Sesamolin suppresses adipocyte differentiation through Keap1-dependent Nrf2 activation in adipocytes.

Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation.

Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3ß/ß-catenin signaling.

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological cancers. Herein, we aimed to define the role of specific myosin family members in EC because this protein family is involved in the progression of various cancers. METHODS: Bioinformatics analyses were performed to reveal EC patients' prognosis-associated genes in patients with EC. Furthermore, colony formation, immunofluorescence, cell counting kit 8, wound healing, and transwell assays as well as coimmunoprecipitation, cycloheximide chase, luciferase reporter, and cellular thermal shift assays were performed to functionally and mechanistically analyze human EC samples, cell lines, and a mouse model, respectively. RESULTS: Machine learning techniques identified MYH14, a member of the myosin family, as the prognosis-associated gene in patients with EC. Furthermore, bioinformatics analyses based on public databases showed that MYH14 was associated with EC chemoresistance. Moreover, immunohistochemistry validated MYH14 upregulation in EC cases compared with that in normal controls and confirmed that MYH14 was an independent and unfavorable prognostic indicator of EC. MYH14 impaired cell sensitivity to carboplatin, paclitaxel, and progesterone, and increased cell proliferation and metastasis in EC. The mechanistic study showed that MYH14 interacted with MYH9 and impaired GSK3ß-mediated ß-catenin ubiquitination and degradation, thus facilitating the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition. Sesamolin, a natural compound extracted from Sesamum indicum (L.), directly targeted MYH14 and attenuated EC progression. Additionally, the compound disrupted the interplay between MYH14 and MYH9 and repressed MYH9-regulated Wnt/ß-catenin signaling. The in vivo study further verified sesamolin as a therapeutic drug without side effects. CONCLUSIONS: Herein, we identified that EC prognosis-associated MYH14 was independently responsible for poor overall survival time of patients, and it augmented EC progression by activating Wnt/ß-catenin signaling. Targeting MYH14 by sesamolin, a cytotoxicity-based approach, can be applied synergistically with chemotherapy and endocrine therapy to eventually mitigate EC development. This study emphasizes MYH14 as a potential target and sesamolin as a valuable natural drug for EC therapy.

Probing the stability and quality of the cellulose-based Pickering emulsion containing sesamolin-enriched sesame oil by chemometrics-assisted ATR-FTIR spectroscopy.

This study presents the employment of Fourier transform infrared (FTIR) spectroscopy with attenuated total reflection and principal component analysis (PCA) to analyze the stability of a Pickering emulsion stabilized by carboxylated-cellulose nanocrystal (cCNC) comprising sesame oil phases with or without sesamolin. FTIR measurements identified an intermolecular hydrogen bond between the ester group of the triglyceride and the carboxyl group of the cCNC to create the emulsion droplet. The spectral bands from the hydroxyl group vibration (3700-3050 cm-1), carbonyl (1744 cm-1), CO groups of the ester triglyceride and cCNC (1160-998 cm-1) markedly discriminated between stabilized and destabilized emulsions. The PCA of FTIR spectra detected the change of molecular interaction during storage according to creaming, aggregation, and coalescence and changes in physicochemical parameters such as droplet size, refractive index, and zeta potential. Hence, PCA enabled the observation of the destabilization of emulsion in real-time.

Sesamin and sesamolin potentially inhibit adipogenesis through downregulating the peroxisome proliferator-activated receptor γ protein expression and activity in 3T3-L1 cells.

Sesamin and sesamolin are major sesame lignans that have demonstrated anti-inflammatory, anticancer, and neuroprotective properties and potential benefits in the liver, cardiovascular diseases, and metabolic syndrome. However, despite previous research on their antiobesity effects and underlying mechanisms, a comprehensive investigation of these aspects is still lacking. In this study, we evaluated the regulatory effects of 20 to 80 µM sesamin and sesamolin on adipogenesis in vitro using 3T3-L1 cells as a model cell line. We hypothesized that the lignans would inhibit adipogenic differentiation in 3T3-L1 cells through the regulation of peroxisome proliferator-activated receptor γ (PPARγ). Our data indicate that sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation. Sesamin and sesamolin reduced the mRNA and protein expression of the adipogenesis-related transcription factors, PPARγ and CCAAT/enhancer-binding protein α, leading to the dose-dependent downregulations of their downstream targets, fatty acid binding protein 4, hormone-sensitive lipase, lipoprotein lipase, and glucose transporter 4. In addition, glucose uptake was dose-dependently attenuated by sesamin and sesamolin in both differentiated 3T3-L1 cells and HepG2 cells. Interestingly, our results suggested that sesamin and sesamolin might directly bind to PPARγ to inhibit its transcriptional activity. Finally, sesamin and sesamolin decreased the phosphorylation of 3 mitogen-activated protein kinase signaling components in differentiated 3T3-L1 cells. Taken together, our findings suggest that sesamin and sesamolin may exhibit antiobesity effects by potentially downregulating PPARγ and its downstream genes through the mitogen-activated protein kinase signaling pathway, offering important insights into the molecular mechanisms underlying the potential antiobesity effects of sesamin and sesamolin.

Neuroprotective Effects of Sesamum indicum, Sesamin and Sesamolin Against 6-OHDA-induced Apoptosis in PC12 Cells.

BACKGROUND: Sesamum indicum L. (sesame) is one of the most widely used herbs in the world. Sesame oil contains lignans such as sesamin and sesamolin, which are known to possess anti-inflammatory, antioxidant, and anti-apoptotic properties. Parkinson's disease (PD) is recognized as the most common neurodegenerative disease after Alzheimer's disease; however, the exact molecular mechanism of the progression of neural death is not clear yet. In this study, the effect of sesame seed extracts and their main bioactive components (sesamin and sesamolin) on in vitro model of Parkinson's disease has been compared. METHODS: Cell viability, the number of reactive oxygen species (ROS), and apoptosis were determined using resazurin assay, ROS assay, propidium iodide (PI) staining and flow cytometry, and western blot analysis. RESULTS: 6-OHDA caused cellular death and apoptosis but pretreatment with sesame seed extracts, sesamin, and sesamolin significantly increased cell viability (p<0.001) and decreased ROS (p<0.001) and apoptosis. ERK1/2 is activated by 6-OHDA in PC12 cells, and the level of survivin decreased. Pretreatment with sesame significantly reversed the entire cell death induced by 6- OHDA. Sesame seed extracts at 5 and 10 µg/ml, sesamin and sesamolin at 5 and 10 µM increased surviving (p<0.01), and reduced P-ERK1/2/ERK1/2 (p<0.05) levels close to the control values. CONCLUSIONS: Overall, compounds in sesame seed extract and sesamin may assist as adjuvant therapeutics in PD. It seems sesame seeds have more potent protection effects against neural death compared with individual components, which might reflect the synergism among different phytochemicals present in the extract.

Furofuran Lignans for Plant Protection: Discovery of Sesamolin and Its Derivatives as Novel Anti-Tobacco Mosaic Virus and Antibacterial Agents.

Natural products have been a valuable source of efficient and low-risk pesticides. In this work, a series of novel sesamolin derivatives A0-A31 and B0-B4 were designed and synthesized via structural simplification of furofuran lignan phrymarolin II, and their antiviral and antibacterial activities were systematically evaluated. The bioassay results showed that compound A24 displayed remarkable inactivation activity against tobacco mosaic virus (TMV) with an EC50 value of 130.4 µg/mL, which was superior to that of commercial ningnanmycin (EC50 = 202.0 µg/mL). The antiviral mode of action assays suggested that compound A24 may obstruct self-assembly by binding to TMV coat protein (CP), thus resisting the TMV infection. In addition, compound A25 possessed prominent antibacterial activities, especially against Ralstonia solanacearum with an EC50 value of 43.8 µg/mL, which is better than those of commercial bismerthiazol and thiodiazole copper. This research lays a solid foundation for the utilization of furofuran lignans in crop protection.

Formulation Strategies for Enhancing Pharmaceutical and Nutraceutical Potential of Sesamol: A Natural Phenolic Bioactive.

Natural plants and their products continue to be the major source of phytoconstituents in food and therapeutics. Scientific studies have evidenced the benefits of sesame oil and its bioactives in various health conditions. Various bioactives present in it include sesamin, sasamolin, sesaminol, and sesamol; among these, sesamol represents a major constituent. This bioactive is responsible for preventing various diseases including cancer, hepatic disorders, cardiac ailments, and neurological diseases. In the last decade, the application of sesamol in the management of various disorders has attracted the increasing interest of the research community. Owing to its prominent pharmacological activities, such as antioxidant, antiinflammatory, antineoplastic, and antimicrobial, sesamol has been explored for the above-mentioned disorders. However, despite the above-mentioned therapeutic potential, its clinical utility is mainly hindered owing to low solubility, stability, bioavailability, and rapid clearance issues. In this regard, numerous strategies have been explored to surpass these restrictions with the formulation of novel carrier platforms. This review aims to describe the various reports and summarize the different pharmacological activities of sesamol. Furthermore, one part of this review is devoted to formulating strategies to improve sesamol's challenges. To resolve the issues such as the stability, low bioavailability, and high systemic clearance of sesamol, novel carrier systems have been developed to open a new avenue to utilize this bioactive as an efficient first-line treatment for various diseases.

Sesamolin Attenuates Kidney Injury, Intestinal Barrier Dysfunction, and Gut Microbiota Imbalance in High-Fat and High-Fructose Diet-Fed Mice.

This study investigated the effects of sesamolin on kidney injury, intestinal barrier dysfunction, and gut microbiota imbalance in high-fat and high-fructose (HF-HF) diet-fed mice and explored the underlying correlations among them. The results indicated that sesamolin suppressed metabolic disorders and increased renal function parameters. Histological evaluation showed that sesamolin mitigated renal epithelial cell degeneration and brush border damage. Meanwhile, sesamolin inhibited the endotoxin-mediated induction of the Toll-like receptor 4-related IKKα/NF-κB p65 pathway activation. Additionally, sesamolin mitigated intestinal barrier dysfunction and improved the composition of gut microbiota. The correlation results further indicated that changes in the dominant phyla, including Firmicutes, Deferribacterota, Desulfobacterota, and Bacteroidota, were more highly correlated with a reduction in endotoxemia and metabolic disorders, as well as decreases in intestinal proinflammatory response and related renal risk biomarkers. The results of this study suggest that sesamolin attenuates kidney injuries, which might be associated with its effects on the reduction of endotoxemia and related metabolic disorders through the restoration of the intestinal barrier and the modulation of gut microbiota. Thus, sesamolin may be a potential dietary supplement for protection against obesity-associated kidney injury.

Sesamolin Alleviates Nonalcoholic Fatty Liver Disease through Modulating Gut Microbiota and Metabolites in High-Fat and High-Fructose Diet-Fed Mice.

Nonalcoholic fatty liver disease (NAFLD) has become a major public health problem. The effects of sesamolin on obesity-associated NAFLD and its possible mechanism are still poorly understood. The present study investigated the effects of sesamolin on NAFLD and changes in gut microbiota and serum metabolites in high-fat and high-fructose (HF-HF) diet-fed mice. Mice with NAFLD were treated with or without sesamolin. Sesamolin effectively suppressed obesity-associated metabolic disorder, attenuated hepatic steatosis and the infiltration of inflammatory cells, and decreased levels of hepatic proinflammatory cytokines. Sesamolin also altered the composition of gut microbiota at the genus level. Additionally, differential serum metabolite biomarkers identified in an untargeted metabolomics analysis showed that sesamolin changed the levels of metabolites and influenced metabolomics pathways including caffeine metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism. Changes in metabolite biomarkers and the abundances of Faecalibaculum, Lachnoclostridium, Mucispirillum, Allobaculum, and Bacteroides are highly correlated with those factors involved in the progression of NAFLD. These results are important in deciphering new mechanisms by which changes in bacteria and metabolites in sesamolin treatment might be associated with the alleviation of obesity-associated NAFLD in HF-HF diet-fed mice. Thus, sesamolin may be a potential compound for obesity-associated NAFLD treatment.

Developmental effects of sesamolin on zebrafish (Danio rerio) embryos.

Sesamolin is one of the major active compounds found in sesame seeds (Sesamum indicum L.) that are commonly and increasingly used as an ingredient in cuisines and various food products. The compound has been reported to have several pharmaceutical activities such as antioxidant, antimicrobial, neuroprotective, and anticancer. However, the toxicological profile of sesamolin does not currently include developmental toxicity. In this study, we assessed sesamolin toxicity to embryonic development of zebrafish by exposure for 72 h at concentrations ranging from 10 to 50 µM. The evaluation revealed that sesamolin did not affect survival and hatching rates. However, it did induce embryo malformations and reduced embryonic heart rates in a dose-dependent manner. By qRT-PCR analysis, it downregulated the expression of oxidative stress-related genes, including superoxide dismutase 1 (sod1), catalase (cat), and glutathione S-transferase pi 2 (gstp2). Alkaline phosphatase staining of embryos revealed that sesamolin inhibited the development of subintestinal vessels, and hemoglobin staining revealed a negative impact on embryonic erythropoiesis. These findings showed that sesamolin affected genes related to angiogenesis and erythropoiesis. The risks of sesamolin to embryonic development found in this study may imply similar effects in humans and other mammals.

An Insight into Sesamolin: Physicochemical Properties, Pharmacological Activities, and Future Research Prospects.

Sesame seeds are rich in lignan content and have been well-known for their health benefits. Unlike the other sesame lignan compounds (i.e., sesamin and sesamol), the study of the pharmacological activity of sesamolin has not been explored widely. This review, therefore, summarizes the information related to sesamolin's pharmacological activities, and the mechanism of action. Moreover, the influence of its physicochemical properties on pharmacological activity is also discussed. Sesamolin possessed neuroprotective activity against hypoxia-induced reactive oxygen species (ROS) and oxidative stress in neuron cells by reducing the ROS and inhibiting apoptosis. In skin cancer, sesamolin exhibited antimelanogenesis by affecting the expression of the melanogenic enzymes. The anticancer activity of sesamolin based on antiproliferation and inhibition of migration was demonstrated in human colon cancer cells. In addition, treatment with sesamolin could stimulate immune cells to enhance the cytolytic activity to kill Burkitt's lymphoma cells. However, the toxicity and safety of sesamolin have not been reported. And there is also less information on the experimental study in vivo. The limited aqueous solubility of sesamolin becomes the main problem, which affects its pharmacological activity in the in vitro experiment and clinical efficacy. Therefore, solubility enhancement is needed for further investigation and determination of its pharmacological activity profiles. Since there are fewer reports studying this issue, it could become a future prospective research opportunity.

Fine Mapping of a Major Pleiotropic QTL Associated with Sesamin and Sesamolin Variation in Sesame (Sesamum indicum L.).

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 127-127.21cM 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.

Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways.

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.

Development of an ultrasonic system for industrial extraction of unheated sesame oil cake.

Sesame is a popular functional food in Asia. However, research on sesame seed oil cake compounds and their extraction methods is lacking. Ultrasound technology was applied to develop an efficient extraction method for this purpose. First, pilot-scale extraction from sesame oil cake was performed and optimized using response surface methodology. The extract obtained using optimized conditions (0% ethanol for 4 h at 20°C) showed the highest yield (45.1%) and inhibitory effect on reactive oxygen species (ROS; 55.1%). Compared to extracts obtained by conventional extraction methods, those obtained by ultrasound technology exhibited a higher extraction yield, greater antioxidant effect, and increased lignan content. Based on pilot-scale experiments, an industrial-scale ultrasonic extraction system was designed to extract a 2.1-ton solution at once. The extract contained sesaminol 1,2-diglucoside (4.6 mg/g) as the major component and showed 28.3% ROS inhibition activity. Our industrial ultrasound-assisted extraction method has potential application for other compounds.

Lignans of Sesame (Sesamum indicum L.): A Comprehensive Review.

Major lignans of sesame sesamin and sesamolin are benzodioxol--substituted furofurans. Sesamol, sesaminol, its epimers, and episesamin are transformation products found in processed products. Synthetic routes to all lignans are known but only sesamol is synthesized industrially. Biosynthesis of furofuran lignans begins with the dimerization of coniferyl alcohol, followed by the formation of dioxoles, oxidation, and glycosylation. Most genes of the lignan pathway in sesame have been identified but the inheritance of lignan content is poorly understood. Health-promoting properties make lignans attractive components of functional food. Lignans enhance the efficiency of insecticides and possess antifeedant activity, but their biological function in plants remains hypothetical. In this work, extensive literature including historical texts is reviewed, controversial issues are critically examined, and errors perpetuated in literature are corrected. The following aspects are covered: chemical properties and transformations of lignans; analysis, purification, and total synthesis; occurrence in Seseamum indicum and related plants; biosynthesis and genetics; biological activities; health-promoting properties; and biological functions. Finally, the improvement of lignan content in sesame seeds by breeding and biotechnology and the potential of hairy roots for manufacturing lignans in vitro are outlined.

The inhibitory effects of sesamol and sesamolin on the glycidyl esters formation during deodorization of vegetables oils.

BACKGROUND: Glycidyl esters (GEs) have attracted worldwide attention for their potential harm to human health. The GEs in edible oils mainly form during the deodorization of the oil refining processes. We used sesamol and sesamolin to inhibit the formation of GEs in model corn oil (MCO), model palm oil (MPO) and model rice bran oil (MRO) during a deodorization process. RESULTS: The results showed that, in the three model oils, the total GE content was in the following order from highest to lowest: MRO (1437.98 µg kg-1 ) > MPO (388.64 µg kg-1 ) > MCO (314.81 µg kg-1 ). The inhibitory effect of the three antioxidants on the formation of GEs in the MCO was in the following order from strongest to weakest: tert-butylhydroquinone (TBHQ) > sesamol > sesamolin. CONCLUSION: When the mass percentage of sesamol was 0.05%, its inhibition percentage on GEs was close to the inhibition percentage of 0.02% added TBHQ. The present study provides a foundation for understanding how to inhibit the formation of GEs in oils by adding sesamol during the deodorization process.

(+)-Sesamin-oxidising CYP92B14 shapes specialised lignan metabolism in sesame.

Sesamum spp. (sesame) are known to accumulate a variety of lignans in a lineage-specific manner. In cultivated sesame (Sesamum indicum), (+)-sesamin, (+)-sesamolin and (+)-sesaminol triglucoside are the three major lignans found richly in the seeds. A recent study demonstrated that SiCYP92B14 is a pivotal enzyme that allocates the substrate (+)-sesamin to two products, (+)-sesamolin and (+)-sesaminol, through multiple reaction schemes including oxidative rearrangement of α-oxy-substituted aryl groups (ORA). In contrast, it remains unclear whether (+)-sesamin in wild sesame undergoes oxidation reactions as in S. indicum and how, if at all, the ratio of the co-products is tailored at the molecular level. Here, we functionally characterised SrCYP92B14 as a SiCYP92B14 orthologue from a wild sesame, Sesamum radiatum, in which we revealed accumulation of the (+)-sesaminol derivatives (+)-sesangolin and its novel structural isomer (+)-7´-episesantalin. Intriguingly, SrCYP92B14 predominantly produced (+)-sesaminol either through ORA or direct oxidation on the aromatic ring, while a relatively low but detectable level of (+)-sesamolin was produced. Amino acid substitution analysis suggested that residues in the putative distal helix and the neighbouring heme propionate of CYP92B14 affect the ratios of its co-products. These data collectively show that the bimodal oxidation mechanism of (+)-sesamin might be widespread across Sesamum spp., and that CYP92B14 is likely to be a key enzyme in shaping the ratio of (+)-sesaminol- and (+)-sesamolin-derived lignans from the biochemical and evolutionary perspectives.

Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents.

Sesamin (SSM) and sesamolin (SesA) are the two major furofuran lignans of sesame oil and they have been previously noticed to exert various biological actions. However, their modulatory actions on different types of ionic currents in electrically excitable cells remain largely unresolved. The present experiments were undertaken to explore the possible perturbations of SSM and SesA on different types of ionic currents, e.g., voltage-gated Na+ currents (INa), erg-mediated K+ currents (IK(erg)), M-type K+ currents (IK(M)), delayed-rectifier K+ currents (IK(DR)) and hyperpolarization-activated cation currents (Ih) identified from pituitary tumor (GH3) cells. The exposure to SSM or SesA depressed the transient and late components of INa with different potencies. The IC50 value of SSM needed to lessen the peak or sustained INa was calculated to be 7.2 or 0.6 µM, while that of SesA was 9.8 or 2.5 µM, respectively. The dissociation constant of SSM-perturbed inhibition on INa, based on the first-order reaction scheme, was measured to be 0.93 µM, a value very similar to the IC50 for its depressant action on sustained INa. The addition of SSM was also effective at suppressing the amplitude of resurgent INa. The addition of SSM could concentration-dependently inhibit the IK(M) amplitude with an IC50 value of 4.8 µM. SSM at a concentration of 30 µM could suppress the amplitude of IK(erg), while at 10 µM, it mildly decreased the IK(DR) amplitude. However, the addition of neither SSM (10 µM) nor SesA (10 µM) altered the amplitude or kinetics of Ih in response to long-lasting hyperpolarization. Additionally, in this study, a modified Markovian model designed for SCN8A-encoded (or NaV1.6) channels was implemented to evaluate the plausible modifications of SSM on the gating kinetics of NaV channels. The model demonstrated herein was well suited to predict that the SSM-mediated decrease in peak INa, followed by increased current inactivation, which could largely account for its favorable decrease in the probability of the open-blocked over open state of NaV channels. Collectively, our study provides evidence that highlights the notion that SSM or SesA could block multiple ion currents, such as INa and IK(M), and suggests that these actions are potentially important and may participate in the functional activities of various electrically excitable cells in vivo.

Formation of Samin Diastereomers by Acid-Catalyzed Transformation of Sesamolin with Hydrogen Peroxide.

The conversion of sesame lignans is of interest because the derived products may have potential applications. Here, in investigating the transformation of sesamin and sesamolin, main endogenous sesame lignans in sesame seeds, in both acidic aqueous and anhydrous systems, 7R,7'S-samin was identified as one of the major products of sesamolin in both systems catalyzed with common inorganic acids, but sesaminol was not generated. In investigating the effect of different oxidizing agents on the acid-catalyzed conversion of sesame lignans, 7R,7'S-samin was still the major product of sesamolin, whereas sesamolin as well as 7R,7'S-samin stereoselectively rendered 7R,7'R-samin in the presence of hydrogen peroxide. Hydrogen peroxide may play a role in stabilizing the transitional oxonium ions, derived from acid hydrolysis of sesamolin or 7R,7'S-samin by forming a seven-membered ring intermediate through hydrogen bonding, to consequently produce 7R,7'R-samin as the final product.

Simultaneous and rapid determination of sesamin and sesamolin in sesame oils using excitation-emission matrix fluorescence coupled with self-weighted alternating trilinear decomposition.

BACKGROUND: Sesamin and sesamolin are two typical and important lignans isolated from sesame oil. Various studies have shown the bioactivity, physiological activity, and potential health benefits of the two components. In this study, a rapid method for the simultaneous determination of sesamin and sesamolin in sesame oils was proposed. The excitation-emission fluorescence spectra of the oils were obtained after a simple pretreatment, then self-weighted alternating trilinear decomposition was used to extract the quantitative information from the very overlapping spectra. RESULTS: It was found that reasonable quantification results could be obtained with the limits of detection for the two lignans. These limits were 0.05 mg/g and 0.24 mg/g, and the limits of quantitation were 0.14 mg/g and 0.74 mg/g, respectively. The average recoveries for sesamin and sesamolin were 99.05% and 94.97%. CONCLUSION: The results indicate that, with simple sample pretreatment, the application for combining excitation-emission fluorescence spectra and self-weighted alternating trilinear decomposition can be a useful and sensitive tool for the determination of lignans in sesame oil. © 2020 Society of Chemical Industry.