The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG) Protects Non-Malignant Lung Cells from Radiation Damage

Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed’s protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure.     

云南产五味子科药用植物化学成分研究进展

五味子科药用植物中的主要生物活性成分为木脂素、羊毛甾烯型三萜酸及内酯 ,具有抗肝炎、抗癌、抗爱滋病毒、PAF拮抗及保护中枢神经系统等多方面的药理作用。为促进进一步的研究与开发利用 ,本文结合自己的工作 ,对云南产五味子科药用植物化学成分研究进展进行了综述。     

五味子籽压榨油中3种木脂素含量的测定及对酒精肝损伤的保护作用研究

采用高效液相色谱法测定五味子籽压榨油中的五味子醇甲、五味子甲素和五味子乙素,结果显示其含量分别为2.518%、0.577%和2.736%.五味子籽压榨油对小鼠的半数致死量(LD50)为10.8g/kg,30d小鼠喂养试验的血液生化指标均在正常范围内,表明五味子籽压榨油的毒性较低.通过建立小鼠酒精性肝损伤模型,并分别给予小鼠不同量的五味子籽压榨油以研究其对小鼠酒精肝损伤的保护作用,结果表明高剂量组与模型组呈显著性差异,证明五味子籽压榨油具有一定的肝保护作用.     

Conformational Solvation Studies of LIGNOLs with Molecular Dynamics and Conductor-Like Screening Model

Molecular dynamics (MD) simulations were performed on sterically hindered α-conidendrin-based chiral 1,4-diols (LIGNOLs) from the naturally occurring lignan hydroxymatairesinol (HMR) using the GROMACS software. The aim of this study was to explore the conformational behaviour of the LIGNOLs in aqueous solution adopting the TIP4P model. The topologies of the LIGNOLs were constructed manually and they were modeled with the OPLS-AA force field implemented in GROMACS. The four most relevant torsional angles in the LIGNOLs were properly analyzed during the simulations. The determining property for the conformation preferred in aqueous solution was found to be the lowest energy in gas phase. The solvation effects on the LIGNOLs were also studied by quantum chemical calculations applying the COnductor-like Screening MOdel (COSMO). The hydration studies of the MD simulations showed that several of these LIGNOLs, produced from a renewable source, have a great potential of acting as chiral catalysts.     

Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605)

The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS) and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG) is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605) in asbestos-exposed, elicited murine peritoneal macrophages as an in vitro model of tissue phagocytic response to the presence of asbestos in the pleural space. Murine peritoneal macrophages (MFs) were exposed to crocidolite asbestos fibers (20 µg/cm²) and evaluated at various times post exposure for cytotoxicity, ROS generation, malondialdehyde (MDA), and levels of 8-iso Prostaglandin F2α (8-isoP). We then evaluated the ability of LGM2605 to mitigate asbestos-induced oxidative stress by administering LGM2605 (50 µM) 4-h prior to asbestos exposure. We observed a significant (p < 0.0001), time-dependent increase in asbestos-induced cytotoxicity, ROS generation, and the release of MDA and 8-iso Prostaglandin F2α, markers of lipid peroxidation, which increased linearly over time. LGM2605 treatment significantly (p < 0.0001) reduced asbestos-induced cytotoxicity and ROS generation, while decreasing levels of MDA and 8-isoP by 71%–88% and 41%–73%, respectively. Importantly, exposure to asbestos fibers induced cell protective defenses, such as cellular Nrf2 activation and the expression of phase II antioxidant enzymes, HO-1 and Nqo1 that were further enhanced by LGM2605 treatment. LGM2605 boosted antioxidant defenses, as well as reduced asbestos-induced ROS generation and markers of oxidative stress in murine peritoneal macrophages, supporting its possible use as a chemoprevention agent in the development of asbestos-induced malignant mesothelioma.     

Sesame seed is a rich source of dietary lignans

The variation in the contents of sesamin and sesamolin was studied in oils extracted from 65 samples of sesame seeds (Sesamum indicum L.) from plants with shattering (n=29), semishattering (n=7), and nondehiscent (n=29) capsules. The oil content ranged from 32.5 to 50.6% and was greater in white than black seeds (P<0.001). The sesamin and sesamolin contents in seeds ranged from 7 to 712 mg/100 g (mean±SD, 163±141 mg/100 g) and from 21 to 297 mg/100 g (101±58 mg/100 g), respectively, with no difference between black and white seeds. Thus, there was a wide variation in the contents of sesamin and sesamolin, which were positively correlated (R ²=0.66, P<0.001). There were negative correlations between the contents of sesamin and the contents of sesaminol (R ²=0.37) and sesamolinol (R ²=0.36) and between the content of sesamolin and those of sesaminol (R ²=0.35) and sesamolinol (R ²=0.46) (P<0.001). Sesame seeds had an average of 0.63% lignans, making them a rich source of dietary lignans.     

Nutraceutical functions of sesame: a review

The results of recent food chemical and nutraceutical studies on the traditionally well-known health value of sesame are described, including some aspects of the utilization of sesame. The highly antioxidative activity of sesame oil was clarified and found to involve newly discovered lignans. The antiaging effect of sesame was elucidated to be due to the strong vitamin E activity caused by a novel synergistic effect of sesame lignans with tocopherols resulting from the inhibition of metabolic decomposition of tocopherols by sesame lignans. The specific inhibitory action of sesame lignans on Delta5 desaturase in polyunsaturated fatty acid synthesis was found in studies on the microbial production of polyunsaturated fatty acids. This effect of sesame lignans was extended to various effects on fatty acid metabolism involving lowering fatty acid concentration in liver and serum due to acceleration of fatty acid oxidation and suppression of fatty acid synthesis, and the controlling influence on the ratio of n-6/n-3 polyunsaturated fatty acids under excess intake of either n-6 or n-3 fatty acids in the diet. Sesame lignans lowered the cholesterol concentration in serum, especially in combination with tocopherol, due to the inhibition of absorption from the intestine and suppression of synthesis in the liver. Sesame lignans also showed other useful functions such as acceleration of alcohol decomposition in the liver, antihypertensive activity, immunoregulatory activities, anticarcinogenic activity, and others.     

亚麻木酚素对AAPH诱导的红细胞和肝组织氧化应激的保护作用

探讨了亚麻木酚素的抗氧化活性及机制,测定了亚麻木酚素对DPPH自由基的清除能力,建立AAPH氧化损伤大鼠红细胞和肝组织模型,研究了亚麻木酚素对氧化损伤红细胞溶血率和血红蛋白氧化率的影响,以及其对红细胞和肝组织氧化损伤模型丙二醛(MDA)和抗氧化酶的影响。结果显示:亚麻木酚素对DPPH自由基具有清除作用;亚麻木酚素对红细胞溶血和血红蛋白氧化的保护作用呈现浓度依赖性,与AAPH作用4 h的模型组相比,50μmol/L和100μmol/L亚麻木酚素的保护作用显著提高;在AAPH诱导的红细胞氧化应激模型中,100μmol/L和150μmol/L亚麻木酚素显著降低了AAPH损伤4 h时MDA含量,并显著提高了GSH-Px的酶活,150μmol/L亚麻木酚素显著增加了AAPH损伤2 h和4 h时的SOD和CAT的酶活;在AAPH诱导的肝组织模型中,150μmol/L亚麻木酚素能有效降低不同AAPH损伤时间(1～4 h)所增加的MDA含量,增加AAPH损伤4 h时降低的SOD和CAT酶活。说明亚麻木酚素具有抗氧化活性,能够抑制脂质过氧化,保护红细胞和肝组织内抗氧化酶系的活性。     

开环异落叶松树脂酚的提取及其对乳液稳定性的影响研究

以含50%开环异落叶松树脂酚二葡萄糖苷(SDG)的亚麻木酚素粗提物(50%SDG)为水解原料,对制备开环异落叶松树脂酚(SECO)粗提物的HCl浓度和水解时间进行优化,进一步通过溶剂萃取、真空冷冻干燥工艺制备SECO粗提物,并将其应用于磷脂-亚麻籽油乳液体系中,研究水解前后亚麻木酚素粗提物对磷脂-亚麻籽油乳液在65℃高温储藏过程中稳定性的影响。结果表明:在HCl浓度1 mol/L、水解时间120 min的条件下水解,可制备SECO含量为65%的SECO粗提物(65%SECO);在磷脂-亚麻籽油乳液高温储藏(65℃)过程中,65%SECO组乳液粒径无显著变化,但对照组和50%SDG组乳液粒径增大;与对照组乳液相比,储藏7 d,65%SECO和50%SDG可分别将乳液中氢过氧化物含量降低11%和27%。由此可见,在磷脂-亚麻籽油乳液的高温储藏(65℃)过程中,50%SDG具有较好的抑制油脂氧化的效果,但通过水解制备的65%SECO能显著提高磷脂-亚麻籽油乳液的物理稳定性。