Geranylgeraniol 是一种口服有效的维生素 K2亚型，是甲戊酸途径 (mevalonate pathway) 的中间体。Geranylgeraniol 靶向NF-kB信号通路，可在动物模型中减轻脂多糖 (LPS) 诱导的小胶质细胞炎症。
| 生物活性 | Geranylgeraniol is an orally acitve vitamin K2sub-type, an intermediate of the mevalonate pathway. Geranylgeraniol targetsNF-kBsignaling pathway and could alleviate LPS-induced microglial inflammation in animal model[1][2][3][4]. |
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体外研究
(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 bySimvastatin(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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体内研究
(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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Pure form | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(344.26 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.4426 mL | 17.2129 mL | 34.4258 mL | | 5 mM | 0.6885 mL | 3.4426 mL | 6.8852 mL | | 10 mM | 0.3443 mL | 1.7213 mL | 3.4426 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (8.61 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.61 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (8.61 mM); Suspended solution
此方案可获得 ≥ 2.5 mg/mL (8.61 mM，饱和度未知) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (8.61 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.61 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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