Linking biological activity with herbal constituents by systems biology-based approaches: effects of Panax ginseng in type 2 diabetic Goto-Kakizaki rats.
ABSTRACT Although a number of animal experiments and clinical trials have investigated the effects of ginseng roots on diabetes, the relationship between their therapeutic effects on diabetes and the quality and the growth age of this herb have not yet been reported. This study systematically investigated the effects of 3- to 6-year-old ginseng roots on glycemic and plasma lipid control in a rat model of type 2 diabetes. Six groups of male Goto-Kakizaki (GK) rats received either metformin, 3- to 6-year-old ginseng roots, or no treatment. The treatments were administered twice daily for 9 weeks. A combined approach was used that involved applying liquid chromatography-mass spectrometry-based lipidomics, measuring biochemical parameters and profiling the components of ginseng roots of different ages. Compared to the untreated controls, treatment with 4- and 6-year-old ginseng roots significantly improved glucose disposal, and 5-year-old ginseng treatment significantly increased high density lipoprotein cholesterol. Treatment with 6-year-old ginseng significantly decreased total plasma triacylglyceride (TG) and very-low-density lipoprotein cholesterol and improved plasma glycated hemoglobin (HbA1c). In addition, treatment with 4- to 6-year-old ginseng influenced plasma lipidomics in diabetic GK rats by reducing TG lipid species. Metformin significantly reduced fasting blood glucose by 41% and reduced HbA1c by 11%, but showed no effects on the plasma lipid parameters. The present study demonstrates that ginseng roots show growth age-dependent therapeutic effects on hyperlipidemia and hyperglycemia in diabetic GK rats. These age-dependent effects may be linked with the variation in both the ratios and concentrations of specific bioactive ginsenosides in ginseng roots of different growth ages. This study introduced novel systems biology-based approaches for linking biological activities with potential active components in herbal mixtures.
Full-textDOI: · Available from: Chunxiu Hu, Jun 26, 2015
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ABSTRACT: Metabolites have played an essential role in our understanding of life, health, and disease for thousands of years. This domain became much more important after the concept of metabolism was discovered. In the 1950s, mass spectrometry was coupled to chromatography and made the technique more application-oriented and allowed the development of new profiling technologies. Since 1980, TNO has performed system-based metabolic profiling of body fluids, and combined with pattern recognition has led to many discoveries and contributed to the field known as metabolomics and systems biology. This review describes the development of related concepts and applications at TNO in the biomedical, pharmaceutical, nutritional, and microbiological fields, and provides an outlook for the future. © 2013 Wiley Periodicals, Inc. Mass Spec Rev.Mass Spectrometry Reviews 09/2013; 32(5). DOI:10.1002/mas.21370 · 8.05 Impact Factor
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ABSTRACT: Tetramethylpyrazine (TMP) and butylidenephthalide (BP) are two bioactive components isolated from Ligusticum chuanxiong Hort and Angelica sinensis, respectively. These two traditional Chinese medicines have been widely used in clinical treatments for vascular disease. The mechanism by which TMP and BP protect endothelial cells (ECs) against oxidative stress remains unknown, as does their effects on the steady state of the lipidome of ECs. Here, we demonstrate that both compounds protect EA.hy926 cells against H(2)O(2) induced injury in a dose-dependent manner. We then apply an integrated analysis of the lipidome and signal transduction pathways to explore the underlying mechanism of their protective effects. We found that TMP elevates the content of several phosphatidylcholine (PC) species, reduces the release of arachidonic acid (AA) and inhibits the phosphorylation of cytosolic phospholipase A(2) (cPLA(2)). Compared to eicosatetraynoic acid (ETYA), a cPLA(2) inhibitor, TMP preferentially increases the content of arachidonoyl PCs. We also show that BP mainly elevates the pool of phosphatidylinositol (PI) species and inhibits the phosphorylation of both phospholipase C(γ) (PLC(γ)) and extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, specific inhibition of ERK1/2 by PD98059 decreases the cell viability and increases pool of phosphatidylserine (PS). Taken together, these results demonstrate that TMP protects oxidatively stressed ECs through inhibition of cPLA(2) and preferential increase of arachidonoyl PC levels. Conversely, the effects of BP are tied to inhibition of PLC(γ) and an increase in PI levels. The current work suggests that the interaction of the lipidome and phospholipases can serve as a promising therapeutic target in oxidatively stressed ECs.Molecular BioSystems 04/2012; 8(6):1789-97. DOI:10.1039/c2mb05510d · 3.18 Impact Factor
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ABSTRACT: Here, we isolated and characterized a new ginsenoside-transforming β-glucosidase (BglQM) from Mucilaginibacter sp. QM49 that shows biotransformation activity for various major ginsenosides. The gene responsible for this activity, bglQM, consists of 2,346 bp, and is predicted to encode 781 amino acid residues and this enzyme has a molecular mass of 85.6 kDa. Sequence analysis of BglQM revealed that it could be classified into glycoside hydrolase family 3. The enzyme was overexpressed in Escherichia coli BL21(DE3) using a MBP-fused pMAL-c2x (TEV) vector system. Overexpressed recombinant BglQM could efficiently transform the protopanaxatriol-type ginsenosides, Re and Rg1, into Rg2(S) and Rh1(S), respectively, by hydrolyzing one glucose moiety attached to the C20 position at pH 8.0 and 30°C. The Km values for p-nitrophenyl-β-d-glucopyranoside, Re and Rg1 were 37.0 ± 0.4 μM, 3.22 ± 0.15 and 1.48 ± 0.09 mM, and the Vmax values were 33.4 ± 0.6 μmol min(-1) mg(-1) of protein, 19.2 ± 0.2 and 28.8 ± 0.27 nmol min(-1) mg(-1) of protein, respectively. A crude protopanaxatriol-type ginsenoside mixture (PPTGM) was treated with BglQM followed by silica column purification to produce Rh1(S) and Rg2(S) at chromatographic purities of 98±0.5% and 97±1.2%, respectively. This is the first report of gram-scale production of Rh1(S) and Rg2(S) from PPTGM using a novel ginsenoside-transforming β-glucosidase of glycoside hydrolase family 3.Applied and Environmental Microbiology 06/2013; DOI:10.1128/AEM.01150-13 · 3.95 Impact Factor