Protective Effect Of Sesamol Research Articles

The protective effects of sesamol and/or the probiotic, Lactobacillus rhamnosus, against aluminum chloride-induced neurotoxicity and hepatotoxicity in rats: Modulation of Wnt/β-catenin/GSK-3β, 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-β, p-tau, GSK-3β, inflammatory and apoptotic biomarkers, along with marked elevation in brain free β-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.

Protective effect of sesamol on cognitive impairment in APP/PS1 mice

AbstractTo explore the effect of sesamol on the cognition of APP/PS1 mice, 8-week-old APP/PS1 and wild-type male mice were divided into AD model group, AD + sesamol (50 mg kg−1 bw) group, and Control group. Sesamol was orally administered once a day for 5 months. Morris water maze was used to evaluate the learning and memory ability of mice. The number of synapses in the hippocampal neurons was detected by Golgi staining. Nissl staining was used to observe the changes of Nissl bodies in CA1 and CA3 regions of the hippocampus. Western blotting was used to detect the expression of Aβ, SIRT1, BDNF, and p-CREB/CREB in the hippocampus and cortex. Compared with the model group, sesamol decreased the latency period of APP/PS1 mice (P < 0.05) and increased the total number of neuronal dendritic spines in the hippocampal CA3 region, as well as increased the number of Nissl bodies (P < 0.05). Western blotting results showed that sesamol significantly reduced Aβ protein expression in the hippocampus and cortex, increased SIRT1 expression in the cortex, and increased BDNF expression in the hippocampus (P < 0.05). Sesamol improved the learning and memory abilities of APP/PS1 mice probably through increasing the density of neuronal dendritic spines and upregulating the levels of SIRT1 and BDNF.

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.

Lead nitrate and cadmium chloride induced hepatotoxicity and nephrotoxicity: Protective effects of sesamol on biochemical indices and pathological changes.

Lead nitrate (LN) and cadmium chloride (CdCl2 ), regarded as environmental contaminants, are toxic heavy metals. Sesamol is a dietary phytochemical found in sesame oil. We aimed to analyze the hepatotoxic and nephrotoxic effects of LN and CdCl2 and to evaluate the possible protective effect of sesamol. LN (90mg/kg bw per day), CdCl2 (3mg/kg bw per day), and sesamol (50mg/kg bw per day) were given to rats via gavage for 28days. Total protein, albumin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total cholesterol, urea, uric acid, creatinine, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, malondialdehyde, acetylcholinesterase, and histopathological changes were investigated in liver and kidney tissues. Lead and cadmium were found to result in decreases in the antioxidant enzymes and acetylcholinesterase activities, increases in malondialdehyde levels, and changes in serum biochemical parameters and various pathological findings. An improvement in all these parameters was observed in the sesamol-treated groups. PRACTICAL APPLICATIONS: Heavy metals are used in many areas of the industry all over the world. Heavy metals which include lead nitrate and cadmium chloride cause cell damage by oxidative stress. Some of the examining parameters for oxidative stress are SOD, GST, MDA, GPx, and CAT. However, some chemicals such as sesamol are well-liked and widely used as antioxidants against xenobiotic toxicity. We also indicate that sesamol has been shown to protective effect against heavy metals caused cell damage.

Protective Effects of Sesamol on the Brains of Rats with Focal Cerebral Ischemia-Reperfusion Injury

Stroke is an acute cerebrovascular event associated with brain tissue injury, representing the most common cause of death. Thrombolysis and recanalization are the principal treatment modalities for ischemic stroke. Some patients experience cerebral ischemia-reperfusion injury following treatment. A previous study established that sesamol is effective in reducing risk factors for stroke. Here, we aimed to investigate the protective effect of sesame phenol on cerebral ischemia-reperfusion injury. A total of 72 SD rats were randomly divided into a sham group, cerebral ischemia-reperfusion (MCAO) group, cerebral ischemia-reperfusion with low dose sesame phenol (MCAO+sesamol A) group and cerebral ischemia-reperfusion with high dose sesame phenol (MCAO + sesamol B) group. After cerebral ischemia had been induced for 2h and reperfusion conducted for 24h, the volume of cerebral infarction, the degree of cerebral edema and the neurological deficit scores were tested. The results showed sesamin improved the neurological deficit score in a dose-dependent manner, reduced the volume of cerebral infarction, degree of cerebral edema. Prophylactic treatment with sesame phenol provided neuroprotective effects on cerebral ischemia-reperfusion injury.

Protective effects of sesamol against cisplatin-induced nephrotoxicity in rats: A mechanistic approach

BackgroundAcute renal failure specifically denotes tubular necrosis due to induced by ischemic injury or drugs, resulting in electrolyte imbalance along with changes in hormonal levels in renal system, causing accumulation of nitrogenous waste in the kidneys. ObjectiveTo explore the role and mechanism of sesamol as renoprotective using cisplatin mediated nephrotoxicity in male Wistar rats. MethodIn male wistar rats, a single dose of 5 mg per kg of body weight, i.p cisplatin was used to induce nephrotoxicity. Renoprotective effect of sesamol was evaluated by analyzing blood, urine, oxidative stress markers and tissue histology. ResultPresent study shows that cisplatin confirms the nephrotoxicity by modifying the urinary, blood and inflammatory parameters in contrast to the vehicle control group. Sesamol at dose levels of 50 and 100 mg/kg body weight, p.o. significantly & dose dependently reverses the changes. Nephroprotective effect of sesamol was abolished by PPAR-γ inhibitor, BADGE (30 mg/kg, i.p.) in rats. ConclusionOur study clearly indicates the nephroprotective activity of sesamol by PPAR-γ agonism against cisplatin-induced nephrotoxicity in rats.

Protective Effects of Sesamol on Systemic Inflammation and Cognitive Impairment in Aging Mice

Sesamol, a lignan in sesame, possesses several bioactivities, such as antioxidation, anti-inflammation, and neuroprotective capability. In this study, the effects of sesamol on aging-caused cognitive defects are investigated. Twelve-month-old mice were treated with sesamol (0.1%, w/w) as dietary supplementation for 12 weeks. Behavioral tests revealed that sesamol improved aging-associated cognitive impairments. Sesamol decreased aging-induced oxidative stress via suppression of malondialdehyde production and increased antioxidant enzymes. Histological staining showed that sesamol treatment improved aging-induced neuronal damage and synaptic dysfunction in hippocampus. Furthermore, sesamol significantly reduced aging-induced neuroinflammation by inhibiting the microglial overactivation and inflammatory cytokine expressions. Meanwhile, the accumulation of Aβ1-42 was reduced by sesamol treatment. Moreover, sesamol protected the gut barrier integrity and reduced LPS release, which was highly associated with its beneficial effects on behavioral and inflammatory changes. In conclusion, our findings indicated that the use of sesamol is feasible in the treatment of aging-related diseases.

Antioxidant and anti-isomerization effects of sesamol and resveratrol on high oleic acid peanut oil

In the present study, the protective effects of sesamol and resveratrol on high oleic acid peanut oil were investigated. Different amounts of sesamol, resveratrol, and their combinations were added to the high oleic acid peanut oil to investigate the antioxidant effect and anti-isomerization effect to prevent cis to trans isomerization of double bonds. Rancimat results showed that the oil had the longest oxidation inducing time after adding 0.08% sesamol or 0.06% resveratrol (v/v). Thermogravimetric analysis suggested that when sesamol and resveratrol were added at 0.08% and 0.04% (v/v), the oxidation decomposition temperature was the highest. Schaal oven experiments indicated that the addition of sesamol and resveratrol could significantly reduce the peroxide content of high oleic acid peanut oil. The total fatty acid content in the oil samples increased significantly after high temperature treatment at 180 °C or 240 °C, and three new thermal isomerization trans products were measured (C18:1-9t, C18:2-9c,12t, C18:2-9t,12c). Meanwhile, the addition of sesamol (0.08%, v/v) or resveratrol (0.06%, v/v) significantly reduced the content of unsaturated fatty acid. For high oleic acid peanut oil heated to 180 °C, sesamol and resveratrol showed a better inhibitory effect on the production of trans-oleic acid than when heating at 240 °C.

The protective effects of sesamol in a neonatal rat model of necrotizing enterocolitis

Background and aim: Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease associated with high rates of morbidity and mortality. Its pathophysiology includes hypoxic-ischemic injury that may be related to oxygen-derived free radical formation. Sesamol is considered to be an antioxidant and free radical scavenger with anti-inflammatory effects. The aim of this study is to investigate the effects of sesamol in a neonatal rat model of NEC.Materials and methods: The study included 1-day-old Wistar albino rat pups (n = 34) that were randomly divided into four groups: Group 1 (NEC), group 2 (NEC + intraperitoneal sesamol), group 3 (NEC + oral sesamol), and a control group. NEC was induced by exposure to hypoxia/reoxygenation, following cold stress and hyperosmolar enteral formula feeding. Sesamol 100 mg kg−1 dose−1 was administered intraperitoneally to group 2 and orally to group 3 for 3 days. On day 4 all rats were sacrificed. Histological injuries, the Bcl-2, caspase-3, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione-peroxidase (GSH-Px) activities were measured in intestinal samples.Results: The grade of intestinal damage, and Bcl-2 and caspase-3 levels in group 1 were significantly higher than in groups 2 and 3 and the control group, and intestinal damage was significantly more severe in group 1 than in groups 2 and 3. The MDA activity was significantly lower in groups 2 and 3 than in group 1 (112, 89, and 144 nmol mL−1, respectively). Groups 2 and 3 had significantly higher SOD and GSH-Px activities than group 1 (SOD: 1.75, 1.74, and 0.89 U mg−1; GSH-Px: 114, 121, and 110 nmol of NADPH min−1 mg−1, respectively).Conclusions: The present findings highlight that sesamol has beneficial effects on intestinal injury in a rat model of NEC through its antioxidant and anti-inflammatory properties.

Protective effects of sesamol on systemic oxidative stress-induced cognitive impairments via regulation of Nrf2/Keap1 pathway

Oxidative stress is considered as a pivotal culprit in neurodegenerative diseases and brain aging. The aim of present study was to investigate antioxidative and neuroprotective effects of sesamol, a phenolic lignan from sesame oil, on oxidative stress induced neuron damage and memory impairments. C57BL/6J mice were treated by intraperitoneal injections of d-galactose for 8 weeks. Sesamol treatment (0.05% w/v, in drinking water) suppressed d-galactose-induced liver damages and improved HO-1 and NQO1 mRNA levels. Behavioral tests, including Y-maze test and water maze-test, revealed that sesamol significantly improved oxidative stress-induced cognitive impairments. Meanwhile, sesamol ameliorated neuronal damage and improved BDNF level in rat hippocampus. Sesamol elevated mRNA levels and protein expressions of antioxidant enzymes HO-1 and NQO1 as well as decreased inflammatory cytokines TNF-α and IL-1β in d-galactose-treated mice serum. In addition, activity of CAT and GSH level were increased in sesamol-treated mice serum. Moreover, sesamol treatment also balanced cellular redox status, protected mitochondrial dysfunction and upregulated antioxidant enzymes by activating the Nrf2 transcriptional pathway and its nuclear translocation in H2O2-treated SH-SY5Y cells. In conclusion, these results revealed that sesamol could be a potential neuroprotective agent during aging process due to its beneficial effects on liver-brain axis.

Protective Effects of Sesamol on Streptozotocin Induced Diabetic Neuropathy in Rats

Objective(s): To investigate the neuroprotective effect of sesamol on diabetic neuropathy in diabetic rats. Design: A randomized controlled trial. Setting: A research laboratory. Participants: Sprague-Dawley rats (NZ30; weight, 230-300g) were used and divided into 3 study groups. Interventions: The male rats were randomly divided into three groups: group 1, diabetic control rats without sesamol treatment (DM group); group 2, diabetic rats with sesamol treatment (SM group); group 3, normal control. Diabetes was induced by Streptozotocin (60 mg/kg) injection, and Sesamol (10 mg/kg/d) was administered orally for 9 weeks. Main Outcome Measure(s): We measured weight, blood glucose level, behavior tests and electrodiagnostic studies before and at 3, 6 and 9 weeks after the injection. Results: After 3 weeks, SM groups showed a significantly heavier body weight and lower blood sugar level than DM group, which showed delayed response of thermal stimulation compared with normal control group (p<0.05). However, the SM groups showed difference after 6 weeks (p<0.05). While the DM group showed delayed sensory nerve conduction velocity and motor nerve conduction velocity (MNCV) after 6 weeks, the SM group showed delayed MNCV at 9 weeks. H reflex didn’t show difference among three groups. In structural analyses, DM group showed severe myelin degenerations and morphologic changes of nerve fibers compared with SM group. Conclusions: In conclusion, this study suggests that treatment with sesamol may attenuate symptoms of diabetic neuropathy, and it also has protective effects against diabetic neuropathy.

Protective effect of sesamol against 60Co γ-ray-induced hematopoietic and gastrointestinal injury in C57BL/6 male mice

Protection of γ-ray-induced injury in hematopoietic and gastrointestinal (GI) systems is the rationale behind developing radioprotectors. The objective of this study, therefore, was to investigate the radioprotective efficacy and mechanisms underlying sesamol in amelioration of γ-ray-induced hematopoietic and GI injury in mice. C57BL/6 male mice were pre-treated with a single dose (100 or 50 mg/kg, 30 min prior) of sesamol through the intraperitoneal route and exposed to LD50/30 (7.5 Gy) and sublethal (5 Gy) dose of γ-radiation. Thirty-day survival against 7.5 Gy was monitored. Sesamol (100 mg/kg) pre-treatment reduced radiation-induced mortality and resulted survival of about 100% against 7.5 Gy of γ-irradiation. Whole-body irradiation drastically depleted hematopoietic progenitor stem cells in bone marrow, B cells, T cell subpopulations, and splenocyte proliferation in the spleen on day 4, which were significantly protected in sesamol pre-treated mice. This was associated with a decrease of radiation-induced micronuclei (MN) and apoptosis in bone marrow and spleen, respectively. Sesamol pre-treatment inhibited lipid peroxidation, translocation of gut bacteria to spleen, liver, and kidney, and enhanced regeneration of crypt cells in the GI system. In addition, sesamol pre-treatment reduced the radiation-induced pattern of expression of p53 and Bax apoptotic proteins in the bone marrow, spleen, and GI. This reduction in apoptotic proteins was associated with the increased anti-apoptotic-Bcl-x and PCNA proteins. Further, assessment of antioxidant capacity using ABTS and DPPH assays revealed that sesamol treatment alleviated total antioxidant capacity in spleen and GI tissue. In conclusion, the results of the present study suggested that sesamol as a single prophylactic dose protects hematopoietic and GI systems against γ-radiation-induced injury in mice.

Anti-hepatotoxic effects of 3,4-methylenedioxyphenol and N-acetylcysteine in acutely acetaminophen-overdosed mice

3,4-Methylenedioxyphenol (sesamol) is effective against acetaminophen-induced liver injury in rats. Whether sesamol's anti-hepatotoxic effect is comparable to that of N-acetylcysteine has never been studied. We investigated the anti-hepatotoxic effects of sesamol and N-acetylcysteine on acetaminophen-induced hepatotoxicity in mice. Equimolar doses (1 mmol/kg) of sesamol and N-acetylcysteine significantly inhibited acetaminophen (300 mg/kg)-increased serum aspartate transaminase and alanine transaminase levels 6 h post-administration. Sesamol and N-acetylcysteine maintained hepatic glutathione levels and inhibited lipid peroxidation. Moreover, the combination of sesamol and N-acetylcysteine antagonistically inhibited sesamol's protection against acetaminophen-induced liver injury. We conclude that the protective effect of sesamol against acetaminophen-induced liver damage is comparable to that of N-acetylcysteine by maintaining glutathione levels and inhibiting lipid peroxidation in mice.

Protective Effect of Sesamol against 3‐Nitropropionic Acid‐Induced Cognitive Dysfunction and Altered Glutathione Redox Balance in Rats

Sesamol (SML) (Sesamum indicum, Linn, Pedaliaceae) has been used traditionally as a health supplement in India and other countries for a long time. It is a well-known antioxidant, currently being tried against several neurological disorders. The present study was designed to evaluate the potential of sesamol treatment against 3-nitropropionic acid (3-NP)-induced cognitive impairment and oxidative damage in striatal, cortex and hippocampal regions of the rat. The memory performance was assessed by Morris water maze and elevated plus maze paradigms. The oxidative damage was assessed by estimating the total glutathione, reduced glutathione, oxidized glutathione levels and glutathione redox ratio. Glutathione-S-transferase and lactate dehydrogenase enzymes were also measured in different brain areas. 3-NP significantly impaired memory performance as assessed in Morris water maze and elevated plus maze, which was significantly attenuated by sesamol (5, 10 and 20 mg/kg) pre-treatment. On the other hand, 3-NP significantly induced oxidative stress and depleted total glutathione, reduced glutathione, glutathione-S-transferase, lactate dehydrogenase enzyme levels and redox ratio in the striatum, cortex and hippocampal regions as compared to the vehicle-treated group. Sesamol pre-treatment restored oxidative defence possibly by its free radical scavenging activity as compared to the 3NP-treated group. The present study suggests that sesamol could be used as an effective agent in the management of Huntington's disease.

Protective effect of sesamol on the pulmonary inflammatory response and lung injury in endotoxemic rats

We investigated the effect of sesamol on systemic lipopolysaccharide (LPS)-induced lung inflammation in rats. Sesamol decreased lung edema and injury, significantly decreased LPS-induced cell counts, protein concentration, tumor necrosis factor (TNF)-α, and nitrite levels in bronchoalveolar lavage fluid, and decreased the TNF-α, nitrite, and inducible nitric oxide synthase protein expression in lung tissue. Further, sesamol significantly inhibited LPS-induced TNF-α, nitrite, inducible nitric oxide synthase expression, and nuclear factor-κB activation levels in primary alveolar macrophages. We hypothesize that sesamol attenuates systemic LPS-induced lung inflammation by inhibiting the alveolar macrophage inflammatory response in rats.

Protective effect of sesamol against myocardial infarction caused by isoproterenol in Wistar rats

This study was designed to investigate the cardioprotective effect of sesamol on isoproterenol (ISO)-induced myocardial infarction in adult male albino Wistar rats. The heart damage induced by ISO was indicated by elevated levels of the marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-MB (CK-MB) and the levels of troponin T and I in the plasma. In addition, lipid peroxidative markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LHP) significantly increased in the plasma and heart. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) significantly decreased in the heart and (non-enzymic antioxidants) vitamin C, vitamin E and reduced glutathione (GSH)) levels significantly decreased in the plasma and heart in ISO-rats. Histopathological observations correlated with the biochemical parameters. Administration of sesamol at different doses 50, 100 and 200 mg/kg body weight intraperitoneally for 7 days prevented the above changes and improved towards normality; the 50 mg dose was more effective than the other two doses.

FP40-TH-02 Protective effect of sesamol against 3-nitropropionic acid-induced Huntington-like symptoms in rats

FP40-TH-02 Protective effect of sesamol against 3-nitropropionic acid-induced Huntington-like symptoms in rats

THE PROTECTIVE EFFECT OF SESAMOL AGAINST MITOCHONDRIAL OXIDATIVE STRESS AND HEPATIC INJURY IN ACETAMINOPHEN-OVERDOSED RATS

An acetaminophen (APAP) overdose induces oxidative stress and acute hepatic injury or even death. We investigated the prophylactic effect of sesamol (SM) on mitochondrial oxidative stress, hydroxyl-radical-generated lipid peroxidation, and hepatic injury in APAP-overdosed rats. Six male Wistar rats (APAP group) were given only oral APAP (1,000 mg/kg) to induce mitochondrial oxidative-stress-associated hepatic injury, and another six (ASM group) were given the same dose of oral APAP, and then, immediately afterward, were injected with SM (10 mg/kg, i.p.), to assess its prophylactic effects. In the APAP group, APAP had significantly increased the levels of 1) serum aspartate transaminase and alanine transaminase, 2) centrilobular necrosis, 3) ferrous ions, 4) hydrogen peroxide, 5) hydroxyl radicals, and 6) lipid peroxidation, and decreased 7) mitochondrial aconitase activity in the rats' liver tissue 24 h later. In the ASM group, SM had prevented significant rises in the levels of 1) to 6) and a significant decrease (7). Therefore, we hypothesize that the protective effect of SM in APAP-overdosed rats is associated with maintaining the mitochondrial aconitase activity, ferrous ions (Fe2+), and hydrogen peroxide levels and inhibiting hydroxyl-radical-associated lipid peroxidation and hepatic injury.