Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacyReportar como inadecuado




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Journal of Neuroinflammation

, 8:100

First Online: 16 August 2011Received: 17 April 2011Accepted: 16 August 2011

Abstract

BackgroundThe effectiveness of ginseng in preventing and treating various central nervous system CNS diseases has been widely confirmed. However, ginsenosides, the principal components of ginseng, are characterized by poor accessibility to the brain, and this pharmacokinetic-pharmacological paradox remains poorly explained. Anti-inflammatory approaches are becoming promising therapeutic strategies for depression and other CNS diseases; however, previous studies have focused largely on anti-inflammatory therapies directed at the central nervous system. It is thus of interest to determine whether ginsenosides, characterized by poor brain distribution, are also effective in treating lipopolysaccharide- LPS induced depression-like behavior and neuroinflammation.

MethodsIn an LPS-induced depression-like behavior model, the antidepressant effects of ginseng total saponins GTS were assessed using a forced swimming test, a tail suspension test, and a sucrose preference test. The anti-inflammatory efficacies of GTS in brain, plasma, and LPS-challenged RAW264.7 cells were validated using ELISA and quantitative real-time PCR. Moreover, indoleamine 2,3-dioxygenase IDO activity in the periphery and brain were also determined by measuring levels of kynurenine-tryptophan.

ResultsGTS significantly attenuated LPS-induced depression-like behavior. Moreover, LPS-induced increases in 5-HT and tryptophane turnover in the brain were significantly reduced by GTS. IDO activities in brain and periphery were also suppressed after pretreatment with GTS. Furthermore, GTS-associated recovery from LPS-induced depression-like behavior was paralleled with reduced mRNA levels for IL-1β, IL-6, TNF-α, and IDO in hippocampus. Poor brain distribution of ginsenosides was confirmed in LPS-challenged mice. GTS treatment significantly decreased production of various proinflammatory cytokines in both LPS-challenged mice and RAW264.7 cells.

ConclusionThis study suggests that the anti-depression efficacy of GTS may be largely attributable to its peripheral anti-inflammatory activity. Our study also strengthens an important notion that peripheral anti-inflammation strategies may be useful in the therapy of inflammation-related depression and possibly other CNS diseases.

Abbreviations5-HTserotonin

5-HIAA5-Hydroxyindoleacetic acid

CNScentral nervous system

GTSginseng total saponins

HPLChigh performance liquid chromatography

IDOindoleamine 2,3-dioxygenase

ILinterleukin

KYNkynurenine

LPSlipopolysaccharide

NSAIDsNonsteroidal anti-inflammatory drugs

TRYtryptophan, BBB: blood brain barrier.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-8-100 contains supplementary material, which is available to authorized users.

An Kang, Haiping Hao contributed equally to this work.

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Autor: An Kang - Haiping Hao - Xiao Zheng - Yan Liang - Yuan Xie - Tong Xie - Chen Dai - Qijin Zhao - Xiaolan Wu - Lin Xie - Gu

Fuente: https://link.springer.com/







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