3-Hydroxybutyric acid
(Synonyms: 3-羟基丁酸; β-Hydroxybutyric acid) 目录号 : GC30616
3-羟基丁酸（3-Hydroxybutyric acid，D-β-hydroxybutyrate，BHB）是一类组蛋白脱乙酰酶（HDAC）的内源性和特异性抑制剂，抑制HDAC1、HDAC3和HDAC4的IC50分别为5.3、2.4和4.5 mM。
Cas No.:300-85-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
|
Cell experiment [1]: |
|
|
Cell lines |
HEK293 cells |
|
Preparation method |
HEK293 cells were treated with 10 mM 3-Hydroxybutyric acid or PBS for 24 hours. Chromatin was immunoprecipitated with anti-H3 or anti-AcH3K9 and the purified DNA was analyzed with primer pairs specific for the Foxo3a or Mt2 promoters. |
|
Reaction Conditions |
10mM; 24h |
|
Applications |
Chromatin immunoprecipitation (ChIP) analysis of the Foxo3a and Mt2 promoters with two distinct primer pairs for each promoter revealed increased histone H3K9 acetylation at both promoters after treatment of HEK293 cells with a high dose of 3-Hydroxybutyric acid (10mM). |
|
Animal experiment [2]: |
|
|
Animal models |
C57BL/6 male mice |
|
Preparation method |
Mice were anesthetized under isoflurane and placed on a stereotaxic frame. The body temperature of the animals was maintained at 37°C using a homeothermic blanket. 3-Hydroxybutyric acid (2mM and 5mM; 5 µl) was delivered by a Hamilton syringe at a flow rate of 0.5 µl/min using a nanomite syringe pump. |
|
Dosage form |
2mM and 5mM; 5 µl; i.c.v. |
|
Applications |
3-Hydroxybutyric acid (2mM or 5mM) treatment decreased the binding of both HDAC2 and HDAC3 on the pI promoter of Bdnf. |
|
References: [1] Shimazu T , Hirschey M D , Newman J , et al. Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor[J]. Science, 2013, 339(6116):211-4. [2] Sleiman S F , Jeffrey H , Rami A H ,et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate[J].Elife, 2016. |
|
3-Hydroxybutyric acid (D-β-hydroxybutyrate, BHB) is an endogenous and specific inhibitor of histone deacetylase (HDAC). The IC50 for inhibiting HDAC1, HDAC3 and HDAC4 is respectively 5.3, 2.4 and 4.5 mM[1]. 3-Hydroxybutyric acid is a ketone body that can interact with lipids and also reduce the interfacial viscosity of the DPPC monolayer [2]. 3-Hydroxybutyric acid blocks the NLRP3 inflammasome and does not undergo oxidation in the TCA cycle [3].
In vitro, histone H3K9 acetylation at the Foxo3a and Mt2 promoters increased after HEK293 cells were treated with 3-hydroxybutyrate (10 mM) for 24 hours [1]. After treating human monocytes for 24 hours, 3-hydroxybutyric acid (1-20 mM) dose-dependently inhibits the production of interleukin IL-1β and IL-18 mediated by the NLRP3 inflammasome [3]. 3-Hydroxybutyric acid (10 mM) treated mouse glial cells for 48 hours, which significantly promoted cell proliferation [4].
In vivo, 3-hydroxybutyrate (2mM or 5mM) administered to C57BL/6 mice via intracerebroventricular injection can reduce the binding of HDAC2 and HDAC3 to the pI promoter of Bdnf [5]. Intraperitoneal injection of 3-hydroxybutyric acid (5.0 mmol/kg) into suckling mice after hypoxia-ischemia treatment can reduce the number of TUNEL-positive cells in the brain area, reduce cerebral infarction, and thereby reduce brain damage [6].
References:
[1] Shimazu T , Hirschey M D , Newman J ,et al. Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor[J]. Science, 2013, 339(6116):211-4.
[2] Hsu TT, et al. 3-Hydroxybutyric acid interacts with lipid monolayers at concentrations that impair consciousness[J]. Langmuir. 2013 Feb 12;29(6):1948-55.
[3] Youm Y H , Nguyen K Y , Grant R W ,et al. The ketone body β-hydroxybutyrate blocks the NLRP3 inflammasome-mediated inflammatory disease[J]. Nature Medicine, 2015.
[4] Xiao X Q , Zhao Y , Chen G Q .The effect of 3-hydroxybutyrate and its derivatives on the growth of glial cells[J].Biomaterials, 2007, 28(25):3608-3616.
[5]Sleiman S F , Jeffrey H , Rami A H ,et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate[J].Elife, 2016.
[6]Lee B , Woo D C , Woo C W ,et al.Exogenous β-Hydroxybutyrate Treatment and Neuroprotection in a Suckling Rat Model of Hypoxic-Ischemic Encephalopathy[J].Dev Neurosci, 2018.
3-羟基丁酸（3-Hydroxybutyric acid，D-β-hydroxybutyrate，BHB）是一类组蛋白脱乙酰酶（HDAC）的内源性和特异性抑制剂，抑制HDAC1、HDAC3和HDAC4的IC50分别为5.3、2.4和4.5 mM[1]。3-羟基丁酸是一种酮体，能够与脂质相互作用，还会降低DPPC单分子层的界面粘度[2]。3-羟基丁酸阻断NLRP3炎症小体，且在TCA循环中不经历氧化[3]。
在体外，3-羟基丁酸 (10 mM)处理HEK293细胞24h后，Foxo3a 和 Mt2启动子处的组蛋白H3K9乙酰化增加[1]。3-羟基丁酸 (1-20 mM)处理人单核细胞24h后，剂量依赖性抑制NLRP3炎症小体介导的白细胞介素IL-1β和IL-18的产生[3]。3-羟基丁酸 (10 mM)处理小鼠神经胶质细胞48h，具有明显的促进细胞增殖的作用[4]。
在体内，3-羟基丁酸（2mM or 5mM）通过脑室内注射给予C57BL/6小鼠，可降低HDAC2和HDAC3对Bdnf 的pI启动子的结合[5]。3-羟基丁酸（5.0 mmol/kg）腹腔注射给予缺氧缺血处理后的乳鼠，可减少脑区TUNEL阳性细胞的数量，减少脑梗塞，从而减轻脑损伤[6]。
| Cas No. | 300-85-6 | SDF | |
| 别名 | 3-羟基丁酸; β-Hydroxybutyric acid | ||
| Canonical SMILES | CC(O)CC(O)=O | ||
| 分子式 | C4H8O3 | 分子量 | 104.1 |
| 溶解度 | Water : 65 mg/mL (624.40 mM) | 储存条件 | Store at 4°C, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 9.6061 mL | 48.0307 mL | 96.0615 mL |
| 5 mM | 1.9212 mL | 9.6061 mL | 19.2123 mL |
| 10 mM | 0.9606 mL | 4.8031 mL | 9.6061 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
β-Hydroxybutyrate suppresses colorectal cancer
Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed1. Here we identify a metabolite signalling pathway that provides actionable insights towards this goal. We perform a dietary screen in autochthonous animal models of CRC and find that ketogenic diets exhibit a strong tumour-inhibitory effect. These properties of ketogenic diets are recapitulated by the ketone body β-hydroxybutyrate (BHB), which reduces the proliferation of colonic crypt cells and potently suppresses intestinal tumour growth. We find that BHB acts through the surface receptor Hcar2 and induces the transcriptional regulator Hopx, thereby altering gene expression and inhibiting cell proliferation. Cancer organoid assays and single-cell RNA sequencing of biopsies from patients with CRC provide evidence that elevated BHB levels and active HOPX are associated with reduced intestinal epithelial proliferation in humans. This study thus identifies a BHB-triggered pathway regulating intestinal tumorigenesis and indicates that oral or systemic interventions with a single metabolite may complement current prevention and treatment strategies for CRC.
Fuel metabolism in starvation
This article, which is partly biographical and partly scientific, summarizes a life in academic medicine. It relates my progress from benchside to bedside and then to academic and research administration, and concludes with the teaching of human biology to college undergraduates. My experience as an intern (anno 1953) treating a youngster in diabetic ketoacidosis underscored our ignorance of the controls in human fuel metabolism. Circulating free fatty acids were then unknown, insulin could not be measured in biologic fluids, and beta-hydroxybutyric acid, which was difficult to measure, was considered by many a metabolic poison. The central role of insulin and the metabolism of free fatty acids, glycerol, glucose, lactate, and pyruvate, combined with indirect calorimetry, needed characterization in a near-steady state, namely prolonged starvation. This is the main topic of this chapter. Due to its use by brain, D-beta-hydroxybutyric acid not only has permitted man to survive prolonged starvation, but also may have therapeutic potential owing to its greater efficiency in providing cellular energy in ischemic states such as stroke, myocardial insufficiency, neonatal stress, genetic mitochondrial problems, and physical fatigue.
β-Hydroxybutyrate: A Signaling Metabolite
Various mechanisms in the mammalian body provide resilience against food deprivation and dietary stress. The ketone body β-hydroxybutyrate (BHB) is synthesized in the liver from fatty acids and represents an essential carrier of energy from the liver to peripheral tissues when the supply of glucose is too low for the body's energetic needs, such as during periods of prolonged exercise, starvation, or absence of dietary carbohydrates. In addition to its activity as an energetic metabolite, BHB is increasingly understood to have cellular signaling functions. These signaling functions of BHB broadly link the outside environment to epigenetic gene regulation and cellular function, and their actions may be relevant to a variety of human diseases as well as human aging.
β-hydroxybutyrate as an Anti-Aging Metabolite
The ketone bodies, especially β-hydroxybutyrate (β-HB), derive from fatty acid oxidation and alternatively serve as a fuel source for peripheral tissues including the brain, heart, and skeletal muscle. β-HB is currently considered not solely an energy substrate for maintaining metabolic homeostasis but also acts as a signaling molecule of modulating lipolysis, oxidative stress, and neuroprotection. Besides, it serves as an epigenetic regulator in terms of histone methylation, acetylation, β-hydroxybutyrylation to delay various age-related diseases. In addition, studies support endogenous β-HB administration or exogenous supplementation as effective strategies to induce a metabolic state of nutritional ketosis. The purpose of this review article is to provide an overview of β-HB metabolism and its relationship and application in age-related diseases. Future studies are needed to reveal whether β-HB has the potential to serve as adjunctive nutritional therapy for aging.
The Aging Metabolome-Biomarkers to Hub Metabolites
Aging biology is intimately associated with dysregulated metabolism, which is one of the hallmarks of aging. Aging-related pathways such as mTOR and AMPK, which are major targets of anti-aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways. In this review, numerous candidate bio-markers of aging that have emerged using metabolomics are outlined. Metabolomics studies also reveal that not all metabolites are created equally. A set of core "hub" metabolites are emerging as central mediators of aging. The hub metabolites reviewed here are nicotinamide adenine dinucleotide, reduced nicotinamide dinucleotide phosphate, α-ketoglutarate, and β-hydroxybutyrate. These "hub" metabolites have signaling and epigenetic roles along with their canonical roles as co-factors or intermediates of carbon metabolism. Together these hub metabolites suggest a central role of the TCA cycle in signaling and metabolic dysregulation associated with aging.