Hepatocellular cancer (HCC) is a lethal malignancy with poor prognosis and easy recurrence. There are few agents with minor toxic side effects that can be used for treatment of HCC. Evodiamine (Evo), one of the major bioactive components derived from fructus Evodiae, has long been shown to exert anti-hepatocellular carcinoma activity by suppressing activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). In addition, in the Nucleotide-Binding Oligomerization Domain 1 (NOD1) pathway, NOD1 could initiate NF-κB-dependent and MAPK-dependent gene transcription. Recent experimental studies reported that the NOD1 pathway was related to controlling development of various tumors. Here we hypothesize that Evo exerts anti-hepatocellular carcinoma activity by inhibiting NOD1 to suppress NF-κB and MAPK activation. Therefore, we proved the anti-hepatocellular carcinoma activity of Evo on HCC cells and detected the effect of Evo on the NOD1 pathway. We found that Evo significantly induced cell cycle arrest at the G2/M phase, upregulated P53 and Bcl-2 associated X proteins (Bax) proteins, and downregulated B-cell lymphoma-2 (Bcl-2), cyclinB1, and cdc2 proteins in HCC cells. In addition, Evo reduced levels of NOD1, p-P65, p-ERK, p-p38, and p-JNK, where the level of IκBα of HCC cells increased. Furthermore, NOD1 agonist γ-D-Glu-mDAP (IE-DAP) treatment weakened the effect of Evo on suppression of NF-κB and MAPK activation and cellular proliferation of HCC. In an in vivo subcutaneous xenograft model, Evo also exhibited excellent tumor inhibitory effects via the NOD1 signal pathway. Our results demonstrate that Evo could induce apoptosis remarkably and the inhibitory effect of Evo on HCC cells may be through suppressing the NOD1 signal pathway in vitro and in vivo.

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Colorectal cancer (CRC) is one of the most difficult cancers to cure. An important prognostic factor is metastasis, which precludes curative surgical resection. Recent evidences show that Evodiamine (EVO) exerts an inhibitory effect on cancer cell apoptosis, migration, and invasion. In this study, we investigated the effects of EVO on the metastasis of CRC cells in vitro and in vivo . In vitro , wound-healing and transwell assay showed that migration and invasion of HT-29 and HCT-116 CRC cells were inhibited significantly by EVO. Western blot and RT-PCR showed that EVO reduced the expression of matrix metalloproteinase-9 in a dose-dependent manner. In EVO-induced cells, the intracellular NAD+/NADH ratio was increased, the level of Sirt1 was increased, and acetyl-NF-κB P65 was decreased. This process was inhibited by nicotinamide, an inhibitor of Sirt1. In vivo , EVO reduced tumor metastasis markedly. These findings provide evidences that EVO suppresses the migration and invasion of CRC cells by inhibiting the acetyl-NF-κB p65 by Sirt1, resulting in suppression of metalloproteinase-9 expression in vitro and in vivo.

Background End-stage renal disease (ESRD) is the most severe stage during the development of the renal failure. And depression is the most common psychological disorder in patients with ESRD, which in turn aggravates the progression of renal failure and seriously reduce the quality of life in ESRD patients with depression, but its underlying mechanism remains unclear. This study aimed to reveal the pathogenesis and discover novel peripheral biomarkers for ESRD with depression through metabolomics analysis.Methods Ultra-high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to explore changes of serum metabolites among healthy controls (n = 12), ESRD patients (n = 17), and ESRD patients with depression (n = 17). Also, the differential metabolites between groups were subjected to clustering analysis, pathway analysis, receiver operating characteristic (ROC) curve analysis.Results A total of 57 significant serum differential metabolites were identified between the ESRD without depression group and the ESRD with depression group, which were involved in 19 metabolic pathways, such as energy metabolism, glycerolipid metabolism and glutamate-centered metabolism. Moreover, the area under the ROC curve of Gentisic acid, Uric acid, 5-HT, 2-Phosphoglyceric acid, Leucyl-phenylalanine, Propenoyl carnitine, Malaoxon, Pregnenolone, 6-Thioxanthine 5'-monophosphate, Hydroxyl ansoprazole, Zileuton O-glucuronide, Cabergoline, PA (16:0/18:2(9Z,12Z)), PG (18:0/18:1(11Z)), probucol, etc. and their combination was greater than 0.90.Conclusions Inflammation, oxidative stress and metabolic abnormalities in energy metabolism, glycerolipid metabolism and glutamate-centered metabolism may be associated with the pathogenesis of ESRD with depression, which may be promising targets for therapy. Furthermore, the identified differential metabolites may serve as biomarkers for the diagnosis of ESRD patients with depression.