Active ingredients Isorhamnetin of Croci Srigma inhibit stomach adenocarcinomas progression by MAPK/mTOR signaling pathway.

Gastric cancer (GC) remains the third leading cause of cancer-related mortality in the world, and ninety-five percent of GC are stomach adenocarcinomas (STAD). The active ingredients of Croci Stigma, such as Isorhamnetin, Crocin, Crocetin and Kaempferol, all have antitumor activity. However, their chemical and pharmacological profiles remain to be elusive. In this study, network pharmacology was used to characterize the action mechanism of Croci Stigma. All compounds were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database, and active ingredients were selected by their oral bioavailability and drug-likeness index. The targets of Croci Stigma active ingredients were obtained from the traditional Chinese medicine integrated database (TCMID), whereas the related genes of STAD were obtained from DisGeNET platform. Cytoscape was used to undertake visual analyses of the Drug Ingredients-Gene Symbols-Disease (I-G-D) network, and 2 core genes including MAPK14, ERBB3 were obtained, which are the predicted targets of isorhamnetin (IH) and quercetin, respectively. Data analysis from TCGA platform showed that MAPK14 and ERBB3 all upregulated in STAD patients, but only the effect of MAPK14 expression on STAD patients' survival was significant. Molecular docking showed that IH might affect the function of MAPK14 protein, and then the underlying action mechanisms of IH on STAD were experimentally validated using human gastric cancer cell line, HGC-27 cells. The results showed that IH can inhibit cell proliferation, migration, clonal formation, and arrest cell cycle, but promote the apoptosis of HGC-27 cells. qRT-PCR data demonstrated that IH downregulated the MAPK14 mRNA expression and EMT related genes. WB results showed that IH regulates MAPK/mTOR signaling pathway. These findings suggest that IH has the therapeutic potential for the treatment of STAD.

Asperorydines N-P, three new cyclopiazonic acid alkaloids from the marine-derived fungus Aspergillus flavus SCSIO F025.

Three new tricyclic cyclopiazonic acid (CPA) related alkaloids asperorydines N-P (1-3), together with six known compounds (4-9) were isolated and characterized from the fungus Aspergillus flavus SCSIO F025 derived from the deep-sea sediments of South China Sea. The structures including absolute configurations of 1-3 were deduced from spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism (ECD). All compounds were evaluated for the antioxidative activities against DPPH, cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), and antimicrobial activities. Compound 9 showed significant radical scavenging activities against DPPH with an IC50 value of 62.23 µM and broad-spectrum cytotoxicities against four tumor cell lines with IC50 values ranging from 24.38 to 48.28 µM. Furthermore, compounds 4-9 exhibited weak antimicrobial activities against E scherichia coli, and compound 9 also showed antibacterial activity against Bacillus thuringiensis, Micrococcus lutea, Staphylococcus aureus, Bacillus subtilis, Methicillin resistant Staphylococcus aureus.

Use of ascorbate-rich dialysate to attenuate oxidative stress in maintenance hemodialysis patients.

BACKGROUND: Oxidative stress exists in uremic milieu, particularly in maintenance hemodialysis (MHD) patients, and accounts for certain long-term complications. Yet little is known about whether supplementation of ascorbic acid (vitamin C, or vitC) via extracorporeal circuit has substantial effects on minifying oxidative impairment. SUBJECTS AND METHODS: The entire experiment consisted of three sections: 1) Practicing ascorbate dialysate among 8 MHD patients in a single dialysis session, compared with a conventional hemodialysis session and another one with intravenous injection of vitC. In each session, oxidative stress markers--namely, plasma total ascorbic acid (TAA), ratio of dehydroascorbic acid (DHAA) to TAA (DHAA/TAA), vitamin E (vitE), and malondialdehyde (MDA)--in both plasma and erythrocytes were measured. 2) A relatively long-term application of ascorbate dialysate in 12 of 23 MHD patients, who were randomly allocated to experimental group (n = 12), and control group (n = 11). Oxidative stress markers and main hematological and biochemical indices were determined at the beginning and end of the period. 3) Application of ascorbate dialysate in 10 MHD patients with intravenous iron treatment, performed in similar procedures as section 1. In addition to determining the aforementioned oxidative stress markers, area under the curve (AUC0-180 min) of ratio of plasma MDA to cholesterol (MDA:Cho) was calculated to evaluate the extent of lipoperoxidation. RESULTS: 1) Plasma TAA gradually decreased during dialysis, whereas a mild increase appeared in MDA. A protruding TAA concentration peak, as well as an extreme DHAA/TAA reduction, followed the injection of vitC, but soon a precipitous fall in DHAA/TAA ensued. Stable plasma TAA and slightly raised vitE were observed when applying ascorbate dialysate. 2) Plasma TAA augmented (27.4 +/- 13.3 vs. 16.8 +/- 9.5 mg/dL, P < .05) and plasma low-density lipoprotein (oxLDL) became two-thirds of baseline data (32.6 +/- 25.2 vs. 83.8 +/- 56.5 micromol/L, P < .05) in the experimental group, whereas oxLDL in the control group reduced quantitatively but not significantly in statistics. (3) As iron sucrose was infused, the decline of TAA and ascending of MDA would be abated not only by intravenous drop of vitC, but also by ascorbate dialysate; however, TAA or MDA curve manifested totally distinguished in the two modalities. AUC0-180 min in ascorbate dialysate group was significantly less than that in control group (400.25 +/- 28.54 vs. 487.25 +/- 109.82). CONCLUSION: Plasma ascorbic acid diminished a great deal during hemodialysis, and at the same time oxidative stress formed and intensified, which will be exacerbated by a remedy of frequent intravenous iron. Ascorbate supplementation, by means of either infusion or extracorporeal circuit, can lessen the loss and therefore attenuate oxidative stress. The latter pattern takes the advantage of retaining the approximate internal balance instead of exquisite change in vivo due to administration of intravenous vitC.