| Description | Geranylgeraniol
is an orally acitve vitamin K2 sub-type, an intermediate of the
mevalonate pathway. Geranylgeraniol targets NF-kB signaling pathway and
could alleviate LPS-induced microglial inflammation in animal
model[1][2][3][4]. |
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| Related Catalog | Research Areas >> Inflammation/Immunology |
|---|
| Target | NF-kB[1] |
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| In Vitro | Geranylgeraniol
(0-10 μM; 24 h) dose-dependently suppresses the LPS-induced increase in
the mRNA levels of Il-1β, Tnf-α, Il-6, and Cox-2[1]. Geranylgeraniol
(10 μM; 24 h) inhibits the phosphorylation of TAK1, IKKα/β, and NF-κB
p65 proteins as well as NF-κB nuclear translocation induced by LPS while
maintaining IκBα expression[1]. Geranylgeraniol, (50 μM; 24 h)
eliminates cell damage caused by Simvastatin (HY-17502) (10 µM) and
Mevalonat (10 mM), and reduces the inflammatory marker and the damage of
the mitochondria, maintaining its shape and component[2]. Western Blot
Analysis[1] Cell Line: MG6 cell Concentration: 0, 1, 10 μM Incubation
Time: 24 hours Result: Suppressed by TAK1, IKKα/β, and NF-κB p65
proteins level at 10 μM. RT-PCR[1] Cell Line: MG6 cell Concentration: 10
μM Incubation Time: 0, 6, 12, 24 hours Result: Significantly inhibited
pro-inflammatory cytokine Il-1β, Tnf-α, Il-6, and Cox-2 mRNA level. |
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| In Vivo | Geranylgeraniol
(725 mg/kg/d; p.o.; 90 d) is not toxicologically significant with a
dose below 725 mg/kg/d in rats[3]. Geranylgeraniol (483 mg/kg/d; p.o.;
10 d) suppresses lipopolysaccharide-induced inflammation via inhibition
of nuclear factor-κB activation in rats[4]. Animal Model: Han Wistar
rats (169-192 g for male; 116-152 g for female)[3] Dosage: 0, 725, 1450,
and 2900 mg/kg Administration: Oral gavage; once daily; 90 days Result:
Showed the lowest observed adverse effect level (LOAEL) for local
effects and the no observed adverse effect level (NOAEL) for systemic
effects as 725 mg/kg/d. Reduced body weights by 12.9 and 21.6% in the
intermediate- and high-dose group males, respectively, compared to
controls. Animal Model: Wistar rats (male, 8-week-old, 130-150 g)[4]
Dosage: 0, 48.3, 483, 4830 mg/kg Administration: Oral gavage; once
daily; 10 days; with or not LPS challenge (i.p.; 0.5 mg/kg) Result:
Suppressed LPS-induced inflammatory cytokines and mRNA expression of
LPS-induced inflammatory genes in liver with doses of 483 mg/kg and 4830
mg/kg. Suppressed protein levels of IRAK1, TRAF6, and TAK1, originating
from transcriptional down-regulation with doses of 483 mg/kg and 4830
mg/kg. |
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| References | [1]. Saputra
WD, et al. Geranylgeraniol Inhibits Lipopolysaccharide-Induced
Inflammation in Mouse-Derived MG6 Microglial Cells via NF-κB Signaling
Modulation. Int J Mol Sci. 2021 Sep 29;22(19):10543. [2]. Marcuzzi
A, et al. Geranylgeraniol and Neurological Impairment: Involvement of
Apoptosis and Mitochondrial Morphology. Int J Mol Sci. 2016 Mar
11;17(3):365. [3]. Preece K, et al. A toxicological evaluation of geranylgeraniol. Regul Toxicol Pharmacol. 2021 Aug;124:104975. [4]. Giriwono
PE, et al. Dietary supplementation with geranylgeraniol suppresses
lipopolysaccharide-induced inflammation via inhibition of nuclear
factor-κB activation in rats. Eur J Nutr. 2013 Apr;52(3):1191-9. |
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