GERANYLGERANIOL

Names

[ Name ]:
GERANYLGERANIOL

[Synonym ]:
MFCD00129083
Geranylgeraniol
(2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-ol
all trans-3,7,11-15-Tetramethyl-2,6,10,14-hexadecatetraen-1-ol

Biological Activity

[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].

[Related Catalog]:

Research Areas >> Inflammation/Immunology

[Target]

NF-kB[1]

[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.

[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.

[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.

Chemical & Physical Properties

[ Density]:
0.88 g/cm3

[ Boiling Point ]:
397.1ºC at 760 mmHg

[ Molecular Formula ]:
C₂₀H₃₄O

[ Molecular Weight ]:
290.48300

[ Flash Point ]:
128.3ºC

[ Exact Mass ]:
290.26100

[ PSA ]:
20.23000

[ LogP ]:
6.12440

[ Vapour Pressure ]:
0mmHg at 25°C

[ Index of Refraction ]:
1.492

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
Eyeshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2905290000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2905290000

[ Summary ]:
2905290000 unsaturated monohydric alcohols。Supervision conditions:None。VAT:17.0%。Tax rebate rate:9.0%。MFN tariff:5.5%。General tariff:30.0%

Articles

Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

PLoS ONE 10 , e0132761, (2015)

The acyclic diterpenoid acid geranylgeranoic acid (GGA) has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remain...

PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation.

Cancer Cell Int. 15 , 27, (2015)

PDZ binding-kinase (PBK) (also named T-lymphokine-activated killer cell-originated protein kinase (TOPK)), a serine/threonine kinase, is tightly controlled in normal tissues but elevated in many tumor...

Novel High Content Screen Detects Compounds That Promote Neurite Regeneration from Cochlear Spiral Ganglion Neurons.

Sci. Rep. 5 , 15960, (2015)

The bipolar spiral ganglion neurons (SGN) carry sound information from cochlear hair cells to the brain. After noise, antibiotic or toxic insult to the cochlea, damage to SGN and/or hair cells causes ...