Sesamol Research Articles

Design and Optimization of Sesamol Nanosuspensions to Potentiate the Anti-Tumor Activity of Epirubicin against Ehrlich Solid Carcinoma-Bearing Mice.

There is a growing interest in discovering natural sources of anti-cancer drugs. Sesamol (SES) is a phenolic compound with antitumor effects. The present study aimed to investigate the anticancer properties of SES and its nano-suspensions (SES-NS) combined with Epirubicin (EPI) in breast cancer (BC) using mice bearing a solid Ehrlich tumor. The study involved 35 female albino mice and investigated the effects of SES and EPI on tumor growth, proliferation, apoptosis, autophagy, angiogenesis, and oxidative stress. Methods including ELISA, qRT-PCR, and immunohistochemistry were utilized. The findings revealed reductions in tumor growth and proliferation using SES either alone or combined and evidenced by decreased AKT (AKT Serine/Threonine kinase1) levels, angiogenesis indicated by lower levels of VEGFR (vascular endothelial growth factor), and apoptosis demonstrated by elevated caspase3 and BAX levels. Furthermore, autophagy increased and was indicated by increased levels of beclin1 and lc3, along with decreased oxidative stress as evidenced by elevated TAC (total antioxidant capacity) and reduced MDA (malondialdehyde) levels. Interestingly, SES-NS demonstrated more significant effects at lower doses. In summary, this study underscores the potential of SES as a promising agent for BC treatment. Moreover, SES-NS potentiated the beneficial effects of EPI while mitigating its adverse effects.

Investigating the role of sesamol in promoting the healing of diabetic wounds by analyzing molecular expression patterns in human diabetic dermal fibroblasts.

Background: Sesamol (3,4-methylenedioxyphenol) is one of the plant compounds tested in vivo for diabetic wound healing, normal wound healing, and dexamethasone-induced delayed wound healing. Elucidation of mechanisms underlying the wound healing effect of sesamol through modulation of various molecular and cellular pathways is the crux of this paper. Objectives: The objective of the current work was to uncover the mechanism of sesamol underlying the treatment of diabetic wounds using gene expression analysis. Methods: The cytotoxicity assay was performed using an SRB colorimetric assay, from which two doses were selected for further studies. The expression of various molecular markers was performed using RT-PCR. Results: An SRB assay was carried out to identify the safe concentration of molecules in HDDF cell lines. Two doses that showed more than 80 % viability were selected and used for gene expression analysis. It was observed that sesamol enhanced the expression of VEGF, TGFβ, AKT, JNK, ERK, and TIMP3 significantly (P≤0.001, P≤0.05, P≤0.001, P≤0.0001) when compared to control and significantly (P≤0.0001) downregulated the expression of MMP2, MMP-9 when compared to control, which promote wound healing in diabetes. The migration studies also showed a significant increase when compared to the control. Conclusion: Sesamol (SM) is a promising molecule that can accelerate wound healing in diabetes by modulating different markers involved in the process.

Inhibition and eradication of Listeria monocytogenes biofilm using the combined treatment with nisin and sesamol

Listeria monocytogenes can form biofilms, which enables it to persist in the food industry and poses a significant threat to food safety. The combination of nisin (NS) and sesamol (SE) has been found to inhibit the proliferation of L. monocytogenes. The objective of this study is to evaluate the effects of the combined use of NS and SE on the biofilm formation of L. monocytogenes and investigate the potential underlying mechanisms. The results showed that the combination of NS and SE completely inhibited the biofilm formation of both strains on the stainless steel sheet within 48 h. The existing L.monocytogenes biofilm on the stainless steel sheet was completely removed within 4 h after the combined treatment of NS and SE. Compared with individual treatment, the combined use of NS and SE resulted in a more significant downregulation in gene expression of fbpA, which is associated with L. monocytogenes biofilm formation. The findings suggest that the combined strategy of NS and SE in food processing has greater potential to control the formation of L. monocytogenes biofilms and eliminate existing ones, compared with using NS or SE alone.

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 defends neuronal damage following cerebral ischemia/reperfusion: a crosstalk of autophagy and Notch1/NLRP3 inflammasome signaling

ObjectiveSesamol (SES) is a phenolic compound found in sesame seed oil. Several studies have revealed its anti-inflammatory and antioxidant properties. However, its complete underlying mechanistic perspective about cerebral ischemia/reperfusion (I/R) lesions has not yet been disclosed. Consequently, we aimed to scrutinize its neuroprotective mechanism against cerebral injury during a global cerebral I/R in a rat model, considering its impact on autophagy and Notch1/NLRP3 inflammasome signaling regulation.MethodsTo affirm our purpose, adult Wistar rats were allotted into five groups: sham and the other four groups in which transient global cerebral ischemia was induced by bilateral common ligation (2VO) for 1 h, then reperfusion for either 24 h or 5 days: I/R (1/24), I/R (1/5), SES + I/R (1/24), and SES + I/R (1/5). In treated groups, SES (100 mg/kg, p.o., for 21 days) was administered before cerebral I/R induction. The assessment of histopathological changes in brain tissues, immunohistochemistry, biochemical assays, ELISA, and qRT-PCR were utilized to investigate our hypothesis.ResultsAdvantageously, SES halted the structural neuronal damage with lessened demyelination induced by cerebral I/R injury. Restoring oxidant/antioxidant balance was evident by boosting the total antioxidant capacity and waning lipid peroxidation. Furthermore, SES reduced inflammatory and apoptosis markers. Additionally, SES recovered GFAP, Cx43, and autophagy signaling, which in turn switched off the Notch-1/NLRP3 inflammasome trajectory.ConclusionsOur results revealed the neuroprotective effect of SES against cerebral I/R injury through alleviating injurious events and boosting autophagy, consequently abolishing Notch1/NLRP3 inflammasome signaling.

Effect of simultaneous application of antioxidants in oil and in chicken on heterocyclic aromatic amine formation in deep-fat fried chicken breast

This study aimed to estimate the effects of simultaneous application of antioxidants in meat and in oil on heterocyclic aromatic amine (HAA) formation in fried chicken during 40 deep-fat frying cycles. The experiment was carried out by adding Adinandra nitida leaf extract (ANE) (200 mg/100 g) to chicken while adding tea polyphenols (TP) (40 mg/100 g), sesamol (SL) (40 mg/100 g), or rosemary extract (RE) (40 mg/100 g) to soybean oil. It was found that the addition of TP, SL or RE in oil reduced the lipid oxidation and the formation of total HAAs in meats. Adding ANE alone to meat reduced total HAA contents in meats by 11.98%–38.00%; simultaneously adding TP, SL or RE to oil reduced total HAA contents in meats by 33.98%–61.46%, 15.86%–44.94%, and 25.22%–48.01%, respectively, during 40 frying cycles. Pearson correlation analysis revealed significant correlations (all absolute values of correlation coefficients > 0.53) between HAA formation and oxidation indices. This research supplies evidence that adding antioxidants to both meat and oil inhibits HAA formation during deep-fat frying.

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.

Bacteriostatic potential of nisin and sesamol combination against Listeria monocytogenes in chilled raw tuna fillets

Chilled tuna fillets are easy to be contaminated by Listeria monocytogenes, which is an important risk factor for the outbreak of foodborne diseases. Nisin (NS) in combination with sesamol (SE) has showed to have the ability to inhibit the growth of L. monocytogenes in bacterial culture-medium, however, their bacteriostatic effect in actual food model has been not evaluated. Therefore, in this study, the combined effect of NS and SE on the growth of L. monocytogenes in yellowfin tuna fillet (Thunnus albacares) which was stored at constant and fluctuating temperatures were evaluated. The results showed that the combined use of NS (25 μg/mL) and SE (1.0 mg/mL) significantly reduced the growth potential of L. monocytogenes to 1.1–3.2 log10 CFU/g compared with the control group at constant and fluctuating 10 °C. The combined treatment of NS and SE delayed the lipid oxidation activity and increased the catalase activity and glutathione peroxidase activity of tuna fillets, but did not significantly change the texture and color characteristics of tuna fillets. These results indicated that the combined of NS and SE may be a promising technology to reduce L. monocytogenes pollution and maintain the physical and chemical properties of tuna fillets products.

The Identification of certain chemical disruptors of the estrogen receptor α: Structural and docking analyses

Due to the active role of estrogen receptor α (ERα) in certain breast cancer, finding possible ERα antagonists is important for lowering the growth rate of ERα-motivated breast cancer cells. Here, the current work was conducted to computationally find ERα inhibitors based on the use of certain docking methods. The three-dimensional (3D)-ERα structure was freely docked with the 3D structure of certain ligands, including milbemycin_A3_5-oxime (MA), Baloxavir marboxil (BM), tadalafil (TF), sesamol (SM), raspberry ketone (RK), guaiacol (GuC), proanthocyanidins (PAC), epicatechin (EC), and catechin (CC). The results of the protein-ligand based binding affinity values (kcal/mol) revealed the following; MA= -9.7, TF= -8.5, BM= -8.2, PAC= -8.1, CC= -7.5, EC= -7.2, RK= -6.1, SM= -5.7, and GuC= -4.8. According to the above-mentioned data, milbemycin_A3_5-oxime, tadalafil, Baloxavir marboxil, and proanthocyanidins show the highest binding affinity, which can further be studied in vitro and in vivo for their proposed activity. In addition, catechin, epicatechin, raspberry ketone, sesamol, and guaiacol can also further be investigated for their anti-ERα activity, in which some structural modification to the ligand molecules can be performed to increase their binding action, if they show low ERα-based blocking via in vitro and in vivo research.

Sesamol promotes browning of white adipocytes through liver-adipose crosstalk signal of hepatic fibroblast growth factor 21

Sesamol (SEM), a lignan from sesame oil, exhibited potential benefits on obesity treatment by promoting browning of adipocytes, and the current study is aimed to explore the molecular mechanisms of SEM from the aspect of systemic liver-adipose crosstalk that mediated by hepatic fibroblast growth factor 21 (FGF21). Our in vivo data showed that SEM induced energy expenditure and white adipose tissue (WAT) browning by increasing the expression level of uncoupling protein-1 in high fat diet induced obese C57BL/6J mice. Elevated levels of circulating FGF21 associated with the increased expression of hepatic FGF21 were observed after SEM intervention. Simultaneously, the increased adipose fibroblast growth factor tyrosine kinase receptor 1/beta-klotho indicated that FGF21 sensitivity was enhanced by SEM in WAT. Furthermore, our in vitro results from HepG2 and 3T3-L1 cell lines confirmed the effects and revealed the mechanism of SEM on the white adipocytes browning. We found that with the specific inhibitors of PPARα, the SEM-mediated hepatic FGF21 expression was decreased, and with the specific inhibitors of PPARγ, the browning effect of adipocytes by SEM combining with FGF21 was significantly suppressed. Taken together, the mechanism of SEM for inducing the WAT browning might be the modulation of SEM on liver-adipose crosstalk mediated by FGF21, and the PPARs family might be the targets of SEM. The novel findings from the present study provided evidence that SEM could be a potent obesity-treating compound.

Design and fabrication of Sesamol-loaded transfersomal gel for wound healing: physicochemical characterization and in-vivo evaluation

Objective In the present study, an attempt has been made to develop SL-loaded transfersomal gel for the effective treatment of delayed wound healing. Significance The wound healing process consists of a complex series of biochemical events and changes in cellular activity that restore the integrity of the skin and the subcutaneous tissue. Sesamol (SL), which is a natural phenolic compound, is known for its antioxidant properties, anti-inflammatory properties, and wound-healing abilities. Methods A thin-film hydration method was used to prepare SL-loaded transfersomes. Different formulations containing Tween-80 and Span-80 as edge activators were prepared and optimized. Various characteristics of vesicles were assessed, such as size, shape, loading efficiency, deformability, and in vitro skin penetration. The optimized formulation was then incorporated into 1% carbopol 940 gel. An in vivo wound healing potential of the selected formulation was assessed by an excision wound model. Results The SL-loaded transfersomal gel displayed improved skin penetration and better skin deposition. Wound healing studies showed that the highest wound contraction was observed with SL-loaded transfersomes. Following 21 days of application of the transfersomal gel, a marked improvement in skin histological architecture was found. Conclusion The study findings suggest that transfersomal gel has great potential as a therapeutic option in wound healing.

Effective combination of nisin and sesamol against Listeria monocytogenes

Nisin (NS) has been considered as a food preservative against Listeria monocytogenes, an important foodborne pathogen that causes serious public health problems. However, the effectiveness of NS is also affected due to its instability and resistance of L. monocytogenes to NS. Combining NS with other antimicrobial substances is an excellent strategy to improve the effect. Sesamol (SE) has been reported to have the ability to inhibit the growth of L. monocytogenes. Thus, in this study, based on the determination of the fractional inhibitory concentration indices, the in vitro synergistic antibacterial activity of NS and SE was confirmed using standard L. monocytogenes ATCC19112 and L. monocytogenes isolated from food and clinical sources. The inhibition of NS and SE combination on the growth of L. monocytogenes was higher than that of NS or SE alone in tryptic soy yeast extract broth (TSB-YE) and pasteurized milk. The changes and damages of the cell structure and the cell morphology in the combination group were more significant than those in the single use of NS or SE. These results indicate that the combined application of NS and SE may be a promising alternative to NS for controlling the contamination of L. monocytogenes in food.

The Antioxidant Effects of Sesamol on Bleomycin-Induced Oral Submucous Fibrosis

Objective: Oral submucous fibrosis (OSF) is a disease characterized by abnormal collagen deposition that causes inflammation and malignancy in oral mucosal tissue. Fibroblasts and myofibroblasts, are the cells that show significant activation in the development of OSF. Bleomycin (BL) is a chemotherapeutic agent commonly used in cancer treatment that also causes inflammatory changes in the oral mucosa, initiating fibrosis in the oral submucosal tissue. Sesamol (SE) has antioxidative and anti-inflammatory properties which are abundant in sesame seeds and sesame oil, and SE has a beneficial effect on the mucosal layer. This experimental study aimed to investigate SE’s effects on BL-induced OSF. Materials and Methods: The study obtained 18 healthy adult male albino rats aged 3-4 months and weighing 200-250g from Bolu Abant Izzet Baysal University’s Experimental Animal Application and Research Center. The rats were divided randomly into control, BL, and BL + SE groups (n = 6 in each group). A model of OSF was established in the rats by administering 0.5 mg/mL of BL and 50 mg\kg of SE to the BL+SE group each day. The hematoxylin and eosin stain and Masson’s trichrome stain were used to assess histopathological changes in the oral mucosa. Results: The results revealed SE to have beneficial effects on BL-induced OSF through its antioxidant and anti-inflammatory properties. Histopathological evaluations and biochemical analysis of oral submucosal tissue samples also revealed SE to provide statistically significant protection against fibrosis in the oral mucosa (p < 0.01). Conclusion: This study has demonstrated oral submucous fibrosis that develops due to BL as well as SE to have an antioxidant effect on OSF regarding BL-induced reactive oxygen species (ROS) activation and collagen synthesis.

Sesamol Attenuates Renal Inflammation and Arrests Reactive-Oxygen-Species-Mediated IL-1β Secretion via the HO-1-Induced Inhibition of the IKKα/NFκB Pathway In Vivo and In Vitro.

Chronic nephritis leads to irreversible renal fibrosis, ultimately leading to chronic kidney disease (CKD) and death. Macrophage infiltration and interleukin 1β (IL-1β) upregulation are involved in inflammation-mediated renal fibrosis and CKD. Sesamol (SM), which is extracted from sesame seeds, has antioxidant and anti-inflammatory properties. We aimed to explore whether SM mitigates macrophage-mediated renal inflammation and its underlying mechanisms. ApoE-/- mice were subjected to 5/6 nephrectomy (5/6 Nx) with or without the oral gavage of SM for eight weeks. Blood and urine samples and all the kidney remnants were collected for analysis. Additionally, THP-1 cells were used to explore the mechanism through which SM attenuates renal inflammation. Compared with the sham group, the 5/6 Nx ApoE-/- mice exhibited a significant increase in the macrophage infiltration of the kidneys (nephritis), upregulation of IL-1β, generation of reactive oxygen species, reduced creatinine clearance, and renal fibrosis. However, the administration of SM significantly alleviated these effects. SM suppressed the H2O2-induced secretion of IL-1β from the THP-1 cells via the heme oxygenase-1-induced inhibition of the IKKα-NF-κB pathway. SM attenuated renal inflammation and arrested macrophage accumulation by inhibiting IKKα, revealing a novel mechanism of the therapeutic effects of SM on renal injury and offering a potential approach to CKD treatment.

Formulation, Characterization, Anti-Inflammatory and Cytotoxicity Study of Sesamol-Laden Nanosponges.

Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into β-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (-17 to -26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (β-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC50 values of SES-NS (67.38 μg/mL) in comparison to SES (106 μg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery.

Sesamol protects against liver fibrosis induced in rats by modulating lysophosphatidic acid receptor expression and TGF-β/Smad3 signaling pathway

The present study aimed to investigate the hepatoprotective effect of sesamol (SML), a nutritional phenolic compound obtained from sesame seeds, in liver fibrosis induced by thioacetamide (TAA) in rats and to explore the underlying mechanisms. Thirty-two male Sprague–Dawley rats were equally divided into four groups: control, TAA, TAA + SML 50 mg/kg, and TAA + SML 100 mg/kg groups. Liver functions and hepatic contents of glutathione (GSH) and malondialdehyde (MDA) were measured colorimetrically. Gene expressions of lysophosphatidic acid receptor (LPAR)-1 and -3, connective tissue growth factor (CTGF), transforming growth factor (TGF)-β1, small mothers against decapentaplegic (Smad)-3 and -7, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK19) were analyzed by qRT-PCR. Moreover, phosphorylated Smad3 (pSmad3) was quantified by ELISA. Additionally, TGF-β1, α-SMA, CK19, and vascular endothelial growth factor (VEGF) protein concentrations were semi-quantitatively analyzed by immunostaining of liver sections. SML treatment markedly improved liver index and liver functions. Moreover, SML protected against liver fibrosis in a dose-dependent manner as indicated by down-regulation of LPAR1, LPAR3, CTGF, TGF-β1/Smad3, and α-SMA expressions and a decrease in pSmad3 level, as well as an up-regulation of Smad7 expression. In addition, SML suppressed ductular reaction hinted by the decrease in CK19 expression. These results reveal the anti-fibrotic effect of SML against liver fibrosis that might be attributed to down-regulation of LPAR1/3 expressions, inhibition of TGF-β1/Smad3 pathway, and ductular reaction.

Sesamol protects against aluminum oxide nanoparticles-induced hepatorenal toxicity in rats via modulation of oxidative stress, inflammation, apoptosis, and DNA damage.

Aluminum oxide nanoparticles (Al2 O3 -NPs) are exceedingly used in various industrial and commercial applications, providing growing concerns about their potential adverse impacts on animals and human health. Therefore, the present study was conducted to evaluate the potential protective effect of sesamol (SML) against the induced hepatorenal toxicity of Al2 O3 -NPs. Forty male rats were randomly assigned into four groups and treated orally for 28 consecutive days. Control group received distilled water. SML group received SML (100 mg/kg bw). Al2 O3 -NPs group received Al2 O3 -NPs (100 mg/kg bw). SML + Al2 O3 -NPs group received SML 2 h prior to Al2 O3 -NPs. The results revealed that Al2 O3 -NPs significantly increased serum alanine aminotransferase and aspartate aminotransferase activities and serum urea and creatinine levels. Moreover, Al2 O3 -NPs induced a significant elevation in malondialdehyde level with significant reduction in reduced glutathione content and catalase and superoxide dismutase activities, together with a marked increase of 8-hydroxy-2-desoxyguanosine level in the hepatic and renal tissues. Also, up-regulations of glutathione-S-transferase, tumor necrosis factor-alpha, and caspase-3 mRNA gene expressions were recorded in the liver and kidneys. Additionally, Al2 O3 -NPs induced multifocal areas of necrosis in hepatic parenchyma with glomerular mesangial cell proliferation and glomerular sclerosis in kidney tissues. Conversely, concomitant treatment with sesamol mitigated Al2 O3 -induced hepatorenal toxicity evidenced by improvement of liver and kidney functions that correlated with regulation of oxidant/antioxidant status, inflammatory, and apoptotic biomarkers and reduction of DNA and tissues damages. In conclusion, sesamol could exert a promising protective role against hepatorenal toxicity of Al2 O3 -NPs, possibly via its antioxidant, anti-inflammatory and anti-apoptotic properties.

Protective Effects of Sesamol against Liver Oxidative Stress and Inflammation in High-Fat Diet-Induced Hepatic Steatosis.

Chronic high-fat diet (HFD) is associated with the onset and progression of hepatic steatosis, and oxidative stress is highly involved in this process. The potential role of sesamol (SEM) against oxidative stress and inflammation at the transcriptional level in a mice model of hepatic steatosis is not known. In this study, we aimed to investigate the scavenging effects of SEM towards reactive oxygen generated by lipid accumulation in the liver of obese mice and to explore the mechanisms of protection. Markers of oxidative stress, vital enzymes involved in stimulating oxidative stress or inflammation, and nuclear transcription of Nrf2 were examined. Our results showed that SEM significantly inhibited the activity of the HFD-induced hepatic enzymes CYP2E1 and NOX2, associated with oxidative stress generation. Additionally, SEM reversed HFD-induced activation of NF-κB, a redox-sensitive transcription factor, and attenuated the expression of hepatic TNF-α, a proinflammatory molecule. Moreover, SEM enhanced HFD-induced hepatic Nrf2 nuclear transcription and increased the levels of its downstream target genes Ho1 and Nqo1, which indicated antiinflammation and antioxidant properties. Our study suggests that chronic HFD led to hepatic steatosis, while SEM exhibited protective effects on the liver by counteracting the oxidative stress and inflammation induced by HFD. The underlying mechanism might involve multiple pathways at the transcriptional level; the antioxidant defense mechanism was in partly mediated by the upregulation of Nrf2.

Sesamol-loaded stearic acid-chitosan nanomicelles mitigate the oxidative stress-stimulated apoptosis and induction of pro-inflammatory cytokines in motor neuronal of the spinal cord through NF-ĸB signaling pathway

As natural potential antioxidants suffer from low cellular uptake, the development of drug-loaded nanoplatforms may provide useful information about the treatment of spinal cord injury (SCI). In the present study, sesamol (SM)-loaded stearic acid (SA) -chitosan (CS) nanomicelles were fabricated and well-characterized. Afterwards, the neuroprotective effects of SM@SA-CS nanomicelles against lipopolysaccharide (LPS)-induced oxidative stress in NSC-34 cells was assessed by different cellular and molecular pathways. It was deduced that the size of synthesized SM@SA-CS was in the range of 10–20 nm and the hydrodynamic radii of SA-CA and SM@SA-CA nanomicelles were 53.12 ± 6.21 nm and 59.12 ± 7.31 nm, respectively. Furthermore, SM@SA-CS nanomicelles displayed a sustained drug release at physiological pH, potential dissolution rate and stability even up to 15 days. Cellular assay showed that SM@SA-CS nanomicelles co-incubation with LPS for 24 h in comparison with free drug remarkably regulated cell survival, membrane leakage, generation of ROS, activity of non-enzymatic and enzymatic antioxidant systems, and apoptotic and inflammatory signaling pathway through NF-ĸB signaling pathway. These data indicated that SM@SA-CS nanomicelles can be developed as a promising platform for the mitigation of oxidative stress-mediated apoptosis in neural cells.

Cyclodextrin decorated nanosponges of sesamol: Antioxidant, anti-tyrosinase and photostability assessment

Sesamol (SES), a natural phenolic bioactive, is endowed with benefits in food and pharmaceuticals. However, its utility is compromised by certain unfavorable physicochemical characteristics, particularly poor stability. Therefore, present work is aimed at formulating novel SES loaded cyclodextrin nanosponges (CDNS) to protect the drug from degradation. For this purpose, blank CDNS were fabricated employing solvent evaporation technique and subsequently SES loading via lyophilization. Characterization of SES-CDNS was carried out by Fourier transform infrared analysis, differential scanning calorimetry, and nuclear magnetic resonance. These nanostructures were also evaluated for entrapment efficiency, particle size, polydispersity index, and zeta potential. Further, photostability assessment was conducted for SES-CDNS, along with stability evaluation. Antioxidant potential of SES was determined using DPPH assay, after its encapsulation and storage. Lastly, in vitro anti-tyrosinase assay was also performed for SES-CDNS. Results demonstrated that SES was successfully entrapped in CDNS having size in nano-range (189.46 ± 6.57) and assuring high encapsulation efficiency (90.66%). The findings of the photostability evaluation showed that CDNS was able to protect SES from photodegradation. Furthermore, oxygen radical absorbance capacity was found preserved for SES, especially when encapsulated in CDNS. No significant differences were observed after three months storage (at room temperature), with regard to loss of structural and functional features of SES. Hence, the results confirmed that nanoformulation is ideal for encapsulation of SES to enhance its physicochemical stability and to preserve antioxidant and anti-tyrosinase activity of this bioactive.