ArticleLiterature Review

A comprehensive review on the anti-cancer properties and mechanisms of action of sesamin, a lignan in sesame seeds ( Sesamum indicum )

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Abstract

Sesamin is the major active ingredient is Sesamum indicum seeds. Several studies revealed that sesamin possesses potent anti-cancer properties. The anti-cancer effects of sesamin have been mainly attributed to its anti-proliferative, pro-apoptotic, anti-inflammatory, anti-metastatic, anti- and pro-angiogenic, and pro-autophagocytic activities. In this review, we provide a comprehensive summary of the reported anti-cancer effects of sesamin, both in vitro and in vivo. Experimental findings related to the potential of sesamin to attenuate oxidative stress, inflammation, proliferation, metastasis, and angiogenesis in various cancer cells and tumors are analyzed. Studies focusing on the ability of sesamin to induce apoptosis and autophagy in cancer cells are also underscored. Moreover, the molecular mechanisms underlying the anti-cancer effects of sesamin are highlighted, and the major signaling pathways targeted by sesamin are identified. Although the exact signaling events triggered by sesamin in cancer cells are not fully revealed, our analysis indicates that NF-κB, STAT3, JNK, ERK1/2, p38 MAPK, PI3K/AKT, caspase-3, and p53 signaling pathways are critically involved in mediating the anti-cancer effects of sesamin. In sum, the experimental evidence suggesting that sesamin could exert potent anti-cancer activities in vitro and in vivo is compelling. Hence, sesamin can potentially be employed as an effective adjuvant therapeutic agent in ameliorating tumor development and progression, and therefore, it could be used in the prevention and/or treatment of various types of cancer.

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... Sesamolin is hydrolyzed into sesamol [4]. These three sesame compounds-sesamol, sesamin, and sesamolin-are responsible for sesame seed's anticancer activity [6][7][8], cardio-protection [9,10], neuro-protection [11,12], and skin whitening [13]. Sesamol can reduce colon cancer [14], hepatocellular carcinoma cancer [15], non-small cells lung cancer [16,17], and malignant melanoma skin cancer [18,19]. ...
... Sesamol can reduce colon cancer [14], hepatocellular carcinoma cancer [15], non-small cells lung cancer [16,17], and malignant melanoma skin cancer [18,19]. Sesamin can suppress breast cancer [7,20], non-small cell lung cancer [21], myeloid leukemia cells [22], and malignant melanoma skin cancer [23]. Sesamin and sesamol can induce apoptotic cell death in cancer cells [7,19], and sesamolin can enhance NK cells for suppressing lymphoma cell growth [8]. ...
... Sesamin can suppress breast cancer [7,20], non-small cell lung cancer [21], myeloid leukemia cells [22], and malignant melanoma skin cancer [23]. Sesamin and sesamol can induce apoptotic cell death in cancer cells [7,19], and sesamolin can enhance NK cells for suppressing lymphoma cell growth [8]. Many studies have reported the safe use of these three compounds in normal cells [6,7,15,18]. ...
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The intracellular uptake concentration determines drug absorption, drug activity, and toxicity. Sesamol, sesamin, and sesamolin are promising bioactive components from Sesame indicum L. Their respective intracellular uptake pathway and cytotoxicity were evaluated using melanoma and non-cancerous cells. Quantitative structure-activity relationship (QSAR) models were built to identify the molecular features affecting drug uptake in cells. The respective intracellular uptake pathway for sesamol vs. sesamin and sesamolin was carrier-mediated vs. passive transport. Topological polar surface area (PSA) and 2D autocorrections increase the intracellular concentration (C/M ratio) of these compounds. Sesamol has the lowest C/M ratio compared to sesamin and sesamolin, but only sesamol inhibits the cell viability of melanoma and provides an inhibition concentration at 50% (IC50) against melanoma cells. The slightly aqueous solubility of sesamin and sesamolin, therefore, limits testing of their cytotoxicity. In conclusion, sesamol has the potential to inhibit melanoma cell growth, but requires improvement of the C/M ratio to increase its physicochemical properties. Thus, in order to investigate the cytotoxicity of sesamin and sesamolin against melanoma cells a solubility enhancer is needed.
... It is distributed in countries such as India, China, and Malaysia. Chinese people have used sesame seeds for more than 5000 years [1,3]. Globally, India, Sudan, Myanmar, China, and Tanzania are the major producers of sesame. ...
... Sesamin is one of the most abundant lignans in the composition of sesame seeds and has good physiological activity. Studies have found that sesamin has good antioxidant properties, cholesterol lowering, lipid metabolism regulation, blood pressure stabilization, and anti-tumor effects [3]. Sesamin is metabolized in the body mainly by the action of cytochrome P-450. ...
... The anticancer effects of sesamin are mainly attributed to its anti-proliferative, pro-apoptotic, anti-inflammatory, anti-metastatic, anti-angiogenic, and pro-autophagocytic activities. Although the exact signaling events triggered by sesamin in cancer cells have not been fully revealed, STAT3, JNK, ERK1/2, p38 MAPK, PI3K/AKT, caspase-3, and p53 signaling pathways play a key role in mediating the anticancer effects of sesamin [3]. ...
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Sesame (Sesamum indicum L.), of the Pedaliaceae family, is one of the first oil crops used in humans. It is widely grown and has a mellow flavor and high nutritional value, making it very popular in the diet. Sesame seeds are rich in protein and lipids and have many health benefits. A number of in vitro and in vivo studies and clinical trials have found sesame seeds to be rich in lignan-like active ingredients. They have antioxidant, cholesterol reduction, blood lipid regulation, liver and kidney protection, cardiovascular system protection, anti-inflammatory, anti-tumor, and other effects, which have great benefits to human health. In addition, the aqueous extract of sesame has been shown to be safe for animals. As an important medicinal and edible homologous food, sesame is used in various aspects of daily life such as food, feed, and cosmetics. The health food applications of sesame are increasing. This paper reviews the progress of research on the nutritional value, chemical composition, pharmacological effects, and processing uses of sesame to support the further development of more functionalities of sesame.
... This oil crop is regarded as "queen of oilseeds" because of its property of resistance to oxidation and rancidity (Dalibalta et al., 2020). Sesame is widely cultivated in the tropical parts of Africa and Asia, India being one of the major producers with Myanmar, China, and Sudan (Majdalawieh et al., 2017). A plethora of nutrients including proteins, carbohydrates, antioxidants, lignans, tocopherols, phytates, phytosterols, and polyunsaturated fatty acids are exclusively found in sesame (Nagendra Prasad et al., 2012;Kumar et al., 2018;Pathak et al., 2019). ...
... A plethora of nutrients including proteins, carbohydrates, antioxidants, lignans, tocopherols, phytates, phytosterols, and polyunsaturated fatty acids are exclusively found in sesame (Nagendra Prasad et al., 2012;Kumar et al., 2018;Pathak et al., 2019). These bioactive compounds possess certain medicinal properties like hepatoprotective, hypoglycemic, antihypertensive, anti-estrogenic, and anticancer (Kumar and Singh, 2014;Majdalawieh et al., 2017). Active ingredients of sesame have also been investigated as potential inhibitors of Parkinson's disease (PD) (Kappo et al., 2016). ...
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The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has now spread across the nations with high mortality rates and multifaceted impact on human life. The proper treatment methods to overcome this contagious disease are still limited. The main protease enzyme (Mpro, also called 3CLpro) is essential for viral replication and has been considered as one of the potent drug targets for treating COVID-19. In this study, virtual screening was performed to find out the molecular interactions between 36 natural compounds derived from sesame and the Mpro of COVID-19. Four natural metabolites, namely, sesamin, sesaminol, sesamolin, and sesamolinol have been ranked as the top interacting molecules to Mpro based on the affinity of molecular docking. Moreover, stability of these four sesame-specific natural compounds has also been evaluated using molecular dynamics (MD) simulations for 200 nanoseconds. The molecular dynamics simulations and free energy calculations revealed that these compounds have stable and favorable energies, causing strong binding with Mpro. These screened natural metabolites also meet the essential conditions for drug likeness such as absorption, distribution, metabolism, and excretion (ADME) properties as well as Lipinski’s rule of five. Our finding suggests that these screened natural compounds may be evolved as promising therapeutics against COVID-19.
... Furthermore, NEs can be formulated from natural oils, which are usually safe and may have therapeutical effects against many diseases, thereby, they can enrich the anticancer effect of the loaded chemotherapeutic drug. Sesame oil (SO), which is usually extracted from Sesamum indicum L. seeds, can be preferable to formulate NE because of its many reported beneficial pharmacological effects, such as the antioxidant, antiproliferative, and anti-inflammatory effects [14][15][16][17]. These effects are due to the characteristics of SO components; the lignans' (polyphenols) like sesamin and sesamol, and SO fatty acid constituents like palmitic, stearic, oleic, and linoleic acids. ...
... In fact, SO-NE effect was even more intense in HCT116 cells when compared to TOPO-SO-NE treated cells. This can be due to the anticancer effects of the SO lignans like sesamin and sesamol, which were found to have potent pro apoptotic and anticancer effects in different kinds of human cancer cells [14,15]. The Data were expressed as mean ± SD in triplicate. ...
Article
Purpose To incorporate the topoisomerase I inhibitor, topotecan (TOPO), into oil-in-water nanoemulsion delivery system based on sesame oil (SO-NE), with the aim to enhance its anti-proliferative effect on MCF-7 breast, HCT116 colon, HeLa cervical, and HepG2 liver cancer cells. Methods SO-NE was formulated by mixing different volume fractions of SO (3%), Tween 80 (10%), Span 20 (5%), and water (82%) using the high-pressure ultrasonication technique. SO-NE and TOPO-loaded SO-NE (TOPO–SO–NE) were physically characterized by zeta sizer and transmission electron microscope. The in vitro drug release of TOPO–SO–NE relative to the free TOPO solution was assessed by the dialysis bag technique. The cytotoxicity of the TOPO–SO–NE formula was determined in vitro using crystal violet assay. DAPI fluorescent stains were used for cellular morphology and death assessments. Additionally, TOPO cellular uptake and inflammatory effect after TOPO loading into SO-NE formula were determined. Results SO-NE formula was found to have negatively charged nanosized particles even after TOPO loading (Z-diameter = 73.66 ± 5.5 nm, Zetapotential = −7.63 ± 0.24 mV). In addition, TOPO–SO–NE formulation exhibited a beneficial TOPO prolonged and sustained release over 24 h. In all tested cell lines, TOPO–SO–NE formula exhibited considerable anti-proliferation effect with decreased IC50 and caused distinct apoptotic changes in cancer cells, which was evidenced by the enhanced cellular uptake of TOPO. The concentrations of interlukin-6 (IL-6), an inflammatory marker, in MCF-7, HCT116 and HepG2 cells were suppressed by TOPO–SO–NE treatment, but they got reversed in HeLa cells. Conclusion Incorporation of TOPO into SO-NE has remarkably improved its cytotoxicity in MCF-7, HCT116, HeLa and HepG2 cancer cells. The mechanisms of cell death were through the induction of apoptosis, enhancement of TOPO cellular accumulation ratios and affecting the inflammatory agent, interlukin-6 (IL-6), concentrations.
... It represents a priceless material for food, cosmetics, and medicine [4]. various physiological properties, such as antioxidant, antiaging, serum lipid-lowering, blood pressure-lowering, anti-cancer, etc. [5][6][7]. Therefore, the global market of sesame products is being expanded. Unfortunately, sesame productivity, yield, and seed quality are influenced by several abiotic stresses, including drought, waterlogging, salt, and heat [8,9]. ...
... To study the structural characteristics of the SiERF genes, the conserved motifs and the number of exons and introns were identified and analyzed. Totally, we identified 16 conserved motifs (motif [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] through MEME motif detection software (Fig. 3A). The motifs were constituted of 6 to 49 aa (Fig. S2). ...
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Background The adverse effects of climate change on crop production are constraining breeders to develop high-quality environmentally stable varieties. Hence, efforts are being made to identify key genes that could be targeted for enhancing crop tolerance to environmental stresses. ERF transcription factors play an important role in various abiotic stresses in plants. However, the roles of the ERF family in abiotic stresses tolerance are still largely unknown in sesame, the “queen” of oilseed crops. Results In total, 114 sesame ERF genes ( SiERFs) were identified and characterized. 96.49% of the SiERFs were distributed unevenly on the 16 linkage groups of the sesame genome. The phylogenetic analysis with the Arabidopsis ERFs ( AtERFs ) subdivided SiERF subfamily proteins into 11 subgroups (Groups I to X; and VI-L). Genes in the same subgroup exhibited similar structure and conserved motifs. Evolutionary analysis showed that the expansion of ERF genes in sesame was mainly induced by whole-genome duplication events. Moreover, cis -acting elements analysis showed that SiERFs are mostly involved in environmental responses. Gene expression profiles analysis revealed that 59 and 26 SiERFs are highly stimulated under drought and waterlogging stress, respectively. In addition, qRT-PCR analyses indicated that most of SiERFs are also significantly up-regulated under osmotic, submerge, ABA, and ACC stresses. Among them, SiERF23 and SiERF54 were the most induced by both the abiotic stresses, suggesting their potential for targeted improvement of sesame response to multiple abiotic stresses. Conclusion This study provides a comprehensive understanding of the structure, classification, evolution, and abiotic stresses response of ERF genes in sesame. Moreover, it offers valuable gene resources for functional characterization towards enhancing sesame tolerance to multiple abiotic stresses.
... The oil extracted from the tiny seeds is odorless, very stable, and contains an antioxidant system comprising sesamol and sesamolinol formed from sesamolin, which substantially reduce its oxidation rate. Sesame oil effectively reduces stress and tension, prevents nervous disorders and various types of cancers, relieves fatigue, and promotes strength and vitality (Nakimi, 1995;Majdalawieh et al., 2017). The global demand for vegetable oils is increasing and it is estimated to reach 240 million tons by 2050 (Barcelos et al., 2015). ...
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Phytophthora blight (PB) caused by Phytophthora nicotianae is a highly destructive disease in sesame (Sesamum indicum L.). In this study, we used linkage mapping and genome-wide association study (GWAS) to identify quantitative trait loci (QTL) and candidate genes associated with PB resistance. The QTL mapping in 90 RILs of the Goenbaek × Osan cross using genotyping-by-sequencing detected significant QTLs for PB resistance on chromosome 10, explaining 12.79%-13.34% of phenotypic variation. Association of this locus to PB resistance was also revealed through bulked segregant analysis in second RIL population (Goenbaek × Milsung cross) comprising 188 RILs. The GWAS of 87 sesame accessions evaluated against three P. nicotianae isolates identified 29 SNPs on chromosome 10 significantly associated with PB resistance. These SNPs were located within a 0.79 Mb region, which co-located with the QTL intervals identified in RIL populations, and hence scanned for identifying candidate genes. This region contained several defense-related candidate R genes, five of which were selected for quantitative expression analysis. One of these genes, SIN_1019016 was found to show significantly higher expression in the resistant parent compared to that in the susceptible parents and selected RILs. Paired-end sequencing of the gene SIN_1019016 in parental cultivars revealed two synonymous SNPs between Goenbaek and Osan in exon 2 of coding DNA sequence. These results suggested SIN_1019016 as one of the candidate gene conferring PB resistance in sesame. The findings from this study will be useful in the marker-assisted selection as well as the functional analysis of PB resistance candidate gene(s) in sesame.
... Sesame is a prominent oilseed crop grown worldwide for its nutritional and therapeutical values (34,35). Due to the huge repertory of pharmacological proprieties associated with its lignans (36)(37)(38), sesame seeds occupy an important place in food pharmacy (8). Unfortunately, the sesame seed's biological abilities are greatly influenced by the seed coat color (15,(39)(40)(41), and little is known about the dark sesame seed coat pigmentation. ...
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Sesame is a worldwide oilseed crop used in the food pharmacy. Its seed phenotypes determine the seed quality values. However, a thorough assessment of seed coat metabolites is lacking, and the dark pigment in the seed coat is not well-characterized. Herein, we report the isolation of melanin by the alkali method from the black and brown sesame seeds. Physicochemical methods, including scanning electron microscopy (SEM), solubility, precipitation, UV-Vis spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and thermogravimetric-differential scanning calorimetry (TG-DSC), were used to characterize the sesame melanins. The results clearly showed that the isolated pigments were similar to melanin from other sources. Both melanins were heat-stable and exhibited numerous characteristic absorption peaks. Through a comprehensible LC-MS/MS-based metabolome profiles analysis of NaOH and methanol extracts of black and white sesame seeds, caffeic, protocatechuic, indole-carboxylic, homogentisic, ferulic, vanillic, and benzoic acids were identified as the potential precursors of the sesame melanin. Our findings widen our understanding of dark seeds pigmentation in sesame. Furthermore, they show that black sesame seeds are promising sources of edible melanin for food and biotechnological applications.
... None study was focused on the nutritional value of other colored sesame seeds, including yellow and brown seeds. Moreover, the huge repertory of pharmacological proprieties of sesamin, sesamolin, sesaminol, and sesamol (Dar & Arumugam, 2013;Majdalawieh et al., 2017;Wu et al., 2019), trends to associate the antioxidative and antiproliferative capacities of sesame seeds to its lignans only. However, compared to white sesame seeds, black sesame seeds exhibited low content of sesamin and sesamolin but high antioxidative and antiproliferative activities (Kancharla & Arumugam, 2020;Shahidi et al., 2006;L. ...
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Sesame seeds are considered worldwide as a functional food due to their nutritional and therapeutical values. Several physiological functions are being associated with sesame seeds and their derived products. However, the phytochemicals responsible for these various proprieties are not well understood. Thus, to acknowledge the diversity and variability of metabolites in sesame seeds of different colors and reveal key metabolites and pathways contributing to differences in antioxidant activities, black, brown, yellow, and white sesame seeds from 12 varieties were subjected to LC-MS/MS-based widely targeted metabolomics analysis. Totally, 671 metabolites were identified and chemically classified. The metabolic compounds varied significantly with the seed coat color and genotype. Many flavonoids, amino acids, and terpenoids were up-regulated in dark seeds. Sixty key differential metabolites were filtered out. Phenylpropanoid biosynthesis, amino acids biosynthesis, and tyrosine metabolism were the main differently regulated pathways. The DPPH, ABTS, and FRAP assays showed that the antioxidant activities of the seeds increased with the seed coat darkness. Therefore, the pharmacological proprieties of black seeds might be related to their high content of flavonoids and essential amino acids mostly. These findings expanded phytochemicals composition information of different colored sesame seeds and provided resources for their comprehensive use and quality improvement.
... Also, there is no effective drug targeting this defect to ameliorate male infertility. Sesamin is the main natural lignolipid bioactive component in sesame, which exists in large quantities in sesame oil and has strong bioactive effects such as antioxidant, anti-inflammatory, and hypoglycemic activities Ahmad et al., 2016;Guo et al., 2016;Majdalawieh et al., 2017). Sesamin commonly induces hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance. ...
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Most of the clinically infertile patients show spermatogenesis dysfunction. Cyclophosphamide, as an anticancer drug, can induce spermatogenesis dysfunction. Sesamin is the main bioactive component of natural lignans in sesame. It is abundant in sesame oil and has strong biological activities such as antioxidant, antibacterial, and hypoglycemic properties. By establishing the model of spermatogenic dysfunction induced by cyclophosphamide in male mice and then feeding sesamin (50, 100, and 200 mg/kg) for 2 weeks, we proved that sesamin can improve the reproductive organ damage induced by cyclophosphamide and increase the number and activity of sperms. Sesamin can resist cyclophosphamide-induced sperm nuclear maturity and DNA damage by increasing the expression levels of histones H2A and H2B in the testis. In addition, sesamin can improve the ubiquitination of histones regulated by RNF8 to protect the testis. In conclusion, these results suggest that sesamin can improve spermatogenic dysfunction induced by cyclophosphamide, which may be mediated by ubiquitination of histones.
... from sesame seeds (Fukuda 1985;Dar and Arumugam 2013). Among sesame lignans, sesamin and sesamolin are the primary ones that have gained the attentiveness of pharmacologists and clinicians due to their health-promoting properties against lifestyle-related diseases (Dar and Arumugam 2013; Majdalawieh et al. 2017Majdalawieh et al. , 2020Abe-Kanoh et al. 2019). Sesamolin and mostly sesamin have been detected in more than 40 plant species (Table 2). ...
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Sesame (Sesamum indicum L.) is a significantly lucrative cash crop for millions of smallholder farmers. Its seeds are an important source of a world highly appreciated oil and two clinically essential antioxidant lignans, sesamin and sesamolin. Accordingly, many countries import annually millions of tons of sesame seeds. The demand for lignan-rich sesame seeds is increasing yearly due to the continuous discovery of several pharmacological attributes of sesamin and sesamolin. To meet the demand, the sesame breeder's primary objective is to release sesame cultivars enriched in oil and lignans. Thus, it is necessary to summarize the information related to sesamin and sesamolin contents in sesame in order to promote joint efforts of specialized research teams on this oilseed crop. In the following, we present the current knowledge on sesamin and sesamolin content in S. indicum L. with respect to the updated biosynthesis pathway, associated markers, governing loci, available variability in sesame germplasm, their in planta potential roles in sesame, and the newly discovered pharmacological abilities. In addition, we propose and discuss some required studies that might afford genomics-assisted breeding of high lignans content sesame varieties.
... Apart from vitamin E, they also contain thiamine (vitamin B1), phytosterols and lignans (sesamin, episesamin, sesamol, sesamolin, pinoresinol, sesaminol diglucoside and sesaminol triglucoside), among other phenolics. It has been reported that these antioxidants have antiproliferative activity, stimulate the function of hepatic FA oxidation enzymes, have lowering effects in cholesterol levels, blood pressure and serum lipids, decrease heart disease risk and prevent cancer development [48][49][50]. Phenolics have high antioxidant capacity, protect against oxidative damage, bind to biological polymers, chelate transient metal ions, neutralize free radicals and decompose peroxides. From a nutritional approach, obtaining food formulations rich in these compounds may decrease the use of antioxidant additives and/or improve the products nutritional profile, allowing to obtain healthier and functional foods [51]. ...
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Whole sesame seeds and sesame oil, which is obtained after cold pressing the seeds, are foodstuffs globally consumed due to their nutritional characteristics. The press cake that remains from the oil extraction process can be ground to form a defatted flour that can be incorporated into the human diet, contributing to the valorisation of this product. The nutritional comparison between the whole seeds and the press cake reveals the potential of this by-product to be incorporated in the formulation of diverse foodstuff, since it is richer than the seeds in proteins (30%) and fibre (25%) and still contains a proportion of oil (32%) with a fatty acid pattern characterized by the abundance of unsaturated fatty acids. The protein fraction of both the seeds and the cake shows a balanced composition regarding amino acid composition, with all the essential amino acids included. On the other hand, the oil obtained by cold pressing is shown as a high-quality oil, where the predominant fatty acids are oleic (42.66%) and linoleic (41.25%), which are essential fatty acids because they are not synthetised in the organism and must be obtained through the diet. In addition, it is rich in vitamin E, especially in γ-tocopherol, that was the main isomer found. Regarding these results, all products (sesame seeds, oil and press cake) are components suitable to be included in a healthy diet.
... In liver microsome assay, curcumin could inhibit 49% of D5D and 18% D6D, whereas sesamin barely inhibits D6D, D9D, and D12D [99,100]. The anti-cancer properties of sesamin and curcumin have been widely studied in different types of cancers [101,102]. Notably, curcumin has been involved in several clinical trials (stage I to III) for the treatment of breast, prostate, and cervical and uterine cancers [101]. Although many studies have demonstrated the effect of sesamin and curcumin on cancer in vivo and in vitro [103][104][105][106][107]. We are still unclear what is the role of D5D in the anti-cancer properties of sesamin and curcumin. ...
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Delta-5 desaturase (D5D) is a rate-limiting enzyme that introduces double-bonds to the delta-5 position of the n-3 and n-6 polyunsaturated fatty acid chain. Since fatty acid metabolism is a vital factor in cancer development, several recent studies have revealed that D5D activity and expression could be an independent prognostic factor in cancers. However, the mechanistic basis of D5D in cancer progression is still controversial. The classical concept believes that D5D could aggravate cancer progression via mediating arachidonic acid (AA)/prostaglandin E2 production from dihomo-γ-linolenic acid (DGLA), resulting in activation of EP receptors, inflammatory pathways, and immunosuppression. On the contrary, D5D may prevent cancer progression through activating ferroptosis, which is iron-dependent cell death. Suppression of D5D by RNA interference and small-molecule inhibitor has been identified as a promising anti-cancer strategy. Inhibition of D5D could shift DGLA peroxidation pattern from generating AA to a distinct anti-cancer free radical byproduct, 8-hydroxyoctanoic acid, resulting in activation of apoptosis pathway and simultaneously suppression of cancer cell survival, proliferation, migration, and invasion. Hence, understanding the molecular mechanisms of D5D on cancer may therefore facilitate the development of novel therapeutical applications. Given that D5D may serve as a promising target in cancer, in this review, we provide an updated summary of current knowledge on the role of D5D in cancer development and potentially useful therapeutic strategies.
... Sesamin is widely used against inflammatory diseases [17], neurodegenerative disease [18], liver disease [19], diabetes, eye problem [20], cardiovascular disease [21], and lung disease [22]. Furthermore, the anticancer activities of sesamin have been documented against numerous human cancers in various in vitro and animal models [23]. However, therapeutic advantage of sesamin again breast cancer is limited. ...
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The use of dietary phytochemical rather than conventional therapies to treat numerous cancers is now a well-known approach in medical science. Easily available and less toxic dietary phytochemicals present in plants should be introduced in the list of phytochemical-based treatment areas. Sesamin, a natural phytochemical, may be a promising chemopreventive agent aiming to manage breast cancer. In this study, we discussed the pharmacological properties of sesamin that determine its therapeutics opportunity to be used in breast cancer treatment and other diseases. Sesamin is available in medicinal plants, especially in Sesamum indicum, and is easily metabolized by the liver. To better understand the antibreast cancer consequence of sesamin, we postulate some putative pathways related to the antibreast cancer mechanism: (1) regulation of estrogen receptor (ER-α and ER-β) activities, (2) suppressing programmed death-ligand 1 (PD-L1) overexpression, (3) growth factor receptor inhibition, and (4) some tyrosine kinase pathways. Targeting these pathways, sesamin can modulate cell proliferation, cell cycle arrest, cell growth and viability, metastasis, angiogenesis, apoptosis, and oncogene inactivation in various in vitro and animal models. Although the actual tumor intrinsic signaling mechanism targeted by sesamin in cancer treatment is still unknown, this review summarized that this phytoestrogen suppressed NF-κB, STAT, MAPK, and PIK/AKT signaling pathways and activated some tumor suppressor protein in numerous breast cancer models. Cotreatment with γ-tocotrienol, conventional drugs, and several drug carriers systems increased the anticancer potentiality of sesamin. Furthermore, sesamin exhibited promising pharmacokinetics properties with less toxicity in the bodies. Overall, the shreds of evidence highlight that sesamin can be a potent candidate to design drugs against breast cancer. So, like other phytochemicals, sesamin can be consumed for better therapeutic advantages due to having the ability to target a plethora of molecular pathways until clinically trialed standard drugs are not available in pharma markets.
... Huang et al. [87] found that gallic acid inhibited TNF-α-induced apoptosis and ADAMTS-4 production in NP cells by regulating NF-κB signalling. Sesamin is a natural polyphenol of sesame seeds that inhibits inflammation, proliferation, apoptosis, and other cellular actions [88]. Li et al. [89] found that sesamin reduced matrix catabolic enzyme expression (MMP1, MMP3, MMP13, ADAMTS-4, and ADAMTS-5) and the levels of the inflammatory factors IL-1β, TNF-α, iNOS, COX-2, and PGE2 in rat NP cells by inhibiting the MAPK pathway. ...
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Intervertebral disc degeneration (IDD) is one of the main causes of low back pain (LBP), which severely reduces the quality of life and imposes a heavy financial burden on the families of affected individuals. Current research suggests that IDD is a complex cell-mediated process. Inflammation, oxidative stress, mitochondrial dysfunction, abnormal mechanical load, telomere shortening, DNA damage, and nutrient deprivation contribute to intervertebral disc cell senescence and changes in matrix metabolism, ultimately causing IDD. Natural products are widespread, structurally diverse, afford unique advantages, and exhibit great potential in terms of IDD treatment. In recent years, increasing numbers of natural ingredients have been shown to inhibit the degeneration of nucleus pulposus cells through various modes of action. Here, we review the pharmacological effects of natural products on nucleus pulposus cells and the mechanisms involved. An improved understanding of how natural products target signalling pathways will aid the development of anti-IDD drugs. This review focuses on potential IDD drugs.
... Sesamin, a lignan found abundantly in sesame seeds and oil, is a major bioactive component that ensures sesame's superior health benefits. For example, sesamin exerts anti-cancer (14) and hypotensive (13) activity, and improves lipid metabolism by reducing fatty acid synthesis, increasing fatty acid oxidation, and attenuating cholesterol synthesis (15). Episesamin, a stereoisomer of sesamin, is rarely found in unrefined sesame oil but is obtained from sesamin during the acid-clay bleaching in the oil refining process (16). ...
Article
Sesamin and episesamin are the main lignans found in refined sesame oil and have been reported to exert various health benefits. However, the health benefits of these lignans and their molecular mechanisms have not been fully understood. This study evaluated the effects of sesamin, episesamin, and their metabolites on the nuclear bile acid receptor, farnesoid X receptor (FXR, NR1H4), which regulate gene expression involved in bile acid metabolism and gluconeogenesis. By using two different cell-based luciferase reporter assay systems, we found that sesamin, sesamin metabolites, and some episesamin metabolites inhibited FXR activation driven by a bile acid and a synthesized agonist, and it is suggested that these compounds exert their antagonist activity by competing with the FXR agonists on the ligand-binding domain. Sesamin and its major metabolite SC-1 suppressed the expression of several gluconeogenesis-related genes governed by FXR in HepG2 cells but did not affect the expression level of CYP7A1, the rate-limiting enzyme for bile acid synthesis. Dietary sesamin supplementation (AIN-93G supplemented with 0.5% sesamin) led to the decreased hepatic expression of several gluconeogenesis-related genes and reduced blood glucose levels in mice, without adverse effects on bile acid metabolism. These results shed light on the health benefits of taking sesamin and episesamin.
... By 2035, the estimated number of cancer cases will be approximately 24 million per year, with 14.6 million associated deaths (Stewart et al., 2016). Therefore, sesamin is a potential adjuvant therapeutic agent for developing tumors and could be used to treat/prevent various types of cancer (Majdalawieh et al., 2017). Limited progress has been made using desirable traits through plant breeding due to the lack of appropriate genomic tools. ...
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Climate change is shifting agricultural production, which could impact the economic and cultural contexts of the oilseed industry, including sesame. Environmental threats (biotic and abiotic stresses) affect sesame production and thus yield (especially oil content). However, few studies have investigated the genetic enhancement, quality improvement, or the underlying mechanisms of stress tolerance in sesame. This study reveals the challenges faced by farmers/researchers growing sesame crops and the potential genetic and genomic resources for addressing the threats, including: (1) developing sesame varieties that tolerate phyllody, root rot disease, and waterlogging; (2) investigating beneficial agro-morphological traits, such as determinate growth, prostrate habit, and delayed response to seed shattering; (3) using wild relatives of sesame for wide hybridization; and (4) advancing existing strategies to maintain sesame production under changing climatic conditions. Future research programs need to add technologies and develop the best research strategies for economic and sustainable development.
... Nowadays, the attention of researchers about has been increased on lignans as di-phenolic compounds in sesame seeds; sesamin, sesamol and sesamolin have been reported as the main components of sesame lignans [13]. The molecular structures of sesamin and sesamol are shown in figure 1. Numerous biological studies have been conducted in humans and animals on the diverse effects of these lignans in health and treatment of diseases such as lipid lowering effects [14], antihypertensive [15], anti-atherosclerotic [16,17], anti-oxidative [14,18], anti-inflammatory [19], cancer-preventing [20,21], hepato-protective [22] and neuroprotective properties [23]. Also, previous studies have revealed that enough intake of sesamin can improve vitamin E efficacy in human body and has a modification role in fatty acid metabolism [24,25]. ...
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Background and objectives: Sesame (Sesamum indicum L.) seeds have been a well-known oil crop in the world for many centuries. Lignans are functionally important compartments of sesame. Sesamin and sesamol are the main sesame lignans, which have recently shown various activities with health benefits, like anti-oxidative, anti-proliferative, anti-atherosclerotic, anti-inflammatory and anticancer effects. The aim of this study was determination of sesamin and sesamol concentration in sesame seeds from three different regions of Iran with diverse climatic conditions (Dezful, Ardakan and Neka). In addition, the effect of roasting process on sesamin and sesamol content were investigated. Methods: Analysis of sesamin and sesamol was performed using the mobile phase water: methanol (70:30) on a reversed phase ACE C 18 with flow rate of 0.6 mL/min and UV detection at 290 nm. Results: HPLC analysis revealed that the highest content of sesamin (1.156±0.002 mg/g of seeds) and sesamol (2.393±0.002 mg/g of seeds) were observed in roasted Dezful seeds samples and hulled roasted Dezful sesame seeds, respectively. The amount of sesamin and sesamol in roasted seeds was higher than unroasted samples. Conclusion: The present study showed that the roasting process and hot semi-arid climate increase the content of lignans in sesame seeds. Consuming sesame seeds with such characteristics will improve dietary lignan intake and has nutritive value. Moreover, sesame seed characterized by the highest amount of sesamin and sesamol is more strongly suggested for achieving biological properties of these components.
... Lignans have attracted extensive attention of researchers owing to their wide bioactivities including antioxidant, antitumor, and hepatoprotective effects, as well as antileishmanial and antimalarial activities in recent years [1][2][3][4]. Galgravin is a new tetrahydrofuran lignan, which has been found in some medicinal plants, such as Piper wallichii [5], leaves of Tridax procumbens [6], rhizomes of Acorus tatarinowii Schott [7], and the stems of Schisandra propinqua [8]. ...
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This paper presents a new high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method with a rapid analysis of 6 min to determine the concentration of galgravin in rat plasma so as to study its pharmacokinetic features and bioavailability in vivo. Schisandrin was selected as the internal standard (IS). After extracting the analyte from plasma samples with ethyl acetate, methanol-H2O (0.1% formic acid) (85 : 15, v/v) was used as mobile phase to achieve chromatographic separation on a C18 reversed phase column. The MS detection was performed in positive ion mode using electrospray ionization (ESI) source. This method showed good linearity over the range of 1~500 ng/mL (R 2 > 0.999), and the lower limit of quantitation (LLOQ) was 1.0 ng/mL. The intraday precision and interday precision were both within 8.5%, whereas the accuracies were in the range of -2.6%-6.0%. The average recoveries of galgravin in rat plasma were between 92.3% and 99.3%. Moreover, galgravin was stable throughout storage and processing with all RSDs below 12.1%. After the successful application of this optimized method, the oral bioavailability of galgravin was determined to be 8.5%. This study will be helpful to the future research and development of galgravin.
... The sesame plant tissues such as leaves, flowers, and carpels are currently underused while the global market of its seeds is increasing due to their various benefits to human health [10,11]. The recorded pharmacological functions of sesame are mainly attributed to its specific class of lignans sesamin, sesamolin, sesaminol, sesamol, and sesamolinol [12][13][14][15]. The content of the most abundant lignan in sesame, sesamin in leaves was 1/5000 or less than that of seeds [16]. ...
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Background Sesame ( Sesamum indicum L.) leaves, flowers, especially seeds are used in traditional medicine to prevent or cure various diseases. Its seed’s market is expanding. However, the other tissues are still underexploited due to the lack of information related to metabolites distribution and variability in the plant. Herein, the metabolite profiles of five sesame tissues (leaves, fresh seeds, white and purple flowers, and fresh carpels) have been investigated using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS)-based widely targeted metabolomics analysis platform. Results In total, 776 metabolites belonging to diverse classes were qualitatively and quantitatively identified. The different tissues exhibited obvious differences in metabolites composition. The majority of flavonoids predominantly accumulated in flowers. Amino acids and derivatives, and lipids were identified predominantly in fresh seeds followed by flowers. Many metabolites, including quinones, coumarins, tannins, vitamins, terpenoids and some bioactive phenolic acids (acteoside, isoacteoside, verbascoside, plantamajoside, etc.) accumulated mostly in leaves. Lignans were principally detected in seeds. 238 key significantly differential metabolites were filtered out. KEGG annotation and enrichment analyses of the differential metabolites revealed that flavonoid biosynthesis, amino acids biosynthesis, and phenylpropanoid biosynthesis were the main differently regulated pathways. In addition to the tissue-specific accumulation of metabolites, we noticed a cooperative relationship between leaves, fresh carpels, and developing seeds in terms of metabolites transfer. Delphinidin-3-O-(6ʺ-O-p-coumaroyl)glucoside and most of the flavonols were up-regulated in the purple flowers indicating they might be responsible for the purple coloration. Conclusion This study revealed that the metabolic processes in the sesame tissues are differently regulated. It offers valuable resources for investigating gene-metabolites interactions in sesame tissues and examining metabolic transports during seed development in sesame. Furthermore, our findings provide crucial knowledge that will facilitate sesame biomass valorization.
... Sesame seeds and products contain a large number of lignans, among which sesamin and sesamolin are the major ones [6]. Many studies had reported various pharmacological abilities of sesamin and sesamolin, including anti-inflammatory, anti-oxidative, anti-cancerogenic, anti-hypertensive, anti-proliferative, anti-melanogenesis, auditory-protective, anti-cholesterol and anti-aging [7][8][9][10]. The total lignan content is a critical factor in sesame seed quality evaluation [11]. ...
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Deciphering the genetic basis of quantitative agronomic traits is a prerequisite for their improvement. Herein, we identified loci governing the main sesame lignans, sesamin and sesamolin variation in a recombinant inbred lines (RILs, F8) population under two environments. The content of the two lignans in the seeds was investigated by HPLC. The sesamin and sesamolin contents ranged from 0.33 to 7.52 mg/g and 0.36 to 2.70 mg/g, respectively. In total, we revealed 26 QTLs on a linkage map comprising 424 SSR markers, including 16 and 10 loci associated with sesamin and sesamolin variation, respectively. Among them, qSmin_11.1 and qSmol_11.1 detected in both the two environments explained 67.69% and 46.05% of the phenotypic variation of sesamin and sesamolin, respectively. Notably, qSmin11-1 and qSmol11-1 were located in the same interval of 127–127.21 cM on LG11 between markers ZMM1776 and ZM918 and acted as a pleiotropic locus. Furthermore, two potential candidate genes (SIN_1005755 and SIN_1005756) at the same locus were identified based on comparative transcriptome analysis. Our results suggest the existence of a single gene of large effect that controls expression, both of sesamin and sesamolin, and provide genetic information for further investigation of the regulation of lignan biosynthesis in sesame.
... In mammals, (+)-Sesamin metabolites attenuate oxidation and inflammation for the protection of the liver 6,7 . (+)-Sesamin also shows anti-cancer properties 8 . (+)-Sesamin is commercially available via extraction at concentrations (4-6 mg/g) from Sesamum indicum (sesame) seed oil 5,9,10 . ...
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Lignans are widely distributed plant secondary metabolites that have received attention for their benefits to human health. Sesamin is a furofran lignan that is conventionally extracted from Sesamum seeds and shows anti-oxidant and anti-inflammatory activities in the human liver. Sesamin is biosynthesized by the Sesamum-specific enzyme CYP81Q1, and the natural sources of sesamin are annual plants that are at risk from climate change. In contrast, Forsythia species are widely distributed perennial woody plants that highly accumulate the precursor lignan pinoresinol. To sustainably supply sesamin, we developed a transformation method for Forsythia leaf explants and generated transgenic Forsythia plants that heterologously expressed the CYP81Q1 gene. High-performance liquid chromatography (HPLC) and LC-mass spectrometry analyses detected sesamin and its intermediate piperitol in the leaves of two independent transgenic lines of F. intermedia and F. koreana. We also detected the accumulation of sesamin and piperitol in their vegetatively propagated descendants, demonstrating the stable and efficient production of these lignans. These results indicate that CYP81Q1-transgenic Forsythia plants are promising prototypes to produce diverse lignans and provide an important strategy for the cost-effective and scalable production of lignans.
... We have shown that eudesmin can control Candida yeast with moderate activity, but that the furan ring is susceptible to epimerization in acidic media, producing the corresponding epimer. Similar results were obtained for sesamin, a furofuran lignan isolated from sesame seeds, with anti-cancer properties (Majdalawieh et al. 2017) which maintains an equilibrium with its epimer asarinin (Li et al. 2005). The bromination of eudesmin produces mono and di bromo derivatives in ortho-position of the phenyl ring. ...
Article
Furofuran lignanes show important biological activities for the treatment of infectious diseases, inflammatory and metabolic pathologies. They have been isolated from leaves and barks of many plants. In Chile the native conifer Araucaria araucana produces eudesmin, matairesinol, secoisolariciresinol and lariciresinol in stemwood, branchwood and knotwood. These compounds were previously isolated by laborious flash chromatography on silica gel. Here we report the easy isolation of eudesmin by soxhlet extraction from milled knots of Araucaria araucana with hexane, followed by cryo-crystallization at −20 °C. Upon bromination of the isolated eudesmin epimerization at one benzylic position occurs, giving epieudesmin and the corresponding mono and di-brominated derivatives. The structures were determined by 1D, 2D NMR and X-ray diffraction. The analysis of products against Candida yeast showed that eudesmin has a moderate activity against different strains of Candida from 62.5 to 500 µg/mL. This activity decreases for epieudesmin, while bromine derivatives are not active.
... Flavonoids of BZL, including scutellarin and baicalein from CBC, have been found to significantly treat liver tumors [43,44]. e antitumor effects of sesamin have been mainly attributed to apoptotic, inflammatory, metastatic, and autophagocytic activities [45,46]. Quercetin exhibits anticancer properties, especially in cancers located in the digestive and urogenital systems [47,48]. ...
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Purpose: Compound banmao capsule (CBC), a well-known traditional Chinese medical material, is known to inhibit various tumors. However, its material basis and pharmacological mechanisms remain to be elucidated. This study aimed to investigate the effective material basis and mechanisms of action of CBC against tumors. Methods: Active compounds of CBC were identified using public database and reports to build a network. The corresponding targets of active compounds were retrieved from online databases, and the antitumor targets were identified by GeneCards database. The antitumor hub targets were generated via protein-protein interaction analysis using String, and key compounds and targets from the integrative network were detected by molecular docking and ADMET. Top targets in hepatocellular carcinoma were confirmed by quantitative real-time PCR (qPCR). Finally, the multivariate biological network was built to identify the integrating mechanisms of action of CBC against tumor cells. Results: A total of 128 compounds and 436 targets of CBC were identified successfully. Based on the generated multivariate biological network analysis, 25 key compounds, nine hub targets, and two pathways were further explored. Effective material bases of cantharidin, baicalein, scutellarin, sesamin, and quercetin were verified by integrative network analysis. PTGS2, ESR1, and TP53 were identified as hub targets via multivariate biological network analysis and confirmed using qPCR. Furthermore, VEGF and estrogen signaling pathways seem to play a role in the antitumor activity of CBC. Thus, breast cancer may be a potential clinical indication of CBC. Conclusion: This study successfully identified the material basis of CBC and its synergistic mechanisms of action against tumor cells.
... Sesamin is a type of sesame lignans that can be extracted from sesame oil (Dalibalta et al., 2020). Many studies have shown that sesamin has potential antiinflammatory, antioxidant, and anti-tumor effects in different tissues (Majdalawieh et al., 2017;Dalibalta et al., 2020). The role of sesamin in IDD development has also been confirmed. ...
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Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.
... The anti-cancer effects of sesamin have been mainly attributed to its anti-proliferative, pro-apoptotic, anti-inflammatory, anti-metastatic, anti-and pro-angiogenic, and pro-autophagocytic activities. Also, the previous researches indicate that NF-κB, STAT3, JNK, ERK1/2, p38 MAPK, PI3K/AKT, caspase-3, and p53 signaling pathways are critically involved in mediating the anti-cancer effects of (−)-sesamin [28]. In addition, oral sesamin administration (50 mg/kg·bodyweight/day) significantly attenuated depressive, aversive, repetitive, and anxiety-like be- haviors in a long-term multiple nonsocial stress-treated CD-1 mice model. ...
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Acanthopanax henryi (Oliv.) Harms (Araliaceae), also known as Eleutherococcus henryi and Caoyewujia (Hengliwujia) in Chinese, is a widely used traditional Chinese herb with the effects of expelling wind and removing dampness, relaxing the muscles and stimulating the blood circulation, and regulating the flow of qi to alleviate pain in the theory of Traditional Chinese Medicine. Acanthopanax henryi (AH, thereafter) possesses ginseng-like activities and is known as ginseng-like herb. In the past decade, a great number of phytochemical and pharmacological studies on AH have been carried out. Several kinds of chemical compositions have been reported, including terpenoids (monoterpenoids, diterpenoids, and triterpenoid saponins), phenylpropanoids, caffeoyl quinic acid derivatives, flavonoids, lignans, sterols, fatty acids, etc., among which, triterpenoid saponins were considered to be the most active components. Considerable pharmacological experiments in vitro have demonstrated that AH possessed anti-neuroinflammatory, anti-adipogenic, anti-inflammatory, antibacterial, anti-cancer, anti-oxidation, anti-AChE, anti-BuChE, and antihyaluronidase activities. The present review is an up-to-date and comprehensive analysis of the botany, phytochemistry, and pharmacology of AH.
... Sesamin is a well-known antitumor molecule that has garnered increasing attention in recent years [28,29]. Sesamin can modulate cancer cell progression via the Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3) pathway in colorectal cancer [30]. ...
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Suppression of cellular O-GlcNAcylation can repress proliferation and migration of various cancer cells, which opens a new avenue for cancer therapy. Based on the regulation of insulin gene transcription, we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells. The fluorescent reporter mainly consists of a reporter (GFP), an internal reference (RFP), and an operator (NeuroD1), which serves as a “sweet switch” to control GFP expression in response to cellular O-GlcNAcylation changes. The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines. Using the fluorescent reporter, we screened 120 natural products and obtained one compound, sesamin, which could markedly inhibit protein O-GlcNAcylation in HeLa and HCT-116 cells and repress their migration in vitro. Altogether, the present study demonstrated the development of a novel strategy for anti-tumor drug screening, as well as for conducting gene transcription studies.
... In mammals, (+)-sesamin metabolites attenuate oxidation and inflammation, thereby protecting the liver (Nakai et al., 2003;Kabe et al., 2020). (+)-Sesamin also exhibits several anti-tumor and anti-bacterial effects (Majdalawieh et al., 2017;Oikawa et al., 2022). (-)-Podophyllotoxin is an aryltetralin lignan found in the rhizomes of Podophyllum plants, and is utilized as a leading compound in anti-cancer drugs (Ardalani et al., 2017;Changxing et al., 2020). ...
... World production in 2016 was 6.1 million tonnes, with Tanzana, Myanmar, India, and Sudan producing the most. Sesame seeds are good source of fibre, reduce cholesterol, triglycerides, nutrious source of plant protein, lower blood pressure, containing vitamins B, may aid blood cell formation, aid blood cell sugar, rich in antioxidants, improve immune system, soothe arthritic knee pain, support thyroid health (Science Service 1927), aid harmone balance during menopause, regulating cholesterol, Neurological role, prevent anemia, cardiovascular health, prevent diabetes (Musumeci et al. 2011), regulating and anti-cancer properties (Majdalawieh et al. 2017). As seeds contain magnesium which has anti cancer properties, relief from rheumatoid arthritis, respiratory health, protection from radiation damage, bone health, oral health (Amalraj and Gopi 2017), nullify the effects of alcohol, treatment of anxiety, magnesium and calcium act as antispasmodic by regulating the muscle function, helps in treatment of anxiety, nourish the organ, eye health (Hussien et al. 2013), blood pressure reduction, skin detoxifier, treatment of sun burn, glowing skin, suitable for babies, treatment of cracked heels, prevention of scalp problems, encourage hair growth and hair darkening qualities. ...
Article
Natural products, especially plants and herbs, have always been a common medicament source, either as pure active principles or traditional preparations. Traditional medicine has been used in developing and developed countries for centuries, and still, 80% of the population uses plant-based medicines for their health care needs. The present review discusses all the possible pharmacological activity reported in various literature and active chemical constituents of herbs. A list of various herbs/plants used by Ayurvedacharya Ratiram Sharma (93-year-old and practicing since 1952) and mentioned in Ayurvedic texts. The curated list was prepared by their general availability in the household and local market. This study comprehensively documented the medicinal value of sixty-six dominant plant species used in Ayurveda and local people. In the present review, each herb is discussed with its scientific and common names, geographical distribution, traditional medicinal uses, beneficial plant parts, and active chemical constituents. For each plant, pharmacological activities of different parts of plants are displayed with their chemical constituents and structure. Toxicologists, phytologists, medicinal chemists, and other researchers who are interested in the various therapeutic and related applications of plant materials will be benefited from present review. This information will open new horizons of application for the many novel drugs and drug candidates.
Article
Sesamin is a lignan compound in plants that has various pharmacological effects, including reducing diabetes-associated injuries, regulating fatty acid and cholesterol metabolism, and exerting antiinflammatory and antitumour effects. Previous studies have reported that sesamin can inhibit the proliferation of several types of tumour cells and exert antitumour effects. However, the antitumour effect of sesamin on T-cell lymphoma is still unknown. In this study, we selected a T-cell lymphoma mouse model to investigate the mechanism of sesamin against T-cell lymphoma via programmed cell death in vivo and in vitro. We found that sesamin could significantly inhibit the growth of EL4 cells in a tumour-bearing mouse model. Sesamin markedly inhibited the proliferation of EL4 cells by inducing apoptosis, pyroptosis and autophagy. Autophagy occurred earlier than apoptosis and pyroptosis in EL4 cells after sesamin treatment. Blocking autophagy inhibited apoptosis and pyroptosis in EL4 cells after sesamin treatment. Taken together, these results suggested that sesamin promoted apoptosis and pyroptosis via autophagy to enhance antitumour effects on murine T-cell lymphoma. This study expands our knowledge of the pharmacological effects of sesamin on T-cell lymphoma, and provides a theoretical basis for the development of new antitumour drugs and treatments for T-cell lymphoma.
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Background: Sesame is a great reservoir of bioactive constituents and unique antioxidant components and is widely used for its nutritional and medicinal value. The expanding demands for sesame seeds are putting pressure on sesame breeders to develop reliable high-yielding varieties. Heterosis utilization is an efficient way to increase sesame yield. Polyketide synthases (PKSs) are critical enzymes in the biosynthesis of sporopollenin, a primary component of pollen exine. Their in planta functions are being investigated for application in crop breeding. Results: In this study, we cloned the sesame POLYKETIDE SYNTHASE A (SiPKSA) and examined its function in male sterility. SiPKSA was specifically expressed in sesame flower buds, and its expression was significantly higher in sterile sesame anthers than in fertile anthers at the tetrad and microspore development stage. Further overexpression of SiPKSA in Arabidopsis caused transgenic plants male sterile. Ultrastructural observation showed that the pollen grains of SiPKSA-overexpressing plants contained few cytoplasmic inclusions and exhibited an abnormal pollen wall structure, with a thicker exine layer compared with wild type. In agreement with it, the expression of a set of sporopollenin biosynthesis-related genes and the contents of fatty acids and phenolics were significantly altered in anthers of SiPKSA-overexpressing plants compared with wild type during anther development. Conclusion: These findings highlighted that overexpression of SiPKSA in Arabidopsis might cause excessive sporopollenin biosynthesis to influence pollen and pollen wall development, leading to male sterile, suggesting that its manipulation might improve hybrid breeding in sesame and other crop species.
Article
Tripartite motif‐containing 44 (TRIM44) is known to play an oncogenic role in multiple human cancers, including esophageal cancer. Sesamin possesses potent anti‐inflammatory and anti‐cancer properties for various cancers. This study is designed to unravel the biological functions of sesamin and TRIM44 in esophageal cancer. TRIM44 expression in esophageal squamous cell cancer (ESCC) cell lines and tissues was determined by RT‐qPCR assay and Western blot. The effects of sesamin and TRIM44 on ESCC cell growth in vivo and in vitro were assessed by the mouse model and CCK‐8 assay, respectively. We found that TRIM44 was significantly upregulated in ESCC cell lines and tissues when compared to their counterparts. Sesamin treatment or depletion of TRIM44 markedly reduced ESCC cell proliferation. The nuclear factor kappa B (NF‐κB) and toll‐like receptor 4 (TLR4) signaling pathway may be involved in sesamin‐mediated TRIM44 suppression. Finally, we showed that oral‐administration of sesamin dramatically inhibited tumor growth or ESCC in nude mice. Our results suggest that sesamin exerts antitumor activity in ESCC via inhibition of NF‐κB signaling pathway, demonstrating its potential for the treatment of esophageal cancer. The nuclear factor kappa B (NF‐κB) and toll‐like receptor 4 (TLR4) signaling pathway may be involved in sesamin‐mediated TRIM44 suppression. Finally, we showed that oral‐administration of sesamin dramatically inhibited tumor growth or ESCC in nude mice.
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A large body of evidence indicates that lignans as polyphenolic compounds are beneficial against life-threatening diseases such as cancer. Plant lignans have the potential to induce cancer cell death and interfere with carcinogenesis, tumor growth, and metastasis. Epidemiological studies have revealed that the intake of lignans is inversely associated with the risk of several cancers. Moreover, numerous experimental studies demonstrate that natural lignans significantly suppress cancer cell proliferation with minimal toxicity against non-transformed cells. Dietary lignans arctigenin and sesamin have been found to have potent antiproliferative activities against various types of human cancer. The purpose of this review is to provide the reader with a deeper understanding of the cellular and molecular mechanisms underlying anticancer effects of arctigenin and sesamin. Our review comprehensively describes the effects of arctigenin and sesamin on the signaling pathways and related molecules involved in cancer cell proliferation and invasion. The findings of present review show that the dietary lignans arctigenin and sesamin seem to be promising carcinopreventive and anticancer agents. These natural lignans can be used as dietary supplements and pharmaceuticals for prevention and treatment of cancer.
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Phytoestrogens are non-steroidal, polyphenolic compounds that are derived from plants and have biological properties similar to those of human estrogens. Their bioactivity, which is based on the core ring system, is caused by their structural resemblance to estrogen. Flavonoids, coumestans, lignans, and stilbenes are the four major categories into which they can be divided. They are structurally and functionally related to ovarian and placental estrogens, which are essential in female reproductive processes. Phytoestrogens are present in numerous dietary supplements and find application in hormone replacement therapy as an alternative to synthetic hormones. In addition, they provide health benefits for osteoporosis, heart disease, breast cancer, and prostate cancer. There is a growing interest in using phytoestrogen as preventative medicine in the form of nutraceuticals. This literature provides comprehensive information about the types, sources, and biological actions of phytoestrogens in the reproductive system.
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Doxorubicin (DOX) is a potent antitumor agent with a broad spectrum of activity; however, irreversible cardiotoxicity resulting from DOX treatment is a major issue that limits its therapeutic use. Sirtuins (SIRTs) play an essential role in several physiological and pathological processes including oxidative stress, apoptosis, and inflammation. It has been reported that SIRT1 and SIRT3 can act as a protective molecular against DOX‐induced myocardial injury through targeting numerous signaling pathways. Several natural compounds (NCs), such as resveratrol, sesamin, and berberine, with antioxidative, anti‐inflammation, and antiapoptotic effects were evaluated for their potential to suppress the cardiotoxicity induced by DOX via targeting SIRT1 and SIRT3. Numerous NCs exerted their therapeutic effects on DOX‐mediated cardiac damage via targeting different signaling pathways, including SIRT1/LKB1/AMPK, SIRT1/PGC‐1α, SIRT1/NLRP3, and SIRT3/FoxO. SIRT3 also ameliorates cardiotoxicity by enhancing mitochondrial fusion.
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Cancer as a long-lasting and dramatic pandemic affects almost a third of the human being worldwide. At present, chemotherapy is the main clinical treatment strategy, but it is difficult to achieve satisfactory efficacy due to drug resistance and side effects. Natural products are becoming increasingly popular in cancer therapy due to their potent broad-spectrum anticancer potency and slight side effects. Lignans are complex diphenolic compounds, comprising a family of secondary metabolites existing widely in plants. Naturally occurring lignans have the potential to act on cancer cells by a range of mechanisms of action and could inhibit the colony formation, arrest the cell cycle in different phases, induce apoptosis, and suppress migration, providing privileged scaffolds for the discovery of novel anticancer agents. In recent five years, a variety of naturally occurring lignans were isolated and screened for their in vitro and/or in vivo anticancer efficacy, and some of them exhibited promising potential. This review has systematically summarized the resources, anticancer activity, and mechanisms of action of naturally occurring lignans, covering articles published between January 2017 and January 2022.
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Mitochondria, the main provider of energy in eukaryotic cells, contains more than 1000 different proteins and is closely related to the development of cells. However, damaged proteins impair mitochondrial function, further contributing to several human diseases. Evidence shows mitochondrial proteases are critically important for protein maintenance. Most importantly, quality control enzymes exert a crucial role in the modulation of mitochondrial functions by degrading misfolded, aged, or superfluous proteins. Interestingly, cancer cells thrive under stress conditions that damage proteins, so targeting mitochondrial quality control proteases serves as a novel regulator for cancer cells. Not only that, mitochondrial quality control proteases have been shown to affect mitochondrial dynamics by regulating the morphology of optic atrophy 1 (OPA1), which is closely related to the occurrence and progression of cancer. In this review, we introduce mitochondrial quality control proteases as promising targets and related modulators in cancer therapy with a focus on caseinolytic protease P (ClpP), Lon protease (LonP1), high‐temperature requirement protein A2 (HrtA2), and OMA‐1. Further, we summarize our current knowledge of the advances in clinical trials for modulators of mitochondrial quality control proteases. Overall, the content proposed above serves to suggest directions for the development of novel antitumor drugs.
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Cancer is the transformation of healthy cells into tumor cells in a multistage process that can affect any organ of the body. This disease is the second leading cause of death globally. There are now more than 10 million cancer cases per year worldwide, and the most common occurs in the lung, breast, and colon. Several studies demonstrate that lifestyle and eating habits are directly related to tumor cells’ appearance, such as high body mass index, low fruit and vegetable intake, lack of physical activity, and tobacco and alcohol use. It is widely believed that diet and nutrients can act as cancer risk-modifiers throughout the process of carcinogenesis, including initiation, promotion, progression, and/or conversion. Different plants have been the source of therapeutic agents. Plant-derived compounds have become indispensable for modern pharmacotherapy, and phenolic compounds are one of the most investigated due to their antitumor activity. Their cellular targets and mechanisms are compiled in the present work. Phenolic compounds are secondary metabolites present in large quantities in medicinal herbs and dietary plants (e.g., fruits, vegetables, and spices). They possess a diverse range of beneficial biological activities, which contribute to their potent effects on inhibiting carcinogenesis. Some benefits include cell proliferation and angiogenesis inhibition and anti-inflammatory, antioxidant, and antimetastatic activities. Thus, the present review supports the recommendations for consuming foods and drinks rich in phenolic compounds to prevent and possibly treat cancer.
Article
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. Tumor angiogenesis plays a critical role in CRC metastasis, and hypoxia, which widely existed in the tumor mass, drives tumor angiogenesis. Sesamin, a phytochemical derived from sesame seeds, has been reported to inhibit tumor cell growth and metastasis, however, the role of sesamin in CRC angiogenesis and its underlying mechanism have not been investigated yet. Here, an in vitro tube formation assay and an in vivo angiogenesis assay were used to explore the role of sesamin in CRC angiogenesis. In this study, we found that sesamin significantly inhibited hypoxia-stimulated CRC angiogenesis in a dose-dependent manner in vitro. Moreover, oral intake of sesamin dramatically suppressed neovessel formation of matrigel plugs with CRC cells in nude mice. In mechanism, sesamin reduced the expression of VEGFA to inhibit hypoxia-induced CRC angiogenesis. In addition, sesamin inhibited the phosphorylation of IκBα and thus restrained NF-κB p65 to activate HIF-1α transcription under hypoxic conditions. Finally, our results indicated that sesamin inhibited hypoxia-induced CRC angiogenesis via the NF-κB/HIF-1α/VEGFA signaling pathway. Our study might provide a theoretical and experimental basis for the use of sesamin in the prevention and treatment of CRC.
Chapter
Lignans are naturally-occurring compounds produced and accumulated in several edible and medicinal plants, which can be subdivided biosynthetically into lignans and neolignans. Once consumed, they can be transformed by gut microbiota into bioactive mammalian lignans. Such is the case of the conversion of the most studied and known dietary lignan, secoisolariciresinol diglucoside (SDG), into enterolactone (ENL) and enterodiol (END). Updated results comprising the action of these lignans (even other (neo)lignans) suggest that they exhibited positive effects on different diseases/disorders due to their free radical scavenging activity or capacity and capability to coordinate divalent transition metal ions to form complexes, in spite of a plausible, partially-registered prooxidant action. Therefore, some (neo)lignans are described as favorable chemical entities to human health, which their safety is also suitable since no detrimental effects are reported for the intake of some dietary lignans, exhibiting a more preventive than curative effect on diseases. Hence, in order to cover such an information about dietary (neo)lignans and their potential on human health as antioxidants, this document gathers the available information from chemical and biological point-of-views, including several topics such as sources, chemistry, bioavailability, antioxidant activity and action mechanisms, beneficial effects, and in vitro and animal/clinical studies.
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Sesamin, a major lignin mainly found in sesame (Sesamum indicum) oil and sesame seeds, has been demonstrated to possess lipoclasis-promoting, antiobesity, and antidiabetic effects. Irisin is a newly discovered myokine that has attracted great interest as a key target to prevent/treat obesity and its related metabolic diseases. However, the effect and potential mechanism of sesamin on FNDC5/irisin are still vacant. In this study, we showed that sesamin treatment increased FNDC5/irisin activation and regulated SIRT1, PGC-1α, and p-SMAD3/SMAD3 expression in C2C12 cells. By using specific inhibitors and lentivirus in C2C12 cells, we found that the SIRT1/SMAD3 axis plays an important role in sesamin regulated FNDC5/irisin activation. We also found that sesamin treatment activated FNDC5 expression and regulated the SIRT1/SMAD3 signaling axis in mice's skeletal muscle. What is more, by the high-fat diet induced obese model, we further showed that sesamin improved the high-fat diet induced decrease in irisin production and secretion, which results in an improvement of body weight gain and skeletal muscle dysfunction. Our results suggested that sesamin could activate FNDC5 expression and stimulate irisin secretion through the SIRT1 pathway both in vitro and in vivo, which may provide a new strategy for preventing and improving irisin deficiency related diseases.
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Sesame seeds are promulgated as traditional high-quality edible oil crops, which are rich in lipid (40%–65%), protein (19%–35%), and a variety of bioactive compounds. The review starts with bioactive components (fatty acid, tocopherol, phytosterol, sesamin, sesamolin, sesamol) of sesame seeds. The main part of the review considers processing techniques for extracting oil (aqueous extraction and pressing) from seeds. Novel technologies, such as enzyme-assisted aqueous, supercritical CO2, and microwave-assisted solvent extraction, are also discussed. The methods of utilization of sesame seed cake are also analyzed. In the future, the processing technology of tree peony seed will be further developed in the direction of improving comprehensive utilization rate to meet new consumption demand.
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Background Sesame is a great reservoir of bioactive constituents and unique antioxidant components. It is widely used for its nutritional and medicinal value. The expanding demand for sesame seeds is putting pressure on sesame breeders to develop high-yielding varieties. A hybrid breeding strategy based on male sterility is one of the most effective ways to increase the crop yield. To date, little is known about the genes and mechanism underlying sesame male fertility. Therefore, studies are being conducted to identify and functionally characterize key candidate genes involved in sesame pollen development. Polyketide synthases (PKSs) are critical enzymes involved in the biosynthesis of sporopollenin, the primary component of pollen exine. Their in planta functions are being investigated for applications in crop breeding. Results In this study, we cloned the sesame POLYKETIDE SYNTHASE A ( SiPKSA ) and examined its function in male sterility. SiPKSA was specifically expressed in sesame flower buds, and its expression was significantly higher in sterile sesame anthers than in fertile anthers during the tetrad and microspore development stages. Furthermore, overexpression of SiPKSA in Arabidopsis caused male sterility in transgenic plants. Ultrastructural observation showed that the pollen grains of SiPKSA -overexpressing plants contained few cytoplasmic inclusions and exhibited an abnormal pollen wall structure, with a thicker exine layer compared to the wild type. In agreement with this, the expression of a set of sporopollenin biosynthesis-related genes and the contents of their fatty acids and phenolics were significantly altered in anthers of SiPKSA -overexpressing plants compared with wild type during anther development. Conclusion These findings highlighted that overexpression of SiPKSA in Arabidopsis might cause male sterility through defective pollen wall formation. Moreover, they suggested that SiPKSA modulates vibrant pollen development via sporopollenin biosynthesis, and a defect in its regulation may induce male sterility. Therefore, genetic manipulation of SiPKSA might promote hybrid breeding in sesame and other crop species.
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Normal cells express surface proteins that bind to immune checkpoint proteins on immune cells to turn them off, whereby the immune system does not attack normal healthy cells. Cancer cells can also utilize this same protective mechanism by expressing surface proteins associated with checkpoint proteins on immune cells to overcome the immune surveillance. Immunotherapy is making the best use of the body’s own immune system to reinforce anti-tumor responses. The most generally used immunotherapy is the control of immune checkpoints including the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), or programmed cell death ligand-1 (PD-L1). In spite of the clinical effectiveness of these immune checkpoint inhibitors, the overall response rate still remains low. Therefore, there have been considerable efforts in searching for alternative immune checkpoint proteins that may work as new therapeutic targets for treatment of cancer. Recent studies have identified several additional novel immune checkpoint targets, including lymphocyte activation gene-3, T cell immunoglobulin and mucin-domain containing-3, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain, V-domain Ig suppressor of T cell activation, B7 homolog 3 protein, B and T cell lymphocyte attenuator, and Inducible T-cell COStimulator. Natural compounds, especially those present in medicinal or dietary plants, have been investigated for their anti-tumor effects in various in vitro and in vivo models. Some phytochemicals exert anti-tumor activities based on immunoregulation, capable of blocking interaction between proteins involved in immune checkpoint signal transduction or regulation of their expression. Recently, synergistic anti-cancer effects of diverse phytochemicals with anti-PD-1/PD-L1 or anti-CTLA-4 monoclonal antibody drugs have been continuously reported. Considering an increasing attention to noteworthy therapeutic effects of immune checkpoint inhibitors in the cancer therapy, this review focuses on regulatory effects of selected phytochemicals on immune checkpoint protein network and their combinational effectiveness with immune checkpoint inhibitors targeting tumor cells.
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Vegetable oils have been suggested in polymer science as an environmentally friendly feedstock existing in abundance in nature, with worldwide availability and low cost. Although they have been widely explored as building blocks for polymers synthesis, their functional roles as owners of potent biomolecules are less unexplored. Their ancient biomolecules support natural biological roles such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor properties, which are considered a great promise for biomedical proposes. This comprehensive review provides an overview of grape, soybean, castor, sesame, olive vegetable oils where their native anti-inflammatory, anti-tumor, antioxidant, and antibacterial biological compounds bring health benefits that can be translated to the biomedical field. These plant oils are considered the most relevant for the molecular design of functional and high-performance biomaterials that can contribute to the reduction of carbon footprint. The representative examples of vegetable oil-derived biomaterials, their main composition, shape, and the processing technology will be covered and innovative strategies toward the development of new multifunctional polymeric materials for pharmacological patches, wound healing devices, drug carriers, and scaffolds for tissue engineering applications will be discussed.
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Lignans are widely distributed plant secondary metabolites that have received attention for their benefits to human health. Sesamin is a furofran lignan that is conventionally extracted from Sesamum seeds and shows anti-oxidant and anti-inflammatory activities in the human liver. Sesamin is biosynthesized by the Sesamum -specific enzyme CYP81Q1, and the natural sources of sesamin are annual plants that are at risk from climate change. In contrast, Forsythia species are widely distributed perennial woody plants that highly accumulate the precursor lignan pinoresinol. To sustainably supply sesamin, we developed a transformation method for Forsythia leaf explants and generated transgenic Forsythia plants that heterologously expressed the CYP81Q1 gene. High-performance liquid chromatography (HPLC) and LC-mass spectrometry analyses detected sesamin and its intermediate piperitol in the leaves of two independent transgenic lines of F. intermedia and F. koreana . We also detected the accumulation of sesamin and piperitol in their vegetatively propagated descendants, demonstrating the stable and efficient production of these lignans. These results indicate that CYP81Q1-transgenic Forsythia plants are promising platforms to produce diverse lignans and provide an important strategy for the cost-effective and scalable production of lignans.
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Inflammation is a major factor affecting human health. Nuclear factor-kappa B (NF-κB) plays a vital role in the development of inflammation, and the promoters of most inflammatory cytokine genes have NF-κB-binding sites. Targeting NF-κB could be an exciting route for the prevention and treatment of inflammatory diseases. As important constituents of natural plants, lignans are proved to have numerous biological functions. There are growing pieces of evidence demonstrate that lignans have the potential anti-inflammatory activities. In this work, the type, structure and source of lignans and the influence on mitigating the inflammation are systematically summarized. This review focuses on the targeting NF-κB signaling pathway in the inflammatory response by different lignans and their molecular mechanisms. Lignans also regulate gut microflora and change gut microbial metabolites, which exert novel pathway to prevent NF-κB activation. Taken together, lignans target NF-κB with various mechanisms to inhibit inflammatory cytokine expressions in the inflammatory response. It will provide a scientific theoretical basis for further research on the anti-inflammatory effects of lignans and the development of functional foods.
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Desert and semi‐desert areas are rich in vegetation, despite their often extreme climate conditions. The Chihuahuan desert is the largest in North America where different plant species predominate, mainly shrubs and grasslands, and common species found in these areas are Jatropha dioica, Flourensia cernua, Turnera diffusa, Eucalyptus camaldulensis, Euphorbia antisyphilitica Zucc, Larrea tridentata, Lippia graveolens, Opuntia, Agave , and Prosopis . Some of these endemic plant species have been used as food, nonalcoholic and alcoholic beverage, feed, fuel source, construction, medicine, a source of textile fibers, wax, and for making ornaments, among others. Most of these plant species have been studied and their application in various fields evaluated, due to the potential of their different bioactive compounds with beneficial health effects such as antioxidants, carotenoids, polyphenols, vitamins and flavonoids. Among these positive health effects are anticancer, antidiabetic, antimicrobial effect, increased immune response, anti‐inflammatory, cardioprotective, hepatoprotective, neuroprotective, and skin‐repaired activities, associated with the nature of the bioactive components. In addition to these beneficial properties, various compounds present in these plant species have antioxidant and antimicrobial activities, characteristics that are important in the food industry, since these bioactive components such as polyphenols or carotenoids can potentially replace some of the commonly used chemical additives providing a healthy option to the food product. The endemic plant species of the Mexican semi‐desert are a potential source of bioactive ingredients for the food industry; however, research is still required to apply them and thus meet the increasingly high demand of consumers for healthy, natural foods with nutraceutical properties.
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A unique morphological Sesamum radiatum oil/polyvinylpyrrolidone/gold polymeric bionanocomposite film was synthesized using the S. radiatum oil dispersed in a polymeric polyvinylpyrrolidone (PVP) matrix and decorated with gold nanoparticles (AuNPs). The chemical and physical characteristics as well as the thermal stability of the synthesized bionanocomposite film were investigated using various spectroscopic and microscopic techniques. The microscopic analysis confirmed well dispersed AuNPs in the PVP- S. radiatum oil matrix with particle size of 100 nm. Immunomodulatory and antiprotozoal potentials of the suggested bionanocomposite film were evaluated for lipopolysaccharide-induced BV-2 microglia and against L. amazonensis, L. mexicana promastigotes and T. cruzi epimastigotes, respectively. The results exerted outstanding reduction of inflammatory cytokines’ (IL-6 and TNFα) secretions after pretreatment of bionanocomposite. The bionanocomposite exhibited large inhibitory effects on certain cell signaling components that are related to the activation of expression of proinflammatory cytokines. Additionally, AuNPs and bionanocomposite exhibited excellent growth inhibition of L. mexicana and L. amazonensis promastigotes with IC50 (1.71 ± 1.49, 1.68 ± 0.75) and (1.12 ± 1.10, 1.42 ± 0.69), respectively. However, the nanomaterials showed moderate activity towards T. cruzi. All outcomes indicated promising immunomodulatory, antiprotozoal, and photocatalytic potentials for the synthesized S. radiatum oil/PVP/Au polymeric bionanocomposite.
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The authors conducted studies to assess the quality and calculation of biological value of the developed curd product. Estimation of organoleptic parameters was carried out with use of tasting scale of curd and curd products estimation, on the basis of which the profilogram was built and it was established that the developed curd product received the maximum quantity for taste and smell, appearance and consistency. Nutritional value of the experimental sample increased due to introduction of whey proteins and sesame seeds: protein (by 2.0%), appearance of carbohydrates (0.3%) and dietary fibers (0.05%). In the experimental sample the number of lactic acid microorganisms considerably exceeds both the normal values and the values of the control sample, which proves its probiotic properties and indicates a high physiological value. The calculated amino acid scoring of the eight essential amino acids is quite high and ranges from 105.9% valine to 191.0% tryptophan, which is well balanced and significantly exceeds the ideal protein. The biological value of the experimental sample with sesame seeds and whey proteins was 65.2%, the utility coefficient was 0.77, which indicates its high biological value and high balance of the amino acid composition.
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Nigella sativa has been used as traditional medicine for centuries. The crude oil and thymoquinone (TQ) extracted from its seeds and oil are effective against many diseases like cancer, cardiovascular complications, diabetes, asthma, kidney disease etc. It is effective against cancer in blood system, lung, kidney, liver, prostate, breast, cervix, skin with much safety. The molecular mechanisms behind its anticancer role is still not clearly understood, however, some studies showed that TQ has antioxidant role and improves body’s defense system, induces apoptosis and controls Akt pathway. Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history of last 2~3 decades. There are not so many research works done with this important traditional medicine and very few reports exist in the scientific database. In this article, we have summarized the actions of TQ and crude oil of N. sativa against different cancers with their molecular mechanisms. Key words: Traditional medicine, Nigella sativa, Thymoquinone, Antioxidant, Anti-cancer mechanism doi: 10.4314/ajtcam.v8i5S.10
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Objective: Nigella sativa is a medicinal plant that has long been used in traditional medicine for treating various conditions. Numerous animal studies provided evidences that the seed may elicit a broad anti-inflammatory/anti-oxidant activity. The aim of the present clinical trial was to evaluate anti-inflammatory and antioxidant properties of Nigella sativa oil in patients with rheumatoid arthritis (RA). Materials and methods: Forty-two patients with RA were assigned into two groups in this randomized, double blind, placebo-controlled clinical trial. Subjects in intervention group received two capsules, 500 mg each, of Nigella sativa oil, each day for 8 weeks. The other group consumed two capsules as placebo per day for the same period of time. Serum TNF-α, IL-10, and whole blood levels of oxidative stress parameters were measured at baseline and end of the trial. Results: The serum level of IL-10 was increased in the Nigella sativa group (p<0.01). Moreover, treatment with Nigella sativa led to significant reduction of serum MDA and NO compared with baseline (p<0.05). There were no significant differences in the TNF-α, SOD, catalase, and TAS values between or within the groups, before and after the intervention (p>0.05). Conclusion: This study indicates that Nigella sativa could improve inflammation and reduce oxidative stress in patients with RA. It is suggested that Nigella sativa may be a beneficial adjunct therapy in this population of patients.
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Cancer burden worldwide is projected to rise from 14 million new cases in 2012 to 24 million in 2035. While the greatest increases will be in developing countries, where cancer services are already hard pressed, even the richest nations will struggle to meet demands of increasing patient numbers and spiralling treatment costs. No country can treat its way out of the cancer problem. Consequently, cancer control must combine improvements in treatment with greater emphasis on prevention and early detection. Cancer prevention is founded on describing the burden of cancer, identifying the causes and evaluating and implementing preventive interventions. Around 40-50% of cancers could be prevented if current knowledge about risk factors was translated into effective public health strategies. The benefits of prevention are attested to by major successes, for example, in tobacco control, vaccination against oncogenic viruses, reduced exposure to environmental and occupational carcinogens, and screening. Progress is still needed in areas such as weight control and physical activity. Fresh impetus for prevention and early detection will come through inter-disciplinary approaches, encompassing knowledge and tools from advances in cancer biology. Examples include mutation profiles giving clues about aetiology and biomarkers for early detection, to stratify individuals for screening or for prognosis. However, cancer prevention requires a broad perspective stretching from the sub-microscopic to the macro-political, recognizing the importance of molecular profiling and multi-sectoral engagement across urban planning, transport, environment, agriculture, economics, etc., and applying interventions that may just as easily rely on a legislative measure as on a molecule.
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Ovarian cancer is the most lethal gynecologic malignancy, with limited treatment options for chemoresistant disease. An important link between inflammation and peritoneal spread of ovarian cancer is NF-κB signaling. Thymoquinone (TQ) exerts multiple anti-tumorigenic cellular effects, including NF-κB inhibition. We aimed to investigate the therapeutic potential of TQ in an established murine syngeneic model of ovarian cancer. ID8-NGL mouse ovarian cancer cells stably expressing an NF-κB reporter transgene were injected intra-peritoneally into C57BL/6 mice, and mice were treated with TQ or vehicle for 10 or 30 days. TQ was combined with the macrophage depleting drug, liposomal clodronate, in selected experiments. Effects on peritoneal tumor burden were measured by volume of ascites, number of peritoneal implants and mesenteric tumor mass. NF-κB reporter activity and markers of proliferation and apoptosis were measured in tumors and in confirmatory in vitro experiments. Protein or mRNA expression of M1 (anti-tumor) and M2 (pro-tumor) macrophage markers, and soluble cytokine profiles, were examined from harvested ascites fluid, peritoneal lavages and/or tumor sections. 2-tailed Mann–Whitney tests were used for measuring differences between groups in in vivo experiments. Consistent with its effects in vitro, TQ reduced proliferation and increased apoptosis in ID8-NGL tumors after 10 and 30 day treatment. Prolonged TQ treatment did not significantly alter tumor number or mass compared to vehicle, but rather exerted an overall deleterious effect by stimulating ascites formation. Increased ascites was accompanied by elevated NF-κB activity in tumors and macrophages, increased pro-tumor M2 macrophages and expression of pro-tumorigenic soluble factors such as VEGF in ascites fluid, and increased tumor infiltration of M2 macrophages. In contrast, a 10 day exposure to TQ produced no ascites, and reduced tumor NF-κB activity, M2 macrophages and soluble VEGF levels. Peritoneal macrophage depletion by clodronate significantly reduced tumor burden. However, TQ-stimulated ascites was further enhanced by co-treatment with clodronate, with macrophages present overwhelmingly of the M2 phenotype. Our findings show that pro-tumorigenic microenvironmental effects limited the efficacy of TQ in a syngeneic mouse model of ovarian cancer, and provide caution regarding its potential use in clinical trials in ovarian cancer patients.
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We aimed to investigate the protective role of thymoquinone (TQ) by targeting its antiapoptotic and antioxidant properties against kidney damage induced by arsenic in rats. We have used the 24 male Sprague-Dawley rats. Rats were divided into three groups. Physiological serum in 10 mL/kg dose as intragastric was given to the control group. Sodium arsenite (10 mg/kg, intragastric by gavage for fifteen days) was given to the arsenic group. Sodium arsenite (10 mg/kg, intragastric by gavage for fifteen days) and TQ (10 mg/kg, intragastric by gavage for 15 days) was given to the arsenic + TQ group. After 15 days, the animals' kidneys were taken theirs, then we have performed histological and apoptotic assessment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) enzyme activities and malondialdehyde (MDA) levels have examined as the oxidative stress parameters. We have determined the levels of arsenic. Increased renal injury and apoptotic cells have been detected in the arsenic group. Degenerative changes in the arsenic + TQ group were diminished. Although the MDA levels were augmented in the arsenic group, SOD, CAT and GSH-Px enzyme activities were lessened than the other groups. Our findings suggest that TQ may impede the oxidative stress, the cells have been damaged and also the generation of apoptotic cells arisen from arsenic. TQ plays a protective role against arsenic-induced toxicity in kidney and may potentially be used as a remedial agent.
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Thymoquinone (TQ) is the active ingredient of Nigella sativa which has a therapeutic potential in cancer therapy and prevention. In this study, TQ has been shown to induce specific cytotoxicity and apoptosis and to inhibit wound healing in triple-negative breast cancer cell line. TQ also inhibited cancer growth in a mouse tumor model. Moreover, TQ and paclitaxel (Pac) combination inhibited cancer growth in cell culture and in mice. Genes involved in TQ and TQ-Pac-mediated cytotoxicity were studied using focused real-time PCR arrays. After bioinformatic analysis, genes in apoptosis, cytokine, and p53 signaling categories were found to be modulated with a high significance in TQ-treated cells (p < 10(-28), p < 10(-8), and p < 10(-6), respectively). Important to note, TQ has been found to regulate the genes involved in the induction of apoptosis through death receptors (p = 5.5 × 10(-5)). Additionally, tumor suppressor genes such as p21, Brca1, and Hic1 were highly upregulated by TQ and TQ-Pac combination. Interestingly, when cells were treated with high dose TQ, several growth factors such as Vegf and Egf were upregulated and several pro-apoptotic factors such as caspases were downregulated possibly pointing out key pathways manipulated by cancer cells to resist against TQ. In cells treated with the combination of TQ and Pac, genes in apoptosis cascade (p < 10(-12)), p53 signaling (p = 10(-5)), and JAK-STAT signaling (p < 10(-3)) were differentially expressed. TQ has also been shown to induce protein levels of cleaved Caspase-3, Caspase-7, and Caspase-12 and PARP and to reduce phosphorylated p65 and Akt1. The in vivo therapeutic potential of TQ-Pac combination and the genetic network involved in this synergy have been shown for the first time to the best of our knowledge.
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Thymoquinone (TQ) has been reported to possess anti-tumor activity in various types of cancer. However, its effects and molecular mechanism of action in hepatocellular carcinoma (HCC) are still not completely understood. We observed that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2 expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive impact on the Notch pathway, where overexpression of NICD1 reversed the inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2 levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell growth by inducing cell cycle arrest and apoptosis, achieving these effects by repression of the Notch signaling pathway, suggesting that TQ represents a potential preventive or therapeutic agent in HCC patients.
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Cadmium (Cd), an environmental and industrial pollutant, generates free radicals responsible for oxidative stress. Cd can also lead to various renal toxic damage such as the proximal tubules and glomerulus dysfunction. Thymoquinone (TQ) is the main constituent of the essential oil obtained from black seeds (Nigella sativa) and has various pharmacological effects. The aim of the present study was to examine the nephroprotective, anti-oxidant, and anti-apoptotic effect of the TQ against Cd-induced nephrotoxicity. A total of 24 male Wistar albino rats were divided into three groups: control, Cd-treated, and Cd-treated with TQ; each group contain eight animals. The Cd-treated group was injected subcutaneously with CdCl2 dissolved in saline in the amount of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in TQ-treated groups were given TQ (50 mg/kg body weight) once a day orally together with first Cd injection during the study period. The histopathological studies in the kidney of rats also showed that TQ markedly reduced the toxicity of Cd and preserved the normal histological architecture of the renal tissue. Immunohistochemical analysis revealed that TQ significantly decreased the Cd-induced over expression of nuclear factor-κB in renal tissue. Furthermore, TQ treatment resulted in decreased the number of apoptotic cells. TQ significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses (reduced superoxide dismutase, glutathione peroxidase and catalase activities) in renal tissue resulted from Cd administration. These findings suggest that the nephroprotective potential of TQ in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced nephrotoxicity.
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The traditional preparation process of Nigella sativa (NS) oil starts with roasting of the seeds, an allegedly unnecessary step that was never skipped. The aims of this study were to investigate the role and boundaries of thermal processing of NS seeds in the preparation of therapeutic extracts and to elucidate the underlying mechanism. NS extracts obtained by various seed thermal processing methods were investigated in vitro for their antiproliferative activity in mouse colon carcinoma (MC38) cells and for their thymoquinone content. The effect of the different methods of thermal processing on the ability of the obtained NS oil to inhibit the nuclear factor kappa B (NF-κB) pathway was then investigated in Hodgkin's lymphoma (L428) cells. The different thermal processing protocols yielded three distinct patterns: heating the NS seeds to 50°C, 100°C, or 150°C produced oil with a strong ability to inhibit tumor cell growth; no heating or heating to 25°C had a mild antiproliferative effect; and heating to 200°C or 250°C had no effect. Similar patterns were obtained for the thymoquinone content of the corresponding oils, which showed an excellent correlation with the antiproliferative data. It is proposed that there is an oxidative transition mechanism between quinones after controlled thermal processing of the seeds. While NS oil from heated seeds delayed the expression of NF-κB transcription, non-heated seeds resulted in only 50% inhibition. The data indicate that controlled thermal processing of NS seeds (at 50°C-150°C) produces significantly higher anticancer activity associated with a higher thymoquinone oil content, and inhibits the NF-κB signaling pathway.
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Thymoquinone (TQ), an active component of Nigella sativa L., is known to have anti-cancer and anti-inflammatory effects; however, no studies on its analytical detection in serum and its protein binding have been published. Using high performance liquid chromatography analysis, we show that the average recovery of TQ from serum is 2.5% at 10 μg/ml of TQ and 72% at 100 μg/ml. The low recovery of TQ from serum is due to its extensive binding to plasma proteins, as more than 99% of TQ was bound within 30 min of incubation. The binding of TQ to the major plasma proteins, bovine serum albumin (BSA) and alpha -1 acid glycoprotein (AGP), was studied and found to be 94.5 ± 1.7% for BSA and 99.1 ± 0.1% for AGP. Mass spectrometric analysis revealed that TQ was bound covalently to BSA, specifically on Cyst-34. Using WST-1 proliferation assay, we showed that BSA plays a protective role against TQ-induced cell death; pre-incubation with BSA prevented TQ from exerting its anti-proliferative effects against DLD-1 and HCT-116 human colon cancer cells. On the other hand, binding of TQ to AGP did not alter its anti-proliferative activity against both cell lines. When TQ was pre-incubated with AGP prior to the addition of BSA, the activity of TQ against DLD-1 was maintained, suggesting that AGP prevented the binding of TQ to BSA. This is the first time the covalent binding and inhibitory effect of BSA on TQ is documented. These data offer new grounds for TQ future pharmacokinetic analysis in vivo.
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Thymoquinone (TQ), a component of black seed essential oil, is known to induce apoptotic cell death and oxidative stress, however, the direct involvement of oxidants in TQ-induced cell death has not been established yet. Here, we show that TQ inhibited the proliferation of a panel of human colon cancer cells (Caco-2, HCT-116, LoVo, DLD-1 and HT-29), without exhibiting cytotoxicity to normal human intestinal FHs74Int cells. Further investigation in DLD-1 revealed that apoptotic cell death is the mechanism for TQ-induced growth inhibition as confirmed by flow cytometry, M30 cytodeath and caspase-3/7 activation. Apoptosis was induced via the generation of reactive oxygen species (ROS) as evidenced by the abrogation of TQ apoptotic effect in cells preincubated with the strong antioxidant N-acetyl cysteine (NAC). TQ increased the phosphorylation states of the mitogen-activated protein kinases (MAPK) JNK and ERK, but not of p38. Their activation was completely abolished in the presence of NAC. Using PD98059 and SP600125, specific ERK and JNK inhibitors, the two kinases were found to possess pro-survival activities in TQ-induced cell death. These data present evidence linking the pro-oxidant effects of TQ with its apoptotic effects in colon cancer and prove a protective role of MAPK.
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Proteins that promote epithelial to mesenchymal transition (EMT) are associated with cancer metastasis. Inhibition of EMT regulators may be a promising approach in cancer therapy. In this study, Thymoquinone (TQ) was used to treat cancer cell lines to investigate its effects on EMT-regulatory proteins and cancer metastasis. We show that TQ inhibited cancer cell growth, migration and invasion in a dose-dependent manner. At the molecular level, TQ treatment decreased the transcriptional activity of the TWIST1 promoter and the mRNA expression of TWIST1, an EMT-promoting transcription factor. Accordingly, TQ treatment also decreased the expression of TWIST1-upregulated genes such as N-Cadherin and increased the expression of TWIST1-repressed genes such as E-Cadherin, resulting in a reduction of cell migration and invasion. TQ treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mice but partially attenuated the migration and invasion in TWIST1-overexpressed cell lines. Furthermore, we found that TQ treatment enhanced the promoter DNA methylation of the TWIST1 gene in BT 549 cells. Together, these results demonstrate that TQ treatment inhibits TWIST1 promoter activity and decreases its expression, leading to the inhibition of cancer cell migration, invasion and metastasis. These findings suggest TQ as a potential small molecular inhibitor of cancer growth and metastasis.
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Liver cancer is the fifth commonest malignancy worldwide and the third leading cause of death. Identifying novel curative and preventive therapy may improve its prognosis. In this study, thymoquinone (TQ), the most active biological ingredient of Nigella sativa Linn, was investigated for its antitumor activity. Mechanistic perspectives underlying this antitumor activity were explored by testing its effect on cell cycle, apoptosis, and angiogenesis. In addition, the chemopreventive effect of TQ was carried out by measuring its effect on phase I CYP1A1 and phase II glutathione S-transferase (GST) drug-metabolizing enzymes. The results of the present study revealed the effectiveness of TQ as an antitumor agent against different types of cancer including brain, colon, cervix and liver at both a time- and concentration-dependent manner. In HepG2 cells, it induced G2/M phase cell cycle arrest and a concentration-dependent increase in the percentage of apoptotic cells with an increase in the ratio of Bax/BCL-2. Moreover, the expression of mRNA and protein level of vascular endothelial growth factor decreased as the concentration of TQ increased. Our data showed a significant inhibition of induced phase I CYP1A1 enzyme, and elevation in the content of glutathione and activity of phase II enzyme GST, in HepG2 cells. Our results provide support for the beneficial use of TQ as a therapeutic and chemopreventive agent against liver cancer.
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Thymoquinone (TQ) is the main constituent of black seed (Nigella sativa, spp) essential oil which shows promising in vitro and in vivo anti-neoplastic activities in different tumor cell lines. However, to date there are only a few reports regarding the apoptotic effects of TQ on cervical cancer cells. Here, we report that TQ stimulated distinct apoptotic pathways in two human cervical cell lines, Siha and C33A. TQ markedly induced apoptosis as demonstrated by cell cycle analysis in both cell lines. Moreover, quantitative PCR revealed that TQ induced apoptosis in Siha cells through p53-dependent pathway as shown by elevated level of p53-mediated apoptosis target genes, whereas apoptosis in C33A cells was mainly associated with the activation of caspase-3. These results support previous findings on TQ as a potential therapeutic agent for human cervical cancer.
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