Pharmacokinetics of 6-Gingerol, 8-Gingerol, 10-Gingerol, and 6-Shogaol and Conjugate Metabolites in Healthy Human Subjects

Zick, Suzanna M.; Djurić, Zora; Ruffin, Mack T.; Litzinger, Amie; Normolle, Daniel P.; Alrawi, Sara; Feng, Mingchen; Brenner, Dean E.

doi:10.1158/1055-9965.epi-07-2934

Cited by 258 publications

(240 citation statements)

References 33 publications

(42 reference statements)

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“…Previous studies have shown that 6-shogaol [1-(4-hydroxymethoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has various neurobiological and anti-inflammatory effects( Figure 1) [5][6][7] . It reduced cell death and restored motor function in rat spinal cord injury, attenuated dopamine depression in response to 6-hydroxydopamine, and prevented the proliferation of glial cells via an increase of brain-derived neurotrophic factor in lipopolysaccharide-treated astrocytes [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation

Park

Kim

et al. 2013

Acta Pharmacol Sin

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Aim: 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown various neurobiological and anti-inflammatory effects. The aim of this study was to examine the effects of 6-shogaol on neuroinflammatory-induced damage of dopaminergic (DA) neurons in Parkinson's disease (PD) models. Methods: Cultured rat mesencephalic cells were treated with 6-shogaol (0.001 and 0.01 μmol/L) for 1 h, then with MPP + (10 µmol/L) for another 23 h. The levels of TNF-α and NO in medium were analyzed spectrophotometrically. C57/BL mice were administered 6-shogaol (10 mg·kg -1 ·d -1 , po) for 3 d, and then MPTP (30 mg/kg, ip) for 5 d. Seven days after the last MPTP injection, behavioral testings were performed. The levels of tyrosine hydroxylase (TH) and macrophage antigen (MAC)-1 were determined with immunohistochemistry. The expression of iNOS and COX-2 was measured using RT PCR. Results: In MPP + -treated rat mesencephalic cultures, 6-shogaol significantly increased the number of TH-IR neurons and suppressed TNF-α and NO levels. In C57/BL mice, treatment with 6-shogaol reversed MPTP-induced changes in motor coordination and bradykinesia. Furthermore, 6-shogaol reversed MPTP-induced reductions in TH-positive cell number in the substantia nigra pars compacta (SNpc) and TH-IR fiber intensity in stratum (ST). Moreover, 6-shogaol significantly inhibited the MPTP-induced microglial activation and increases in the levels of TNF-α, NO, iNOS, and COX-2 in both SNpc and ST. Conclusion: 6-Shogaol exerts neuroprotective effects on DA neurons in in vitro and in vivo PD models.

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Section: Introductionmentioning

confidence: 99%

6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation

Park

Kim

et al. 2013

Acta Pharmacol Sin

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“…It has been reported that 6-, 8-, and 10-gingerol exist in ginger-containing dietary supplements, spices, food products and beverages [16] . Pharmacokinetic studies in humans have shown that after absorption and metabolism, 6-, 8-, and 10-gingerol are present in the serum as glucuronide and sulfate conjugates [17] .…”

Section: Introductionmentioning

confidence: 99%

Pungent ginger components modulates human cytochrome P450 enzymes in vitro

Chen

Yue

et al. 2013

Acta Pharmacol Sin

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Aim: Ginger rhizome is used worldwide as a spicy flavor agent. This study was designed to explore the potential effects of pungent ginger components, 6-, 8-, and 10-gingerol, on human cytochrome P450 (CYP450) enzymes that are responsible for the metabolism of many prescription drugs. Methods: The activities of human CYP2C9, CYP2C19, CYP2D6, and CYP3A4 were analyzed using Vivid P450 assay kits. The mRNA expression of CYP3A4 in human hepatocellular carcinoma cell line HepG2 was measured using quantitative real-time PCR assay. Results: All three gingerols potently inhibited CYP2C9 activity, exerted moderate inhibition on CYP2C19 and CYP3A4, and weak inhibion on CYP2D6. 8-Gingerol was the most potent in inhibition of P450 enzymes with IC 50 values of 6.8, 12.5, 8.7, and 42.7 μmol/L for CYP2C9, CYP2C19, CYP3A4, and CYP2D6, respectively. By comparing the effects of gingerols on CYP3A4 with three different fluorescent substrate probes, it was demonstrated that the inhibition of gingerols on CYP3A4 had no substrate-dependence. In HepG2 cells, 8-gingerol and 10-gingerol inhibited, but 6-gingerol induced mRNA expression of CYP3A4. Conclusion: 6-, 8-, and 10-gingerol suppress human cytochrome P450 activity, while 8-and 10-gingerol inhibit CYP3A4 expression. The results may have an implication for the use of ginger or ginger products when combined with therapeutic drugs that are metabolized by cytochrome P450 enzymes.

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“…Tais estudos incluem o papel dos compostos na atividade motora, efeito antipirético, analgésico (SUEKAWA et al, 1984), antioxidante (MASUDA et al, 2004), inibidor da angiogênese (KIM et al, 2005), inibidor de metástase de câncer de mama (LEE et al, 2008), antibacteriano (PARK;LEE, 2008), além das atividades imunomoduladoras e anti-inflamatórias que serão tratadas no presente trabalho. Há também estudos abordando suas propriedades físicas (DING et al, 1991) Dentre os componentes, destacam-se o 6-gingerol e o 6-shogaol e gingerdiones, que representam 3% do óleo volátil, sendo os mais abundantes componentes da raiz (ZICK et al, 2008;VRIENS et al, 2008), motivo pelo qual são atualmente as moléculas mais exploradas individualmente (SAHA et al, 2014;KUMAR et al, 2014;DUGASANI, 2010;GAUS et al, 2009;TRIPATHI et al, 2007;ALI el al., 2007;KOH et al, 2009). …”

Section: Gengibre E Seus Componentesunclassified

Efeito anti-inflamatório do gengibre e possível via de sinalização

Vieira

Tomiotto

Melo

et al. 2014

Semin. Cienc. Biol. Saude

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O gengibre (Zingiber officinale Roscoe) vem sendo utilizado tanto na medicina natural tradicional quanto contemporânea, sendo descritos mais de 115 componentes do gengibre fresco e seco. Dentre esses componentes, os compostos fenólicos, gingerol e o shoagol, têm sido amplamente estudados apresentando diferentes propriedades destas moléculas como efeito antipirético, analgésico, inibidor da angiogênese, atividades imunomoduladoras, entre outras. Esta revisão tem como objetivo apresentar os componentes do gengibre assim como o seu efeito antagônico sobre o lipopolissacarídeo (LPS), propriedade anti-inflamatória e possível via de sinalização envolvida. O efeito do gengibre sobre o LPS consiste na inibição da produção de Interleucina 12 (IL -12), resultando em menor ativação de macrófagos induzidos pelo LPS; diminuição na expressão de moléculas co-estimulatórias e expressão de MHC classe II e diminuição de Interleucina 2 (IL-2), suprimindo a ativação e proliferação de células T CD4+. A propriedade anti-inflamatória do composto está relacionada com a capacidade de modular o linfócito T, de forma a inibir a eosinofilia, reduzir a quantidade de mastócitos, inibir a liberação de IL-4 e reduzir a resposta Th2. Além disso, pode ocorrer inibição da translocação da subunidade p65 para o núcleo e inibição da fosforilação do complexo IkB-α, culminando com a diminuição dos níveis de COX-2. Através deste estudo, podemos concluir que componentes do gengibre podem atuar antagonicamente sobre o efeito de ativação do LPS em macrófagos, conduzindo um efeito imunomodulador e anti-inflamatório, no qual a possível via de sinalização afetada seja do NFkB com envolvimento das MAPquinases. Palavras-Chave: Zingiber officinale Roscoe. Gingerol. Shogaol. Inflamação AbstractGinger (Zingiber officinale Roscoe) has been used in both traditional and contemporary natural medicine, with over 115 described components of fresh and dried ginger. Among these components, the phenolic compounds: gingerol and shoagol have been broadly studied and these molecules have different properties, such as antipyretic, analgesic, angiogenesis inhibitor, immunomodulatory activities, among others. This review aims to present the components of ginger as well as its antagonistic effect on LPS, anti -inflammatory property and possible signaling pathway involved. The effect of ginger on lipopolysaccharide (LPS) consists in inhibiting the production of interleukin 12 (IL-12), resulting in reduced activation of macrophages induced by LPS; decreased expression of co-stimulatory molecules and MHC class II expression and reduced IL-2, impairing the activation and proliferation of CD4 + T cells. The anti-inflammatory property of the compound is associated with the ability to modulate T lymphocyte, in order to inhibit eosinophilia, reducing the amount of mast cells and inhibit the release

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Pharmacokinetics of 6-Gingerol, 8-Gingerol, 10-Gingerol, and 6-Shogaol and Conjugate Metabolites in Healthy Human Subjects

Cited by 258 publications

References 33 publications

6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation

6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation

Pungent ginger components modulates human cytochrome P450 enzymes in vitro

Efeito anti-inflamatório do gengibre e possível via de sinalização

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