Endogenous Antioxidant Defense System Research Articles

Optimization in continuous phase-transition extraction of crude flavonoids from finger citron fruit and evaluation on their antiaging activities.

The development of antiaging functional products is a hot topic in the field of functional foods. However, the efficient extraction of functional ingredients is the limiting step for the functional food industry. Continuous phase‐transition extraction (CPE) is a new extraction technique that combines the advantages of Soxhlet extraction and supercritical extraction, which may have a distinct advantage over traditional methods in the extraction of flavonoids. In our study, the Box–Behnken design combined with response surface methodology was used to optimize CPE of crude flavonoids from finger citron fruit. The antiaging activities of finger citron crude flavonoids (FCCF) were evaluated by Caenorhabditis elegans (C. elegans) model. The optimal extraction conditions for CPE were as follows: ethanol concentration 85%, temperature 90°C, time 120 min, and pressure 0.2 MPa. Compared with the heat reflux extraction, the extraction rate and content of FCCF extracted by CPE increased by 24.28% and 33.22% (p < .05), respectively. FCCF extended the lifespan of C. elegans by 14.94% without causing adverse effects on their reproduction and locomotion ability. A further analysis suggested that FCCF prolonged the lifespan of nematodes under normal and oxidative stress by increasing the activity of major enzymes in endogenous antioxidant defense system and reducing the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA). The results confirmed the effectiveness of CPE in extracting crude flavonoids from finger citron fruit, and the extracted FCCF exhibited strong antiaging activities.

Dimethyl fumarate alleviates the nitroglycerin (NTG)-induced migraine in mice

BackgroundOxidative stress and inflammatory pathways are involved in migraine and endogenous antioxidant defense system has a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of the most pharmacologically effective molecules among the fumaric acid esters (FAEs), dimethyl fumarate, nuclear factor E2-related factor 2/antioxidant response element (Nrf-2/ARE) pathway-mediated, in regulating the hypersensitivity in a mouse model of nitroglycerine (NTG)-induced migraine.MethodsMice were orally administered with DMF at the doses of 10, 30, and 100 mg/kg, 5 min after NTG intraperitoneal injections. We performed histological and molecular analysis on the whole brain and behavioral tests after 4 h by NTG-migraine induction. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) subunit p65, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), inducible nitrite oxide synthase (iNOS), cyclooxygenase 2 (COX-2), Nrf-2, manganese superoxide dismutase (Mn-SOD), and heme-oxygenase-1 (HO-1) were detected by Western blot. Tail flick, hot plate, orofacial formalin, and photophobia tests were used to evaluate migraine-like pain and migraine-related light sensitivity.Moreover, we evaluate Nrf-2-dependent mechanism by the in vitro stimulation of cells extracted by trigeminal ganglia with diethylenetriamine/nitric oxide (DETA/NO), a nitric oxide (NO) donor. The cells were pre-treated with DMF and an antagonist of Nrf-2, trigonelline (TR) 2 h before DETA/NO stimulation.ResultsDMF treatment notably reduced histological damage as showed by cresyl violet staining; also, regulating both NF-κB and Nrf-2 pathway, DMF treatment decreased the severity of inflammation and increased the protective antioxidant action. Moreover, the headache was significantly reduced. The protective effect of DMF treatment, via Nrf-2, was confirmed in in vitro studies, through inhibition of Nrf-2 by trigonelline. Cytotoxicity, iNOS, and MnSOD expression were evaluated.ConclusionThese results provided the evidence that DMF, by Nrf-2 modulation, has a protective effect on central sensitization induced by NTG, suggesting a new insight into the potential application of DMF as novel candidates in drug development for migraine.

Nitroxides affect neurological deficits and lesion size induced by a rat model of traumatic brain injury

Research has attributed tissue damage post-traumatic brain injury (TBI) to two-pronged effects, increased reactive oxygen species (ROS) and impairment of endogenous antioxidant defence systems, underpinned by manganese superoxide dismutase (MnSOD). Novel antioxidant nitroxides have been shown to mimic MnSOD to ameliorate oxidative stress related disorders. This study aimed to investigate the effects of two nitroxides, CTMIO and DCTEIO, on the neurological outcomes following moderate TBI in rats induced by a weight drop device. The rats were immediately treated with CTMIO and DCTEIO (40 mM in drinking water) post-injury for up to 2 weeks. The brains were histologically examined at 24 h and 6 weeks post injury. DCTEIO reduced the lesion size at both 24h and 6 weeks, with normalised performance in sensory, motor and cognitive tests at 24h post-injury. Astrogliosis was heightened by DCTEIO at 24h and still elevated at 6 weeks in this group. In TBI brains, cellular damage was evident as reflected by changes in markers of mitophagy and autophagy (increased fission marker dynamin-related protein (Drp)-1, and autophagy marker light chain 3 (LC3)A/B and reduced fusion marker optic atrophy (Opa)-1). These were normalised by DCTEIO treatment. CTMIO, on the other hand, seems to be toxic to the injured brains, by increasing injury size at 6 weeks. In conclusion, DCTEIO significantly improved tissue repair and preserved neurological function in rats with TBI possibly via a mitophagy mechanism. This study provides evidence for DCTEIO as a promising new option to alleviate lesion severity after moderate TBI, which is not actively treated.

Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes.

Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine- or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.

Potential neuroprotection of wheat alkylresorcinols in hippocampal neurons via Nrf2/ARE pathway.

5-n-Alkylresorcinols (ARs) are abundant in wheat bran and potentially antioxidative, although the neuroprotective mechanism is not fully understood. The neuroprotective effect of wheat bran ARs on H2O2-induced neuronal cells and the relationship between neuroprotection and the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant-response element (ARE) pathway were investigated in this study. Seven homologs were identified in the purified ARs by high-performance liquid chromatography-tandem mass spectrometry. Pretreatment with 80 μg mL-1 ARs alleviated 23% HT22 cell death and the up-regulation of intracellular reactive oxygen species level and malondialdehyde under H2O2 stimulation. The neuroprotection effect was proved by the increase in the Nrf2 nuclear location and up-regulation of mRNA and protein expressions of heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase catalytic subunit, and glutamate-cysteine ligase modifier subunit l. Wheat bran ARs displayed a neuroprotective function, possibly by promoting the endogenous antioxidant defense system. ARs may be regarded as a functional food ingredient for preventing neurodegenerative diseases in the future.

Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. Selenomethionine (SeMet) is an organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response by both bolstering the endogenous thioredoxin and glutathione antioxidant defence systems and by directly scavenging damaging oxidant species. This study evaluated the effect of dietary SeMet supplementation within a high fat diet fed apolipoprotein E deficient (ApoE−/-) mouse model of atherosclerosis. Dietary supplementation with SeMet (2 mg/kg) increased the tissue concentration of Se, and the expression and activity of glutathione peroxidase, compared to non-supplemented controls. Supplementation with SeMet significantly reduced atherosclerotic plaque formation in mouse aortae, resulted in a more stable lesion phenotype and improved vessel function. Concurrent with these results, SeMet supplementation decreased lesion accumulation of M1 inflammatory type macrophages, and decreased the extent of extracellular trap release from phorbol myristate acetate (PMA)-stimulated mouse bone marrow-derived cells. Importantly, these latter results were replicated within ex-vivo experiments on cultured neutrophils isolated from acute coronary syndrome patients, indicating the ability of SeMet to alter the acute inflammatory response within a clinically-relevant setting. Together, these data highlight the potential beneficial effect of SeMet supplementation as a therapeutic strategy for atherosclerosis.

Aqueous Partition of Methanolic Extract of Dicranopteris linearis Leaves Protects against Liver Damage Induced by Paracetamol.

This study aimed to determine the antioxidant and hepatoprotective activities of semi-purified aqueous partition obtained from the methanol extract of Dicranopteris linearis (AQDL) leaves against paracetamol (PCM)-induced liver intoxication in rats. The test solutions, AQDL (50, 250, and 500 mg/kg), were administered orally to rats (n = 6) once daily for seven consecutive days followed by the hepatotoxicity induction using 3 g/kg PCM (p.o.). Blood was collected for serum biochemical parameters analysis while the liver was collected for histopathological examination and endogenous antioxidant enzymes analysis. AQDL was also subjected to antioxidant determination and phytochemical analysis. Results obtained show that AQDL possessed high total phenolic content (TPC) value and remarkable radical scavenging activities. AQDL also significantly (p < 0.05) reduced the liver weight/body weight (LW/BW) ratio or serum level of ALT, AST, and total bilirubin while significantly (p < 0.05) increase the level of superoxide dismutase (SOD) and catalase (CAT) without affecting the malondialdehyde (MDA) in the liver indicating its hepatoprotective effect. Phytoconstituents analyses showed only the presence of saponins and triterpenes, but lack of flavonoids. In conclusion, AQDL exerts hepatoprotective activity via its high antioxidant potential and ability to modulate the endogenous enzymatic antioxidant defense system possibly via the synergistic action of saponins and triterpenes.

Effects of Moringa oleifera Leaf Extract on Human Promyelocytic Leukemia Cells Subjected to Oxidative Stress.

Oxidative stress is initiated by reactive oxygen species, the primary factor in many chronic diseases. Moringa oleifera possesses strong antioxidant properties due to the presence of various phytochemicals. In this study, we investigated the effect of M. oleifera leaf extract on markers of oxidative stress in HL60 cells exposed to oxidative stress. HL60 cells were incubated with different concentrations of M. oleifera leaf extract, and cells were harvested for viability assays on days 1, 2, and 3. Antioxidant indexes (malondialdehyde, reduced glutathione, superoxide dismutase, and catalase) were measured on days 1, 2, and 3. Supplementation with the moringa leaf extract at all concentrations resulted in significant reductions in lipid peroxidation in cells that were or were not incubated in an environment with excess oxidative stress. The most significant reduction in this parameter occurred after 24 h of incubation. The results show that reductions seen in this parameter may be due to the modulation of the endogenous antioxidant defense system by extract supplementation. Cell viability was also improved in cells incubated in moringa leaf extract at concentrations of 800 and 1000 μg/mL. This finding, however, did not corroborate with lipid peroxidation results at 1000 μg/mL extract supplementation. Further investigations are needed to clarify the underlying mechanism responsible for increased cell viability at this concentration. We can, therefore, conclude that the moringa leaf extract offered added protection from oxidative stress within the first 24 h, as well as increasing cell viability at certain concentrations.

Microalgae carotenoids intake: Influence on cholesterol levels, lipid peroxidation and antioxidant enzymes.

The objective of this study was to evaluate the effect of carotenoids intake of Scenedesmus obliquus, on lipid peroxidation, the endogenous antioxidant defense system as well as the serum lipid profile in vivo. Male mice were divided into control groups and supplemented with different doses of microalgae carotenoids: 0.25 (MC1) and 2.5 (MC2) mg·kg-1 bodyweight. The lipid profile (total cholesterol, triglycerides, low and high-density lipoprotein) and markers of hepatic toxicity were determined in serum samples. Antioxidant enzymes and thiobarbituric acid reactive substances were determined in the heart, liver, kidneys, and spleen. Both doses used to treat the animals did not show adverse effects by markers of hepatic toxicity. MC1 did not cause significant changes in the serum lipid profile. In contrast, it created a significant reduction in lipid peroxidation of the spleen (46%) as well as an increase in the GR in the heart (40%) and GPx in the kidneys (79%) activity. The MC2 treatment also increased GR (49%) in the heart and GPx (243%) in the heart and kidneys (58%) activity, however, significantly increased levels of lipid peroxidation in the liver (160%) as well as serum triglycerides (60%). According to results, it is suggested that the consumption of S. obliquus carotenoids at the MC1 dose was safe to the animals and could be explored as an alternative to improve the activity of antioxidant enzymes and reduce lipid peroxidation.

Stigmasterol Exerts Neuro-Protective Effect Against Ischemic/Reperfusion Injury Through Reduction Of Oxidative Stress And Inactivation Of Autophagy.

PurposeStroke remains the primary cause of pain, suffering, and death in patients. One of the major thrusts in stroke therapy is to find an effective prevention strategy. Objectives of this study are to testify the neuro-protection effect of stigmasterol in ischemic/reperfusion injury model.MethodsThe dosage-dependent effects (20, 40, and 80 mg/kg) of stigmasterol on physiological behaviors and oxidative stress biomarkers were investigated. Expression and phosphorylation of beclin1, microtubule-associated protein 1 light chain 3 (LC3), adenosine monophosphate-activated protein kinase (AMPK), mTOR, and N-terminal kinase (JNK) were detected.ResultsThe results showed that stigmasterol was able to effectively reduce neurological deficits and infarct damage induced by the ischemic/reperfusion injury, improve histopathology changes, and restore the levels of the endogenous antioxidant defense system in a dose–response mode. Stigmasterol effectively depressed the expression level of beclin1, and the conversion of LC3 I to LC3 II, while promoted the phosphorylation of mTOR, and remarkably inhibited the phosphorylation of AMPK and JNK, as well as the expression of JNK induced by 24 hrs of reperfusion.ConclusionThese findings reveal that stigmasterol has neuro-protective effect against the ischemic/reperfusion injury, possibly associated with reduction of oxidative stress and inactivation of autophagy via AMPK/mTOR and JNK pathways.

Resistance Training, Antioxidant Status, and Antioxidant Supplementation.

Resistance training is known to promote the generation of reactive oxygen species. Although this can likely upregulate the natural, endogenous antioxidant defense systems, high amounts of reactive oxygen species can cause skeletal muscle damage, fatigue, and impair recovery. To prevent these, antioxidant supplements are commonly consumed along with exercise. Recently, it has been shown that these reactive oxygen species are important for the cellular adaptation process, acting as redox signaling molecules. However, most of the research regarding antioxidant status and antioxidant supplementation with exercise has focused on endurance training. In this review, the authors discuss the evidence for resistance training modulating the antioxidant status. They also highlight the effects of combining antioxidant supplementation with resistance training on training-induced skeletal muscle adaptations.

Pachypodol, a Methoxyflavonoid Isolated from Pogostemon cablin Bentham Exerts Antioxidant and Cytoprotective Effects in HepG2 Cells: Possible Role of ERK-Dependent Nrf2 Activation.

Oxidative stress has been implicated in the pathogenesis of many diseases including chronic liver diseases. Nrf2 is a master transcriptional factor regulating the induction of cellular antioxidant defense systems. Here, the Nrf2-activating effect of the crude methanol extract of dried leaves of Pogostemon cablin Bentham was demonstrated by measuring the antioxidant response element (ARE)-driven luciferase activity and pachypodol, 4′,5-dihydroxy-3,3′,7-trimethoxyflavone, was isolated by bioactivity-guided fractionation and further separation using chromatographic techniques. To our knowledge, this is the first study to evaluate the antioxidant and cytoprotective effects of pachypodol in HepG2 cells as well as the underlying molecular mechanisms. Indeed, pachypodol protected HepG2 cells from cell death caused by tert-butylhydroperoxide-induced oxidative stress and also attenuated ROS production. The ability of pachypodol to activate Nrf2/ARE pathway was further confirmed by observing Nrf2 expression in nuclear fraction, mRNA levels of Nrf2 target antioxidants, and cellular glutathione content in HepG2 cells. Extracellular signal-regulated kinase (ERK) is one of the important kinases involved in Nrf2 activation. Pachypodol increased ERK phosphorylation and ERK inhibition by PD98059 totally abrogated the increase in ARE luciferase activity, nuclear Nrf2 accumulation and mRNA levels of antioxidant enzymes by pachypodol. In conclusion, pachypodol isolated from P. cablin can protect hepatocytes from oxidative injury, possibly mediated by enhancing endogenous antioxidant defense system through ERK-dependent Nrf2 activation.

Neuroprotective Effect of Natural Alkaloid Fangchinoline Against Oxidative Glutamate Toxicity: Involvement of Keap1-Nrf2 Axis Regulation.

Oxidative glutamate toxicity plays a vital role in the neurodegeneration diseases, including Alzheimer's diseases (AD). This study set out with the aim to investigate the beneficial effects of fangchinoline (FAN), a natural alkaloid, against glutamate-induced oxidative damage, and to clarify the underlying cellular and biochemical mechanisms. FAN prevented HT22 cells death from oxidative glutamate cytotoxicity in a dose-dependent manner, and significantly attenuated the overproduction of intracellular reactive oxygen species (ROS) and reversed the reduction of superoxide dismutase (SOD) activity induced by glutamate. Further investigations on the underlying mechanisms demonstrated that FAN potently up-regulated the protein level of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO-1), in glutamate-exposed HT22 cells. The protective effects of FAN were almost completely antagonized by inhibitor of Nrf2. Subsequent studies revealed that FAN could down-regulate Kelch-like ECH-associated protein 1 (Keap1) in both mRNA level and protein level. To sum up, our result demonstrated the protective effects of FAN against glutamate-induced oxidative neuronal damage, and for the first time clarified the anti-oxidative mechanisms of FAN involve activating endogenous antioxidant defense system including enhancing SOD activity and regulating Keap1/Nrf-2 antioxidation signaling through modulation of Keap1 expression. Above results shed more light on the molecular mechanisms of FAN's neuroprotective effects, and may provide important clues for the drug development in preventing oxidative stress-associated neurodegenerative diseases.

Dimethyl fumarate alleviates the nitroglycerin (NTG)‐induced migraine in mice

Oxidative stress and inflammatory pathways are involved in nitroglycerin (NTG)‐induced migraine and endogenous antioxidant defense system has a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of the most pharmacologically effective molecules among the Fumaric acid esters (FAEs), dimethyl fumarate (DMF), nuclear factor E2‐related factor 2/antioxidant response element (Nrf‐2/ARE) pathway‐mediated, in regulating the hypersensitivity in a mouse model of NTG‐induced migraine. Mice were orally administered with DMF at the doses of 10, 30 and 100 mg/kg, 5 minutes after NTG intraperitoneal injections. We performed histological and molecular analysis on the whole brainand behavioral tests after 4 h by NTG‐migraine induction. The expression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) subunit p65, nuclear factor of kappa light polypeptide gene enhancer in B‐cells inhibitor alpha (IκBα), inducible nitrite oxide synthase (iNOS), cyclooxygenase 2 (COX‐2), Nrf‐2, manganese superoxide dismutase (Mn‐SOD) and heme‐oxygenase‐1 (HO‐1) were detected by Western blot. Tail flick, hot plate, formalin and photophobia tests were used to evaluate neuropathic pain and migraine‐related light sensitivity. DMF treatment notably reduced histological damage as showed by cresyl violet staining; also, regulating both NF‐κB and Nrf‐2 pathway, DMF treatment decreased the severity of inflammation and increased the protective antioxidant action. Moreover, the headache‐associated neuropathic pain was significantly reduced. These results provide the evidence that DMF has a modulating effect on central sensitization induced by NTG, suggesting a new insight into the potential application of DMF as novel candidates in drug development for migraine.Support or Funding InformationNo fundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Phytochemical constituents and antioxidant activities of two Nigerian retailed polyherbal formulations

Oxidative stress has been implicated in many neurodegenerative diseases, cancers and even ageing processes. This warrants that dietary antioxidants are needed to complement endogenous antioxidant defence system and prevent the development of these chronic diseases. In this study, the phytochemical constituents and antioxidant activities of two retailed Nigerian polyherbal formulations (DRHM® and GCHM®) were evaluated in vitro using DPPH radical scavenging activity, total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP) models. Aside for saponins, glycosides, anthraquinones and anthocyanins which were higher in DRHM and alkaloids which were higher in GCHM, there was no significant (p &lt; 0.05) difference among the amount of other phytochemicals detected in the two polyherbal formulations. The DPPH radical scavenging effect exhibited by DRHM (EC50 = 1.62x106 µg/ml) was significantly (p &lt; 0.05) higher than GCHM (EC50 = 574.5 µg/ml) but that of ascorbic acid (EC50 = 10.58 µg/ml) was significantly (p &lt; 0.05) higher than both DRHM and GCHM. Similarly, GCHM (EC50 = 0.005414 µg/ml) had higher FRAP than DRHM (EC50 = 5.302 µg/ml). However, the TAC of GCHM (EC50 = 1675 µg/ml) was significantly (p &lt; 0.05) higher than that of DRHM (EC50 = 6.101 µg/ml). These findings suggest that the two polyherbal formulations possess appreciable antioxidant potentials which could be attributed to the presence of phytochemicals with antioxidant potentials. The polyherbal formulations can further be explored for possible harnessing of their antioxidant effect in prevention and management of oxidative stress-related disorders and ageing process. Keywords: polyherbal formulations, phytochemicals, antioxidants, DPPH, FRAP, TAC

Combination treatment of podophyllotoxin and rutin promotes mouse Lgr5+ ve intestinal stem cells survival against lethal radiation injury through Wnt signaling.

It has been well established that radiation-induced gastrointestinal injury is manifested through loss of intestinal crypt stem cells and disruption of the mucosal layers, resulting in diarrhoea, weight loss, electrolyte imbalance, infection and mortality. Podophyllotoxin and rutin in combination (G-003M) has been reported to regulate endogenous cellular antioxidant defense systems and inflammatory response. However, the mechanism by which G-003M ameliorates radiation-induced intestinal stem cell (ISC) injury remains unclear. Here, we hypothesize the radioprotective potential of G-003M would amplify the intestinal crypt stem cells through upregulation of Wnt/β-catenin signaling and accelerate the reconstitution of the irradiated intestine. Our results showed significant functional and structural intestine regeneration in irradiated animals following G-003M treatment which resulted in improved animal survival. Immunohistochemical examination revealed an enhancement in Lgr5+ ve crypt stem cells. Increased β-catenin nuclear translocation resulted in upregulation of β-catenin target genes that supported ISC renewal and expansion in G-003M-treated mice, as compared to IR-treated mice. However, G-003M could not rescue the Wnt knockdown cohorts (XAV939 treated) which exhibited greater incidence of intestinal apoptosis, DNA damage and crypt depopulation upon radiation exposure. These findings suggest the involvement of Wnt pathway during G-003M mediated amelioration of IR-induced ISC injury. G-003M also minimised acute inflammation by restricting the infiltration of immune cells into the intestinal venules. Furthermore, G-003M treated animals showed improved anti-tumor response compared to FDA approved Amifostine. Taken together, our findings suggest that G-003M may be used as a potential countermeasure for radiation injuries as well as an adjuvant during anti-cancer therapy.

Edible Insects bio-actives as anti-oxidants: Current status and perspectives.

Background: Oxidative stress mediated cell damage is implicated in ageing and pathogenesis of several diseases including inflammation, rheumatoid arthritis, cancer, cardiovascular and neurodegenerative disorders. Combating the menace of oxidative stress requires improvement in endogenous antioxidant defense system or supplementation with exogenous antioxidants. Although synthetic and plant derived antioxidant food, supplements and molecules have been discovered, insects, the largest class in the animal kingdom remains an unexploited resource. Aim: This present review evaluated insects and their products as sources of natural antioxidants, as wildly documented in literatures. Method: Information related to this topic was retrieved using Pubmed, google scholars and google electronic databases. Insects’ chemical constituents, nutritional and therapeutic benefits in oxidative stress intermediated disorders were emphasized. Results: Insects possess antioxidant compounds which aid in curbing various pathologies. Out of various categories of insects, termites, beetles, grasshopper and blowfly evaluated, the bees, Apis mellifera’s products, royal jelly and Propolis were the most extensively studied and also displayed promising antioxidant activities compared to other insects. In-vitro, in-vivo and clinical studies from the aforementioned literatures, especially the bee category validates the fact that edible insects are a potential source of novel bioactive compounds in chronic diseases and ageing. Conclusion: As numerous diseases are oxidative stress mediated, application of edible insects and their products for culinary and therapeutic purposes is crucial. More researches in this field would aid in the development of insect derived antioxidant molecules.

D3T acts as a pro-oxidant in a cell culture model of diabetes-induced peripheral neuropathy

Diabetes mellitus is one of the most common chronic diseases in the United States and peripheral neuropathy (PN) affects at least 50% of diabetic patients. Medications available for patients ameliorate symptoms (pain), but do not protect against cellular damage and come with severe side effects, leading to discontinued use. Our research group uses differentiated SH-SY5Y cells treated with advanced glycation end products (AGE) as a model to mimic diabetic conditions and to study the mechanisms of oxidative stress mediated cell damage and antioxidant protection. N-acetylcysteine (NAC), a common antioxidant supplement, was previously shown by our group to fully protect against AGE-induced damage. We have also shown that 3H-1,2-dithiole-3-thione (D3T), a cruciferous vegetable constituent and potent inducer of nuclear factor (erythroid-derived 2)- like 2 (Nrf2), can significantly increase cellular GSH concentrations and protect against oxidant species–induced cell death. Paradoxically, D3T conferred no protection against AGE-induced cell death or neurite degeneration. In the present study we establish a mechanism for this paradox by showing that D3T in combination with AGE increased oxidant species generation and depleted GSH via inhibition of glutathione reductase (GR) activity and increased expression of the NADPH generating enzyme glucose-6-phosphate dehydrogenase (G6PD). Blocking NADPH generation with the G6PD inhibitor dehydroepiandrosterone was found to protect against AGE-induced oxidant species generation, loss of viability, and neurite degeneration. It further reversed the D3T potentiation effect under AGE-treated conditions. Collectively, these results suggest that strategies aimed at combating oxidative stress that rely on upregulation of the endogenous antioxidant defense system via Nrf2 may backfire and promote further damage in diabetic PN.

Antiobesity activity and hypolipidemic effect of Proanthocyanidins in rats fed a high fat diet

Proanthocyanidins, also known as condensed tannins, can prevent obesity induced oxidative stress damage in the liver. This study aimed to evaluate the protective effect of Proanthocyanidins on obesity induced oxidative stress and biochemical abnormalities in male rats. Forty -eight male albino rats were divided into three equal groups. Group I (control normal): rats received normal diet. Group II (Obesity): rats received high fat diet (HFD). Group III (Obesity+ Proanthocyanidins): rats received Proanthocyanidins (50 mg/kg.b.wt.) orally for two months after induction of obesity. The obtained results showed significant increase in serum insulin, lipids profile (total cholesterol and triacylglycerols) concentrations, liver L-MDA in addition to up regulation of leptin and Nuclear factor kappa B (NF-κB) gene expression level in liver tissues of obese rats. However, liver catalase activity and GSH concentration were markedly decreased. These results suggested that, Proanthocyanidins treatment exerts a protective effect on obesity by reduction of oxidative stress, inflammation and hyperlipidemia in rats through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidant defense system mechanisms.

Moringa Oleifera improve lipid metabolic disorders in obesity induced oxidative stress in rats

Moringa Oleifera leaves have therapeutic functions such as antioxidant, anti-bacterial, anti-viral, anti-cancer, anti-inflammatory, anti-allergic and anti-diabetic. The purpose of this study was to evaluate the protective effect of Moringa Oleifera on obesity induced oxidative stress and biochemical abnormalities in male rats. Forty-eight male albino rats were divided into three equal groups. Group I (control normal): rats fed normal diet. Group II (Obesity): rats received high fat diet (HFD).Group III (Obesity+ Moringa oleifera): rats received Moringa Oleifera (600 mg/kg.b.wt.) orally for two months after induction of obesity. The obtained results showed significant increase in levels of serum insulin, lipids profile (total cholesterol and triacylglycerols), liver L-MDA in addition to up regulation of Leptin and Nuclear factor kappa B (NF-κB) gene expression level in obese rats. However, liver catalase activity and GSH concentration were markedly decreased. Moringa Oleifera treatment to high fat diet-induced obesity in rats caused significant improvement of all previous parameters towards its normal ranges. These results suggested that, Moringa Oleifera treatment exerts a protective effect on obesity by reduction of oxidative stress markers, inflammation and hyperlipidemia in rats through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidant defense system mechanisms.