Inhibition of two stages of melanin synthesis by sesamol,sesamin and sesamolin

Objective: To investigate the antimelanogenesis properties of three sesame compoundssesamol, sesamin and sesamolin via two stages of melanin synthesis vis-à-vis sunscreen function and enzyme inhibition in melanoma cell line in order to search for alternative depigmenting agents.Methods: Antimelanogenic effects of sesame lignans were assessed in SK-MEL2 compared with the reference depigmenting agents, kojic acid and b-arbutin, in order to evaluate:(a) the sunscreen function of sesamol, sesamin and sesamolin by measurement of UV absorbtion property;(b) the inhibition of tyrosinase activity through mushroom and cellular tyrosinase; and(c) the effect on melanin content and melanogenic protein expression(tyrosinase, TRP-1 and TRP-2) by Western blot analysis; and(d) the toxicity of sesamol, sesamin and sesamolin to cells using cell cytotoxicity assay.Results: The results showed that sesamin, sesamolin and sesamol exerted satisfiable sunscreen function by absorbed UVB at 290 nm. Sesamol exhibited the highest inhibition of mushroom tyrosinase activity, but lipophilic sesamolin exhibited the highest cellular tyrosinase inhibition(IC_(50) of 1.6 μM) followed by sesamin, sesamol, and kojic acid,respectively. The order from high to low inhibition of melanin pigment was detected in the SK-MEL2 treated with sesamolin, sesamin, sesamol, kojic acid, and b-arbutin,respectively. Sesamolin and sesamin successfully inhibited cellular tyrosinase activity and respectively decreased TRP-1/TRP-2(36%/15%) and TRP-1 levels(16%), thereby inhibiting melanogenesis via antityrosinase activity. No cytotoxicity to SK-MEL2 or Vero(normal) cell lines was observed at the lignan concentrations that exerted an antimelanogenic effect.Conclusions: Three sesame lignans prevent melanin synthesis through 2 stages:(a) by blocking melanin-induction and(b) by interrupting melanogenic enzyme production. This study provides evidence that sesamol, sesamin and sesamolin are potential for antimelanogenesis agents.

Sesamol Alleviates the Cytotoxic Effect of Cyclophosphamide on Normal Human Lung WI-38 Cells via Suppressing RAGE/NF-κB/Autophagy Signaling

Cyclophosphamide(CYL)is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia.Though,CYL has been documented to induce lung toxicity.Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns(DAMPs).Sesamol(SES)is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet.This study aims to inves-tigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells,WI-38 cell line,without suppressing its efficacy.Cells were pretreated with SES and/or CYL for 24 h,then cell viability was estimated by MTS and trypan blue assays.The mode of cell death was determined by AO/EB staining.Additionally,caspase-3 level,oxidative stress,and inflammatory markers were evaluated by colorimetric and ELISA techniques.qRT-PCR was performed to evaluate RAGE,NF-κB,and Beclin-1 mRNA-expression.CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling,which were all attenuated after pretreatment with SES.Thus,we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling,which is a natural safe therapeutic option against CYL toxicities.

Antioxidant Activity of Sesamol Derivatives and Their Drug Delivery via C60 Nanocage: a Theoretical Study

The antioxidant activity of sesamol derivatives and their drug delivery via fullerene were investigated. Fullerene can interact with sesamol derivatives, and their adsorptions were possible from the energetic viewpoint. Adding the NH_2 group to sesamol can improve the sensitivity of sesamol toward fullerene surface. The NH_2 and OMe substitutions increase the antioxidant activity of sesamol. The results can also be used to select novel sesamol derivatives with higher antioxidant activity and higher drug delivery ability.

Sesamol inhibits atherogenic LDL-induced endothelial cell senescence in vivo and in vitro

OBJECTIVE Highly electronegative L5 low-density lipoprotein(LDL),an atherogenic LDL,induces endothelial cell(EC)senescence and has been implicated in the progression of atherosclerosis.We examine whether sesamol,a natural organic compound and component of sesame oil,prevents EC senescence induced by electronegative LDL(L5)and to investigate the underlying mechanisms.METHODS Syrian hamsters,which have a LDL profile similar to that of humans,were fed a normal chow diet(control),a high-fat diet(HFD),or a HFD supplemented with the administration of 50 or 100mg·kg-1 sesamol via oral gavage(HFD+sesamol)for 16 weeks(n=10 per group).Among these groups,we compared plasma L5 levels and aortic endothelial senescence in the aortic arch.In vitro,we examined the effects of sesamol on human aortic endothelial cell(HAEC)senescence and signaling pathways induced by L5.RESULTS Hamsters in the HFD group had higher plasma L5 levels than did the HFD+sesamol groups or control group.Betagalactosidase(gal)staining showed that aortic endothelial senescence was markedly increased in the aortic arch of the HFD group but not in that of the HFD+sesamol groups when compared with the control group.In vitro,treatment of HAECs with sesamol(1-3mol·L-1)blocked L5-induced EC senescence in a dose-dependent manner.Sesamol also markedly inhibited the L5-induced phosphorylation of p38 MAPK and p53 activation and increased Mdm2 and phosphorylation of Akt.CONCLUSION The critical findings of this study suggest that sesamol may provide protection against atherosclerosis and the development of cardiovascular disease in humans.

Biomolecular changes and DNA targeting effect of sesamol in human lung adenocarcinoma (SK-LU-1) cells by FTIR microscopy

Objective: To investigate biomolecular alteration of sesamol on human lung adenocarcinoma(SK-LU-1) cells compared with cisplatin using Fourier transform infrared microscopy(FTIR). Methods: Cytotoxicity of sesamol was investigated against SK-LU-1 cells by using neutral red. DNA fragmentation and the cell cycle analysis were determined by agarose gel electrophoresis and flow cytometry, respectively. The FTIR microscopy technique was applied to explore the changes in cellular biochemical compositions in cells treated with sesamol that the biochemical and biological assays cannot cover. The alkylating property was determined by 4-(4-nitrobenzyl)pyridine assay. Results: Sesamol and cisplatin exerted an antiproliferative effect at 48 h with respective IC50 values of 2.7 and 0.07 m M. Both induced apoptosis by causing DNA damage and accumulation of cell populations at sub-G1. FTIR microscopy and Principle Component Analysis clearly discriminated the sesamol-and cisplatin-treated cells from the untreated cells or control. A significant increase of total lipid content was found in cisplatin-treated cells. Conformational changes in the proteins secondary structure from the β-helix to the β-sheet were found in both sesamol-and cisplatin-treated cells, as well as significant reductions in relative DNA content of both compared to the control were observed, suggesting DNA damage. A shift in the peak position of DNA region provides insight on the DNA interactions. Conclusions: The non-alkylating effect of sesamol based on the nitrobenzyl pyridine assay delineates the non-covalent binding mode of sesamol on DNA. Hydrogen bonding is the binding mode of sesamol on DNA, while for cisplatin it was covalent and hydrogen bonding.

New fluorimetric assay of horseradish peroxidase using sesamol as substrate and its application to EIA

Horseradish peroxidase (HRP) is generally used as a label enzyme in enzyme immunoassay (EIA).The procedure used for HRP detection in EIA is critical for sensitivity and precision.This paper describes a novel fluorimetric assay for horseradish peroxidase (HRP) using sesamol as substrate.The principle of the assay is as follow:sesamol (3,4-methylenedioxy phenol) is reacted enzymatically in the presence of hydrogen peroxide to produce dimeric sesamol.The dimer is fluorescent and can be detected sensitively at ex.347 nm,em.427 nm.The measurable range of HRP was 1.0×10-18 to 1.0×10-15 mol/assay,with a detection limit of 1.0×10-18 mol/assay.The coefficient of variation (CV,n=8) was examined at each point on the standard curve,with a mean CV percentage of 3.8%.This assay system was applied to thyroid stimulating hormone (TSH) EIA using HRP as the label enzyme.

高温条件下芝麻林素转化为芝麻酚的规律及其反应机制

本实验探究不同因素对高温条件下芝麻林素转化为芝麻酚的影响及其转化动力学,并通过液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)分析相关转化路径。结果表明:丙三醇是芝麻林素转化为芝麻酚的理想介质,反应温度和反应时间对芝麻酚生成率影响显著;在160~200℃范围内,芝麻林素的转化符合一级动力学方程特征,且反应速率常数与温度呈正相关,半衰期和十分之一衰期与温度呈负相关,通过阿伦尼乌斯方程计算出该反应活化能为(104.50±4.32)kJ/mol;LC-MS/MS分析结果表明以芝麻林素为底物的反应系统包括芝麻酚的生成和转化两条转化路径。

量子化学计算白藜芦醇与芝麻酚在油脂中的抗氧化协同作用

目的:研究白藜芦醇与芝麻酚间的抗氧化协同机理。方法:通过DPPH和氢过氧化物分别检测葵花子油中自由基和过氧自由基的含量变化,并结合诱导期的测定,优化组合白藜芦醇与芝麻酚二者比例,并采用量子化学计算模拟反应过程。结果:在180℃加热2 h,添加白藜芦醇与芝麻酚的葵花籽油中,总自由基含量分别为(0.08±0.03),(0.20±0.03)mol/L,相比于空白[(0.44±0.01)mol/L],白藜芦醇具有最佳抑制效率,且芝麻酚清除过氧自由基的能力最强。二者在纯化的葵花籽油中发生协同作用的最佳添加量为1400,200 mg/kg,且在180℃降解速率下,白藜芦醇具有保护芝麻酚的作用。结论:利用量子化学的手段发现二者存在动态平衡的过程,由于白藜芦醇的添加量是芝麻酚的7倍,所以反应更倾向于白藜芦醇向芝麻酚自由基供H。

芝麻酚对鱼油酸奶品质及氧化稳定性的影响

目的开发含二十二碳六烯酸(docosahexaenoic acid,DHA)鱼油的强化型酸奶,探究芝麻酚对鱼油酸奶品质及氧化稳定性的影响。方法将含芝麻酚的鱼油乳液应用于发酵酸奶中,通过分析酸奶的感官评价、pH、持水力、质构特性、流变特性、自由基清除活性、脂质氧化产物和DHA保留率的变化,探究芝麻酚对鱼油强化酸奶发酵品质和氧化稳定性的影响。结果鱼油乳液的添加对酸奶的pH和自由基清除活性无显著性影响,但降低了感官评价、持水力、硬度、4℃恒温黏度、储能模量、损耗模量和4~30℃变温黏度,加速了脂质氧化。芝麻酚的添加未显著改变含鱼油酸奶的pH,增加了感官评价、持水力、硬度、4℃恒温黏度、储能模量、损耗模量和4~30℃变温黏度,提高了自由基清除活性、脂质氧化稳定性和DHA保留率(81.19%)。结论添加300μmol/L芝麻酚显著改善鱼油酸奶的品质,并提高了酸奶的抗氧化功效,为DHA酸奶产品的开发提供了理论参考。

芝麻酚对小鼠银屑病样炎症的抑制作用

目的:探究芝麻酚对银屑病所致皮肤损伤的改善作用。方法:采用小鼠背部连续7 d涂抹5%咪喹莫特(IMQ)乳膏构建银屑病模型,建模前1周至结束使用芝麻酚皮肤表面涂抹干预,探究芝麻酚对皮肤的保护作用;观察及测定各组小鼠背部厚度、银屑病面积与严重性指数(PASI)、脾脏指数、病理组织切片、皮肤组织中细胞因子[白介素(IL)-17、IL-23、肿瘤坏死因子α(TNF-α)等炎症因子及趋化因子(C-X-C基序)配体1(CXCL1)和趋化因子配体20(CCL20)]及血清中炎症因子(IL-17、TNF-α),分析芝麻酚抑制小鼠银屑病样炎症的作用。结果:模型组小鼠背部皮肤出现了典型银屑病的皮损表现及病理特征,涂抹3%的芝麻酚可以减轻皮肤损伤和表皮增生情况,降低脾脏指数,显著降低皮肤组织及血清中炎症因子的表达。结论:芝麻酚可以明显改善银屑病模型小鼠的皮肤损伤,降低其病理特征并下调机体炎症状态。

芝麻酚与季铵盐共催化环加成反应合成植物油基环状碳酸酯

旨在为植物油基环状碳酸酯产品的制备提供新的研究思路,以环氧大豆油脂肪酸甲酯和二氧化碳为原料,在催化剂季铵盐和氢键供体的作用下,合成植物油基环状碳酸酯。通过单因素实验对植物油基环状碳酸酯的合成条件进行优化,对反应动力学进行了分析,同时对产物植物油基环状碳酸酯进行了红外表征。结果表明:植物油基环状碳酸酯最佳合成条件为以芝麻酚为氢键供体、四丁基溴化铵与芝麻酚物质的量比2∶1、四丁基溴化铵用量10%(以原料环氧键物质的量计)、反应温度120℃、反应压力1.0 MPa、反应时间10 h,在此条件下植物油基环状碳酸酯的产率达91.4%;反应动力学分析表明,芝麻酚的加入降低了反应的活化能,有利于植物油基环状碳酸酯的合成;红外光谱表征结果证明成功合成了产物。综上,实现了无溶剂条件下高效合成植物油基环状碳酸酯。

芝麻酚通过AMPK信号通路调控巨噬细胞极化减轻脂肪组织炎症

目的探讨芝麻酚(sesamol,SEM)对高脂饮食诱导的肥胖小鼠脂肪组织炎症的影响及对脂多糖(lipopolysaccharide,LPS)诱导的RAW264.7巨噬细胞极化的调控分子机制。方法将C57BL/6J小鼠随机分成正常对照组、肥胖模型对照组和SEM干预组。干预结束后取小鼠血清和脂肪组织,ELISA法测定小鼠血清和脂肪组织中炎症因子、抗炎因子及趋化因子的分泌水平,Western blot法测定脂肪组织巨噬细胞M1型极化标志物的蛋白表达水平。以LPS刺激RAW264.7巨噬细胞诱导炎症模型并用SEM进行干预,使用AMPK抑制剂compound C进行机制探讨和验证,Western blot法检测巨噬细胞极化标志物及AMPK信号通路相关蛋白表达水平,ELISA法检测巨噬细胞炎症相关因子。结果体内实验发现,SEM可降低肥胖小鼠血清和脂肪组织中IL-6、TNF-α和MCP-1分泌水平,提高IL-10分泌水平,减少M1型巨噬细胞标志物CD11c蛋白表达。体外实验发现,SEM能够激活巨噬细胞AMPK,上调PGC-1α、下调NF-κB表达,降低CD11c、IL-6、TNF-α,升高CD206、IL-10水平,而compound C可以减弱SEM的上述作用。结论SEM可通过激活AMPK信号通路调控巨噬细胞极化减轻脂肪组织炎症。

芝麻酚通过AMPK/SIRT1/NF-κB信号通路调控食管鳞状细胞癌Eca109细胞的自噬和凋亡

目的:探讨芝麻酚(SEM)通过腺苷酸活化蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)/核因子κB(NF-κB)通路影响食管鳞状细胞癌(ESCC)Eca109细胞自噬和凋亡的机制。方法:用不同浓度的SEM(0、1.5625、3.125、6.25、12.5、25、50、100、200、400μmol/L)分别处理Eca109细胞、人食管上皮细胞HEEpiC 48 h,CCK-8法检测细胞增殖率,筛选适宜的SEM浓度用于后续实验。将Eca109细胞分为对照组(CK组,0μmol/L)、低剂量SEM组(SEM-L组,25μmol/L)、中剂量SEM组(SEM-M组,50μmol/L)、高剂量SEM组(SEM-H组,100μmol/L)、高剂量SEM+Compound C(AMPK抑制剂)组(SEM-H+Compound C组,100μmol/L+10μmol/L),所有各组Eca109细胞在对应的药物浓度下处理48 h后,CCK-8法检测Eca109细胞增殖,流式细胞术检测细胞凋亡,透射电镜观察Eca109细胞内自噬小体,WB法检测Eca109细胞中微管相关蛋白1轻链3(LC3)-Ⅱ/LC3-Ⅰ、Beclin-1、B淋巴细胞瘤2(Bcl2)、Bcl2相关X蛋白(BAX)、p-AMPK、SIRT1、p-NF-κB p65的表达。结果:通过预实验选择SEM实验浓度为25、50、100μmol/L用于正式研究。在SEM处理下,与CK组比较,SEM-L组、SEM-M组、SEM-H组Eca109细胞的增殖水平(24、48 h)和Bcl2、p-NF-κB p65蛋白表达均显著降低,细胞凋亡率和自噬小体数量、LC3-Ⅱ/LC3-Ⅰ、Beclin-1、BAX、p-AMPK、SIRT1蛋白表达显著升高,且呈剂量依赖性(均P<0.05);与SEM-H组比较,SEM-H+Compound C组Eca109细胞增殖水平(24、48 h)和Bcl2、p-NF-κB p65蛋白表达均显著升高,细胞凋亡率和自噬小体数量、LC3-Ⅱ/LC3-Ⅰ、Beclin-1、BAX、p-AMPK、SIRT1蛋白表达均显著降低(均P<0.05)。结论:SEM可能通过激活AMPK/SIRT1信号通路而抑制NF-κB活性来促进Eca109细胞自噬与凋亡。

HPLC测定芝麻油中木脂素类化合物含量研究

建立了HPLC同时测定芝麻油中芝麻素、芝麻林素、芝麻酚和芝麻素酚4种木脂素化合物含量的方法。首先确定了HPLC法分离和测定这4种物质的色谱条件,色谱柱为ODS-C18(250 mm×4.6 mm,5μm);检测波长:芝麻素和芝麻林素为287 nm,芝麻酚和芝麻素酚为293 nm;柱温30℃;流速0.8 mL/min,流动相为甲醇(A)和水(B)进行梯度洗脱,梯度为0 min(A,60%)→6 min(A,60%)→9 min(A,75%)→24min(A,70%)→27 min(A,60%)→32 min(A,60%)。同时比较筛选了皂化法、氧化铝柱层析法和薄层层析法3种去除脂肪类成分的前处理方法,确定薄层层析法为最有效的前处理方法。

抗氧剂芝麻酚制备技术及抗氧化活性评述

芝麻酚是一种优良的抗氧剂和重要药物中间体。本文详细介绍了芝麻酚的植物提取技术、以黄樟油素为原料的半合成技术、从邻苯二酚出发的全合成技术 ,分析了各种技术合成芝麻酚产品的技术优势和工业化研究的重点 ,提出了优先发展半合成技术 ,努力开发全合成技术的发展思路 。

芝麻素的研究及开发

阐述了芝麻素的主要来源 ,开发的意义 ,芝麻素的研究现状 ,存在问题及其发展趋势。并认为芝麻素的产业化在我国具有可行性。

芝麻酚清除O_2^-·自由基的活性研究

通过改良邻苯三酚自氧化法(简称325nm法)测定芝麻酚清除自由基能力。试验表明:在等质量浓度条件下,芝麻酚对超氧阴离子自由基(O2-·)的清除效率高于BHT及VE,当芝麻酚的质量浓度为0.8g/L时,对O2-·自由基的清除率达到80.68%,高于BHT的77.12%及VE的55.65%。因此,芝麻酚具有较强的清除O2-·自由基的能力。

超高效液相色谱法测定芝麻油中芝麻酚含量

目的:建立芝麻油样品中芝麻酚含量的超高效液相色谱(UPLC)测定方法。方法:样品经90%乙腈水提取后,用水定容,进行UPLC定量分析。实验采用BEH C18色谱柱,以水和乙腈为流动相。结果:方法测定低限为5.0mg/kg,在5.0～500.0mg/kg添加水平范围内,芝麻酚回收率为81.5%～90.9%,相对标准偏差为1.8%～3.5%。结论:方法准确度和稳定性较好,操作简单快捷,样品净化效果好,测定低限能够满足限量要求。

芝麻酚对猪精液冷冻保存效果的影响

为了探究芝麻酚对猪精液冷冻保存效果的影响,用手握法采集成年杜洛克公猪精液,预处理后添加不同浓度芝麻酚(0,0.05,0.10,0.15,0.20和0.25g/L)的冷冻稀释液进行稀释,冷冻-解冻后检测猪精子活率、质膜完整性(低渗肿胀试验)、线粒体活性、顶体完整性、DNA完整性以及超氧化歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性等。结果显示:当芝麻酚添加浓度为0.20g/L时,解冻后精子活率、线粒体活性、质膜完整率和顶体完整率为最高,相比较于对照组,分别提高了12.67%、19.07%、18.78%和14.09%(P<0.05);MDA含量最低为2.04nmol/mL(P<0.05);SOD和GSH-Px酶活最高为73.04U/mL和237.59U/I(P<0.05)。当芝麻酚添加浓度为0.25g/L时,DNA完整性最高为72.46%(P<0.05)。当芝麻酚添加浓度为0.15g/L时,CAT酶活最高为3.44U/mL(P<0.05)。结果表明:与对照组相比较,在猪精液冷冻稀释液中添加适当浓度的芝麻酚能显著提高解冻后猪精子活率、功能完整性和抗氧化能力(P<0.05),且当芝麻酚的浓度为0.2g/L时对猪精子冷冻保存效果最好。研究结果表明,芝麻酚作为一种天然抗氧化剂,对猪精子冷冻保存具有良好的效果。

芝麻酚对茶油抗氧化活性研究

以茶油为底物,以过氧化值为指标,研究了芝麻酚对油脂的抗氧化性能。结果表明,芝麻酚对茶油具有显著的抗氧化活性;在茶油中添加浓度为0.01%、0.02%、0.04%、0.06%、0.08%、0.1%(质量分数)6个油样中,样品均表现出较强的抗氧化活性,经过10d强化处理的茶油样品(空白对照)的POV值达到32.16mmol/kg,而添加0.10%(质量分数)芝麻酚的样品的POV值仅为7.94mmol/kg。芝麻酚的抗氧化效果与同浓度的BHT相当,强于同浓度的VE。