Sesamol Alleviates Sarcopenia via Activating AKT/mTOR/FoxO1 Signal Pathway in Aged Obese Mice.

Sesamol is a major bioactive component extracted from sesame seeds and has various medicinal properties. However, the effects of sesamol on sarcopenia associated with aging and obesity remains unclear. Therefore, the protective effects and underlying mechanisms of sesamol on sarcopenia was evaluated in aged and obese C57BL/6 J male mouse models fed a high fat diet and C2C12 myotubes co-treated with D-gal and PA in this study. Our in vivo data showed that sesamol activated AKT/mTOR/FoxO1 signal pathway, and then upregulated p-p70S6K and p-4EBP1 to promote myoprotein synthesis, and downregulated Atrogin-1 and MuRF1 to inhibit myoprotein degradation, thus ameliorating sarcopenia related to aging and obesity. Furthermore, our in vitro results confirmed the protective effect and aforementioned mechanisms of sesamol on sarcopenia. Collectively, sesamol could alleviate sarcopenia associated with aging and obesity via activating the AKT/mTOR/FoxO1 signal pathway. Our findings highlight the therapeutic potentials of sesamol for aging and obesity-related metabolic muscular complications.

Sesame lignans modulate aroma formation in sesame oil through the Maillard reaction and lipid oxidation in model systems.

The unknown effect of sesame lignans on aroma formation in sesame oil via the Maillard reaction (MR) and lipid oxidation was investigated. Sesamin, sesamolin, or sesamol was added to 3 models: lysine+glucose (MR), cold-pressed sesame oil (SO), and MR + SO, and were heated at 120 °C for 60 min. All three lignans suppressed SO oxidation while increasing DPPH scavenging ability (p < 0.05). Lignans increased depletions of lysine and glucose and MR browning (p < 0.05). Lignans reduced most aroma-active pyrazines, aldehydes, ketones, alcohols, and esters (p < 0.05). Sesamol and sesamolin increased perceptions of the preferable aromas of nutty, roasted sesame, and popcorn while reducing the undesirable green and rancid aromas (p < 0.05). Sesamol demonstrated a stronger effect on lipid oxidation, MR browning, aroma formation, and sensory perception than sesamin and sesamolin. This study suggests that sesame lignans can modulate aroma formation and sensory perception of sesame oil by interacting with the MR and lipid oxidation pathways.

The interaction between lipid oxidation and the Maillard reaction model of lysine-glucose on aroma formation in fragrant sesame oil.

The formation mechanism behind the sophisticated aromas of sesame oil (SO) has not been elucidated. The interaction effects of the Maillard reaction (MR) and lipid oxidation on the aroma formation of fragrant sesame oil were investigated in model reaction systems made of l-lysine (Lys) and d-glucose (Glc) with or without fresh SO (FSO) or oxidized SO (OSO). The addition of OSO to the Lys-Glc model increased the MR browning at 294 nm and 420 nm and enhanced the DPPH radical scavenging activity greater than the addition of FSO (p < 0.05). The presence of lysine and glucose inhibited the oxidation of sesame oil, reduced the loss of γ-tocopherol, and facilitated the formation of sesamol (p < 0.05). The Maillard-lipid interaction led to the increased concentrations of some of the alkylpyrazines, alkylfurans, and MR-derived ketones and acids (p < 0.05) while reducing the concentrations of other pyrazines, lipid-derived furans, aliphatic aldehydes, ketones, alcohols, and acids (p < 0.05). The addition of FSO to the MR model enhanced the characteristic roasted, nutty, sweet, and fatty aromas in sesame oil (p < 0.05), while excessive lipid oxidation (OSO) brought about an unpleasant oxidized odor and reduced the characteristic aromas. This study helps to understand the sophisticated aroma formation mechanism in sesame oil and provides scientific instruction for precise flavor control in the production of sesame oil.

Antibacterial Effect and Possible Mechanism of Sesamol against Foodborne Pathogens.

Food safety problems caused by foodborne pathogens have become a major public issue, and the search for efficient and safe bacteriostatic agents has gained attention. Sesamol (SE), a phenolic compound abundant in sesame oil, offers numerous health benefits and exhibits certain antibacterial properties. The purpose of this study was to evaluate the antibacterial effect and potential mechanisms of SE against representative foodborne pathogens, including Listeria monocytogenes, Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Salmonella serovar Enteritidis. The results showed that SE significantly inhibited the growth of the five pathogenic bacteria in sterile saline and pasteurized milk by 2.16-4.16 log10 CFU/g within 48 h. The results of the minimum bactericidal concentration and time-kill assay showed that SE had a greater inhibitory effect on L. monocytogenes compared with other bacteria. Additionally, SE was found to alter the cell membranes' permeability in these bacteria, resulting in the release of intercellular proteins and DNA. A scanning electron microscopy analysis showed that exposure to SE resulted in significant changes in bacterial morphology, producing cell shrinkage and deformation. These findings suggest that SE could inhibit both Gram-negative and Gram-positive bacteria by interfering with the function and morphology of bacterial cells.

Sesamol as a potent anticancer compound: from chemistry to cellular interactions.

Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.

Sesamol as a potential candidate for the treatment of hepatic fibrosis, based on its regulation of FXR/LXR axis-mediated inhibition of autophagy through crosstalk between hepatic cells and macrophage.

BACKGROUND: Sesamol (SEM), a natural lignan compound isolated from sesame, has strong anti-oxidant property, regulating lipid metabolism, decreasing cholesterol and hepatoprotection. However, its anti-hepatic fibrosis effect and mechanisms have not been comprehensively elucidated. HYPOTHESIS/PURPOSE: This study aims to investigate the anti-hepatic fibrosis of SEM and its underlying mechanisms. METHOD: C57BL/6 mice with hepatic fibrosis were induced by TAA, then administrated with SEM or curcumin, respectively. HSCs were stimulated by TGF-ß or conditioned medium, and then cultured with SEM, GW4064, GW3965, Rapamycin (RA) or 3-methyladenine (3-MA), respectively. Mice with hepatic fibrosis also were administrated with SEM, RA or 3-MA to estimate the effect of SEM on autophagy. RESULTS: In vitro, SEM significantly inhibited extracellular matrix deposition, P2 × 7r-NLRP3, and inflammatory cytokines. SEM increased FXR and LXRα/ß expressions and decreased MAPLC3α/ß and P62 expressions, functioning as 3-MA (autophagy inhibitor). In vivo, SEM reduced serum transaminase, histopathology changes, fibrogenesis, autophagy markers and inflammatory cytokines caused by TAA. LX-2 were activated with conditioned medium from LPS-primed THP-1, which resulted in significant enhance of autophagy markers and inflammatory cytokines and decrease of FXR and LXRα/ß expressions. SEM could reverse above these changes and function as 3-MA, GW4064, or GW3965. Deficiency of FXR or LXR attenuated the regulation of SEM on α-SMA, MAPLC3α/ß, P62 and IL-1ß in activated LX-2. In activated THP-1, deficiency of FXR could decrease the expression of LXR, and vice versa. Deficiency of FXR or LXR in activated MΦ decreased the expressions of FXR and LXR in activated LX-2. Deficiency FXR or LXR in activated MΦ also attenuated the regulation of SEM on α-SMA, MAPLC3α/ß, P62, caspase-1 and IL-1ß. In vivo, SEM significantly reversed hepatic fibrosis via FXR/LXR and autophagy. CONCLUSION: SEM could regulate hepatic fibrosis by inhibiting fibrogenesis, autophagy and inflammation. FXR/LXR axis-mediated inhibition of autophagy contributed to the regulation of SEM against hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. SEM might be a prospective therapeutic candidate, and its mechanism would be a new direction or strategy for hepatic fibrosis treatment.

Sesamol: A Phenolic Compound of Health Benefits and Therapeutic Promise in Neurodegenerative Diseases.

Sesamol, one of the key bioactive ingredients of sesame seeds (Sesamum indicum L.), is responsible for many of its possible nutritional benefits. Both the Chinese and Indian medical systems have recognized the therapeutic potential of sesame seeds. It has been shown to have significant therapeutic potential against oxidative stress, inflammatory diseases, metabolic syndrome, neurodegeneration, and mental disorders. Sesamol is a benign molecule that inhibits the expression of inflammatory indicators like numerous enzymes responsible for inducing inflammation, protein kinases, cytokines, and redox status. This review summarises the potential beneficial effects of sesamol against neurological diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Recently, sesamol has been shown to reduce amyloid peptide accumulation and attenuate cognitive deficits in AD models. Sesamol has also been demonstrated to reduce the severity of PD and HD in animal models by decreasing oxidative stress and inflammatory pathways. The mechanism of sesamol's pharmacological activities against neurodegenerative diseases will also be discussed in this review.

Sesamol: A lignan in sesame seeds with potent anti-inflammatory and immunomodulatory properties.

Inflammation is associated with the development and progression of a plethora of diseases including joint, metabolic, neurological, hepatic, and renal disorders. Sesamol, derived from the seeds of Sesamum indicum L., has received considerable attention due to its well-documented multipotent phytotherapeutic effects, including its anti-inflammatory and immunomodulatory properties. However, to date, no comprehensive review has been established to highlight or summarize the anti-inflammatory and immunomodulatory properties of sesamol. Herein, we aim to address this gap in the literature by presenting a thorough review encapsulating evidence surrounding the range of inflammatory mediators and cytokines shown to be targeted by sesamol in modulating its anti-inflammatory actions against a range of inflammatory disorders. Additionally, evidence highlighting the role that sesamol has in modulating components of adaptive immunity including cellular immune responses and Th1/Th2 balance is underscored. Moreover, the molecular mechanisms and the signaling pathways underlying such effects are also highlighted. Findings indicate that this seemingly potent lignan mediates its anti-inflammatory actions, at least in part, via suppression of various pro-inflammatory cytokines like IL-1ß and TNFα, and downregulation of a multitude of signaling pathways including NF-κB and MAPK. In conclusion, we anticipate that sesamol may be employed in future therapeutic regimens to aid in more effective drug development to alleviate immune-related and inflammatory conditions.

Sesamol serves as a p53 stabilizer to relieve rheumatoid arthritis progression and inhibits the growth of synovial organoids.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease known as a leading cause of disability with considerable mortality. Developing alternative drugs and targets for RA treatment is an urgent issue. Sesamol is a phenolic compound isolated from natural food sesame (Sesamum indicum L.) with various biological activities. PURPOSE: The current research intended to illuminate the bioactivity and mechanisms of sesamol in RA fibroblast-like synoviocytes (FLS), and aimed to estimate the potential clinical application value of sesamol in RA treatment. METHODS: CCK-8, EdU, and flow cytometry assays, as well as transwell tests were applied to observe the effects of sesamol on the abnormal functions of RA-FLS. Moreover, synovial organoids and a collagen-induced arthritis (CIA) mouse model were constructed to further explore the therapeutic capacity of sesamol on RA. Furthermore, RNA sequencing combined with quantitative real-time PCR assay, Western blot as well as co-immunoprecipitation were employed to clarify the mechanism of sesamol in regulating RA progression. RESULTS: Sesamol suppressed the proliferation through inhibiting DNA replication, triggering cell cycle arrest and apoptosis of RA-FLS. Besides, sesamol impaired RA-FLS migration and invasion. Interestingly, sesamol inhibited the growth of constructed synovial organoids and alleviated RA symptoms in CIA mice. Moreover, RNA sequencing further implicated p53 signaling as a downstream pathway of sesamol. Furthermore, sesamol was shown to decrease p53 ubiquitination and degradation, thereby activating p53 signaling. Finally, bioinformatics analyses also highlighted the importance of sesamol-regulated networks in the progression of RA. CONCLUSIONS: Our investigation demonstrated that sesamol served as a novel p53 stabilizer to attenuate the abnormal functions of RA-FLS via facilitating the activation of p53 signaling. Moreover, our study highlighted that sesamol might be an effective lead compound or candidate drug and p53 could be a promising target for the therapy of RA.

Sesamol Alleviates High-Fat Diet-Induced Hepatic Insulin Resistance in C57BL/6 J Mice Through AMPK Activation Mediated by Adipose Adiponectin.

Sesamol is the major bioactive constituent isolated from sesame seeds and has a variety of bioactivities. However, its role and mechanism in liver insulin resistance remain unknown. The current study was designed to investigate the underlying adipose-liver crosstalk mechanism of sesamol ameliorating hepatic insulin sensitivity. The therapeutic effect of sesamol was evaluated in high-fat diet (HFD)-fed C57BL/6 J mice (100 mg/kg for 8 weeks, XYGW-2021-75) and the mechanism was further explored in HepG2 cells with/without adiponectin and adenosine 5 '-monophosphate-activated protein kinase (AMPK) inhibitor administration. Our in vivo data showed that sesamol reduced hepatic insulin resistance in HFD-induced mice with obesity by modulating protein expression levels of glycogen synthase (GS), phosphoenolpyruvate carboxykinase (PEPCK) and protein kinase B (AKT). Moreover, sesamol not only increased the serum and adipose tissue adiponectin concentrations but also activated the phosphorylation of AMPK in the liver. Furthermore, in vitro studies using recombinant human adiponectin and an AMPK inhibitor revealed that adiponectin and sesamol have a synergic impact on increasing glycogenesis and reducing gluconeogenesis, of which the effects could be attenuated by the AMPK inhibitor. Taken together, our results suggested that sesamol stimulated adiponectin secretion from adipocytes, whereby exhibited a co-effect on activating the downstream signal of hepatic AMPK, resulting in the alleviation of hepatic insulin resistance. The novel findings of sesamol on hepatic effects provides prospective therapeutic approaches to treat insulin resistance.

Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.

Ternary Heterojunction Graphitic Carbon Nitride/Cupric Sulfide/Titanium Dioxide Photoelectrochemical Sensor for Sesamol Quantification and Antioxidant Synergism.

Sesamol (SM) is a potent natural antioxidant that can quench free radicals and modulate the cholinergic system in the brain, thereby ameliorating memory and cognitive impairment in Alzheimer's disease patients. Moreover, the total antioxidant capacity can be amplified by synergistic interactions between different antioxidants. Here, we constructed a ternary heterojunction graphitic carbon nitride/cupric sulfide/titanium dioxide (g-C3N4/CuS/TiO2) photoelectrochemical (PEC) sensor for the quantification of SM and its synergistic interactions with other antioxidants. Crucially, the Schottky barrier in ternary semiconductors considerably enhances electron transfer. The PEC sensor showed a wide linear range for SM detection, ranging from 2 to 1277 µmol L-1, and had a limit of detection of 1.8 µmol L-1. Remarkably, this sensing platform could evaluate the synergism between SM and five typical lipid-soluble antioxidants: tert-butyl hydroquinone, vitamin E, butyl hydroxyanisole, propyl gallate, and butylated hydroxytoluene. Owing to its low redox potential, SM could reduce antioxidant radicals and promote their regeneration, which increased the overall antioxidant performance. The g-C3N4/CuS/TiO2 PEC sensor exhibited high sensitivity, satisfactory selectivity, and stability, and was successfully applied for SM determination in both soybean and peanut oils. The findings of this study provide guidance for the development of nutritional foods, nutrition analysis, and the treatment of diseases caused by free radicals.

The protective effects of sesamol and/or the probiotic, Lactobacillus rhamnosus, against aluminum chloride-induced neurotoxicity and hepatotoxicity in rats: Modulation of Wnt/ß-catenin/GSK-3ß, JAK-2/STAT-3, PPAR-γ, inflammatory, and apoptotic pathways.

Introduction: Aluminium (Al) is accumulated in the brain causing neurotoxicity and neurodegenerative disease like Alzheimer's disease (AD), multiple sclerosis, autism and epilepsy. Hence, attenuation of Al-induced neurotoxicity has become a "hot topic" in looking for an intervention that slow down the progression of neurodegenerative diseases. Objective: Our study aims to introduce a new strategy for hampering aluminum chloride (AlCl3)-induced neurotoxicity using a combination of sesamol with the probiotic bacteria; Lactobacillus rhamnosus (L. rhamnosus) and also to test their possible ameliorative effects on AlCl3-induced hepatotoxicity. Methods: Sprague-Dawley male rats were randomly divided into five groups (n = 10/group) which are control, AlCl3, AlCl3 + Sesamol, AlCl3 + L. rhamnosus and AlCl3 + Sesamol + L. rhamnosus. We surveilled the behavioral, biochemical, and histopathological alterations centrally in the brain and peripherally in liver. Results: This work revealed that the combined therapy of sesamol and L. rhamnosus produced marked reduction in brain amyloid-ß, p-tau, GSK-3ß, inflammatory and apoptotic biomarkers, along with marked elevation in brain free ß-catenin and Wnt3a, compared to AlCl3-intoxicated rats. Also, the combined therapy exerted pronounced reduction in hepatic expressions of JAK-2/STAT-3, inflammatory (TNF-α, IL-6, NF-κB), fibrotic (MMP-2, TIMP-1, α-SMA) and apoptotic markers, (caspase-3), together with marked elevation in hepatic PPAR-γ expression, compared to AlCl3 -intoxicated rats. Behavioral and histopathological assessments substantiated the efficiency of this combined regimen in halting the effect of neurotoxicity. Discussion: Probiotics can be used as an add-on therapy with sesamol ameliorate AlCl3 -mediated neurotoxicity and hepatotoxicity.

Enhancing the accumulation of lipid and docosahexaenoic acid in Schizochytrium sp. by co-overexpression of phosphopantetheinyl transferase and ω-3 fatty acid desaturase.

Docosahexaenoic acid (DHA) as one of ω-3 polyunsaturated fatty acids (PUFAs), plays a key role in brain development, and is widely used in food additives and the pharmaceutical industry. Schizochytrium sp. is often considered as a satisfactory strain for DHA industrialization. The aim of this study was to assess the feasibility of phosphopantetheinyl transferase (PPTase) and ω-3 fatty acid desaturase (FAD) for regulating DHA content in Schizochytrium sp. PPTase is essential to activate the polyketide-like synthase (PKS) pathway, which can transfer apo-acyl-carrier protein (apo-ACP) into holo-ACP, and plays a key role in DHA synthesis. Moreover, DHA and docosapentaenoic acid (DPA) are synthesized by the PKS pathway simultaneously, so high DPA synthesis limits the increase of DHA content. In addition, the detailed mechanisms of PKS pathway have not been fully elucidated, so it is difficult to improve DHA content by modifying PKS. However, ω-3 FAD can convert DPA into DHA, and it is the most direct and effective way to increase DHA content and reduce DPA content. Based on this, PPTase was overexpressed to enhance the synthesis of DHA by the PKS pathway, overexpressed ω-3 FAD to convert the co-product of the PKS pathway into DHA, and co-overexpressed PPTase and ω-3 FAD. With these strategies, compared with wild type, the final lipid, and DHA titer were 92.5 and 51.5 g L-1 , which increased by 46.4% and 78.1%, respectively. This study established an efficient DHA production strain, and provided some feasible strategies for industrial DHA production in Schizochytrium sp.

Simultaneous production of high-value lipids in Schizochytrium sp. by synergism of chemical modulators.

The study focuses on the simultaneous improvement of biomass, lipid, and docosahexaenoic acid (DHA) productivities in a single reactor using modulator control strategies. The efficacy of three different biochemical modulators, sesamol (Ses), 6-benzylaminopurine (6-BAP), and ethylenediaminetetraacetic acid (EDTA), as potential stimulants in augmenting the biomass, lipid, and DHA production of Schizochytrium sp. MTCC 5890 was elucidated. After 48 h of cultivation, among tested modulators, the individual supplementation of 6-BAP and Ses showed improvement in biomass, lipid, and DHA accumulation by 28.2%, 56.1%, and 87.2% and 21.7%, 47.9%, and 91%, respectively, over the non-supplemented group. In addition, the cooperative effect of selected concentrations, i.e., 10 mgL-1 6-BAP and 200 mgL-1 Ses, further increased the productivities of biomass of 13.5 gL-1d-1 ± 0.66, lipid of 7.4 gL-1d-1 ± 0.69, and DHA of 3.2 gL-1d-1 ± 1.09 representing 8%, 39%, and 69% increase over the individual addition of 6-BAP or Ses, respectively, in batch culture. Supplementation with 6-BAP + Ses at 12 h of time point eventually increased the lipid yield to 15.6 ± 0.42 gL-1 from 7.88 ± 0.31 gL-1 (control) and DHA yield to 6.4 ± 0.11 gL-1 from 2.23 ± 0.09 gL-1 (control), respectively. Furthermore, the process was optimized in continuous culture supplemented with 6-BAP + Ses for enhanced productivities. Continuous culture resulted in maximum biomass (2.04 ± 1.12 gL-1 day-1), lipid (1.0 ± 0.73 gL-1 day-1), and DHA (0.386 ± 0.22 gL-1 day-1) productivities, which were higher as compared with the batch and fed-batch processes by 26 ± 1.21%, 22 ± 1.01%, and 21 ± 0.98% and 24 ± 0.45%, 16 ± 0.38%, and 14 ± 0.12%, respectively. This work represents the potential application of the combined effect of modulators for the simultaneous enhancement of biomass production and lipid and DHA productivities. KEY POINTS: • The cumulative study of 6-BAP and sesamol proved to be more efficient in the simultaneous production of biomass, lipid, and DHA in a single reactor. • Addition of a combination of 6-BAP + Ses remarkably increased the biomass, lipid, and DHA productivities in tandem in continuous culture.

Sesamol attenuates bleomycin-induced pulmonary toxicity and fibrosis in experimental animals.

Sesamol, a lignan obtained from roasted seeds of Sesamum indicum, has high antioxidant and anti-inflammatory activity. In this study, we have investigated the effect of sesamol on Bleomycin (BLM) induced pulmonary toxicity as well as fibrosis in Wistar rats. Lung toxicity was induced by administration of BLM, 0.015 U/g ip, twice weekly for 28 days whereas lung fibrosis was induced by BLM, 0.015 U/g ip, every 5th day for 49 days. Sesamol administration was started 7 days before first dose of BLM in both the models. It was observed that sesamol 50 mg/kg most effectively attenuated pulmonary toxicity by reducing oxidative stress, inflammation and apoptosis. This dose was further evaluated for its anti-fibrotic effect. It was observed that there was a significant reduction in fibrosis. Lung collagen content was markedly reduced. Furthermore, expression of pro-fibrotic proteins, TGF-ß/SMAD and α-SMA, was reduced and that of anti-fibrotic protein, AMPK, was markedly increased. Even though the combination of sesamol with pirfenidone exhibited no additional protection than either drug alone, it is evident from our study that our test drug, sesamol is comparable in efficacy to pirfenidone. Thus, sesamol has promising therapeutic potential in treatment of pulmonary toxicity and fibrosis.

A computational study to identify Sesamol derivatives as NRF2 activator for protection against drug-induced liver injury (DILI).

Drug-induced liver injury can be caused by any drugs, their metabolites, or natural products due to the inefficient functioning of drug-metabolizing enzymes, resulting in reactive oxygen species generation and leading to oxidative stress-induced cell death. For protection against oxidative stress, our cell has various defense mechanisms. One of the mechanisms is NRF2 pathway, when activated, protects the cell against oxidative stress. Natural antioxidants such as Sesamol have reported pharmacological activity (hepatoprotective & cardioprotective) and signaling pathways (NRF2 & CREM) altering potential. A Computational analysis was done using molecular docking, IFD, ADMET, MM-GBSA, and Molecular dynamic simulation of the Schrödinger suite. A total of 63,345 Sesamol derivatives were downloaded for the PubChem database. The protein structure of KEAP1-NRF2 (PDB: 4L7D) was downloaded from the RCSB protein database. The molecular docking technique was used to screen compounds that can form an interaction similar to the co-crystalized ligand (1VX). Based on MM-GBSA, docking score, and interactions, ten compounds were selected for ADMET profiling and IFD. After IFD, five compounds (66867225, 46148111, 12444939, 123892179, & 94817569) were selected for molecular dynamics simulation (MDS). Protein-ligand complex stability was assessed during MDS. The selected compounds (66867225, 46148111, 12444939, 123892179, & 94817569) complex with KEAP1 protein shows good stability and bond retentions. In our study, we observed that the selected compounds show good interaction, PCA, Rg, binding free energy, and ADMET profile. We can conclude that the selected compounds can act as NRF2 activators, which should be validated using proper in-vivo/in-vitro models.

Sesamol Mitigates Chronic Iron Overload-Induced Cognitive Impairment and Systemic Inflammation via IL-6 and DMT1 Regulation.

SCOPE: Excessive iron contributes to oxidative damage and cognitive decline in Alzheimer's disease. Sesamol, a compound in sesame oil that exhibits both anti-inflammatory and neuroprotective properties, is examined in this study for its ability to alleviate cognitive impairments in iron overload mice model. METHODS AND RESULTS: An iron overload model is established by intraperitoneally injecting dextran iron (250 mg kg-1 body weight) twice a week for 6 weeks, while sesamol (100 mg kg-1 body weight) is administered daily for the same length of time. The results demonstrate that sesamol protects spatial working memory and learning ability in iron overload mice, and inhibits neuronal loss and brain atrophy induced by iron overload. Moreover, sesamol significantly decreases interleukin-6 and malondialdehyde, and increases glutathione peroxidase 4 in the brains of iron overload mice. Additionally, sesamol maintains iron homeostasis in the brain by regulating the expressions of transferrin receptors, divalent metal transporter 1, and hepcidin, and reducing iron accumulation. Furthermore, sesamol suppresses disturbed systemic iron homeostasis and inflammation, particularly liver interleukin-6 expression. CONCLUSION: These findings suggest that sesamol may be effective in mitigating neuroinflammatory responses and cognitive impairments induced by iron overload, potentially through its involvement in mediating the liver-brain axis.

Neuroprotective effects of sesamol against LPS-induced spatial learning and memory deficits are mediated via anti-inflammatory and antioxidant activities in the rat brain.

Objective: Sesamol is a phenolic lignan extracted from sesame seeds, and it possesses anti-inflammatory and antioxidant activities. Lipopolysaccharide (LPS) is known to produce neuroinflammatory responses and memory impairment. The current study aimed to investigate the protective influence of sesamol against LPS-mediated neuroinflammation and memory impairment. Materials and Methods: Sesamol (10 and 50 mg/kg) was injected to Wistar rats for two weeks. Then, animals received LPS injection (1 mg/kg) for five days, while treatment with sesamol was performed 30 min before LPS injection. Spatial learning and memory were assessed by the Morris water maze (MWM), two hours after LPS injection on days 15-19. Biochemical assessments were performed after the end of behavioral experiments. Results: LPS-administered rats showed spatial learning and memory deficits, since they spent more time in the MWM to find the hidden platform and less time in the target quadrant. Besides these behavioral changes, tumor necrosis factor-α (TNF-α) and lipid peroxidation levels were increased, while total thiol level was decreased in the hippocampus and/or cerebral cortex. In addition, sesamol treatment (50 mg/kg) for three weeks decreased the escape latency and increased the time on probe trial. Sesamol also reduced lipid peroxidation and TNF-α level, while enhanced total thiol level in the brain of LPS-exposed rats. Conclusion: Supplementation of sesamol attenuated learning and memory impairments in LPS-treated rats via antioxidative and anti-inflammatory activities in the rat brain.

Transcriptome Profiling Analysis of Breast Cancer Cell MCF-7 Treated by Sesamol.

Background: Breast cancer is a highly malignant tumor that affects a large number of women worldwide. Sesamol, a natural compound, has been shown to exhibit inhibitory effects on various tumors, including breast cancer. However, the underlying mechanism of its action has not been fully explored. In this study, we aimed to investigate the effect of sesamol on the transcriptome of MCF-7 breast cancer cells, in order to better understand its potential as an anti-cancer agent. Methods: The transcriptome profiles of MCF-7 breast cancer cells treated with sesamol were analyzed using Illumina deep-sequencing. The differentially expressed genes (DEGs) between the control and sesamol-treated groups were identified, and GO and KEGG pathway analyses of these DEGs were conducted using ClueGO. Protein-protein interaction (PPI) network of DEGs was mapped on STRING database and visualized by Cytoscape software. Hub genes in the network were screened by Cytohubba plugin of Cytoscape. Prognostic values of hub genes were analyses by the online Kaplan-Meier plotter and validated by qRT-PCR in MCF-7 cells. Results: The results of the study showed that sesamol treatment had a significant effect on the transcriptome of MCF-7 cells, with a total of 351 DEGs identified. Functional enrichment analyses of DEGs revealed their involvement in extracellular matrix (ECM) remodeling, fatty acid metabolism and monocyte chemotaxis. The protein-protein interaction (PPI) network analysis of DEGs resulted in the identification of 10 hub genes, namely IGF2, MMP1, MSLN, CXCL10, WT1, ITGAL, PLD1, MME, TWIST1, and FOXA2. Survival analysis showed that MMP1 and ITGAL were significantly associated with overall survival (OS) and recovery-free survival (RFS) in breast cancer patients. Conclusion: Sesamol may play important roles in extracellular matrix (ECM) remodeling, fatty acid metabolism and cell cycle of MCF-7.