Amelioration Of Oxidative Stress Research Articles

Berberine and/or zinc protect against methotrexate-induced intestinal damage: Role of GSK-3β/NRF2 and JAK1/STAT-3 signaling pathways

AimThe present study was undertaken to elucidate the potential protective mechanism of berberine (BBR) and/or zinc (Zn) against methotrexate (MTX)-induced intestinal injury. MethodsFive groups of rats were assigned; normal group (received vehicle), MTX group (20 mg/kg; i.p. single dose), and the other three groups received a single daily oral dose of BBR (50 mg/kg), Zn (5 mg/kg), and BBR plus Zn respectively, for 5 days before MTX and 5 days after. ResultsOur results emphasized the toxic effect of MTX on rat's intestine as shown by disturbance of oxidant/antioxidant status, down-regulation of NRF2, SIRT1, FOXO-3, Akt, and mTOR expressions, along with up-regulation of GSK-3β, JAK1, and STAT-3 expressions. Besides, severe intestinal histopathological changes were also observed. On the contrary, BBR and/or Zn produced marked protection against MTX-induced intestinal toxicity via amelioration of oxidative stress, improving NRF2, SIRT1, FOXO-3, GSK-3β, Akt, mTOR, JAK1, and STAT-3 alterations. Moreover, our treatments significantly restored histopathological abnormalities. Interestingly, combination therapy of BBR plus Zn exhibited higher effectiveness than mono-therapy. SignificanceBBR plus Zn could be used as a novel therapy for the treatment of MTX-induced intestinal damage through modulation of GSK-3β/NRF2, Akt/mTOR, JAK1/STAT-3, and SIRT1/FOXO-3 signaling pathways.

Cardioprotective Effects of PPARβ/δ Activation against Ischemia/Reperfusion Injury in Rat Heart Are Associated with ALDH2 Upregulation, Amelioration of Oxidative Stress and Preservation of Mitochondrial Energy Production.

Accumulating evidence support the cardioprotective properties of the nuclear receptor peroxisome proliferator activated receptor β/δ (PPARβ/δ); however, the underlying mechanisms are not yet fully elucidated. The aim of the study was to further investigate the mechanisms underlying PPARβ/δ-mediated cardioprotection in the setting of myocardial ischemia/reperfusion (I/R). For this purpose, rats were treated with PPARβ/δ agonist GW0742 and/or antagonist GSK0660 in vivo and hearts were subjected to ex vivo global ischemia followed by reperfusion. PPARβ/δ activation improved left ventricular developed pressure recovery, reduced infarct size (IS) and incidence of reperfusion-induced ventricular arrhythmias while it also up-regulated superoxide dismutase 2, catalase and uncoupling protein 3 resulting in attenuation of oxidative stress as evidenced by the reduction in 4-hydroxy-2-nonenal protein adducts and protein carbonyl formation. PPARβ/δ activation also increased both mRNA expression and enzymatic activity of aldehyde dehydrogenase 2 (ALDH2); inhibition of ALDH2 abrogated the IS limiting effect of PPARβ/δ activation. Furthermore, upregulation of PGC-1α and isocitrate dehydrogenase 2 mRNA expression, increased citrate synthase activity as well as mitochondrial ATP content indicated improvement in mitochondrial content and energy production. These data provide new mechanistic insight into the cardioprotective properties of PPARβ/δ in I/R pointing to ALDH2 as a direct downstream target and suggesting that PPARβ/δ activation alleviates myocardial I/R injury through coordinated stimulation of the antioxidant defense of the heart and preservation of mitochondrial function.

Pt-Coated Au Nanoparticle Toxicity Is Preferentially Triggered Via Mitochondrial Nitric Oxide/Reactive Oxygen Species in Human Liver Cancer (HepG2) Cells.

Reactive nitrogen species (RNS) that are formed from the reaction of versatile nitric oxide (NO) with reactive oxygen species (ROS) have been less explored in potential cancer therapy. This may be partly due to the fewer available agents that could induce NO in cells. Here, we report platinum-coated gold nanoparticles (Pt-coated Au NPs; 27 ± 20 nm) as a strong inducer of NO (assessed by live-cell imaging under NO-specific DAR-1 probe labeling and indirectly using a Griess reagent) in human liver carcinoma (HepG2) cells. In addition to NO, this study found a critical role of ROS from mitochondrial sources in the mechanism of toxicity caused by Pt-coated Au NPs. Cotreatment with a thiol-replenishing general antioxidant NAC (N-acetyl cysteine) led to significant amelioration of oxidative stress against NP-induced toxicity. However, NAC did not exhibit as much ameliorative potential against NP-induced oxidative stress as the superoxide radical (O2•–)-scavenging mitochondrial specific antioxidant mito-TEMPO did. The higher protective potential of mito-TEMPO in comparison to NAC reveals mitochondrial ROS as an active mediator of NP-induced toxicity in HepG2 cells. Moreover, the relatively unaltered NP-induced NO concentration under cotreatment of GSH modulators NAC and buthionine sulfoximine (BSO) suggested that NO production due to NP treatment is rather independent of the cellular thiols at least in HepG2 cells. Moreover, toxicity potentiation by exogenous H2O2 again suggested a more direct involvement of ROS/RNS in comparison to the less potentiation of toxicity due to GSH-exhausting BSO. A steeper amelioration in NP-induced NO and ROS and, consequently, cytotoxicity by mito-TEMPO in comparison to NAC reveal a pronounced role of NO and ROS via the mitochondrial pathway in the toxicity of Pt-coated Au NPs in HepG2 cells.

Dietary supplementation of methionine mitigates oxidative stress in broilers under high stocking density

We aimed to investigate whether dietary supplementation of methionine could mitigate intestinal oxidative injury in broilers under high stocking density (HSD). In the grower phase (d 22–42), 576 broilers with similar body weight were randomly chosen and divided into 8 groups in a 2 × 4 factorial experiment. Two different stocking densities (14 and 20 broilers per m2) were tested with 4 different methionine levels: 0.35%, 0.4%, 0.45%, or 0.5%. Intestinal morphological and oxidative stress markers were assessed at the end of the test period. The results showed that mortality of broilers was significantly higher in the HSD group fed 0.35% methionine diet than the other groups, which was reversed by supplementation with 0.40% to 0.50% methionine. HSD significantly decreased feed intake and daily weight gain. HSD treatment significantly decreased T-AOC, activity of GPX (P < 0.01) and increased the level of PCO (P < 0.01), MDA (P = 0.052) of plasma. The decreased glutathione peroxidase activity in the liver and jejunum caused by HSD was alleviated by additional methionine. Supplementation of methionine increased the ration of GSH/GSSG in the plasma. The jejunum villus height and ratio of villus height to crypt depth under low stocking density conditions with 0.40% methionine diet were the highest, whereas the 0.45% methionine group was the highest under HSD conditions. Thus, additional dietary supplementation of methionine mitigates oxidative stress in broilers under HSD conditions and 0.40% to 0.45% methionine can be applied in cage rearing broiler production for amelioration of oxidative stress caused by HSD.

In vivo anti-inflammatory, anti-nociceptive, and in vitro antioxidant efficacy, and acute oral toxicity effects of the aqueous and methanolic stem bark extracts of Lonchocarpus eriocalyx (Harms.)

Oxidative stress causes and drives many agonising inflammatory conditions, which cause disability, financial burden, and emotional stress. The current anti-inflammatory, analgesic, and antioxidant agents are associated with adverse effects, inaccessibility, high costs, and low efficacies, thereby warranting the need for alternatives, especially from natural sources. Lonchocarpus eriocalyx plant is traditionally used in Kenyan communities to treat various inflammatory and oxidative stress-associated diseases; however, its pharmacologic efficacy and safety have not been empirically validated, hence this study. The in vivo antiinflamatory and antinociceptive efficacy of the aqueous and methanolic stem bark extracts of L. eriocalyx were determined using the xylene-induced ear oedema, and the acetic acid-induced writhing techniques, respectively, in experimental mice. Also, in vitro antioxidant activities of the studied plant extracts were investigated using the Thiobarbituric acid test for lipid peroxidation, 1, 1-diphenyl -2-picrylhydrazyl (DPPH), and Ferric reducing antioxidant power standard assay methods. Moreover, the studied extracts' acute oral toxicity effects were investigated according to the Organisation for Economic Corporation and Development (OECD) guidelines. The studied plant extracts showed significant dose-dependent inhibitions of oedema and writhing, depicting their anti-inflammatory and antinociceptive efficacy. Besides, the extracts revealed significant inhibitions of in vitro lipid peroxidation in varying degrees. Notably, the extracts demonstrated very strong DPPH radical scavenging and ferric-reducing antioxidant efficacies. Furthermore, the two studied plant extracts did not elicit acute oral toxicity, with LD50 values of >2000 mg/kg BW, hence were considered safe. The anti-inflammatory, antinociceptive, and in vitro antioxidant efficacies of these extracts were attributed to antioxidant phytocompounds with diverse pharmacologic effects, especially through the amelioration of oxidative stress. Further studies on the anti-inflammatory, antinociceptive and antioxidant mechanism(s) and isolation and characterisation of responsible compounds are encouraged to spur the development of affordable, accessible, safe, and efficacious drugs.

Amelioration of Oxidative Stress Through Supplementation of Self- formulated Anti-oxidant Mixture for Early Recovery and Prophylaxis of Bovine Mastitis in Kashmir Valley

Background: During lactation, mammary epithelial cells exhibit a high metabolic rate and thus produce large amounts of ROS and lipid peroxides in vivo (Jin et al. 2014; Ganguly et al., 2016). A surplus of ROS and the absence of optimal amounts of antioxidants (which neutralize these free radicals or ROS) results in oxidative stress (Lykkesfeldt and Svendsen, 2007). A clinical study was undertaken on Bovine Mastitis in Kashmir valley to study the relation between oxidative stress and clinical mastitis. An attempt was also made to see the effect of supplementation of self-formulated anti-oxidant trace mineral mixture on recovery and prophylaxis of Bovine mastitis through amelioration of oxidative stress.Methods: The oxidative stress was assessed through estimation of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO). In addition, blood trace mineral status for copper (Cu), zinc (Zn), manganese (Mn) and selenium (Se) were also assessed in mastitic animals and compared with normal healthy lactating animals. The utility of anti-oxidants in clinical management of mastitis was measured through response to treatment with trace minerals like Cu, Zn, Mn and Se in addition to conventional antibiotic therapy. Two groups of mastitic animals received two therapeutic regimens. Group I animals received antibiotics and self formulated anti-oxidant mixture at therapeutic doses while as Group II animals received only antibiotics (at same dose rate and frequency). Clinical recovery was assessed on the basis of CMT point score, milk somatic cell count and milk biochemistry. For prophylactic study, forty recently parturated lactating animals having susceptibility to occurrence of mastitis were divided into two groups of twenty animals each. One group of animals was supplemented with self-formulated anti-oxidant mixture at prophylactic doses for a period of thirty days so as to see the effect of supplementation on oxidative stress parameters and occurrence of clinical mastitis.Result: A significant decrease was found in the values of SOD, catalase, GSH and Cu, Zn, Mn and Se but a significant increase was found in the values of MDA and NO in clinical cases of mastitis as compared to healthy control group. Therapeutic regimen I proved efficacious than the therapeutic regimen II in treatment of clinical mastitis with higher recovery rates and lesser number of mean days required for recovery in group I than group II animals. The efficacy of prophylactic treatment was monitored by occurrence of mastitis during the course of therapy and one month after therapy. Group I animals did not suffer from clinical mastitis and showed considerable improvement in oxidative stress parameters, milk SCC and blood trace mineral status as compared to group II.

Effects of Acupuncture on Oxidative Stress Amelioration via Nrf2/ARE-Related Pathways in Alzheimer and Parkinson Diseases.

Oxidative stress is responsible for the pathogeneses of various diseases. Mitochondrial dysfunction, impaired DNA repair, and cellular damage followed by oxidative stress contribute to neurodegenerative diseases, such as Alzheimer disease (AD) and Parkinson disease (PD). Acupuncture is a traditional therapy that has been practiced for >3000 years in Asia. Many studies have demonstrated that acupuncture has notable antioxidative, anti-inflammatory, and antiapoptotic effects. However, the exact mechanism remains unclear. Nuclear factor erythroid 2-related factor (Nrf2) is crucial in regulating the redox equilibrium. Activated Nfr2 translocates into the nucleus, binds to the antioxidant response element (ARE), and initiates antioxidative enzyme transcription. In this review, we demonstrated the effects of acupuncture on oxidative stress amelioration in AD and PD animal models through Nrf2/ARE pathway activation and Nrf2/ARE-related pathway regulation. Thus, acupuncture could be a therapeutic option for AD and PD.

Melissa officinalis L. as a Nutritional Strategy for Cardioprotection.

This review aimed to provide a summary on the traditional uses, phytochemistry, and pharmacological activities in the cardiovascular system and cardiotoxicity of Melissa officinalis (MO), with the special emphasis on the protective mechanisms in different cardiovascular pathologies. MO is a perennial aromatic herb commonly known as lemon balm, honey balm, or bee balm, which belongs to Lamiaceae family. Active components are mainly located in the leaves or essential oil and include volatile compounds, terpenoid (monoterpenes, sesquiterpenes, triterpenes), and polyphenolic compounds [rosmarinic acid (RA), caffeic acid, protocatechuic acid, quercitrin, rhamnocitrin, luteolin]. For centuries, MO has been traditionally used as a remedy for memory, cognition, anxiety, depression, and heart palpitations. Up until now, several beneficial cardiovascular effects of MO, in the form of extracts (aqueous, alcoholic, and hydroalcoholic), essential oil, and isolated compounds, have been confirmed in preclinical animal studies, such as antiarrhythmogenic, negative chronotropic and dromotropic, hypotensive, vasorelaxant, and infarct size–reducing effects. Nonetheless, MO effects on heart palpitations are the only ones confirmed in human subjects. The main mechanisms proposed for the cardiovascular effects of this plant are antioxidant free radical–scavenging properties of MO polyphenols, amelioration of oxidative stress, anti-inflammatory effects, activation of M2 and antagonism of β1 receptors in the heart, blockage of voltage-dependent Ca2+ channels, stimulation of endothelial nitric oxide synthesis, prevention of fibrotic changes, etc. Additionally, the main active ingredient of MO-RA, per se, has shown substantial cardiovascular effects. Because of the vastness of encouraging data from animal studies, this plant, as well as the main ingredient RA, should be considered and investigated further as a tool for cardioprotection and adjuvant therapy in patients suffering from cardiovascular diseases.

Melatonin Attenuates Sepsis-Induced Small-Intestine Injury by Upregulating SIRT3-Mediated Oxidative-Stress Inhibition, Mitochondrial Protection, and Autophagy Induction.

Melatonin reportedly alleviates sepsis-induced multi-organ injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1–7). However, whether melatonin attenuates small-intestine injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of mice and ameliorated multiple-organ injury (lung/liver/kidney/small intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1. We confirmed this mechanistic effect in a CLP-induced sepsis model of intestinal SIRT3 conditional-knockout mice, and found that melatonin preserved mitochondrial function and induced autophagy of small-intestine epithelial cells; these effects were dependent on SIRT3 activation. This study has shown, to the best of our knowledge, for the first time that melatonin alleviates sepsis-induced small-intestine injury, at least partially, by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial-function protection, and autophagy induction.

Protocatechuic acid attenuates chronic unpredictable mild stress induced-behavioral and biochemical alterations in mice

Amelioration of oxidative stress via promoting the endogenous antioxidant system and enhancement of monoamines in brain were the important underlying antidepressant mechanism of protocatechuic acid (PCA). The aim of the present study is to explore the potential antidepressant mechanism(s) PCA in chronic unpredictable mild stress (CUMS) mice. Mice were subjected to CUMS protocol for 4 weeks, and administered with PCA (100 and 200 mg/kg) and fluoxetine (20 mg/kg) for 24 days (from day 8th to 31st). Behavioral (sucrose preference, immobility time, exploratory behavior), and biochemical alterations such as serum corticosterone, brain derived neurotrophic factor (BDNF), inflammatory cytokines, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and antioxidants parameters were investigated. Experimental findings revealed that CUMS subjected mice exhibited significant impairment in behavioral alterations, such as increased immobility time, impaired preference to the sucrose solution, BDNF levels and, serum corticosterone, cytokines, malondialdehyde (MDA) formation with impaired antioxidants in the hippocampus and cerebral cortex. Administration of PCA to CUMS mice attenuated the immobility time, serum corticosterone, cytokines TNF-α, and IL-6, MDA formation and improved sucrose preference, including restoration of BDNF level. Thus, the present findings demonstrated the antidepressant potential of PCA which is largely achieved probably through maintaining BDNF level, and by modulation of the oxidative stress response, cytokines systems, and antioxidant defense system in mice.

Iron (Fe3+)-mediated redox responses and amelioration of oxidative stress in cadmium (Cd2+) stressed mung bean seedlings: a biochemical and computational analysis

Iron (Fe3+)-mediated redox responses and amelioration of oxidative stress in cadmium (Cd2+) stressed mung bean seedlings: a biochemical and computational analysis

Metabolomic analysis of the egg yolk during the embryonic development of broilers

The chicken egg yolk, which is abundant with lipids, proteins, and minerals, is the major nutrient resource for the embryonic development. In fact, the magnitude and type of yolk nutrients are dynamically changed during the chicken embryogenesis to meet the developmental and nutritional requests at different stages. The yolk nutrients are metabolized and absorbed by the yolk sac membrane and then used by the embryo or other extraembryonic tissues. Thus, understanding the metabolites in the yolk helps to unveil the developmental nutritional requirements for the chicken embryo. In this study, we performed ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) analysis to investigate the change of metabolites in the egg yolk at embryonic (E) 07, E09, E11, E15, E17, and E19. The results showed that 1) the egg yolk metabolites at E07 and E09 were approximately similar, but E09, E11, E15, E17, and E19 were different from each other, indicating the developmental and metabolic change of the egg yolk; and 2) most of the metabolites were annotated in amino acid metabolism pathways from E11 to E15 and E17 to E19. Especially, arginine, lysine, cysteine, and histidine were continuously increased during the embryonic development, probably because of their effects on the growth promotion and oxidative stress amelioration of the embryo. Interestingly, the ferroptosis was found as one of major processes occurred from E15 to E17 and E17 to E19. Owing to the upregulated expression of acyl-CoA synthetase long-chain family member 4 detected in the yolk sac, we assumed that the ferroptosis of the yolk sac was perhaps caused by the accumulation of reactive oxygen species, which was induced by the large amount of polyunsaturated fatty acids and influx of iron in the yolk. Our findings might offer a novel understanding of embryonic nutrition of broilers according to the developmental changes of metabolites in the egg yolk and may provide new ideas to improve the health and nutrition for prehatch broiler chickens.

Amelioration of oxidative stress, inflammation and liver function by nutraceuticals in rat model of hepatic cancer initiation induced by N-nitrosodiethylamine

Introduction:Nutraceuticals might serve as protective agent against liver cancer induced by pro-cancerous chemicals that initiate high oxidative stress, inflammation and affect DNA integrity. The aim of the present research was to study the prevention of hepatocellular carcinoma initiation induced by N-nitrosodiethylamine (NDEA) through treatment by nutraceuticals.Methods:Two nutraceuticals were prepared; the first (NI) was a mixture of different extracts of green tea, wheat germ and tomato, the second one (NII) was composed of extracts mixture of broccoli, hazelnuts and carrot. Total flavonoids and flavonols were determined in the nutraceuticals. Four groups of rats were run; the first served as control normal, the other three groups were treated by intraperitoneal injection of NDEA, one of these groups was designated as control NDEA, the other two groups (test groups) were treated daily with oral doses of NI and NII, respectively. The experiment continued for 8 weeks. Plasma transaminases, alkaline phosphatase and catalase activities, total protein, albumin, malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) along with liver MDA level and catalase activity were assessed.Results:NI showed higher flavonoids and lower flavonols than NII (P&lt; 0.05). High oxidative stress and inflammation biomarkers, liver dysfunction, reduced plasma albumin and total protein were demonstrated in control NDEA compared to control normal (P&lt; 0.05). Test groups showed significant improvement in all parameters (P&lt; 0.05) compared to NDEA control. NI was superior in improving plasma transaminases and catalase activities, MDA and TNF-α levels and liver catalase activity compared to NII (P&lt; 0.05).Conclusion:Both NI and NII might prevent liver cancer initiation during exposure to carcinogenic agents, NI being superior to NII.

Hepatoprotective effects of Tagetes lucida root extract in carbon tetrachloride-induced hepatotoxicity in Wistar albino rats through amelioration of oxidative stress

Context The roots of Tagetes lucida Cav. (Asteraceae) have antioxidant and antimicrobial properties. Objective This study aimed to examine the hepatoprotective effects of T. lucida roots ethanol extract (TLRE) using carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Materials and methods The active ingredients of TLRE were identified by high-performance liquid chromatography, infra-red spectrum, and mass spectrometric procedures. Ninety rats were distributed into four main groups: positive, therapeutic, protective, and negative group. The therapeutic group was implemented using CCl4 (a single dose of 2 mL/kg) before TLRE or silymarin administration. Meanwhile, the protective group was implemented by administering CCl4 (a single dose of 2 mL/kg) after force-feeding TLRE or silymarin. Each therapeutic and protective group was divided into three subgroups: force-fed with saline, TLRE (500 mg/kg), and silymarin (25 mg/kg). The positive group was split into two subgroups that were force-fed TLRE and silymarin. Positive, therapeutic, and protective groups were compared to the negative group (untreated rats). CCl4, TLRE, and silymarin were orally administrated using a gastric tube. Results In the therapeutic and protective groups, TLRE significantly reduced liver enzymes, i.e., aspartate aminotransferase (12.47 and 6.29%), alanine aminotransferase (30.48 and 11.39%), alkaline phosphatase (17.28 and 15.90%), and cytochrome P450-2E1 (39.04 and 48.24%), and tumour necrosis factor-α (53.72 and 53.72%) in comparison with CCl4-induced hepatotoxicity controls. Conclusions TLRE has a potent hepatoprotective effect with a good safety margin. After a repeated study on another type of small experimental animal, their offspring, and an experiment with a large animal, this study may lead to clinical trials.

Hepatoprotective effect of kaempferol glycosides isolated from Cedrela odorata L. leaves in albino mice: involvement of Raf/MAPK pathway.

Background and purpose:Paracetamol is the most implicated xenobiotic in inducing hepatotoxicity. Our study aimed to determine the impact of some kaempferol glycosides isolated from the leaves of Cedrela odorata L. on paracetamol hepatotoxicity.Experimental approach:The methanolic extract of dried leaves of C. odorata L. was subjected to the combination of spectroscopic methods (1H and 13CNMR). Six kaempferol glycosides were isolated: kaempferol-3-O-β-D-glycopyranoside (astragalin), kaempferol-3-O-β-L-rhamnopyranoside, kaempferol-3-O-β-D-rutinoside, kaempferide-3-O-β-D-rutinoside, kaempferide-3-O-β-Drutinosyl-7-O-β-D-rhamnopyranoside, and kaempferol-3-O-β-D- rutinosyl-7-O-a-D-arabinopyranoside. Fifty-four female Swiss Albino mice were divided randomly into 9 groups including (1) control negative (1 mL/kg saline; IP), (2) control positive (paracetamol 300 mg/kg; IP), (3) silymarin 50 mg/kg (IP). Animals of groups 4-9 were injected with 6 different samples of isolated compounds at 100 mg/kg (IP). One h later, groups 3-9 were injected with paracetamol (300 mg/kg IP). Two h later, tissue samples were taken from all animals to assess nitrotyrosine, c-Jun N-terminal protein kinase (c-JNK), Raf -1kinase, and oxidative stress biomarkers viz. reduced glutathione (GSH) and malondialdehyde (MDA).Findings/Results:Isolated glycosides had a prominent anti-apoptotic effect via inhibition of c-JNK and Raf-1 kinase. They also exerted a powerful antioxidant effect by modulating the oxidative stress induced by paracetamol via increasing GSH, reducing MDA and nitrotyrosine concentrations compared to positive control. The glycoside (1) showed a better effect than silymarin (standard) in ameliorating the formation of nitrotyrosine, Raf-1 kinase, c-JNK, and GSH.Conclusion and implication:Kaempferol glycosides isolated for the first time from C. odorata L. leaves exerted antioxidant and antiapoptotic effects via amelioration of oxidative stress and inhibition of Raf/MAPK pathway.

The nephroprotective potential of diosgenin against ischemia-reperfusion acute renal damage via suppression of oxidative stress and downregulating inflammatory mediators

ABSTRACT Renal ischemia/reperfusion injury (I/R) is caused by short impairment of the blood supply to the kidney. Acute renal damage (ARD) is still a major problem in today’s clinical practice. Diosgenin (DG), a steroidal sapogenin mainly present infenugreek, yams, Costus species in high amounts. DG as a leading phytoconstituents is beneficial in several disease conditions due to its multifunction including antioxidant, hypolipidemic, anti-inflammatory, hypoglycemic, anticancer and anti-proliferative effects. The purpose of this study was to investigate the nephroprotective potential of DG on ischemia-reperfusion induced kidney damage in rats. Thirty male Wistar rats were divided into five groups. DG was given orally at doses of 20, 40 and 80 mg/kg for 10 days. On day 11th ARD was induced by unilateral ischemia for 45 min followed by 24-hour reperfusion. The levels of creatinine, blood urea nitrogen, total proteins, pro-inflammatory cytokines were decreased in DG + I/R rats compared to NC rats, along with a significant amelioration of oxidative stress. Histopathological analysis exhibited less histological damage in DG + I/R rats as compared with NC rats. Pretreatment of rats with DG (40 and 80 mg/kg) was able to improve these damages significantly, though DG (20 mg/kg) was insignificantly effective. In conclusion, DG proved nephroprotective potential against kidney damage induced by I/R injury via mitigation of inflammation, oxidative stress, and histopathologic injuries.

Chicoric Acid Ameliorates Nonalcoholic Fatty Liver Disease via the AMPK/Nrf2/NFκB Signaling Pathway and Restores Gut Microbiota in High-Fat-Diet-Fed Mice.

This study examines the effects of chicoric acid (CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat-diet- (HFD-) fed C57BL/6 mice. CA treatment decreased body weight and white adipose weight, mitigated hyperglycemia and dyslipidemia, and reduced hepatic steatosis in HFD-fed mice. Moreover, CA treatment reversed HFD-induced oxidative stress and inflammation both systemically and locally in the liver, evidenced by the decreased serum malondialdehyde (MDA) abundance, increased serum superoxide dismutase (SOD) activity, lowered in situ reactive oxygen species (ROS) in the liver, decreased serum and hepatic inflammatory cytokine levels, and reduced hepatic inflammatory cell infiltration in HFD-fed mice. In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells. In particular, we identified AMPK as an activator of Nrf2 and an inactivator of NFκB. CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFκB protein level both in HFD mice and PA-treated HepG2 cells. Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA. Similarly, Nrf2 inhibitor ML385 partly blocked the regulation of antioxidative genes and ROS overproduction by CA in PA-treated HepG2 cells. Interestingly, high-throughput pyrosequencing of 16S rRNA suggested that CA could increase Firmicutes-to-Bacteroidetes ratio and modify gut microbial composition towards a healthier microbial profile. In summary, CA plays a preventative role in the amelioration of oxidative stress and inflammation via the AMPK/Nrf2/NFκB signaling pathway and shapes gut microbiota in HFD-induced NAFLD.

Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice.

Oxidative stress plays a pivotal part in the manifestation of neuroinflammation, which further leads to neurodegenerative diseases like Alzheimer's disease (AD). Systemic administration of lipopolysaccharide (LPS) induces neuroinflammation resulting in memory impairment (MI) and cognitive decline. In this study, we evaluated whether prophylactic administration of Rosmarinic acid (RA), a naturally occurring compound, exerts a neuroprotective effect in LPS-induced MI and cognitive decline. Herein, Swiss albino mice were pre-treated with RA (0.5mg/kg and 1mg/kg i.p.) for 28 days and were intermittently exposed to LPS (0.25mg/kgi.p.) for 7 days. LPS caused poor memory retention and increased cognitive decline in Morris water maze (MWM) and Y maze paradigms respectively. Additionally, LPS increased oxidative stress which was denoted by a decrease in superoxide dismutase (SOD) activity, decrease in reduced glutathione (GSH) levels, and increased lipid peroxidation in the brain. Imbalance in the cholinergic system was analyzed by measuring the acetylcholinesterase (AChE) activity. Pre-treatment with RA improved memory and behavioral disturbances by alleviating oxidative stress and AChE activity. LPS augmented levels of tumor necrosis factor (TNF-α), interleukin (IL)-6, caspase-3, and c-Jun. Pre-treatment with RA revitalized the elevated levels of proinflammatory cytokines and apoptotic proteins. In conclusion, this study showcases the amelioration of MI by RA in LPS-challenged memory and cognitive decline, which could be credited to its anti-oxidant effect, inhibitory effect on both proinflammatory cytokines and apoptotic regulators, and reduction in AChE activity.

Antifibrotic Activity of Phaleria macrocarpa Extract in Rat Liver-fibrosis Model: Focus on Oxidative Stress Markers, TGF-β1 and MMP-13

AIM: This study was aimed to determine the antifibrotic activity of Phaleria macrocarpa (PM) extract in liver fibrosis (LF) and its possible mechanism in the rat model.&#x0D; METHODS: Sprague Dawley male rats were injected with 2 mL/kg BW of carbon tetrachloride intraperitoneally twice a week for 2 weeks, followed by 1 mL/kg BW for 6 weeks. Afterward, the treatments began from the 3rd week: Silymarin 100 mg/kg BW/day, standardized PM extract (Proliverenol) 75 or 150 mg/kg BW/day orally. Rats were sacrificed in the 8th week. Blood and liver were collected to analyze liver function, liver damage and fibrosis marker, oxidative stress markers, pro-fibrogenic cytokine, and antifibrotic marker.&#x0D; RESULTS: Our study showed that the treatment of silymarin and PM resulted in the normalized activity of liver function, followed by the amelioration of oxidative stress, demonstrated by the decreased malondialdehyde levels and an increased ratio of glutathione and glutathione disulfide. All markers examined showed that PM extract has antioxidant activity due to decreased hepatic stellate cell activation. We also found a decrease in tumor growth factors-β1 and protein expressions of matrix metalloproteinases-13 in all treatment groups compared to the carbon tetrachloride group. There were tendencies of the decreased fibrotic area following improvements of biochemical parameters.&#x0D; CONCLUSION: PM extracts ameliorate carbon tetrachloride-induced LF. The proposed mechanism is by overcoming oxidative stress and regulating pro-fibrogenic cytokine and antifibrotic markers.

Chemical Composition and Antioxidant Potential of Fruit Essential Oil of Laggera pterodonta (DC.) Benth Grown in North Central, Nigeria

This study aimed at isolating, characterizing and evaluating the antioxidant potential of fruit essential oil of Laggera pterodonta native to Nigeria. Pulverized fruits (500 g) of L. pterodonta were hydrodistilled for 3 hours and yielded 0.07±0.02 % (w/w) of essential oil. The oil was analyzed using GC and GC-MS. The analyses revealed the predominance of sesquiterpenoids (92.7 %), while monoterpenoids constituted 1.5 % of the oil. The major compounds in the oil were α-bergamotene (29.3 %), β-bisabolene (16.9 %), α-copaene (8.8 %) and α-bisabolol (6.0 %). Terpinen-4-ol (0.5 %) and α-terpineole (1.0 %) were the only monoterpenoids detected in the oil. The antioxidant activity of the oil was determined using 2,2-diphenyl- 1-picryl hydrazyl (DPPH) radical scavenging assay. The oil exhibited antioxidant activity by scavenging DPPH radicals with IC50 of 6.05 μL/mL. The activity of the oil was higher than the activity of ascorbic acid with IC50 of 12.84 μl/ml used as standard. Therefore, the oil could serve as an alternative to synthetic drugs for the amelioration of oxidative stress.