Lignans Sesamin Research Articles

Alleviation of cognitive deficits via upregulation of chondroitin sulfate biosynthesis by lignan sesamin in a mouse model of neuroinflammation

Lignans are plant-derived compounds that act as partial estrogen agonists. Chondroitin sulfate proteoglycans (CSPGs) represent one of the major components of the extracellular matrix. Here we aimed to understand the role of sesamin (SES), a major lignan compound, in the biosynthesis and degradation of CSPGs in the mouse hippocampus because CSPGs play a key role in the regulation of cognitive functions through the promotion of adult neurogenesis. The expression of the pro-inflammatory cytokine interleukin-1β was decreased by SES administration in the hippocampus of lipopolysaccharide (LPS)-treated mice, a model of neuroinflammation-induced cognitive deficits. The expression of genes related to biosynthesis and degradation of CSPGs in the hippocampus of LPS-treated mice was both increased and decreased by SES administration. Further, the diffuse extracellular matrix labeling of CSPGs by Wisteria floribunda agglutinin (WFA) in the hippocampus of LPS-treated mice was increased by SES administration. The densities of neural stem cells, late transit-amplifying cells, and newborn-granule cells in the hippocampus of LPS-treated mice were also increased by SES administration. Moreover, SES-induced alterations in gene expression, WFA labeling, and adult neurogenesis in LPS-treated mice were more evident in the dorsal hippocampus (center of cognition) than in the ventral hippocampus (center of emotion). Neither LPS nor SES administration affected locomotor activity, anxiety-like behavior, and depression-related behavior. However, impairments in contextual memory and sensorimotor gating in LPS-treated mice were recovered by SES administration. Our results show that SES can promote adult hippocampal neurogenesis through the upregulation of CSPGs, which may alleviate cognitive deficits induced by neuroinflammation.

Neuroprotective Effects of Black Pepper Cold-Pressed Oil on Scopolamine-Induced Oxidative Stress and Memory Impairment in Rats.

Oxidative stress is usually associated with many neurodegenerative diseases. In this study, the gas chromatography–mass spectrometry (GC–MS) analysis of cold-pressed oil (CPO) from black pepper (Piper nigrum) fruits was performed and its neuroprotective effects were evaluated for the first time. The analysis of CPO revealed the presence of the lignan sesamin (39.78%), the alkaloid piperine (33.79%), the monoterpene hydrocarbons 3-carene (9.53%) and limonene (6.23%), and the sesquiterpene β-caryophyllene (10.67%). Black pepper hydrodistilled oil (HDO) was also comparatively analyzed by GC–MS to show the impact of oil isolation by two different methodologies on their components and class of compounds identified. HDO analysis revealed 35 compounds (99.64% of the total peak areas) mainly composed of monoterpene hydrocarbons (77.28%), such as limonene (26.50%), sabinene (21.36%), and β-pinene (15.53%), and sesquiterpene hydrocarbons (20.59%) represented mainly by β-caryophyllene (19.12%). Due to the low yield obtained for HDO (0.01% v/w), only CPO was chosen for the evaluation of its neuroprotective potential. Alzheimer-type dementia was induced in rats by scopolamine intraperitoneal injection (1.5 mg/kg/day) for seven days. CPO was administered orally (100 mg/kg) for a week before scopolamine administration and then concomitantly for another week. Donepezil (1 mg/kg, orally) was used as a reference drug. CPO administration significantly improved the rat behaviors as evaluated by the Morris water maze test, evident from prolongation in time spent in the platform quadrant (262.9%, compared to scopolamine) and increasing in the crossing time by 18.18% compared to the control group. The rat behavior tested by passive avoidance, showed prolongation in the step-through latency compared to control. Moreover, CPO significantly (p < 0.05) ameliorated the activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD) and reduced malondialdehyde (MDA) equivalents by 22.48%, 45.41%, and 86.61%, respectively, compared to scopolamine. Furthermore, CPO administration decreased scopolamine-induced elevated acetylcholinesterase levels in rats’ hippocampi by 51.30%. These results were supported by histopathological and in silico molecular docking studies. Black pepper oil may be a potential antioxidant and neuroprotective supplement.

In Vitro Antimicrobial and Antiproliferative Activities of the Root Bark Extract and Isolated Chemical Constituents of Zanthoxylum paracanthum Kokwaro (Rutaceae).

Zanthoxylum paracanthum Kokwaro (Rutaceae) is an endemic Kenyan and Tanzanian plant used in folk medicine by local populations. Although other Zanthoxylum species have been studied, only Z. paracantum stem extracts have been profiled, even though the roots are also used as herbal remedies. As root extracts may be another source of pharmaceutical compounds, the CH2Cl2/MeOH (1:1) root bark extract was studied in this report. Eight root bark compounds were isolated and their structural identities were confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) (using COSY, HSQC, NOESY and HMBC) analyses. The structural identities were determined as follows: the fatty acid—myristic acid (1); the sterol—stigmasterol (2); the lignan—sesamin (3); two β-carboline alkaloids—10-methoxycanthin-6-one (6) and canthin-6-one (7); and three phenanthridine alkaloids—8-acetonyldihydrochelerythrine (4), arnottianamide (5) and 8-oxochelerythrine (8). Some of these compounds were identified in the species for the first time. These compounds and the extract were then tested in vitro against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213) and Candida albicans (ATCC 10231) before tests for antiproliferative activity against the human breast cancer (HCC 1395), human prostate cancer (DU 145) and normal (Vero E6) cell lines were conducted. Minimum inhibition concentration values of 3.91, 1.95, 0.98 and 7.81 µg/mL against MRSA, S. aureus, E. coli and C. albicans, respectively, were recorded. Among the isolates, canthin-6-one was the most active, followed by 10-methoxycanthin-6-one. The root extract and some of the compounds also had antiproliferative activity against the HCC 1395 cell line. Stigmasterol and canthin-6-one had IC50 values of 7.2 and 0.42. The root bark extract also showed activity, at 8.12 µg/mL, against the HCC 1395 cells. Out of the chemical isolates, 10-methoxycanthin-6-one and canthin-6-one showed the strongest inhibition of the DU 145 cells. The root extract had significant antimicrobial and antiproliferative activities, supporting the traditional use of this plant in treating microbial infections and cancer-related ailments.

EVALUATION THE ANTIOXIDANT ACTIVITY O F SESAME COAT AND SESAME CAKE EXTRACTS

This study was aimed to evaluate the anti-oxidant activity of mmthanol extracts from roasted and unroasted sesame seeds cake (RSC, URSC) and ethanol extracts from sesameccoat (SC) usingDDPPH and reducing power activity (RPA) assay. The quantitative and qualitative analysis of obtained extracts were done using RP-HPLC technique, the results revealed that the extracts were contained anti-oxidents(lignans ) sesamin ,ssesamolin andssesamol in different amounts Also the RPA of URSC extract at (10, 20, &amp; 50 mg/ml) was similar to that ofbBHT , while that for RSC was similar to BHT at 30 mg/ml. Additionally, The RPA SC extract was comparable to that of BHT at ( 20 , 30 , and 50 mg/ml). It has been noticed that the radical scavengingaability (RSA) of BHT was greater than of the experimental samples that evaluated by DPPH assay. Mean time the RSA of the studied extracts was increased with increase of extracts concentrations from 10-50 mg/g. Based on the results of this study, sesame coat, sesame cake (from roasted and unroasted sesame seeds) extracts could be used asppotential natural anti-oxidant topprotectooil-rich food to avoid theppossible risks resulted from using the syntheticaantioxidants to prevent food.

Recovery of Sesamin, Sesamolin, and Minor Lignans From Sesame Oil Using Solid Support-Free Liquid-Liquid Extraction and Chromatography Techniques and Evaluation of Their Enzymatic Inhibition Properties.

In this study, an integrated process for the recovery of sesamin and sesamolin, two high added-value lignans of sesame oil (SO) was developed, using synchronous extraction and chromatography techniques. The extraction of SO phenolic content was studied using two different extraction techniques: Annular centrifugal extraction (ACE) and centrifugal partition extraction (CPE). The derived data of each experiment were compared in terms of revealing the yields, time, and solvents consumption showing that CPE is the most effective technique, concerning the solvent consumption. The isolation of lignans was achieved using centrifugal partition chromatography (CPC) both on semi-preparative and preparative scale. The biphasic system used for this purpose consisted of the following solvents: n-Hex/EtOAc/EtOH/H2O in proportion 2:3:3:2 (v/v/v/v) and direct recovery of the two major lignans sesamin and sesamolin was achieved. In parallel the CPC analysis resulted in the isolation of four minor lignans of sesame oil, i.e., samin, sesamol, sesaminol, and episesaminol. Structure elucidation of isolated lignans was based on HRMS/MS and NMR experiments. High-performance liquid chromatography (HPLC) was employed for quantitative analysis of the obtained extracts to determine the purity of the isolated compounds as well. The results of this study demonstrated that sesamin and sesamolin were recovered in purity higher than 95%, verifying the effectiveness of the purposed separation methodology. Finally, due to the general application of sesame oil in cosmetic industry, all the pure compounds were evaluated for their tyrosinase, elastase, collagenase, and hyaluronidase inhibition activity.

Chiral resolution and bioactivity of enantiomeric furofuran lignans from Juglans mandshurica Maxim

Enantiomers have generally been reported mostly for racemic mixtures with a 1:1 ratio, as in that case there were weak Cotton effects in the ECD spectrum and negligible optical rotations. A furofuran lignan (sesamin), with a remarkable rotation and significant Cotton effects, was isolated from Juglans mandshurica Maxim. Subsequently, sesamin was resolved by chiral HPLC to afford a pair of enantiomers, (+)-sesamin (a) and (−)-sesamin (b), in a ratio of approximately 1:3. Their absolute configurations were determined by computational analysis of their electronic circular dichroism (ECD) spectrum. In addition, the pair of enantiomers were evaluated for the inhibition of self-induced Aβ aggregation. Interestingly, (+)-sesamin (a) (67.7%) and (−)-sesamin (b) (80.6%) exhibited different degrees of anti-Aβ aggregation activity. The different inhibition profiles were further explained by molecular dynamics and docking simulation study.

Isolation of antioxidative compounds from Micromelum minutum guided by preparative thin layer chromatography-2,2-diphenyl-1-picrylhydrazyl (PTLC-DPPH) bioautography method

The application of preparative thin layer chromatography-2,2-diphenyl-1-picrylhydrazyl (PTLC-DPPH) bioautography technique successfully isolated a lignan sesamin (1), two prenylated coumarins (2 and 3) and a marmesin glycosides (4) from Micromelum minutum methanol bark extract. Compounds 2 and 3 were identified as new compounds whereas 1 and 4 were first isolated from Micromelum genus. Structural identification of all compounds were done by detailed spectroscopic analyses and comparison with literature data. Antioxidant capacities of extract, active fraction and compounds were measured based on DPPH free radical savenging activity, oxygen radical absorbance capacity (ORAC) and β-carotene bleaching. The DPPH activity of methanol extract and its fraction present the IC50 values of 54.3 and 168.9 µg/mL meanwhile the β-carotene bleaching results were 55.19% and 5.75% respectively. The ORAC measurements of M. minutum extract, compounds 2 and 4 showed potent antioxidant activity with the values of 5123, 5539 and 4031 µmol TE/g respectively.

Determination and purification of sesamin and sesamolin in sesame seed oil unsaponified matter using reversed-phase liquid chromatography coupled with photodiode array and tandem mass spectrometry and high-speed countercurrent chromatography.

In Asian countries, sesame seed oil unsaponified matter is used as a natural food additive due to its associated antioxidant effects. We determined and purified the primary lignans sesamin and sesamolin in sesame seed oil unsaponified matter using reversed-phase liquid chromatography coupled with photodiode array and tandem mass spectrometry and high-speed countercurrent chromatography. Calibration curves showed good correlation coefficients (r2 > 0.999, range 0.08 and/or 0.15 to 5 μg/mL) with a limit of detection (at 290 nm) of 0.02 μg/mL for sesamin and 0.04 μg/mL for sesamolin. Sesame seed oil unsaponified matter contained 2.82% sesamin and 2.54% sesamolin, respectively. Direct qualitative analysis of sesamin and sesamolin was achieved using quadrupole mass spectrometry with positive-mode electrospray ionization. Pure (>99%) sesamin and sesamolin standards were obtained using high-speed countercurrent chromatographic purification (hexane/ethyl acetate/methanol/water; 7:3:7:3). An effective method for determining and purifying sesamin and sesamolin from sesame seed oil unsaponified matter was developed by combining these separation techniques for standardized food additives.

Synthesis of furofuran lignans as antidiabetic agents simultaneously achieved by inhibiting α-glucosidase and free radical.

Furofuran lignans such as sesamin have been recognized as promising antidiabetic agents as they possess curative as well as preventive effects toward diabetes complications. However, to date the structure-activity relationship has not been investigated due to the lack of a practical synthetic route capable of producing diverse furofuran lignans. Herein, we first introduced a single-step synthesis of these compounds starting from samin (4). Reaction of samin with a variety of electron-rich phenolics under acidic conditions afforded a total of 23 diverse furofuran lignans. On examination their inhibitions against α-glucosidase and free radicals, lignans having a free hydroxy group showed considerably enhanced inhibition, compared with their corresponding starter 4 and related lignans sesamin (1) and sesamolin (3). In addition, the mechanism underlying the α-glucosidase inhibition of a particular active lignan (epi -6) was verified to be mixed manner between competitive and noncompetitive inhibition.

Identification of chemical constituents of Zanthoxylum heitzii stem bark and their insecticidal activity against the malaria mosquito Anopheles gambiae.

BackgroundZanthoxylum heitzii bark extracts have insecticidal properties and have been reported to be used against malaria in Western Africa. Previously, it has been shown that a hexane extract of the bark is toxic to adult females of the mosquito Anopheles gambiae, a malaria vector. As part of our project on the control of malaria vectors using plant extracts, the phytochemistry of Z. heitzii bark hexane extract has been investigated with the aim to identify the major components with adulticidal and larvicidal effects on An. gambiae.MethodsZ. heitzii stem bark was extracted with hexane, and the extract was fractionated to isolate major components from the bark, identified by NMR spectroscopy. Isolated compounds were tested for toxicity towards adult female An. gambiae mosquitoes and for larvicidal effects towards An. gambiae.ResultsThe alkaloid dihydronitidine, the sesquiterpenoid caryophyllene oxide, the amide pellitorine and the lignan sesamin were identified as the major constituents in Z. heitzii bark. Pellitorine was toxic to both adult insects (LD50 50 ng/mg insect) and larvae (LD50 13 μg/ml). None of the other compounds were toxic to adults, but caryophyllene oxide and sesamin exhibited moderate larvicidal effects (LD50 > 150 μg/ml). A mixture of the four compounds in the same ratio as in the hexane extract showed higher toxicity (LD50 34 ng/mg insect) towards adult insects than the pure compounds.ConclusionThe toxicity of Z. heitzii bark hexane extract to An. gambiae is mostly due to pellitorine, although interactions between pellitorine and other, inactive constituents may enhance the activity of the extract.

Antimycobacterial furofuran lignans from the roots of Anemopsis californica.

Topical preparations of Anemopsis californica have been used by Native American tribes in the southwestern United States and northern Mexico to treat inflammation and infections. We report results of bioassay-guided isolation conducted on a sample of A.californica roots. The furofuran lignans sesamin (1) and asarinin (2) were isolated and shown to have MIC values ranging from 23 to 395 µM against five different species of environmental nontuberculous mycobacteria. These findings are significant given that these bacteria can cause skin, pulmonary, and lymphatic infections. Crude A.californica extracts were analyzed by liquid chromatography-mass spectrometry, and it was determined that sesamin and asarinin were extracted at relatively high levels from the roots (1.7-3.1 g/kg and 1.1-1.7 g/kg, respectively), but at lower levels from the leaves (0.13 g/kg for both compounds). Our findings suggest that the majority of activity of crude A.californica root extracts against nontuberculous mycobacteria can be attributed to the presence of sesamin and asarinin. This paper is the first to report the isolation of these compounds from a member of the Saururaceae family, and the first to describe their activity against nontuberculous mycobacteria.

Bioactive Lignans from Zanthoxylum alatum Roxb. stem bark with cytotoxic potential

Ethanopharmacological relevanceZanthoxylum alatum is used in traditional medicinal systems for number of disorders like cholera, diabetes, cough, diarrhea, fever, headache, microbial infections, toothache, inflammation and cancer. The aim of the present study was to evaluate Zanthoxylum alatum stem bark for its cytotoxic potential and to isolate the bioactive constitiuents. Material and methodsCytotoxicity of the different extracts and isolated compounds was studied on lung carcinoma cell line (A549) and pancreatic carcinoma cell line (MIA-PaCa) using MTT assay. Isolation of compounds from most active extract (petroleum ether) was done on silica gel column. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1H NMR, 13C NMR and mass spectroscopy. The type of cell death caused by most active compound C was explored by fluorescence microscopy using the acridine orange/ethidium bromide method. ResultPetroleum ether extract of plant has shown significant cytotoxic potential. Three lignans sesamin (A), kobusin (B), and 4'O demethyl magnolin (C) has been isolated. All lignans showed cytotoxic activities in different ranges. Compound C was the novel bioactive compound from a plant source and found to be most active. In apoptosis study, treatment caused typical apoptotic morphological changes. It enhances the apoptosis at IC50 dose (21.72µg/mL) however showing necrotic cell death at higher dose after 24h on MIA-PaCa cell lines. ConclusionPetroleum ether extract (60–80°C) of Zanthoxylum alatum has cytotoxic potential. The lignans isolated from the petroleum ether extract were responsible for the cytotoxic potential of the extract. 4'O demethyl magnolin was novel compound from Zanthoxylum alatum. Hence the Zanthoxylum alatum can be further explored for the development of anticancer drug.

The sesame lignan sesamin attenuates vascular dysfunction in streptozotocin diabetic rats: Involvement of nitric oxide and oxidative stress

The effect of chronic administration of sesamin was studied on aortic reactivity of streptozotocin diabetic rats. Male diabetic rats received sesamin for 7 weeks after diabetes induction. Contractile responses to KCl and phenylephrine and relaxation response to acetylcholine were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to phenylephrine was significantly lower in sesamin-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine was significantly higher in sesamin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde and decreased superoxide dismutase activity and sesamin treatment significantly improved these changes. Therefore, chronic treatment of diabetic rats with sesamin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and via attenuation of oxidative stress and tissue integrity of endothelium is necessary for its beneficial effect.

Quercetin and Sesamin Protect Neuronal PC12 Cells from High-Glucose-Induced Oxidation, Nitrosative Stress, and Apoptosis

Complications of diabetes are now well-known to affect sensory, motor, and autonomic nerves. Diabetes is also thought to be involved in neurodegenerative processes characteristic of several neurodegenerative diseases. Indeed, it has been acknowledged recently that hyperglycemia-induced oxidative stress contributes to numerous cellular reactions typical of central nervous system deterioration. The goal of the present study was to evaluate the effects of the polyphenol quercetin and the lignan sesamin on high-glucose (HG)-induced oxidative damage in an in vitro model of dopaminergic neurons, neuronal PC12 cells. When incubated with HG (13.5 mg/mL), neuronal PC12 cells showed a significant increase of cellular death. Our results revealed that quercetin and sesamin defend neuronal PC12 cells from HG-induced cellular demise. An elevated level of reactive oxygen and nitrogen species is a consequence of improved oxidative stress after HG administration, and we demonstrated that this production diminishes with quercetin and sesamin treatment. We also found that quercetin and sesamin elicited an increment of superoxide dismutase activity. DNA fragmentation, Bax/Bcl-2 ratio, nuclear translocation of apoptosis-inducing factor, as well as poly(adenosine diphosphate [ADP]-ribose) polymerase cleavage were significantly reduced by quercetin and sesamin administration, affirming their antiapoptotic features. Also, HG treatment impacted caspase-3 cleavage, supporting caspase-3-dependent pathways as mechanisms of apoptotic death. Our results indicate a powerful role for these natural dietary compounds and emphasize preventive or complementary nutritional strategies for diabetes control.

Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system.

A growing body of evidence indicates that the majority of Parkinson's disease (PD) cases are associated with microglia activation with resultant elevation of various inflammatory mediators and neuroinflammation. In this study, we investigated the effects of 2 natural molecules, quercetin and sesamin, on neuroinflammation induced by the Parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+) in a glial-neuronal system. We first established that quercetin and sesamin defend microglial cells against MPP+-induced increases in the mRNA or protein levels of 3 pro-inflammatory cytokines (interleukin-6, IL-1β and tumor necrosis factor-alpha), as revealed by real time-quantitative polymerase chain reaction and enzyme-linked immunoabsorbent assay, respectively. Quercetin and sesamin also decrease MPP+-induced oxidative stress in microglial cells by reducing inducible nitric oxide synthase protein expression as well as mitochondrial superoxide radicals. We then measured neuronal cell death and apoptosis after MPP+ activation of microglia, in a microglial (N9)-neuronal (PC12) coculture system. Our results revealed that quercetin and sesamin rescued neuronal PC12 cells from apoptotic death induced by MPP+ activation of microglial cells. Altogether, our data demonstrate that the phytoestrogen quercetin and the lignan sesamin diminish MPP+-evoked microglial activation and suggest that both these molecules may be regarded as potent, natural, anti-inflammatory compounds.

Alcaloides das cascas das raízes de Zanthoxylum spp

In 1959, Gottlieb and Antonaccio published a study reporting the occurrence of lignan sesamin and triterpene lupeol in Zanthoxylum tingoassuiba. In this work we describe the phytochemical study of the root bark of the Z. tingoassuiba which allowed the identification of the lupeol, sesamin, and alkaloids dihydrochelerythrine, chelerythrine, anorttianamide, cis-N-methyl-canadine, predicentine, 2, 3-methylenedioxy-10,11-dimethoxy-tetrahydro protoberberine. The investigation of hexane and methanol extracts of the root bark of Z. rhoifolium and Z. stelligerum also investigated showed the presence of alkaloids dihydrochelerythrine, anorttianamide, cis-N-methyl-canadine, 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine and angoline. The occurrence of 2,3-methylenedioxy-10,11-dimethoxy-tetrahydro protoberberine is first described in Z. tingoassuiba and Z. stelligerum. This is also the first report of the presence of hesperidin and neohesperidin in roots of Z. stelligerum.

Comparative Effects of Sesame Seed Lignan and Flaxseed Lignan in Reducing the Growth of Human Breast Tumors (MCF-7) at High Levels of Circulating Estrogen in Athymic Mice

Flaxseed (FS) has a breast tumor-reducing effect, possibly because of its high content of secoisolariciresinol diglucoside (SDG) lignan. Sesame seed (SS) is rich in the lignan sesamin (SES) but is non-protective. Both lignans are metabolized to estrogen-like enterodiol and enterolactone. The objective of this study was to differentiate the effects of SDG and SES on established human estrogen receptor-positive breast tumors (MCF-7) in athymic mice with high serum estrogen to help explain the different effects of FS and SS. Mice were fed for 8 wk the basal diet (BD, control) or BD supplemented with 1 g/kg SDG or SES. SES reduced palpable tumor size by 23% compared to control, whereas SDG did not differ from SES or control. Both treatments reduced tumor cell proliferation, but only SES increased apoptosis. SDG and SES reduced human epidermal growth factor receptor 2 and endothelial growth factor receptor expressions, but only SES reduced downstream pMAPK. Neither treatment affected IGF-1R, vascular endothelial growth factor receptor-2, Akt, pAkt, or MAPK of the growth factor signaling pathway. Thus, at high serum estrogen levels, SDG may not account for the tumor reducing effect of FS. SES was more effective than SDG in reducing breast tumor growth, but its effect may have been lost when consumed as a component of SS.

A Phytochemical Investigation of Zanthoxylum setulosum

The crude bark extract of Zanthoxylum setulosum from Monteverde, Costa Rica was notably cytotoxic (100% kill at 100 microg/mL) to MCF-7, MDA-MB-231, and MDA-MB-468 cells in vitro. Phytochemical studies of the bark extract revealed the triterpenoid lupeol, the lignan sesamin, the sesquiterpene sesquichamaenol, and the xanthone lichexanthone. This is the first report of the isolation of sesquichamaenol and lichexanthone from the bark extract of Z. setulosum. All structures were determined using NMR spectroscopic techniques (1H NMR and 13 degrees C NMR) and GC-MS and by comparison with literature data. Lupeol proved to be the cytotoxic component of Z. setulosum bark.

The Sesame Lignan Sesamin Attenuates Vascular Permeability in Rats with Streptozotocin-Induced Diabetes: Involvement of Oxidative Stress

Background: Cardiovascular disorders are a major cause of morbidity and mortality in diabetic patients. Increased vascular permeability is a hallmark of diabetic vasculopa- thy, and the administration of natural products with antioxidant activity could restore vascular function. Objectives: In this study, the effect of chronic treatment with sesamin on vascular per- meability in rats with streptozotocin (STZ)-induced diabetes was investigated. Materials and Methods: Male diabetic rats received sesamin at a dose of either 10 or 20 mg/kg for 7 weeks, beginning 1 week after diabetes induction. Vascular permeability was estimated by measuring Evans blue dye extravasation. Oxidative stress markers, including malondialdehyde (MDA) and superoxide dismutase (SOD) activity, were also measured in aortic tissue. Results: Extravasation of Evans blue dye increased significantly in the diabetic group compared to that in the control group (p < 0.05), and treatment with sesamin signifi- cantly and dose-dependently decreased this extravasation (p < 0.05). Diabetic rats also had elevated malondialdehyde (MDA) and reduced superoxide dismutase (SOD) activ- ity (p < 0.005-0.001), and chronic treatment with sesamin (20 mg/kg) significantly re- versed the elevated MDA content (p < 0.05) and reduced SOD activity (p < 0.05). Conclusions: Chronic treatment of diabetic rats with sesamin could dose-dependently improve aortic permeability, partly through the attenuation of oxidative stress in aor- tic tissue. ARTICLE INFO

Sesamin attenuates intercellular cell adhesion molecule‐1 expression in vitro in TNF‐α‐treated human aortic endothelial cells and in vivo in apolipoprotein‐E‐deficient mice

Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.