Metabolic Profiling Analysis of the Alleviation Effect of Treatment with Baicalin on Cinnabar Induced Toxicity in Rats Urine and Serum

Objectives: Baicalin is the main bioactive flavonoid constituent isolated from Scutellaria baicalensis Georgi. The mechanisms of protection of liver remain unclear. In this study, 1H NMR-based metabonomics approach has been used to investigate the alleviation effect of Baicalin.Method:1H NMR metabolomics analyses of urine and serum from rats, was performed to illuminate the alleviation effect of Baicalin on mineral medicine (cinnabar)-induced liver and kidney toxicity.Results: The metabolic profiles of groups receiving Baicalin at a dose of 80 mg/kg were remarkably different from cinnabar, and meanwhile, the level of endogenous metabolites returned to normal compared to group cinnabar. PLS-DA scores plots demonstrated that the variation tendency of control and Baicalein are apart from Cinnabar. The metabolic profiles of group Baicalein were similar to those of group control. Statistics results were confirmed by the histopathological examination and biochemical assay.Conclusion: Baicalin have the alleviation effect to the liver and kidney damage induced by cinnabar. The Baicalin could regulate endogenous metabolites associated with the energy metabolism, choline metabolism, amino acid metabolism, and gut flora

Synthesis and Anticancer Activity Evaluation of Hydrolyzed Derivatives of <i>Panaxnotoginseng</i> Saponins

To increase the antitumor activity of ginsenosides and acetylsalicylic acid, acid hydrolysis products of Panaxnotoginseng saponin were used as raw materials to be combined with salicylic acid to obtain ginsenoside salicylic acid derivatives. All derivatives were assessed for anti-cancer activity. A total of 20 target compounds were designed and synthesized. The cytotoxic activity on five cancer cell lines, including human colon cancer (HT-29), gastric cancer (BGC-823), cervical cancer (Hela), human breast cancer (MCF-7), human lung cancer cells (A549), and two normal cancer cell lines (human gastric epithelial cells (GES-1), and human ovarian epithelial cells (IOSE144)) was evaluated following treatment with the compounds. The results showed that all compounds inhibited the growth of cancer cells. Compounds 1a, 3a, 7a, 1b, 2b, 3b and 8b showed strong anticancer activity. For MCF-7 cells, compound 3b showed the strongest inhibitory activity, IC50 = 2.56 &#177; 0.09 &#956;M. In the cytotoxicity test, all compounds showed low toxicity or no toxicity (IC50 &gt; 100 &#956;M). In addition, a cell cycle distribution assay and wound healing assay demonstrated that compound 3b specifically inhibited MCF-7 proliferation and migration ability. Our results indicate that compound 3b represents a promising compound for further cancer studies

1H-NMR-Based Metabonomics of the Protective Effect of Coptis chinensis and Berberine on Cinnabar-Induced Hepatotoxicity and Nephrotoxicity in Rats

Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which include hepatoprotective effects on liver injuries, has been studied intensively, yet the therapy of liver injuries and underlying mechanism remain unclear. We investigated the detoxification mechanism of Coptis chinensis and berberine using metabolomics of urine and serum in the present study. After the treatment with Coptis chinensis and berberine, compared with the cinnabar group, Coptis chinensis and berberine can regulate the concentration of the endogenous metabolites. PLS-DA score plots demonstrated that the urine and serum metabolic profiles in rats of the Coptis chinensis and berberine groups were similar those of the control group, yet remarkably apart from the cinnabar group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism and metabolism of intestinal flora in rats. Meanwhile, liver and kidney histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabonomics

Metabonomic Evaluation of Chronic Unpredictable Mild Stress-Induced Changes in Rats by Intervention of Fluoxetine by HILIC-UHPLC/MS

<div><p>Hydrophilic interaction-ultra high performance liquid chromatography (HILIC-UHPLC) allows the analysis of highly polar metabolites, providing complementary information to reversed-phase (RP) chromatography. By optimization of the preparation and analytical conditions in HILIC mode, HILIC-UHPLC/MS was applied for the global metabolic profiling of rat plasma samples generated in an experimental model of chronic unpredictable mild stress (CUMS), and the concomitant investigation of the protective effect of fluoxetine was also evaluated. Identification of plasma metabolic profiles indicated that significant changes in specific metabolites occurred after fluoxetine exposure, including increased phenylalanine, serine, acetyl-L-carnitine, carnitine and decreased creatine, betaine, proline, tryptophan, tyrosine, C16:0 LPC. Some novel biomarkers from this HILIC-UHPLC/MS approach were betaine, proline, tyrosine creatine and serine compared with the results of RP-UHPLC/MS. The complementary nature of this technique is confirmed and is on agreement with previously published studies.</p></div

Base peak intensity (BPI) chromatograms of plasma metabolite profiles from (A) a control rat and (B) a model rat measured by HILIC-UHPLC/MS.

<p>Base peak intensity (BPI) chromatograms of plasma metabolite profiles from (A) a control rat and (B) a model rat measured by HILIC-UHPLC/MS.</p

Extracted ion chromatograms of proline from plasma metabolite profiles measured by (a) RP-UPLC-MS and (b) HILIC-UPLC-MS.

<p>Extracted ion chromatograms of proline from plasma metabolite profiles measured by (a) RP-UPLC-MS and (b) HILIC-UPLC-MS.</p

Biomarkers related to antidepressant mechanism of fluoxetine based on plasma metabolite profiles measured by HILIC-UHPLC/MS.

<p>^aMetabolites identified by comparing with database and authentic standards</p><p>^bMetabolites identified by comparing with literatures and database resources</p><p>*<i>p</i> < 0.05</p><p>**<i>p</i> < 0.01 and</p><p>***<i>p</i> < 0.001.</p><p>Biomarkers related to antidepressant mechanism of fluoxetine based on plasma metabolite profiles measured by HILIC-UHPLC/MS.</p

(A) Score plot and (B) loading plot derived from PCA model classifying control rats (■) and model rats (▲) based on plasma metabolite profiles measured by HILIC-UHPLC/MS.

<p>(A) Score plot and (B) loading plot derived from PCA model classifying control rats (■) and model rats (▲) based on plasma metabolite profiles measured by HILIC-UHPLC/MS.</p