α-生育酚（(+)-α-生育酚）充当过氧自由基的清除剂。这一作用至关重要，因为它使细胞膜中的长链多不饱和脂肪酸保持完整，从而保留了脂肪酸的生物活性[1]。据报道，α-维生素E（(+)-α-生育酚）可抑制多种细胞类型中的PKC，进而抑制内皮细胞形成超氧化物、一氧化氮以及中性粒细胞和巨噬细胞中的血小板聚集。暴露于 α-生育酚 ((+)-α-生育酚) 会增强 MAP 激酶和 PI3 激酶 (PI3K) 通路的激活，表明氧化应激会上调激酶通路和 α- 的抗氧化作用。细胞膜中的脂肪酸被生育酚屏蔽[1]。研究表明，α-维生素 E，也称为 (+)-α-生育酚，可预防甲型流感病毒感染，也可能有效预防乙型和丙型肝炎。观察到α-生育酚的促病毒作用，特别是在HEK293T/17 细胞 [3]。

与未经治疗的猪的缺血再灌注心肌相比，α-维生素 E ((+)-α-生育酚) 抑制促炎细胞因子 IL-1、IL-6 和 IFN-γ mRNA 和蛋白质的发育，增加未受损面积[1]。 α-维生素 E（D-α-生育酚；腹腔注射或口服）治疗可通过激活二酰基甘油激酶 α (DGKα) 和减少足细胞损失来改善小鼠糖尿病肾病 [2]。

Absorption, Distribution and Excretion
The absorption of tocopherol in the digestive tract requires the presence of fat. The bioavailability of tocopherols is highly dependent on the type of isomer that is administered where the alpha-tocopherol can present a bioavailability of 36%. This isomer specificity also determines the intestinal permeability in which the gamma-tocopherol presents a very low permeability. After oral administration, the Cmax was 1353.79 ng/ml for δ-tocopherol, 547.45 ng/ml for γ-tocopherol, 704.16 ng/ml for β-tocopherol, and 2754.36 ng/ml for α-tocopherol. The Tmax is three to four hours for δ-tocopherol, γ-tocopherol, and β-tocopherol and about six hours for α-tocopherol.
The pharmacokinetic profile of tocopherol indicates a longer time of excretion for tocopherols when compared to tocotrienols. The different conjugated metabolites are excreted in the urine or feces depending on the length of their side-chain. Due to their polarity, intermediate-chain metabolites and short-chain metabolites are excreted via urine as glucoside conjugates. A mixture of all the metabolites and precursors can be found in feces. The long-chain metabolites correspond to >60% of the total metabolites in feces. It is estimated that the fecal excretion accounts for even 80% of the administered dose.
The apparent volume of distribution was 0.284 ± 0.021 mL for δ-tocopherol, 0.799 ± 0.047 mL for γ-tocopherol, and 0.556 ± 0.046 mL for β-tocopherol.
Clearance ranged from 0.081 to 0.190 L/h for δ-tocopherol, γ-tocopherol, and β-tocopherol.

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Metabolism / Metabolites
Excess tocopherol is converted into their corresponding carboxyethylhydroxychroman (CEHC), based on the isomer of tocopherol. More deeply, the metabolism of tocopherol begins with the hepatic metabolism which is led by a CYP4F2/CYP3A4-dependent ω-hydroxylation of the side chains which leads to the formation of 13'-carboxychromanol. The metabolic pathway is followed by five cycles of β-oxidation. The β-oxidation cycles function by shortening the side chains, the first cycle results in the formation of carboxydimethyldecylhydroxychromanol followed by carboxymethyloctylhydroxychromanol. These two metabolites are categorized as long-chain metabolites and they are not excreted in the urine. Some intermediate-chain metabolites that are products of two rounds of β-oxidation are carboxymethylhexylhydroxychromanol and carboxymethylbutylhydroxychromanol. These intermediate-chain metabolites can be found in human feces and urine. The catabolic end-product of tocopherols, as stated before, is CEHC which can be largely found in urine and feces. Two new metabolites have been detected in human and mice feces. These new metabolites are 12'-hydroxychromanol and 11'-hydroxychromanol. Because of their chemistry, it is thought that these metabolites can be the evidence for a ω-1 and ω-2 hydroxylation which leads to an impaired oxidation of 12'-OH followed side-chain truncation.
Hepatic.

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Biological Half-Life
The elimination half-life ranged from 2.44 to 3.02 hours for δ-tocopherol, γ-tocopherol, and β-tocopherol.

Toxicity Summary
Although all forms of Vitamin E exhibit antioxidant activity, it is known that the antioxidant activity of vitamin E is not sufficient to explain the vitamin's biological activity.
Vitamin E's anti-atherogenic activity involves the inhibition of the oxidation of LDL and the accumulation of oxLDL in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in atherogenesis as it triggers a number of events which lead to the formation of atherosclerotic plaque. In addition, vitamin E inhibits protein kinase C (PKC) activity. PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis.
Vitamin E's antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. In addition, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase (COX)-1 which in turn enhances the release of prostacyclin. Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. It is also known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. GPIIb is the alpha-subunit of this platelet membrane protein. Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. A metabolite of vitamin E called vitamin E quinone or alpha-tocopheryl quinone (TQ) is a potent anticoagulant. This metabolite inhibits vitamin K-dependent carboxylase, which is a major enzyme in the coagulation cascade.
The neuroprotective effects of vitamin E are explained by its antioxidant effects. Many disorders of the nervous system are caused by oxidative stress. Vitamin E protects against this stress, thereby protecting the nervouse system.
The immunomodulatory effects of Vitamin E have been demonstrated in vitro, where alpha-tocopherol increases mitogenic response of T lymphocytes from aged mice. The mechanism of this response by vitamin E is not well understood, however it has been suggested that vitamin E itself may have mitogenic activity independent of its antioxidant activity.
Lastly, the mechanism of action of vitamin E's antiviral effects (primarily against HIV-1) involves its antioxidant activity. Vitamin E reduces oxidative stress, which is thought to contribute to HIV-1 pathogenesis, as well as to the pathogenesis of other viral infections. Vitamin E also affects membrane integrity and fluidity and, since HIV-1 is a membraned virus, altering membrane fluidity of HIV-1 may interfere with its ability to bind to cell-receptor sites, thus decreasing its infectivity.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Vitamin E is a normal component of human milk. Maternal obesity, smoking and possibly preterm birth (<37 weeks gestational age) are associated with lower milk vitamin E levels. Lactating mothers may need to supplement their dietary intake of vitamin E to achieve the recommended daily intake of 19 mg. Daily maternal vitamin E supplementation from prenatal multivitamins can safely and modestly increase milk vitamin E levels and improve the vitamin E status of the breastfed infant compared to no supplementation. Higher daily dosages have not been studied.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
There has not been described a specific plasma transport protein for tocopherol but it is thought that it is highly bound to lipoproteins such as VLDL, HDL and chylomicrons.

[1]. Vitamin E, antioxidant and nothing more. Free Radic Biol Med. 2007 Jul 1;43(1):4-15.

[2]. Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms. Biosci Biotechnol Biochem. 2018 Jan;82(1):65-73.

[3]. Screening of melatonin, α-tocopherol, folic acid, acetyl-L-carnitine and resveratrol for anti-dengue 2 virus activity. BMC Res Notes. 2018 May 16;11(1):307.

Pharmacodynamics
The antioxidant effects of tocopherol can be translated into different changes at the pharmacodynamic level. In vitro studies have shown that this antioxidant activity can produce modification in protein kinase C (PKC) which will later be translated into an inhibition of cell death. Some other derivate effects are the anti-inflammatory properties of tocopherol which can be related to the modulation of cytokines or prostaglandins, prostanoids and thromboxanes.

C29H50O2

430.7061

430.381

59-02-9

59-02-9 (vitamin E);58-95-7 (acetate);17407-37-3 (Hemisuccinate);9002-96-4 (PEG 1000 succinate);

14985

Colorless to light yellow liquid

0.9±0.1 g/cm3

485.9±0.0 °C at 760 mmHg

2.5-3.5ºC

210.2±24.4 °C

0.0±1.2 mmHg at 25°C

1.495

11.9

29.46

1

2

12

31

503

3

O1C2C(C([H])([H])[H])=C(C([H])([H])[H])C(=C(C([H])([H])[H])C=2C([H])([H])C([H])([H])[C@@]1(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])O[H]

GVJHHUAWPYXKBD-IEOSBIPESA-N

InChI=1S/C29H50O2/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1

(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-ol

Vitamin E

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 本产品在运输和储存过程中需避光。  (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~100 mg/mL (~232.17 mM)
DMSO : ~100 mg/mL (~232.17 mM)
H2O : < 0.1 mg/mL

配方 1 中的溶解度: ≥ 11.25 mg/mL (26.12 mM) (饱和度未知) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 112.5 mg/mL 澄清 EtOH 储备液加入到400 μL PEG300 中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL 生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 11.25 mg/mL (26.12 mM) (饱和度未知) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 112.5 mg/mL 澄清乙醇储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 11.25 mg/mL (26.12 mM) (饱和度未知) in 10% EtOH + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 112.5 mg/mL 澄清 EtOH 储备液加入900 μL 玉米油中，混合均匀。

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配方 4 中的溶解度: ≥ 2.5 mg/mL (5.80 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清的 DMSO 储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL 生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 5 中的溶解度: 2.5 mg/mL (5.80 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将100μL 25.0mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 6 中的溶解度: ≥ 2.5 mg/mL (5.80 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 7 中的溶解度: 10 mg/mL (23.22 mM) in 0.5% CMC-Na/saline water (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。