Natural product; delta 5 desaturase

芝麻素预处理可有效降低脂多糖激活的大鼠原代小胶质细胞中过量一氧化氮的产生[1]。

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芝麻素和sesamolin 对LPS刺激的小胶质细胞中NO产生的抑制作用[1]
小胶质细胞已被证明是介导LPS诱导的神经元-胶质细胞培养物神经毒性的炎症因子的主要来源。因此，将用芝麻素或sesamolin 预处理的大鼠原代小胶质细胞进行LPS处理，检测诱导的NO释放，以评估芝麻素和sesamolin 是否具有神经保护作用。结果表明，芝麻素或sesamolin 预处理以剂量依赖的方式抑制了LPS刺激的小胶质细胞中NO的过量产生（图1）。对于LPS刺激的小胶质细胞中NO产生的显著减弱，芝麻素似乎比sesamolin 更有效。

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与芝麻油一起孵育增加了产花生四烯酸真菌高山孢霉的菌丝体二高γ-亚麻酸含量，但降低了其花生四烯酸含量[Shimizu，S.，K.Akimoto，H.Kawashima，Y.Shinmen和H.Yamada（1989）J.Am.oil Chem.Soc.66237-241]。导致这些影响的因素被分离并确定为（+）-芝麻素。在真菌无细胞提取物和大鼠肝微粒体的实验中获得的结果表明，（+）-芝麻素在低浓度下特异性抑制δ5去饱和酶，但不抑制δ6、δ9和δ12去饱和酶。动力学分析表明，（+）-芝麻素是一种非竞争性抑制剂（Ki用于大鼠肝脏δ5去饱和酶，155微M）。（+）-芝麻素、（+）-芝麻素和（+）-episamin也仅抑制真菌和肝脏的δ5脱氢酶。这些结果表明，芝麻或其油中存在的（+）-芝麻素和相关木脂素化合物是微生物和动物多不饱和脂肪酸生物合成中δ5去饱和酶的特异性抑制剂[2]。

芝麻素（op；20 毫克/公斤/天）可显着降低雄性沙鼠 (60-85 克) 的梗死面积约 50%[1]。还使用沙土鼠在体内观察了Sesamin/芝麻素和芝麻素的神经保护作用，沙土鼠受到右颈总动脉和右大脑中动脉闭塞引起的局灶性脑缺血。与对照组相比，反复治疗芝麻素或含有芝麻素和芝麻素的粗芝麻油提取物可显著减少梗死面积，通过2,3,5-三苯基四唑氯化物染色可见，减少约50%。这些结果表明，芝麻素和芝麻素对脑缺血具有有效的神经保护作用。

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芝麻素和芝麻素对脑缺血沙土鼠的神经保护作用 观察到芝麻素和芝麻素在LPS刺激的小胶质细胞中的神经保护作用，引发了人们对这些芝麻木脂素是否可以在体内作为抗缺血药物的探究。为了研究这种可能性，沙土鼠在局灶性脑缺血前反复服用芝麻素或含有芝麻素和芝麻素的粗芝麻油提取物。所有接受治疗的动物都发现皮质和尾状壳核梗死。通过TTC染色显示的三组（对照组、纯化芝麻素和粗芝麻油提取物）的平均总梗死面积（图2）分别为91.9 mm3（19.4±2.0%）、46.5 mm3（9.8±3.1%）和40.2 mm3（8.5±3.9%）（图3）。这些结果表明，用芝麻素或粗芝麻油提取物预处理四天，脑缺血时沙土鼠脑的梗死面积分别显著减少了56%和49%（p<0.05）。

NO生成检测[1]
通过测量条件培养基中稳定的NO代谢产物亚硝酸盐的水平来测定NO的产生。简而言之，在室温和黑暗中，将100 L培养上清液与等体积的Griess试剂（1份0.1%萘乙二胺和1份1%磺胺溶于5%H3PO4中）在96孔组织培养板中反应10分钟。用微孔板读数器记录540 nm处的吸光度。

LPS刺激经芝麻素/Sesamin或sesamolin 预处理的小胶质细胞[1]
为了评估芝麻素/Sesamin和sesamolin 预处理是否具有潜在的神经保护活性，进行了一项初步测试，以检测它们对LPS刺激的大鼠小胶质细胞NO水平的抑制能力。在该试验中，在补充LPS之前，将细胞与溶于二甲亚砜（DMSO）的芝麻素或芝麻素一起孵育1小时，该溶剂的最终浓度不得超过0.1%。

Cerebral ischemia of gerbils [1]
Eighteen male gerbils (60-85 g) were randomly divided into three groups fed by regular meal supplemented (op., 20 mg/kg/day), respectively, with saline (control), purified Sesamin, and the crude sesame oil extract containing 90% Sesamin and 10% sesamolin. After feeding for 4 days, each gerbil was anesthetized with chlorohydrate (400 mg/kg) intraperitoneally and its body temperature was maintained at 37°C with a heating pad (CMA/150). A midline neck incision was made and the right carotid artery was exposed and separated from the vago-sympathetic trunk. The right carotid artery was loosely encircled with a 4-0 suture for later occlusion. The gerbil’s head was placed in a stereotaxic frame with the nose bar positioned 4.0 mm below the horizontal line. Following a midline incision, the skull was partially removed to expose the right middle cerebral artery. The middle cerebral artery was loosely encircled with an 8-0 suture for later occlusion. A focal cerebral ischemia was induced by occlusion of the right common carotid artery (CCA) and the right middle cerebral artery (MCA) for 60 min, followed by reperfusion for 3 h. MBF 3D, a laser probe (0.8 mm in diameter) of a Laser Doppler Blood Flow monitor was positioned onto the cortex with its tip close to the middle cerebral artery. Cerebral blood flow dropped to less than 5% of basal after the occlusion of the MCA. Cerebral blood flow reached its minimal level within 5 min after the start of the occlusion and was confirmed to remain at this level throughout the monitoring period to ensure the validity of the stroke model.

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LD50: Mice 3800mg/kg (i.g.); Rats 6150mg/kg (i.g.)

Mice and rats

[1]. Neuroprotective effects of sesamin and sesamolin on gerbil brain in cerebral ischemia. Int J Biomed Sci. 2006 Sep;2(3):284-8.

[2]. Sesamin is a potent and specific inhibitor of delta 5 desaturase in polyunsaturated fatty acidbiosynthesis. Lipids. 1991 Jul;26(7):512-6.

(+)-sesamin is a lignan that consists of tetrahydro-1H,3H-furo[3,4-c]furan substituted by 1,3-benzodioxole groups at positions 1 and 4 (the 1S,3aR,4S,6aR stereoisomer). Isolated from Cinnamomum camphora, it exhibits cytotoxic activity. It has a role as an antineoplastic agent, a neuroprotective agent and a plant metabolite. It is a lignan, a member of benzodioxoles and a furofuran.
Sesamin has been reported in Otanthus maritimus, Apis, and other organisms with data available.
See also: Sesame Oil (part of).

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Sesamin and sesamolin, abundant lignans found in sesame oil, have been demonstrated to possess several bioactivities beneficial for human health. Excess generation of nitric oxide in lipopolysaccharide-stimulated rat primary microglia cells was significantly attenuated when they were pretreated with sesamin or sesamolin. The neuroprotective effect of sesamin and sesamolin was also observed in vivo using gerbils subjected to a focal cerebral ischemia induced by occlusion of the right common carotid artery and the right middle cerebral artery. Repeated treatment of sesamin or a crude sesame oil extract containing both sesamin and sesamolin significantly reduced the infarct size, visualized via 2,3,5-triphenyltetrazolium chloride staining, by approximately 50% when compared with the control group. These results suggest that sesamin and sesamolin exert effective neuroprotection against cerbral ischemia. [1]

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Repeated pretreatment with Sesamin or the crude sesame oil extract containing both sesamin and sesamolin for four days significantly reduced infarct sizes by approximately 50% in the present study. Although the mechanism of neuroprotection is not understood, the combined results of in vitro and in vivo experiments suggest that a reduction of neuronal injury may be related to an inhibition of the induced NO release when the brain produces free radicals during cerebral ishemia at a rate sufficient to overcome endogenous antioxidant defenses. It has also been proposed that sesamin and sesamolin may act as free radical-scavengers and inhibitors of lipid peroxidation (8). The neuroprotective efficacy of sesamin and sesamolin may also reflect their ability to scavenge free radicals over-produced during cerebral ischmia.
In conclusion, oral administration of Sesamin or the crude sesame oil extract was neuroprotective in terms of reducing ischemic damage in experimental MCA+CCA occluded gerbils. The present results provide experimental data to sustain the potency of sesamin and sesamolin for neuroprotection against hypoxia or brain damage. Further investigation of optimal dosages of sesamin, sesamolin and the crude sesame oil extract are warranted in the future. Moreover, it is noteworthy that the crude sesame oil extract and the pure form of sesamin were equally effective in providing neuroprotection in this study. The pure form of sesamin requires many steps in its purification that leads to a relatively low recovery yield. Since the crude sesame oil extract demonstrates the same neuroprotective effect as the purified sesamin, this crude sesame oil extract seems to possess market potential as a supplement in health food products. [1]

C20H18O6

354.35

354.11

C, 67.79; H, 5.12; O, 27.09

607-80-7

(-)-Sesamin;13079-95-3

72307

White to off-white solid powder

1.4±0.1 g/cm3

504.4±50.0 °C at 760 mmHg

122-124ºC

212.3±30.0 °C

0.0±1.2 mmHg at 25°C

1.623

3.32

55.38

0

6

2

26

482

4

C1[C@H]2[C@H](CO[C@@H]2C3=CC4=C(C=C3)OCO4)[C@H](O1)C5=CC6=C(C=C5)OCO6

PEYUIKBAABKQKQ-AFHBHXEDSA-N

InChI=1S/C20H18O6/c1-3-15-17(25-9-23-15)5-11(1)19-13-7-22-20(14(13)8-21-19)12-2-4-16-18(6-12)26-10-24-16/h1-6,13-14,19-20H,7-10H2/t13-,14-,19+,20+/m0/s1

5-[(3S,3aR,6S,6aR)-3-(1,3-benzodioxol-5-yl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-6-yl]-1,3-benzodioxole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (7.06 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DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；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: ≥ 2.5 mg/mL (7.06 mM) (饱和度未知) 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), 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: ≥ 2.5 mg/mL (7.06 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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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。