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Gentiannine

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PMID

28501981

Abstract

The anti-inflammatory property of gentianine (GE) aroused our interest. To investigate the effect of GE on Freund’s complete adjuvant (FCA)-induced arthritis in rats was the aim of this study. Adjuvant-induced arthritis (AA) was induced by the administration of 0.1 ml FCA in the surface of hind paw. Diclofenac sodium (DS) and Fasudil were administered as positive controls. Downregulation of cytokines including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) revealed anti-inflammatory effect of GE, which was consisted with pathological conditions of rat paws. In addition, western blot analysis revealed that GE could strikingly suppressed the expressions of Rho/NF-κB signaling pathways as well as TGF-β/smad-3 pathways. In conclusion, data indicated that GE might contribute to treat arthritis as a potential therapeutic candidate.

KEYWORDS

Freund’s complete adjuvant; arthritis; gentianine; inflammation

Title

Protective Effect of Gentianine, a compound from Du Huo Ji Sheng Tang, against Freund's Complete Adjuvant-Induced Arthritis in Rats.

Author

Wenjin C1, Jianwei W2.

Publish date

2017 Aug

PMID

25813903

Abstract

We investigated the metabolic fate of gentianine after oral administration to Wistar rats for the first time. Liquid chromatography/ion trap mass spectrometry detected four metabolites secogentianoxide, gentiandiol, gentianepoxide and gentianoxide in rat plasma together with the original compound gentianine. The structures of the metabolites were identified by comparing the retention times, as well as MS (mass) and MS/MS (tandem mass) spectra with those of authentic compounds, which were synthesized from gentianine or isolated from the urine. Three of the metabolites, secogentianoxide, gentianepoxide and gentianoxide, are novel compounds. The major in vivo metabolic processes associated with gentianine include N-oxide, epoxidation, dihydroxylation of double bond and hydrolysis of lactone. Gentianine together with the metabolites in plasma were quantified using gentianone as the internal standard. The mean C(max) of G0, G1, G2 and G3 are 425.76, 287.56, 188.45 and 85.05 ng/mL, respectively. The mean T(max) of G0, G1, G2 and G3 are 1.16, 3.87, 6.23 and 4.28 h, respectively. The mean T(1/2) of G0, G1, G2 and G3 are 5.23, 12.34, 7.78 and 5.64 h, respectively. A comprehensive metabolic pathway was proposed. The new metabolites may shed light on clinical efficacy of gentianine.

Copyright ? 2015 Elsevier B.V. All rights reserved.

KEYWORDS

Gentianine; LC-MS; Metabolite

Title

Determination of the metabolic profile of gentianine after oral administration to rats by high performance liquid chromatography/electrospray ionization-trap mass spectrometry.

Author

Wu X1, Tang S2, Jin Y3, Wang S1, Wang X1, Hattori M4, Zhang H5, Wang Z6.

Publish date

2015 May 1

PMID

22718571

Abstract

We have previously shown the anti-diabetic effects of swertiamarin; however, pharmacokinetic analysis showed that swertiamarin had a plasma half-life of 1.3 h. Gentianine is an active metabolite of swertiamarin that possesses a pharmacophoric moiety. The aim of this study was to explore the possibility whether the anti-diabetic effect of swertiamarin is due to gentianine. Swertiamarin treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-γ and GLUT-4; however, there was a significant increase in the mRNA expression of adiponectin. On the other hand, treatment with gentianine significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, GLUT-4 and adiponectin. These findings suggest, for the first time, that the anti-diabetic effect of swertiamarin is due to gentianine, an active metabolite of swertiamarin.

Copyright ? 2012 John Wiley & Sons, Ltd.

Title

Anti-diabetic activity of swertiamarin is due to an active metabolite, gentianine, that upregulates PPAR-γ gene expression in 3T3-L1 cells.

Author

Vaidya H1, Goyal RK, Cheema SK.

Publish date

2013 Apr