Identification of serotonin 5-HT1A receptor partial agonists in ginger

Nievergelt, Andreas; Huonker, Peter; Schoop, Roland; Altmann, Karl‐Heinz; Gertsch, Jürg

doi:10.1016/j.bmc.2010.02.062

Cited by 41 publications

(33 citation statements)

References 28 publications

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“…The 1-hexadecyl-2-arachidonoylthio-2-deoxy-sn-glycero-3-phosphorylcholine (thio-PC) was purchased from Cayman Chemicals. The 8-and 10-shogaol were isolated by liquid chromatography and HPLC, as described previously (17).…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

“…A significant inhibition of PGE 2 formation by ginger constituents has already been shown in vivo (13). Furthermore, different gingerols and shogaols at low mM concentrations have been shown to directly bind to and partially activate the cation channel transient receptor potential vanilloid 1 (14)(15)(16), the molecular clue for the spiciness of ginger, as well as the serotonin 5-HT 1A G proteincoupled receptor (17). Although the latter studies have elucidated feasible molecular mechanisms of action of the major biologically active ginger constituents, they cannot explain the range of antiinflammatory effects observed in vivo.…”

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confidence: 94%

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Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Nievergelt

Marazzi

Schoop³

et al. 2011

The Journal of Immunology

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The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1β expression in monocytes/macrophages. Both the calcium-independent phospholipase A2 (iPLA2)-triggered maturation and the cytosolic phospholipase A2 (cPLA2)-dependent secretion of IL-1β from isolated human monocytes were inhibited. In a fluorescence-coupled PLA2 assay, most major ginger phenylpropanoids directly inhibited i/cPLA2 from U937 macrophages, but not hog pancreas secretory phospholipase A2. The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA2 and methyl arachidonyl fluorophosphonate for cPLA2, with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 μg/ml) and 10-shogaol (2 μM) potently inhibited the release of PGE2 and thromboxane B2 (>50%) and partially also leukotriene B4 in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA2 and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA2, the resulting attenuation of IL-1β secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.

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Section: Chemicals and Reagentsmentioning

confidence: 99%

mentioning

confidence: 94%

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Nievergelt

Marazzi

Schoop³

et al. 2011

The Journal of Immunology

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“…The prediction of the possible target of action (table 2), showed that most of the targets such as 5-hydroxytryptamine receptors, carbonic anhydrases (CAs) and zinc finger proteins, have not been adequately researched in relation to the therapeutic potential of ginger, except lipoxygenases [4,[17][18][19][20]. Previous computational study has showed that ginger components could be optimized as lead for the treatment of neurodegenerative diseases, such as Alzheimer's disease, because of its wide spectrum of potential targets which include acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-site amyloid precursor protein cleaving enzyme (BACE-1), human carboxylesterase (hCE-1), and nitric oxide synthase (NOS) among others [24].The lipoxygenases has been reported to have intimately linked activities [21].…”

Section: Discussionmentioning

confidence: 99%

“…Previous computational study has showed that ginger components could be optimized as lead for the treatment of neurodegenerative diseases, such as Alzheimer's disease, because of its wide spectrum of potential targets which include acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-site amyloid precursor protein cleaving enzyme (BACE-1), human carboxylesterase (hCE-1), and nitric oxide synthase (NOS) among others [24].The lipoxygenases has been reported to have intimately linked activities [21]. The report of Nievergelt et al [17] indicated that 10-shogaol, 1-dehydro-6-gingerdione, and particularly the whole lipophilic ginger extract partially activated the 5-HT1Areceptor (20-60% of maximal activation). Ginger extract has been reported as an inhibitor of lipoxygenase, cycloxygenase, interlukin, and as an activator of P53 and Bax in cancer management [4].…”

Section: Discussionmentioning

confidence: 99%

Computational Evaluation of Pharmacokinetics and Potential Protein Targets of Ginger (Zingiber officinale)

Sanni

Fatoki

2017

J Microbiol Biotech Res

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“…Ginger is effective in treating diseases such as Alzheimer's disease, irritable bowel syndrome, motion sickness, morning sickness, indigestion, anorexia, joint diseases, and diseases of the upper respiratory tract (9,10). It is also an analgesic, (11) an antivirus, (12) an antimigraine remedy, (13) and a bile secretion regulator, (11) and it has positive inotropic (14) and antitumor effects (15).…”

Section: Introductionmentioning

confidence: 99%

Morphological Effects of Hydroalcoholic Zingiber Officinalis Extract in the Murine Hippocampus of Male Rat Offspring

Ghodrati¹,

Mahmoodi²,

Shahidi³

et al. 2016

Avicenna J Neuro Psych Physio

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Background: The hippocampus is responsible for memory. A diet full of antioxidants improves brain damage and cognitive function. Regard the antioxidant effects of zingiber officinalis (ginger) and its flavonoids components. Objectives: The aim of this study was to evaluate the effect of the extract of ginger on memory by using hippocampus tissue of the male offspring of rats. Materials and Methods: In this study, 60 rats, 15 males and 45 females, were used. We separated pregnant female rats from males on the first day of pregnancy (determined by vaginal plug), and during days 16 -18 of pregnancy, via intraperitoneal injection, three groups received hydroalcoholic extract of ginger, with low (200 mg/kg bw), medium (400 mg/kg bw), and high (800 mg/kg bw) concentration doses. The control group did not receive anything, and the sham group received normal saline during these days. Then at day 50, the males offspring in each group were sacrificed, their brains were removed, and the hippocampus sections were prepared for microscopic studies. Data was analyzed by SPSS 20 and by using one-way ANOVA and then a Tukey post-test (P < 0.05 considered as the significance level). Results: This research showed that the number and thickness of pyramidal and granular layers of the CA1 and dentate gyrus areas of the hippocampus had increased in male offspring according to the increase in the ginger extract dose. Conclusions: It seems as though ginger extract, which contains compounds such as gingerols, shogaols, and zingerone, can affect memory ability in rats through these compounds' antioxidant properties by affecting embryonic acetylcholine content and place cells.

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Identification of serotonin 5-HT1A receptor partial agonists in ginger

Cited by 41 publications

References 28 publications

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Computational Evaluation of Pharmacokinetics and Potential Protein Targets of Ginger (Zingiber officinale)

Morphological Effects of Hydroalcoholic Zingiber Officinalis Extract in the Murine Hippocampus of Male Rat Offspring

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