芝麻素对代谢综合征大鼠主动脉内皮功能损伤的保护作用及机制

目的:观察芝麻素对代谢综合征大鼠主动脉内皮功能损伤的保护作用,探讨其可能机制。方法:高脂高糖诱导大鼠代谢综合征24周,于第9周开始连续口服芝麻素(120,60,30mg.kg^-1·d^-1)16周。测血压、血脂、血糖、血清过氧化氢和硝酸盐/亚硝酸盐含量;采用离体灌流系统,观察大鼠主动脉环对累积浓度去氧肾上腺素的收缩反应和对乙酰胆碱及硝普钠诱发的舒张反应;免疫组织化学法观察主动脉内皮型一氧化氮合酶(eNOS)表达和硝基酪氨酸(NT)含量。结果:芝麻素明显降低代谢综合征大鼠血压、血脂、血糖;提高主动脉环对乙酰胆碱诱导的舒张反应;上调主动脉eNOS表达,降低NT含量;升高血清硝酸盐/亚硝酸盐和减少过氧化氢含量。结论:芝麻素具有改善代谢综合征大鼠的内皮功能障碍,其机制可能与其降低氧自由基生成,上调主动脉eNOS表达,增加和(或)恢复NO的生物活性有关。     

Effect of schisandrin B and sesamin mixture on CCl(4)-induced hepatic oxidative stress in rats

To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl(4))-induced hepatic oxidative stress in male Sprague-Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl(4) group (CCl(4) injection), silymarin group (CCl(4) injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl(4) injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl(4) injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl(4) group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl(4) group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl(4) group by 25%. These results suggest that the schisandrin B-sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl(4)-induced hepatic oxidative stress.     

A randomized,triple‐blind,placebo‐controlled clinical trial,evaluating the sesamin supplement effects on proteolytic enzymes,inflammatory markers,and clinical indices in women with rheumatoid arthritis

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple‐blind, placebo‐controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200‐mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases‐3) and inflammatory biomarkers (hs‐CRP, IL‐1β, IL‐6, TNF‐α, and cyclooxygenase‐2) were measured with enzyme‐linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases‐3 decreased significantly in sesamin group. Also, serum levels of hs‐CRP, TNF‐α, and cyclooxygenase‐2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.     

芝麻素对大鼠骨质疏松症的作用研究

目的 在大鼠模型中探讨芝麻素对骨质结构改变的作用及对骨钙素和I型胶原表达的影响。方法 建立去卵巢(ovariectomized, OVX)大鼠模型,给予芝麻素(sesamin, 80 mg/kg)灌胃作为干预措施并同时建立对照组。应用显微计算机断层扫描(Micro-CT)对大鼠股骨进行分析,并应用免疫组化及免疫荧光检测大鼠股骨中的骨钙素(osteocalcin, OCN)水平以及I型胶原表达。结果 本实验研究条件下,与OVX组相比,OVX+S骨密度(bone mineral density, BMD)增加、小梁间距(trabecular spacing, Tb.Sp)降低,同时,干预组骨钙素和I型胶原表达显著增强(P<0.05)。结论 芝麻素可有效促进去卵巢大鼠骨结构重塑,对大鼠骨质疏松症有积极的治疗和预防作用。     

芝麻素与维生素E联用对代谢综合征大鼠肾病的协同保护作用

目的：观察芝麻素与维生素E联用对代谢综合征大鼠肾脏的保护作用并探讨两药联用的协同关系。方法：采用高脂高糖饮食24周诱导大鼠代谢综合征,第9周（57 d）口服含芝麻素（30 mg.kg^-1.d^-1）、芝麻素＋维生素E[（30＋20）、（15＋20）mg.kg^-1.d^-1]和维生素E（20mg.kg^-1.d^-1）饲料16周。24周末称体重和左肾湿重;测血糖、血脂、血压、肾功能、肾皮质氧化和抗氧化指标;HE和Masson染色观察肾脏形态及胶原沉积;免疫组化法表达诱导型一氧化氮合酶和硝基酪氨酸。结果：（1）模型组肾功能明显损害,肾小球发生硬化和肾间质纤维化,并出现大量炎症细胞浸润,肾小球和肾间质胶原沉积,脂质过氧化物损伤因子MDA、NO2-/NO3-和OH-含量升高,iNOS蛋白和硝基酪氨酸表达明显上调,抗氧化酶保护因子T-SOD、CAT、GSH-Px活性显著降低;（2）芝麻素＋维生素E[（30＋20 mg/kg）]组能明显降低血糖、血脂和血压,提高肾皮质总超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化酶活性,减少丙二醛、NO2^-/NO3^-和羟自由基含量,下调诱导型一氧化氮合酶和硝基酪氨酸,减轻肾小球与肾间质胶原沉积,逆转肾小球硬化和肾间质纤维化,改善肾功能,并且优于单用芝麻素组和维生素E组（P〈0.01或P〈0.05）。结论：芝麻素（30 mg/kg）与维生素E（20 mg/kg）联用具有协同抗氧化和抗代谢综合征大鼠肾脏损伤作用。     

The mechanism underlying the synergetic hypocholesterolemic effect of sesamin and α-tocopherol in rats fed a high-cholesterol diet

Sesamin is a major lignan in sesame seed. We confirmed that ingestion of sesamin and α-tocopherol synergistically reduced the concentration of blood cholesterol in rats given a high-cholesterol diet. To elucidate the molecular mechanism behind this effect, we analyzed the gene-expression profiles in rat liver after co-ingestion of sesamin and α-tocopherol. Six-week-old male Sprague-Dawley rats were fed a 1% cholesterol diet (HC) or HC containing 0.2% sesamin, 1% α-tocopherol or sesamin + α-tocopherol for 10 days. Blood samples were collected on days 1, 3, 7, and 10 and livers were excised on day 10. The gene expressions of ATP-binding cassette, sub-family G (WHITE), members 5 (ABCG5) and 8 (ABCG8) were significantly increased, while the gene expression of apolipoprotein (Apo) A4 was significantly decreased. ABCG5 and ABCG8 form a functional heterodimer that acts as a cholesterol efflux transporter, which contributes to the excretion of cholesterol from the liver. ApoA4 controls the secretion of ApoB, which is a component of low-density-lipoprotein cholesterol. These studies indicate that the cholesterol-lowering mechanism underlying the effects of co-ingestion of sesamin and α-tocopherol might be attributable to increased biliary excretion of cholesterol and reduced ApoB secretion into the bloodstream.     

In vitro Antitumoral Activity of Compounds Isolated from Artemisia gorgonum Webb

Artemisia gorgonum (Asteraceae) is an endemic plant to the Cape Verde islands and plays an important role in traditional medicine. The chloroform extract of the plant aerial parts afforded six sesquiterpene lactones, two methoxylated flavonoids, two lignans, and one tetracyclic triterpene, which were isolated by chromatographic methods and their structure established by physical and spectroscopic techniques. The cytotoxic activity of the three major constituents, namely, arborescin, artemetin, and sesamin, was evaluated on neuroblastoma (SH‐SY5Y), hepatocarcinoma (HepG2), and nontumoral bone marrow stromal (S17) cell lines. The application of different concentrations of the compounds significantly decreased tumor cells viability at different extents, especially at the highest concentrations tested. Arborescin is the most promising compound as it was able to reduce tumoral cell viability with an IC₅₀ significantly lower (229–233 μM; p < 0.01) than that of S17 cells (445 μM). Arborescin and artemetin were less toxic to nontumoral cells than the antitumoral drug tested, etoposide. Our results indicate that arborescin has a significant cytotoxic activity in vitro, more pronounced on the cancer cell lines, confirming A. gorgonum as a source of potential antitumoral molecules. Copyright © 2014 John Wiley & Sons, Ltd.     

Inhibitory effects of sesamin on CYP2C9-dependent 7-hydroxylation of S-warfarin

A recent report demonstrated that sesamin strongly and non-competitively inhibits S-warfarin 7-hydroxylation activity in human liver microsomes with a K_i value of 0.2 μM. This finding suggests that sesamin predominantly binds to CYP2C9 at another site for which it has a higher affinity than its affinity for the active site, thereby inhibiting the activity of CYP2C9 non-competitively. In this study, we found that sesamin competitively inhibited the 7-hydroxylation activity of S-warfarin in human liver microsomes with a K_i value of 15.7 μM. In addition, the recombinant CYP2C9-dependent 7-hydroxylation activity of S-warfarin was competitively inhibited by sesamin with a Ki value of 13.1 μM. These results are consistent with the fact that sesamin is a good substrate of CYP2C9, and its activity follows Michaelis-Menten kinetics. As the plasma concentration of sesamin after its administration is usually lower than 0.01 μM, the inhibition of S-warfarin metabolism by sesamin does not appear to be severe.     

芝麻素对高脂血症大鼠糖代谢的作用

目的探讨芝麻素对高脂血症大鼠糖代谢的作用。方法选择SD大鼠,喂饲高脂饲料,建立高脂血症大鼠模型。然后对高脂模型大鼠进行芝麻素干预7w后,检测各组大鼠的血脂、空腹血糖(FBS)、糖化血红蛋白(HbA1c)、血清胰岛素等水平以及观察大鼠胰腺组织的病理学变化。结果芝麻素可以降低高脂血症大鼠血清TC、TG、LDL-C及apoB水平,适当升高HDL-C和apoA的含量(P0.05);降低高脂血症大鼠血清胰岛素水平、调节脂代谢紊乱下的血糖水平,改善机体对胰岛素的敏感性(P0.05);抑制高脂血症大鼠胰腺胰岛素和生长抑素的分泌水平。结论芝麻素可以调节高脂血症大鼠脂代谢紊乱下的糖代谢,改善高脂血症时机体的胰岛素抵抗(IR)状态。     

Improvement of Liver Function in Humans Using a Mixture of Schisandra Fruit Extract and Sesamin

This was a randomized, parallel, and placebo‐controlled study. Forty subjects were divided into a test group and a placebo group. The study was focused on the potential effects of a mixture of Schisandra fruit extract and sesamin (hereinafter called ‘SCH’) in the subjects with borderline high levels (40–60 U/L) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Twenty subjects taking SCH (four tablets per day) and 20 subjects taking a placebo (four tablets per day) were studied. The effects of SCH on ALT, AST, total bilirubin, direct bilirubin, free radical levels, total antioxidant status, glutathione peroxidase, glutathione reductase, and the lag time for low‐density lipoprotein oxidation were determined. The total test period was 5 months. Intervention of SCH clearly reduced the levels of ALT and AST, but it made no change in the total bilirubin and direct bilirubin. Intake of SCH also greatly increased the antioxidant capacity and decreased the values of thiobarbituric acid reactive substances, total free radicals, and superoxide anion radicals in the plasma. The activities of glutathione peroxidase and reductase in the erythrocytes were significantly increased. In addition, the lag time for low‐density lipoprotein oxidation, an inflammatory marker, was evidently increased. Fatty liver was found to have been significantly improved in this study. SCH proved to have the effects of antioxidation and improving liver function. Copyright © 2012 John Wiley & Sons, Ltd.