Sesamin inhibits RANKL-induced osteoclastogenesis and attenuates LPS-induced osteolysis via suppression of ERK and NF-κB signalling pathways.

Infection by bacterial products in the implant and endotoxin introduced by wear particles activate immune cells, enhance pro-inflammatory cytokines production, and ultimately promote osteoclast recruitment and activity. These factors are known to play an important role in osteolysis as well as potential targets for the treatment of osteolysis. Sesamin has been shown to have a variety of biological functions, such as inhibiting inflammation, anti-tumour and involvement in the regulation of fatty acid and cholesterol metabolism. However, the therapeutic effect of sesamin on osteolysis and its mechanism remain unclear. Present studies shown that in the condition of in vitro, sesamin could inhibit osteoclastogenesis and bone resorption, as well as suppressing the expression of osteoclast-specific genes. Further studies on the mechanism suggest that the effect of sesamin on human osteoclasts was mediated by blocking the ERK and NF-κB signalling pathways. Besides, sesamin was found to be effective in treating LPS-induced osteolysis by decreasing the production of pro-inflammatory cytokines and inhibiting osteoclastogenesis in vivo. Sesamin was non-toxic to heart, liver, kidney, lung and spleen. Therefore, sesamin is a promising phytochemical agent for the therapy of osteolysis-related diseases caused by inflammation and excessive osteoclast activation.

Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells.

Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.

Specialized metabolites degradation by microorganisms.

Secondary metabolites are specialized metabolic products synthesized by plants, insects, and bacteria, some of which exhibit significant physiological activities against other organisms. Plants containing bioactive secondary metabolites have been used in traditional medicine for centuries. In developed countries, one-fourth of medicines directly contain plant-derived compounds or indirectly contain them via semi-synthesis. These compounds have contributed considerably to the development of not only medicine but also molecular biology. Moreover, the biosynthesis of these physiologically active secondary metabolites has attracted substantial interest and has been extensively studied. However, in many cases, the degradation mechanisms of these secondary metabolites remain unclear. In this review, some unique microbial degradation pathways for lignans and C-glycosides are explored.

Evaluation the effect of dietary vitamin E, sesamin and thymoquinone bioactive compounds on immunological response, intestinal traits and MUC-2 gene expression in broiler Japanese quails (Coturnix japonica).

The current study was performed to determine the effect of dietary vitamin E, sesamin and thymoquinone bioactive lignans derived from sesame and black seed on immunological response, intestinal traits and Mucin2 gene expression in broiler quails. Three hundred and fifty (one days-old) quails were allotted to seven dietary treatments with five replicates as an experimental randomized design study. Treatments were basal diet as a control, control +100 and +200 mg of vitamin E, sesamin and thymoquinone per each kg of diet respectively. At 35 d of age, two quails from each pen were chosen, weighted, slaughtered, eviscerated and lymphoid organ relative weights were measured. Anti-body titers against Newcastle disease (ND), Sheep red blood cell (SRBC), and infectious bronchitis virus (IBV) and Avian influenza (AI) vaccination were determined. The serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum antioxidant activates such as superoxide dismutase (SOD),glutathione peroxidase(GPX), catalase (CAT) and total antioxidant capacity (TAC) were examined. The cell mediated immunity by dinitrochlorobenzene (DNCB) and phytohemagglutinin (PHA) challenges were assessed. The microflora populations of ileum, morphological traits of jejunum and mucin2 gene expression were analyzed. Data showed that the lymphoid organ (thymus, spleen and Bursa) relative weights and antibody titer against HI, AI, SRBC and IB vaccination were increased compared to the control (p ≤ 0.05). Serum activities of ALP, ALT and AST were decreased under influences of dietary treatments (p ≤ 0.05). The serum antioxidant activates of GPX,SOD,CAT and TAC were increased and Increasing in mean skin thickness after DNCB challenge and decrease wing web swelling response to PHA mitojen injection were observed (p ≤ 0.05). Salmonella enterica, E-coli and Coliforms colonies were decrease and Lactobacillus colonies increased instead (p ≤ 0.05). The villus height and surface, crypt depth and goblet cells density were increased compared to the control (p ≤ 0.05). The expression of MUC2 gene increased under influnces of vitamin E, sesamin and thymoquinone supplemented diets (p ≤ 0.05).

The antioxidant, anti-inflammatory, and anti-apoptotic effects of sesamin against cisplatin-induced renal and testicular toxicity in rats.

PURPOSE: The present study investigated the nephron-testicular protective effects of sesamin against cisplatin (CP)-induced acute renal and testicular injuries. METHODS: Thirty-two male Wistar rats were allocated to receive carboxymethylcellulose (0.5%, as sesamin vehicle), CP (a single i.p. 5 mg/kg dose), CP plus sesamin at 10 or 20 mg/kg orally for 10 days. RESULTS: Data analysis showed significant increases in serum urea, creatinine, interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), as well as renal and testicular tissue malondialdehyde and nitric-oxide concentrations in CP-intoxicated rats in comparison to control animals. On the contrary, rats treated with CP only exhibited significantly lower (p < .05) serum testosterone, tissue glutathione, and activities of endogenous antioxidant enzymes compared to control rats. Histopathologically examining CP-intoxicated rats' tissues using H&E and PAS stains showed atrophied glomeruli, interstitial inflammatory cells, atypic tubular epithelium with focal apoptosis, and reduced mucopolysaccharide content. Further, immunohistochemical staining of the same group revealed an increase in p53 and cyclooxygenase-II (Cox-II) expression in renal and testicular tissues. Treatment with sesamin alleviated almost all the changes mentioned above in a dose-dependent manner, with the 20 mg/kg dose restoring several parameters' concentrations to normal ranges. CONCLUSIONS: In brief, sesamin could protect the kidneys and testes against CP toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Sesamin Induces the Transdifferentiation of Type II Alveolar Epithelial Cells via AnnexinA1 and TRPV1.

PURPOSE: Acute lung injury (ALI) with high rates of morbidity is often accompanied by the apoptosis in the type I alveolar epithelial cells (ATIs). Thus, the transdifferentiation of type II alveolar epithelial cells (ATIIs) into ATIs is crucial for the maintenance of alveolar epithelial functions. We aimed to elucidate the role of sesamin in the transdifferentiation of ATIIs to ATIs and the involvement of the TRPV1/AKT pathway. METHODS: In vivo, the mouse model of ALI was simulated by intraperitoneal and intratracheal injections of lipopolysaccharide (LPS), respectively. The protective effects of sesamin on ALI were investigated using the survival rate, lung/body weight ratio, histological analysis of lung with HE staining, and mRNA levels of inflammatory factors. Western blot analysis and immunofluorescence detection of ATIs marker AQP5 were used to evaluate the protective effect of sesamin on ATIs. Western blot, EdU, and qPCR analyses were applied to detect changes in apoptosis, proliferation, and transdifferentiation markers of ATII A549 cell lines. Small interfering RNA (siRNA) was used to detect the involvement and relationships between the sesamin receptors (ANXA1 and TRPV1) and the AKT pathway in transdifferentiation. RESULTS: Sesamin (200 mg/kg) significantly improved LPS-induced ALI and inhibited LPS-induced ATIs reduction. A low concentration of sesamin (20 µM) promoted the transdifferentiation of ATIIs to ATIs. Both ANXA1 and TRPV1 were involved in sesamin-promoted transdifferentiation, while the P-AKT (S473) level was down-regulated by TRPV1 siRNA. CONCLUSION: Sesamin may promote transdifferentiation of ATII to ATI to ultimately rescue ALI, with TRPV1/AKT pathway involved in this transdifferentiation. This study revealed a novel role of sesamin in promoting the transdifferentiation of ATIIs to ATIs, providing experimental supports for the potential targets of ALI therapy.

Effects of sesamin on Aß1-42-induced oxidative stress and LTP impairment in a rat model of Alzheimer's disease.

The present study examined the protective effect of sesamin (Ses) on ß-amyloid (Aß)-induced long-term potentiation (LTP) impairment at the PP-DG synapses in male rats. Wistar rats were randomly assigned to seven groups: control, sham, Aß; ICV Aß1-42 microinjection, Ses, Aß + Ses; first, ICV Aß injections and then receiving Ses, Ses + Aß: four weeks of pretreatment with Ses and then Aß injection, and Ses + Aß + Ses: pre (four weeks) and post (four weeks) treatment with Ses. Ses-treated groups received 30 mg/kg of Ses once a day by oral gavage for four weeks. After the treatment period, the animals were positioned in a stereotaxic device for surgery and field potential recording. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were evaluated in the DG region. Serum oxidative stress biomarkers (total oxidant status (TOS) and total antioxidant capacity (TAC)) were measured. Aß impaired LTP induction at the PP-DG synapses evidenced by a decrease in EPSP slope and PS amplitude of LTP. In Aß rats, Ses increased EPSP slope and PS amplitude of LTP in the DG granular cells. Also, an increase in TOS and a reduction in TAC caused by Aß were significantly corrected by Ses. Ses could prevent Aß-induced LTP impairment at the PP-DG synapses in male rats, which can be due to its preventive effects on oxidative stress.

Sesamin suppresses angiotensin-II-enhanced oxidative stress and hypertrophic markers in H9c2 cells.

Myocardial hypertrophy plays a crucial role in cardiovascular disease (CVD) development. Myocardial hypertrophy is an adaptive response by myocardial cells to stress after cardiac injury to maintain cardiac output and function. Angiotensin II (Ang-II) regulates CVD through the renin-angiotensin-aldosterone system, and its signaling in cardiac myocytes leads to excessive reactive oxygen species (ROS) production, oxidative stress, and inflammation. Sesamin (SA), a natural compound in sesame seeds, has anti-inflammatory and anti-apoptotic effects. This study investigated whether SA could attenuate hypertrophic damage and oxidative injuries in H9c2 cells under Ang-II stimulation. We found that SA decreased the cell surface area. Furthermore, Ang-II treatment reduced Ang-II-increased ANP, BNP, and ß-MHC expression. Ang-II enhanced NADPH oxidase activity, ROS formation, and decreased Superoxide Dismutase (SOD) activity. SA treatment reduces Ang-II-caused oxidative injuries. We also found that SA mitigates Ang-II-induced apoptosis and pro-inflammatory responses. In conclusion, SA could attenuate Ang-II-induced cardiac hypertrophic injuries by inhibiting oxidative stress, apoptosis, and inflammation in H9c2 cells. Therefore, SA might be a potential supplement for CVD management.

Sesamin: A Promising Therapeutic Agent for Ameliorating Symptoms of Diabetes.

Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin's efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.

Sesamin suppresses high glucose-induced microglial inflammation in the retina in vitro and in vivo.

Diabetic retinopathy (DR) is the most common microvascular complication in diabetes and the leading cause of vision loss and blindness globally. Due to the unsatisfied outcome of current therapies, a novel strategy needs to be developed. BV2 microglial cells were treated with 25 natural compounds, respectively, stimulated by high glucose (HG) to screen for a potential candidate drug. Streptozotocin (STZ)-induced diabetic mice were injected with different doses of the candidate sesamin every 2 days for 1 mo. Then, its protective role and possible mechanism were evaluated. Sesamin was selected as the candidate drug due to its inhibition on the secretion of tumor necrosis factor-α (TNFα) in the screen assay. Sesamin also dose-dependently inhibited mRNA levels of HG-induced inflammatory cytokines, including TNFα, interleukin (IL)-1ß, and IL-6, activated NF-κB signaling pathway, and reduced oxidative stress by decreasing reactive oxygen species levels and increasing antioxidant enzymes in the BV2 and primary retinal microglia. In addition, sesamin alleviated brain-retinal barrier breakdown by Evans blue leakage assay and reduced inflammation in streptozotocin-induced diabetic mice. In conclusion, sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, suggesting that sesamin might serve as a candidate drug for DR treatment.NEW & NOTEWORTHY Sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, which suggests that sesamin might serve as a candidate drug for diabetic retinopathy treatment.

(+)-Sesamin, a sesame lignan, is a potent inhibitor of gut bacterial tryptophan indole-lyase that is a key enzyme in chronic kidney disease pathogenesis.

The progression of chronic kidney disease (CKD) increases the risks of cardiovascular morbidity and end-stage kidney disease. Indoxyl sulfate (IS), which is derived from dietary l-tryptophan by the action of bacterial l-tryptophan indole-lyase (TIL) in the gut, serves as a uremic toxin that exacerbates CKD-related kidney disorder. A mouse model previously showed that inhibition of TIL by 2-aza-l-tyrosine effectively reduced the plasma IS level, causing the recovery of renal damage. In this study, we found that (+)-sesamin and related lignans, which occur abundantly in sesame seeds, inhibit intestinal bacteria TILs. Kinetic studies revealed that (+)-sesamin and sesamol competitively inhibited Escherichia coli TIL (EcTIL) with Ki values of 7 µM and 14 µM, respectively. These Ki values were smaller than that of 2-aza-l-tyrosine (143 µM). Molecular docking simulation of (+)-sesamin- (or sesamol-)binding to EcTIL predicted that these inhibitors potentially bind near the active site of EcTIL, where the cofactor pyridoxal 5'-phosphate is bound, consistent with the kinetic results. (+)-Sesamin is a phytochemical with a long history of consumption and is generally regarded as safe. Hence, dietary supplementation of (+)-sesamin encapsulated in enteric capsules could be a promising mechanism-based strategy to prevent CKD progression. Moreover, the present findings would provide a new structural basis for designing more potent TIL inhibitors for the development of mechanism-based therapeutic drugs to treat CKD.

Immunomodulatory and anti-inflammatory effects of sesamin: mechanisms of action and future directions.

Inflammation is associated with the development and progression of various disorders including atherosclerosis, diabetes mellitus and cancer. Sesamin, a fat-soluble lignan derived from Sesamum indicum seeds and oil, has received increased attention due to its wide array of pharmacological properties including its immunomodulatory and anti-inflammatory potential. To date, no review has been conducted to summarize or analyze the immunomodulatory and anti-inflammatory roles of sesamin. Herein, we provide a comprehensive review of experimental findings that were reported with regards to the ability of sesamin to modulate inflammation, cellular and humoral adaptive immune responses and Th1/Th2 paradigm. The potential influence of sesamin on the cytotoxic activity of NK cells against cancer cells is also highlighted. The molecular mechanisms and the signal transduction pathways underlying such effects are underscored. The metabolism, pharmacokinetics, absorption, tissue distribution and bioavailability of sesamin in different species, including humans, are reviewed. Moreover, we propose future preclinical and clinical investigations to further validate the potential preventive and/or therapeutic efficacy of sesamin against various immune-related and inflammatory conditions. We anticipate that sesamin may be employed in future therapeutic regimens to enhance the efficacy of treatment and dampen the adverse effects of synthetic chemical drugs currently used to alleviate immune-related and inflammatory conditions.

A comprehensive mechanistic insight into the dietary and estrogenic lignans, arctigenin and sesamin as potential anticarcinogenic and anticancer agents. Current status, challenges, and future perspectives.

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.

The Protective Effects of Sesamin against Cyclophosphamide-Induced Nephrotoxicity through Modulation of Oxidative Stress, Inflammatory-Cytokines and Apoptosis in Rats.

Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1ß and TNFα) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.

(+)-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.

Regulatory role of endogenous and exogenous fibroblast growth factor 1 in the cardiovascular system and related diseases.

Fibroblast growth factor 1 (FGF1) has a critical regulatory role in the development of the cardiovascular system (CVS) and is strongly associated with the progression or treatment of cardiovascular diseases (CVDs). However, the regulatory mechanisms of FGF1 in CVS and CVDs have not yet been fully elucidated. Therefore, this review article summarized the existing literature reports on the role of FGF1 in CVS under physiological and pathological conditions. First, the expression and physiological functions of endogenous FGF1 is fully demonstrated. Then, we analyzed the role of exogenous FGF1 in normal CVS and related pathological processes. Specifically, the potential signaling pathways might be mediated by FGF1 in CVDs treatment is discussed in detail. In addition, the barriers and feasible solutions for the application of FGF1 are further analyzed. Finally, we highlight therapeutic considerations of FGF1 for CVDs in the future. Thus, this article may be as a reference to provide some ideas for the follow-up research.

Sesamin promotes apoptosis and pyroptosis via autophagy to enhance antitumour effects on murine T-cell lymphoma.

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.

Sesamin and sesamol attenuate H2O2-induced oxidative stress on human neuronal cells via the SIRT1-SIRT3-FOXO3a signaling pathway.

Background: An imbalance of free radicals and antioxidant defense systems in physiological processes can result in protein/DNA damage, inflammation, and cellular apoptosis leading to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Sesamin and sesamol, compounds derived from sesame seeds and oil, have been reported to exert various pharmacological effects, especially antioxidant activity. However, their molecular mechanisms against the oxidative stress induced by exogenous hydrogen peroxide (H2O2) remain to be elucidated. Aim: In this study, neuroprotective effects of sesamin and sesamol on H2O2-induced human neuroblastoma (SH-SY5Y) cell death and possible signaling pathways in the cells were explored. Methods: MTT assay and flow cytometry were conducted to determine cell viability and apoptotic profiles of neuronal cells treated with sesamin and sesamol. Carboxy-DCFDA assay was used to measure reactive oxygen species (ROS). Moreover, Western blot analysis was performed to investigate protein profiles associated with neuroprotection. Results: Pretreatment of the cells with 1 µM of sesamin and sesamol remarkably reduced the SH-SY5Y cell death induced by 400 µM H2O2 as well as the intracellular ROS production. Moreover, the molecular mechanisms underlying neuroprotection of the compounds were associated with activating SIRT1-SIRT3-FOXO3a expression, inhibiting BAX (proapoptotic protein), and upregulating BCL-2 (anti-apoptotic protein). Conclusion: The findings suggest that sesamin and sesamol are compounds that potentially protect neuronal cells against oxidative stress similar to that of the resveratrol, the reference compound. These antioxidants are thus of interest for further investigation in in vivo models of neuroprotection.

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.

Sesamin suppresses NSCLC cell proliferation and induces apoptosis via Akt/p53 pathway.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a disappointing prognosis. The aim of this study was to investigate the anticancer effect of sesamin and the underlying mechanism. The MTT assay was used to detect the proliferation of NSCLC cells. The cell cycle and apoptosis were analyzed by flow cytometry. The protein levels of Akt, p-Akt (Ser473), p53, cyclin D1, CDK2, MDM2, p-MDM2 (Ser166) were detected by western blotting. The expression of p-Akt (Ser473), p53 and Ki67 in vivo was analyzed by IHC. Histopathologic analyses of major organs (heart, liver, spleen, lung and kidney) were performed by H&E staining. The results show that sesamin suppressed cell proliferation and induced apoptosis of NSCLC cells (A549 and H1792) in a dose-dependent manner. Treatment with sesamin caused cell cycle arrest at G1 phase and inhibited cyclin D1 and CDK2 expression. In addition, sesamin inhibited Akt activity and upregulated p53 expression both in vivo and in vitro. When Akt and p53 were suppressed by LY294002 and PFTα, respectively, sesamin exerted no additional effects. The in vivo results mostly matched the in vitro findings. Specifically, sesamin exerted little damage to major organs. Taken together, this study demonstrates that sesamin suppresses NSCLC cell proliferation by induction of G1 phase cell cycle arrest and apoptosis via Akt/p53 pathway. Therefore, sesamin may be a promising adjuvant treatment for NSCLC therapy.