could be detected in intestinal sac. In different concentrations of Gentianae Radix et Rhizoma, gentiopicroside and swertiamarin in various intestinal sections were the linear absorption (R2 > 0.9), conformed to zero order absorption rate. In jejunum the constant of absorption rate (Ka) of gentiopicroside and swertiamarin increased with the raised dosage of Gentianae Radix et Rhizoma (P < 0.05), which indicated a passive absorption manner, and the value of Ka of high and middle dosage of those in ileum were higher than that of low dosage, and the difference of Ka between high and middle dosage were not significant, which indicated a positive absorption manner. The Ka of high and middle dosage of sweroside in ileum and jejunum were higher than that of low dosage (P < 0.05), and the difference of Ka between high and middle dosage were not significant, which indicated a positive absorption manner. The Ka of loganin acid in jejunum and ileum increased along with the raised dosage of Gentianae Radix et Rhizoma (P < 0.05), which indicated a passive absorption manner. CONCLUSION: SEMAC could be used as a tool to investigate the absorption ingredients of Gentianae Radix et Rhizoma. Drug in intestine sac was selective, and the absorption part of intestine was also different.

[Quick finding of absorption ingredients of Paeoniae Radix Alba by SEMAC].

OBJECTIVE: To establish a method for quick finding of the absorption ingredients of Paeoniae Radix Alba in order to select the index of quality control. METHOD: The absorption ingredients of three concentration of Paeoniae Radix Alba were investigated with the in vitro-everted intestinal sac (VEIS) model. The intestinal sac fluids of jejunum and ileum were collected in different time and detected by HPLC. The accumulative absorption quantity of albiflorin and paeoniflorin were calculated, respectively. RESULT: Five ingredients could be detected. In different concentrations of Paeoniae Radix Alba, albiflorin and paeoniflorin in various intestinal sections were the linear absorption (R2 > 0.9), conformed to the zero order absorption rate. The values of Ka in the jejunum and ileum were increased along with the raised dosage of the Paeoniae Radix Alba (P < 0.05), indicating a passive absorption manner. CONCLUSION: SEMAC could be used as a tool to find the absorption ingredients of Paeoniae Radix Alba. Compared with the jejunum, the ileum could provide the more absorption information. It was showed that the optimal detecting time was 60 min.