Vitamins as Nrf2 Activators
Vitamins have often been referred to as "direct antioxidants". Dr. Joe McCord in an ABC primetime video mentioned that they were not good enough on their own to fight the enormous battle against free radical damage.
So when are vitamins effective in the fight against free radicals?Vitamins as direct antioxidants eliminate free radicals on a 1:1 basis. In other words, one molecule of a vitamin eliminates one free radical if it is purely acting as a direct antioxidant. However when that vitamin becomes a Nrf2 activator, it turns on the switch to the body's own antioxidant defenses and neutralizes free radicals more like a 1:1,000,000 ratio every second.
Below are the latest 15 Pubmed studies referencing vitamis and Nrf2 activation.
Spermatogenesis dysfunction induced by PM from automobile exhaust via the ROS-mediated MAPK signaling pathway
Long-term exposure to particulate matter 2.5 (PM) from automobile exhaust impairs spermatogenesis through oxidative stress injury, but the underlying mechanism is unknown. To investigate the toxic mechanism of PM-induced spermatogenesis impairment, we focused on the MAPK signaling pathway. We also examined the effects of treatment with vitamins C and E on spermatogenic function. Male SD rats were divided randomly into three groups: control (0.9% sterilized saline), PM exposure (20 mg/kg.b.w.), and PM exposure (20 mg/kg.b.w.) with vitamin intervention (vitamin C, 100 mg/kg.b.w.; vitamin E, 50 mg/kg.b.w.). Male rats showed a marked decline in fertility and decreased sperm quality after PM exposure. The expression of SOD and Nrf2 was significantly decreased, and that of MDA was increased markedly. The expression of blood-testis barrier-associated proteins, such as ZO-1, occludin, connexin 43, and β-catenin, was significantly decreased, the Bcl-2/Bax ratio was downregulated, and the cleaved caspase-3 level was increased. Phosphorylation of MAPKs, including ERKs, JNKs, and p38, was upregulated. Treatment with vitamins C and E reversed the damage induced by PM exposure. These results suggest that PM from automobile exhaust disrupted spermatogenesis via ROS-mediated MAPK pathways, and that a combined vitamin C and E intervention effectively mitigated toxicity in the male reproductive system.
Vitamin D potentiates anti-tumor activity of 5-fluorouracil via modulating caspase-3 and TGF-β1 expression in hepatocellular carcinoma-induced in rats
We investigated the role of vitamin D (Vit D) alone and in combination with 5-fluorouracil (5-FU) in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) in rats. Fifty male Sprague-Dawley rats were randomized into a control group and 4 groups that received TAA (200 mg/kg, i.p.) twice per week for 16 weeks. These 4 groups were further divided as follows: HCC group; 5-FU group (75 mg/kg, i.p., once weekly for 3 weeks starting from the 12th week); Vit D group (200 IU/kg daily by oral tube for 16 weeks); and 5-FU + Vit D group (received the previously mentioned dosage regimens of 5-FU and Vit D). HCC was detected by histopathological changes in liver sections and the elevation of serum α-fetoprotein (AFP). Treatment with 5-FU + Vit D significantly decreased gene expression of nuclear factor erythroid 2-related factor 2 (NrF2) and transforming growth factor β1 (TGF-β1) at both the gene and protein level and serum AFP concentrations in comparison with their corresponding monotherapy. Moreover, 5-FU + Vit D treatment enhanced apoptosis by increasing caspase-3 gene and protein expression. Conclusively, Vit D enhances antitumor activity of 5-FU in an HCC-induced model and improves liver function of treated animals. Combination therapy in a TAA-induced HCC rat model was more effective than 5-FU or Vit D through the modulation of TGF-β1, caspase-3, and NrF2 expressions.
Vitamin D protects human melanocytes against oxidative damage by activation of Wnt/β-catenin signaling
Vitamin D analogs have been widely utilized for the treatment of vitiligo, but the molecular mechanism underlying their pharmacological effects (especially their antioxidant properties) has not yet been investigated. We evaluated the relationship between serum vitamin D level and oxidative damage severity in vitiligo patients, and investigated the molecular mechanism of vitamin D in protecting melanocytes against oxidative stress. Serum levels of 25-hydroxyvitamin D and malondialdehyde (MDA) were first measured in patients. A variety of in vitro experiments such as intracellular reactive oxygen species (ROS), cellular viability, migration, and apoptotic assays were then performed to detect the effects of vitamin D or β-catenin silencing on HO-treated melanocytes. Expression of Wnt/β-catenin, Nrf2, apoptotic, and MITF pathways was finally examined using quantitative real-time PCR and western blot. In this study, we initially found that vitamin D insufficiency was closely associated with the severity of oxidative stress in vitiligo patients. Using ex vivo cell models, we further showed that vitamin D positively modulated β-catenin signaling at both translational and posttranslational levels in melanocytes under oxidative stress. Like WNT agonists, vitamin D significantly inhibited ROS accumulation and cell apoptosis in HO-treated melanocytes and promoted their proliferative and migratory activity, while the protective effects of vitamin D against oxidative stress were abolished by β-catenin silencing in melanocytes. Furthermore, β-catenin deficiency also blocked the activation of Nrf2 and MITF as well as the inhibition of apoptosis induced by vitamin D. Taken together, vitamin D insufficiency was associated with severity of oxidative stress in vitiligo patients. Our work also provides new insights into the mechanism of vitamin D against vitiligo, in which vitamin D protects melanocytes against oxidative stress by activating Wnt/β-catenin signaling.
Serum‑free‑medium‑type mesenchymal stem cell culture supernatant exerts a protective effect on A549 lung epithelial cells in acute lung injury induced by H2O2
The aim of the present study was to investigate the mechanisms and protective effect of serum‑free‑medium‑type fetal placental mesenchymal stem cell (fPMSC) culture supernatant on A549 lung epithelial cells following treatment with hydrogen peroxide (H2O2). A549 lung epithelial cells were stimulated with different concentrations of H2O2, and the survival rate of the cells was examined by Cell Counting Kit‑8 (CCK‑8) assay. It was concluded that the H2O2 concentration when the cell survival rate was at 50% was the optimum condition to create an oxidative damage model. Hoechst 33258 staining and western blot analysis was used to validate the A549 lung epithelial cell model. Serum‑free medium was used to culture fPMSCs, and A549 lung epithelial cells treated with H2O2 were cultured with passage 3 MSC supernatant for 24 h. This was termed the supernatant group. Simultaneously, a damage group that was stimulated with H2O2 only, and a vitamin C (VC) group that was treated with H2O2 followed by 100 µmol/l VC in culture medium was also established. The apoptosis of the three groups was detected by flow cytometry, and western blotting was used to detect apoptosis‑associated and nuclear factor erythroid 2‑like 2 (Nrf2)‑kelch‑like ECH‑associated protein 1 (Keap1)‑antioxidant response element/oxidative stress‑associated protein expression. Following the CCK‑8 test, 600 µmol/l H2O2 was selected to stimulate the A549 lung epithelial cells for 24 h, which resulted in a A549 cell survival rate of 56.41±3.31%. Hoechst 33258 staining and western blotting also confirmed the reliability of the model. Flow cytometry demonstrated that the apoptotic rate of the cells in the VC and supernatant groups was reduced compared with that in the injury group. The difference between the supernatant group and the injury group was statistically significant. The detection of apoptosis‑associated proteins by western blotting revealed that the expression of apoptosis regulator BAX and Caspase‑3 in the VC and supernatant groups was decreased. Furthermore, the expression of B‑cell lymphoma‑2 was increased compared with that in the injury group, and the difference was statistically significant (P<0.05). Compared with that in the injury group, the expression of Nrf2 increased in the VC and supernatant groups, whereas the expression of Keap1 was decreased, and the difference was statistically significant (P<0.05). In conclusion, fPMSC supernatant exhibited an antioxidant capacity in A549 lung epithelial cells treated with H2O2 as a model of acute lung injury. The supernatant was found to reduce oxidative damage and inhibit apoptosis.
CQPC11 Isolated from Sichuan Pickled Cabbages Antagonizes d-galactose-Induced Oxidation and Aging in Mice
Chinese pickled cabbage is a traditional fermented food that contains abundant microbes produced during the process of fermentation. In this work, an in vivo animal study was conducted to investigate the effects of a newly isolated lactic acid bacterium ( CQPC11, LP-CQPC11) on d-galactose-induced oxidation and aging in mice. Analysis of the serum and tissue samples of these mice using molecular biology approaches showed that LP-CQPC11 suppressed the decrease in thymus, brain, heart, liver, spleen, and kidney indices caused by oxidation and aging. Furthermore, LP-CQPC11 increased the levels of SOD (superoxide dismutase), GSH-Px (glutathione peroxidase), and GSH (glutathione), whereas it reduced the levels of NO (nitric oxide) and MDA (malondialdehyde) in the serum, liver, and spleen of oxidation and aging mouse models. Pathological observation indicated that LP-CQPC11 alleviated the damage caused by oxidation and aging on the liver and spleen of mice. qPCR analysis indicated that LP-CQPC11 effectively upregulated the expression of (neuronal nitric oxide synthase), (endothelial nitric oxide synthase), (cuprozinc-superoxide dismutase), (manganese superoxide dismutase), (catalase), (heme oxygenase-1), (nuclear factor-erythroid 2 related factor 2), γ (γ-glutamylcysteine synthetase), and (NAD(P)H dehydrogenase [quinone] 1), but downregulated the expression of (inducible nitric oxide synthase) in the mouse liver and spleen. Western blot analysis showed that LP-CQPC11 effectively upregulated SOD1 (), SOD2 (), CAT, GSH1 (c-glutamylcysteine synthetase), and GSH2 (glutathione synthetase) protein expression in mouse liver and spleen tissues. These findings suggest that LP-CQPC11 can effectively prevent d-galactose-induced oxidation and aging in mice, and the effect is even better than that of the commonly used subsp. (LDSB) and vitamin C in the industry. Thus, LP-CQPC11 may be potentially employed as a probiotic strain.
Diterpenoids from the Chinese liverwort Frullania hamatiloba and their Nrf2 inducing activities
Six previously undescribed labdane diterpenoids, frullanians A-F, along with five known diterpenoids, were isolated from the Chinese liverwort Frullania hamatiloba Stephani. Their structures were determined using NMR data, electronic circular dichroism (ECD) calculations as well as the single crystal X-ray diffraction measurement. NAD(P)H: QR (quinone reductase) assay demonstrated that frullanian D and four known compounds displayed antioxidant effect mediated via Nrf2 (Nuclear factor-erythroid 2-related factor 2) induction. Further investigation of the most bioactive frullanian D in MOVAS cells revealed that it ameliorated HO-induced oxidative insults without toxicity by increasing cell viability, attenuating morphological changes, and reducing intracellular ROS production. In addition, frullanian D promoted the nuclear translocation of Nrf2 and upregulated the expressions of antioxidant proteins NQO1 (NAD(P)H quinone oxidoreductase 1) and γ-GCS (γ-glutamyl cysteine synthetase). Docking analysis using MOE software further supported the activation of the Nrf2 pathway by frullanian D.
The dental monomer 2-hydroxyethyl methacrylate (HEMA) causes transcriptionally regulated adaptation partially initiated by electrophilic stress
Cellular responses including cell death are induced by in vitro exposure to the un-polymerized dental monomer 2-hydroxyethyl methacrylate (HEMA). Activation of the Nrf2/ARE signaling pathway has been suggested to mediate the cellular responses. Activation of this pathway may occur either indirectly through generation of increased oxidative stress or through direct binding to cysteine thiols due to the electrophilic properties of HEMA. The objective of this study was to elucidate the potential mechanism of Nrf2/ARE pathway activation after HEMA exposure.
Dimethyl fumarate and vitamin D derivatives cooperatively enhance VDR and Nrf2 signaling in differentiating AML cells in vitro and inhibit leukemia progression in a xenograft mouse model
Acute myeloid leukemia (AML) is one of the deadliest hematological malignancies without effective treatment for most patients. Vitamin D derivatives (VDDs) - active metabolites 1α,25-dihydroxyvitamin D (1,25D2) and 1α,25-dihydroxyvitamin D (1,25D3) and their analogs - are differentiation-inducing agents which have potential for the therapy of AML. However, calcemic toxicity of VDDs limits their clinical use at doses effective against cancer cells in vivo. Here, we demonstrate that in AML cell cultures, moderate pro-differentiation effects of low concentrations of VDDs can be synergistically enhanced by structurally distinct compounds known to activate the transcription factor Nuclear Factor (Erythroid-derived 2)-Like 2 (NFE2L2 or Nrf2). Particularly, dimethyl fumarate (DMF), which is clinically approved for the treatment of multiple sclerosis and psoriasis, strongly cooperated with 1,25D3, PRI-5100 (19-nor-1,25D2; paricalcitol) and PRI-5202 (a double-point modified 19-nor analog of 1,25D2). The pro-differentiation synergy between VDDs (1,25D3 or PRI-5202) and Nrf2 activators (DMF, tert-butylhydroquinone or carnosic acid) was associated with a cooperative upregulation of the protein levels of the vitamin D receptor (VDR) and Nrf2 as well as increased mRNA expression of their respective target genes. These data support the notion that VDDs and Nrf2 activators synergize in inducing myeloid cell differentiation through the cooperative activation of the VDR and Nrf2/antioxidant response element signaling pathways. We have previously reported that PRI-5202 is more potent by approximately two orders of magnitude than 1,25D3 as a differentiation inducer in AML cell lines. In this study, we found that PRI-5202 was also at least 5-fold less calcemic in healthy mice compared to both its direct precursor PRI-1907 and 1,25D3. In addition, PRI-5202 was remarkably more resistant against degradation by the human 25-hydroxyvitamin D-24-hydroxylase than both 1,25D2 and 1,25D3. Importantly, using a xenograft mouse model we demonstrated that co-administration of PRI-5202 and DMF resulted in a marked cooperative inhibition of human AML tumor growth without inducing treatment toxicity. Collectively, our findings provide a rationale for clinical testing of low-toxic VDD/DMF combinations as a novel approach for differentiation therapy of AML.
Black Sesame Seeds Ethanol Extract Ameliorates Hepatic Lipid Accumulation, Oxidative Stress, and Insulin Resistance in Fructose-Induced Nonalcoholic Fatty Liver Disease
The aim of the present study was to investigate the effect of black sesame seeds ethanol extract (BSSEE) against nonalcoholic fatty liver disease (NAFLD) in fructose-fed mice. Mice were fed a standard diet without or with 30% fructose in drinking water for 8 consecutive weeks, while mice in three BSSEE tested groups received different doses of BSSEE (0.5, 1, and 2 mL/kg) once a day from the fifth week to the eighth week. Administration of BSSEE dose-dependently exerted antiobesity and protective effect against metabolism disorder in fructose-fed mice. Histological examinations indicated that administration of BSSEE obviously reduced hepatic lipid accumulation. Insulin tolerance test (ITT) and glucose tolerance test (GTT) along with decreases of serum insulin and glucose levels by BSSEE treatment suggested the improvement of body insulin resistance, and administration of 1 and 2 mL/kg BSSEE mitigated liver insulin resistance as the evidence of downregulated expression of phospho-JNK1/2/3, phospho-NF-κB p65, phospho-IRS1, and phospho-IKK alpha/beta, up-regulated XBP1 expression, and reductions of TNF-α and IL-6 levels. In addition, BSSEE treatment ameliorated hepatic oxidative stress through increasing GSH, vitamin C, and Nrf2 levels, decreasing MDA and NO levels, and enhancing SOD, CAT, and GSH-Px activities. These results demonstrated that BSSEE showed protective effects against NAFLD-related metabolic diseases in fructose-fed mice. Therefore, BSSEE may be a potent dietary supplement to ameliorate the diseases.
Nociceptive behavior induced by chemotherapeutic paclitaxel and beneficial role of antioxidative pathways
Paclitaxel is used for the treatment of several types of cancers. However, one of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy. In this study we examined the engagement of antioxidative signal pathway of the dorsal root ganglion (DRG) in mechanical and thermal hypersensitivity evoked by paclitaxel. Behavioral test was performed to determine mechanical and thermal sensitivity in rats. Western Blot analysis and ELISA were used to examine expression of Nrf2-antioxidant response element (ARE) and superoxide dismutases (SOD); and the levels of products of oxidative stress in the DRG. Our results show that paclitaxel increased mechanical and thermal sensitivity as compared with vehicle control animals. Paclitaxel also impaired Nrf2-ARE and SOD in the DRG and amplified products of oxidative stress, namely 8-isoprostaglandin F2alpha and 8-hydroxy-2'-deoxyguanosine. Systemic administration of SOD mimetic using tempol, antioxidant vitamin C or blocking oxidative pathway using NADPH oxidase inhibitor (GKT137831) attenuated mechanical and thermal hypersensitivity induced by paclitaxel. This inhibitory effect was accompanied with decreases of proinflammatory cytokines (PICs) such as IL-1beta, IL-6 and TNF-alpha in the DRG. In conclusion, the data revealed impairment of Nrf2-ARE and heightened oxidative and PIC signals in the DRG of paclitaxel rats, leading to neuropathic pain. Balancing of reactive oxygen species by supplying antioxidants and/or inhibiting NADPH oxidase appears significant to yield beneficial effects in neuropathic pain conditions after chemotherapeutic paclitaxel.
The Effect of Long-Term Administration of Fatty Acid Amide Hydrolase Inhibitor URB597 on Oxidative Metabolism in the Heart of Rats with Primary and Secondary Hypertension
Fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl] -cyclohexylcarbamate (URB597) may influence redox balance and blood pressure through the modulation of endocannabinoids levels. Therefore, this study aimed to compare changes in oxidative metabolism and apoptosis in the hearts of rats with spontaneous hypertension (SHR) and secondary hypertension (11-deoxycorticosterone acetate; DOCA-salt rats) treated by URB597 via intraperitoneal injection for 14 days. The results showed that URB597 decreased the activity of NADPH and xanthine oxidases in both groups of rats. Moreover, in the heart of SHR rats, URB597 led to an increase of enzymatic and nonenzymatic antioxidant activity and levels (catalase, vitamin C, glutathione/glutathione disulfide [GSH/GSSG]) and upregulation of the thioredoxin system; however, NRf2 expression was downregulated. The opposite effect in relation to Nrf2 activity and the thioredoxin system was observed in DOCA-salt rats after URB597 administration. Despite improvement in antioxidant parameters, URB597 enhanced oxidative modifications of phospholipids (4-hydroxynonenal and isoprostanes) and proteins (carbonyl groups) in SHR heart, whereas 4-hydroxynonenal and carbonyl groups levels decreased in the heart of DOCA-salt rats. Obtained results suggest that examined lipid mediators are involved in peroxisome proliferator-activated receptors (PPAR)-independent and PPAR-dependent modulation of cardiac inflammatory reactions. Furthermore, decreased expression of pro-apoptotic proteins (Bax and caspase 3 and 9) was observed after URB597 administration in the heart of both groups of hypertensive rats, whereas expression of the antiapoptotic protein (Bcl-2) increased in SHR rats. Long-term administration of URB597 altered cardiac redox status depending on the type of hypertension. URB597 enhanced oxidative metabolism and reduced pro-apoptotic factors in the heart of SHR rats, increasing the probability of heart metabolic disorders occurrence or progression.
The Effect of Sea Buckthorn ( L.) Seed Oil on UV-Induced Changes in Lipid Metabolism of Human Skin Cells
Lipids and proteins of skin cells are the most exposed to harmful ultraviolet (UV) radiation contained in sunlight. There is a growing need for natural compounds that will protect these sensitive molecules from damage, without harmful side effects. The aim of this study was to investigate the effect of sea buckthorn seed oil on the redox balance and lipid metabolism in UV irradiated cells formed different skin layers to examine whether it had a protective effect. Human keratinocytes and fibroblasts were subjected to UVA (ultraviolet type A; 30 J/cm² and 20 J/cm²) or UVB (ultraviolet type B; 60 mJ/cm² and 200 mJ/cm², respectively) radiation and treated with sea buckthorn seed oil (500 ng/mL), and the redox activity was estimated by reactive oxygen species (ROS) generation and enzymatic/non-enzymatic antioxidants activity/level (using electron spin resonance (ESR), high-performance liquid chromatography (HPLC), and spectrophotometry). Lipid metabolism was measured by the level of fatty acids, lipid peroxidation products, endocannabinoids and phospholipase A2 activity (GC/MS (gas chromatography/mass spectrometry), LC/MS (liquid chromatography/mass spectrometry), and spectrophotometry). Also, transcription factor Nrf2 (nuclear erythroid 2-related factor) and its activators/inhibitors, peroxisome proliferator-activated receptors (PPAR) and cannabinoid receptor levels were measured (Western blot). Sea buckthorn oil partially prevents UV-induced ROS generation and enhances the level of non-enzymatic antioxidants such as glutathione (GSH), thioredoxin (Trx) and vitamins E and A. Moreover, it stimulates the activity of Nrf2 leading to enhanced antioxidant enzyme activity. As a result, decreases in lipid peroxidation products (4-hydroxynonenal, 8-isoprostaglandin) and increases in the endocannabinoid receptor levels were observed. Moreover, sea buckthorn oil treatment enhanced the level of phospholipid and free fatty acids, while simultaneously decreasing the cannabinoid receptor expression in UV irradiated keratinocytes and fibroblasts. The main differences in sea buckthorn oil on various skin cell types was observed in the case of PPARs-in keratinocytes following UV radiation PPAR expression was decreased by sea buckthorn oil treatment, while in fibroblasts the reverse effect was observed, indicating an anti-inflammatory effect. With these results, sea buckthorn seed oil exhibited prevention of UV-induced disturbances in redox balance as well as lipid metabolism in skin fibroblasts and keratinocytes, which indicates it is a promising natural compound in skin photo-protection.
Effects of Antioxidants in Reducing Accumulation of Fat in Hepatocyte
The progress of the hepatic steatosis (HS), a clinicopathological status, is influenced by cellular oxidative stress, lipogenesis, fatty acid (FA) oxidation, and inflammatory responses. Because antioxidants are gaining attention as potent preventive agents for HS, we aimed to investigate anti-lipogenic effects of the antioxidants vitamin C (VC), N-acetylcysteine (NAC), and astaxanthin (ATX) using hepatocytes. For this, we established an in vitro model using 1 mM oleic acid (OA) and human liver hepatocellular carcinoma (HepG2) cells; 10 μM antioxidants were evaluated for their ability to reduce fat accumulation in hepatocytes. Our results showed that all three antioxidants were effective to reduce fat accumulation for the molecular targets such as reduction in lipid droplets, triglyceride (TG) concentration, reactive oxygen species (ROS) production, and cell apoptosis, as well as in gene expressions of endoplasmic reticulum (ER) stress-related effectors, lipogenesis, and inflammatory cytokines. There were simultaneous increases in diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, cell survival, AMPK phosphorylation, NRF2-related gene expression for cellular defense, and FA β-oxidation. However, among these, ATX more effectively inhibited ER stress and lipogenesis at the intracellular level than VC or NAC. Consequently, ATX was also more effective in inhibiting cell death, lipotoxicity, and inflammation. Our result emphasizes that ATX achieved greater lipotoxicity reduction than VC and NAC.
The Antidiabetic and Antinephritic Activities of via Modulation of Nrf2-Mediated Oxidative Stress in the db/db Mouse
(TM), a valuable edible fungus, contains 19 types of fatty acid, 17 types of amino acid, 6 vitamins, and 7 minerals. The antidiabetic and antinephritic effects of TM and the underlying mechanisms related to oxidative stress were investigated in db/db mice. Eight-week oral administration of metformin (Met) at 0.1 g/kg and TM at doses of 0.2 and 0.4 g/kg decreased body weight, plasma glucose, serum levels of glycated hemoglobin, triglyceride, and total cholesterol and increased serum levels of high-density lipoprotein cholesterol in the mice, suggesting hypoglycemic and hypolipidemic effects. TM promoted glucose metabolism by increasing the levels of pyruvate kinase and hepatic glycogen. It also regulated the levels of inflammatory factors and oxidative enzymes in serum and/or the kidneys of the mice. Additionally, TM increased the expression of nuclear respiratory factor 2 (Nrf2), catalase, heme oxygenase 1, heme oxygenase 2, and manganese superoxide dismutase 2 and decreased the expression of protein kinase C alpha, phosphor-janus kinase 2, phosphor-signal transducer and activator of transcription 3, and phosphor-nuclear factor-B in the kidneys. The results of this study reveal the antidiabetic and antidiabetic nephritic properties of TM via modulating oxidative stress and inflammation-related cytokines through improving the Nrf2 signaling pathway.
Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence
Tocotrienols (T3) have been shown to represent a very important part of the vitamin E family since they have opened new opportunities to prevent or treat a multitude of age-related chronic diseases. The beneficial effects of T3 include the amelioration of lipid profile, the promotion of Nrf2 mediated cytoprotective activity and the suppression of inflammation. All these effects may be the consequence of the ability of T3 to target multiple pathways. We here propose that these effects may be the result of a single target of T3, namely senescent cells. Indeed, T3 may act by a direct suppression of the senescence-associated secretory phenotype (SASP) produced by senescent cells, mediated by inhibition of NF-kB and mTOR, or may potentially remove the origin of the SASP trough senolysis (selective death of senescent cells). Further studies addressed to investigate the impact of T3 on cellular senescence "in vitro" as well as in experimental models of age-related diseases "in vivo" are clearly encouraged.