Flavonoids profiles,antioxidant, acetylcholinesterase inhibition activities of extract from Dryoathyrium boryanum (Willd.) Ching

The profiles and bioactivities of flavonoids extracted from Dryoathyrium boryanum (Willd.) Ching were investigated. The total flavonoids content in extract from D. boryanum is about 145.8 mg/g. By means of HPLC–DAD–ESI–MS, the main flavonoids in D. boryanum were tentatively identified as 3-hydroxyphloretin 6′-O-hexoside, quercetin-7-hexoside, apigenin7-O-glucoside, luteolin 7-O-glucoside, apigenin 7-O-galactoside, acacetin 7-O-(α-D-apio-furanosyl) (1 → 6)-β-d-glucoside, 3-hydroxy phloretin 6-O-hexoside, luteolin-6-C-glucoside. 0.21 mg/ml flavonoids extract from D. boryanum showed very strong superoxide anion radical scavenging potential, which is higher than that of rutin (0.25 mg/ml). The extract (0.21 mg/ml of flavonoids) from D. boryanum exhibited similar DPPH scavenging potential with that of rutin (0.25 mg/ml). However, rutin (0.25 mg/ml) showed a significantly higher reducing power and ABTS scavenging potential than that of 0.21 mg/ml flavonoids extract from D. boryanum. It had no effect on acetylcholinesterase. D. boryanum can be considered as a medicinal plant and the flavonoids from D. boryanum are excellent antioxidants.     

Characterization of flavonoids from Dryopteris erythrosora and evaluation of their antioxidant,anticancer and acetylcholinesterase inhibition activities

The profiles and bioactivities of flavonoids extracted from Dryopteris erythrosora were investigated. The total flavonoid content in full plant of D. Erythrosora is about 14.33%. The main flavonoids in D. Erythrosora were identified as gliricidin 7-O-hexoside, apigenin7-O-glucoside, quercetin 7-O-rutinoside, quercetin 7-O-galactoside, keampferol 7-O-gentiobioside, keampferol-3-O-rutinoside, myricetin 3-O-rhamnoside and quercitrin by means of HPLC-DAD–ESI-MS. Flavonoids (0.36 mg/ml) extract from D. erythrosora showed similar 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS), superoxide anion scavenging potential and ferric reducing antioxidant potential (FRAP) with that of rutin (0.80 mg/ml). However, the antioxidant power by FRAP assay of 0.36 mg/ml flavonoids extract from D. erythrosora was much weaker than that of 0.80 mg/ml rutin. Moreover, the flavonoids extract from D. erythrosora showed obvious cytotoxic effects on A549 cells. The antioxidant activities of flavonoids extracts from 69 ferns showed a significant reciprocal proportion to the total flavonoids contents. The flavonoids extract from D. erythrosora exhibited a dose-dependent inhibition against acetylcholinesterase. Moreover, the anticancer activity slightly increased with improving antioxidant potential of fern flavonoids. Fern flavonoids are excellent function foods.     

Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLCUV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900 mg, C_max and AUC_012h did not increase with dose escalation. The AUC_012h, C_max, C₀ and T_max for the 540 720 and 900 mg doses were not significantly different, respectively (P >0.05). AUC_012 h and C_max were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_012h, C_max and C₀ were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.     

Ferritin-dependent radical generation in rat liver homogenates

The hypothesis of this study was that mammalian ferritin (FER) has the ability of releasing Fe in the tissue to catalyze the generation of free radicals, such as ascorbyl (A) and hydroxyl radical (OH), that might lead to the damage of FER itself. The rat liver homogenates exhibited an electron paramagnetic resonance (EPR) signal with the spectral features (a_H = 1.88 G, g = 2.0054) of A. The addition to the reaction medium of isolated rat liver FER increased by 3-fold the EPR signal, as compared to the recorded value in its absence. Isolated microsomes from rat liver incubated during 10 min showed a signal with the spectral features (a_H = 15 G, g = 2.0062) of OH. The addition of FER in the presence of either ethylenediamine-tetraacetic acid (EDTA) or adenosine-5′-triphosphate (ATP) significantly increased the recorded spectra. The labile Fe pool (LIP) in the homogenate was assessed by EPR. The rat liver homogenates exhibited an EPR signal with the spectral features (g = 4.3) of the Fe²⁺ and was significantly increased by the addition of FER (3-fold). The oxidation profile of the isolated FER from rat liver was analyzed after incubation with 10 mM ascorbate (AH^?). A drastic increase in the width of the band suggested alterations to the protein structure. The FER content of tryptophan (Trp) and thiols was significantly lower when the incubation was performed in the presence of AH^? as compared to the recorded effect in its absence. The data in tissue homogenates presented here showed that radical generation is associated to FER Fe release, and moreover that the FER protein itself was affected during this process.     

Inhibitory effect of Nymphaea pubescens Willd. flower extract on carrageenan-induced inflammation and CCl4-induced hepatotoxicity in rats

Nymphaea pubescens Willd. is used as ingredient of ethnic diet and folk medicine in South-East Asia. The water (NPW), methanol (NPM) and chloroform (NPC) extracts of N. pubescens flowers were investigated for NO, ${\text{O}}_2^{\text{<mglyph src="https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/16/entities/rad"></mglyph>}-}$ and DPPH radical scavenging and iron chelating activities in vitro. NPW was found to be the most potent free radical scavenger (EC₅₀ < 100 μg/mL) whereas NPC did not show EC₅₀ at 500 μg/mL. Therefore, NPW was selected for further studies on anti-inflammatory and hepatoprotective activities, using standard in vitro and in vivo models. NPW exhibited inhibition of nitrogen radical generation in LPS-activated macrophages (IC₅₀ = 75.5 μg/mL) through suppression of iNOS protein, with no associated toxicity in the cells. Further, 500 mg/kg of NPW reduced rat paw edema by ∼50% after 6 h of carrageenan administration. Hepatoprotective activity of NPW was also evaluated in vivo on CCl4-induced hepatotoxicity model in rats. NPW treatment (500 mg/kg/day for ten days) attenuated CCl4-induced increase in serum enzymes, viz. alanine and aspartate aminotransferases (ALT and AST) and bilirubin. Also, glutathione and superoxide dismutase (SOD)-levels were restored towards normalcy in the liver of CCl4-treated rats, indicating the hepatoprotective role of NPW, which was found to contain a fair amount of flavonoids, phenolics, and saponin constituents.     

Synthesis,characterization and pharmacological evaluation of pyrazolyl urea derivatives as potential anti-inflammatory agents

p38α mitogen activated protein kinase (MAPK) inhibitors provide a novel approach for the treatment of inflammatory disorders. A series of fifteen pyrazolyl urea derivatives (3ao) were synthesized and evaluated for their p38α MAPK inhibition and antioxidant potential. Compounds 3ae, 3g and 3h showed low micromolar range potency (IC₅₀ values ranging from 0.037 ± 1.56 to 0.069 ± 0.07 µmol/L) compared to the standard inhibitor SB 203580 (IC₅₀ = 0.043 ± 3.62 µmol/L) when evaluated for p38α MAPK inhibition by an immunosorbent-based assay. Antioxidant activity was measured by a 2,2′-diphenyl-1-picryl hydrazyl radical (DPPH) free radical scavenging method and one of the compounds, 3c, showed better percentage antioxidant activity (75.06%) compared to butylated hydroxy anisole (71.53%) at 1 mmol/L concentration. Compounds 3ae, 3g and 3h showed promising in vivo anti-inflammatory activity (ranging from 62.25% to 80.93%) in comparison to diclofenac sodium (81.62%). The ulcerogenic liability and lipid peroxidation activity of these compounds were observed to be less in comparison to diclofenac sodium. These compounds also potently inhibited the lipopolysaccharide (LPS)-induced TNF-α release in mice (ID₅₀ of 3ac = 19.98, 11.32 and 9.67 mg/kg, respectively). Among the screened compounds, derivative 3c was found to be the most potent and its binding mode within the p38α MAPK is also reported.     

Hydroxyl radical induced by lipid in Maillard reaction model system promotes diet-derived Nε-carboxymethyllysine formation

N_ε-carboxymethyllysine (CML) is commonly found in food, and is considered as a potential hazard to human health. However, the effect of lipids on CML formation in Maillard reaction is still not clarified. In this study, the content of diet-derived CML and its key intermediates, epsilon-fructoselysine (FL) and glyoxal (GO), is determined with high performance liquid chromatography mass spectrum (HPLC-MS) in model system containing lipid compounds. According to the results, hydroxyl radical (OH) induced by Fenton reagent can promote the three pathways of CML formation. Moreover, in the Maillard reaction system, linoleic acid (Lin), oleic acid (Ole) and glycerol trioleate (Tri) can induce more OH, which promotes CML formation. Their level of promoting CML formation is in the order of Ole > Lin > Tri. On the contrary, glycerol (Gly) can scavenge OH, which inhibit the CML formation. Finally, it is proved that FL content and GO content decreases with heating time in model system, while CML content increases with heating time. Thus, it is concluded that in the Maillard reaction system lipids can induce more OH, which promotes the conversion from FL and GO to CML. Our research may contribute to the development of inhibitory methods for diet-derived CML by scavenging OH.     

Angolan Cymbopogon citratus used for therapeutic benefits: Nutritional composition and influence of solvents in phytochemicals content and antioxidant activity of leaf extracts

Folk medicine is a relevant and effective part of indigenous healthcare systems which are, in practice, totally dependent on traditional healers. An outstanding coincidence between indigenous medicinal plant uses and scientifically proved pharmacological properties of several phytochemicals has been observed along the years.This work focused on the leaves of a medicinal plant traditionally used for therapeutic benefits (Angolan Cymbopogon citratus), in order to evaluate their nutritional value. The bioactive phytochemical composition and antioxidant activity of leaf extracts prepared with different solvents (water, methanol and ethanol) were also evaluated.The plant leaves contained ∼60% of carbohydrates, protein (∼20%), fat (∼5%), ash (∼4%) and moisture (∼9%). The phytochemicals screening revealed the presence of tannins, flavonoids, and terpenoids in all extracts. Methanolic extracts also contained alkaloids and steroids. Several methods were used to evaluate total antioxidant capacity of the different extracts (DPPH, NO, and H₂O₂ scavenging assays, reducing power, and FRAP). Ethanolic extracts presented a significantly higher antioxidant activity (p < 0.05) except for FRAP, in which the best results were achieved by the aqueous extracts. Methanolic extracts showed the lowest radical scavenging activities for both DPPH and NO radicals.     

Effects of red wine intake on human salivary antiradical capacity and total polyphenol content

The protective effects of grape polyphenols have been reported on oral health, though unreasonable alcohol consumption represents a risk factor for developing oral cancer. The possible effects of red wine consumption on salivary antiradical activity were investigated in healthy volunteers for the first time, to the best of our knowledge. Time-course (from 0 min to 240 min) changes of salivary radical-scavenging capacity were measured by the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS⁺) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, in twelve healthy volunteers, after the intake of red wine (125 mL), a capsule of red wine extract (300 mg) or water (125 mL). Furthermore, time-course of salivary total polyphenol levels, detected by the Folin–Ciocalteu colorimetric method, was also determined. Both ABTS and DPPH tests showed that red wine consumption did not increase salivary antiradical activity in volunteers. Conversely, red wine extract administration caused a marked rise in salivary ABTS radical-scavenging capacity within 30 min, followed by a plateau up to 240 min. The same treatment also raised salivary DPPH radical-scavenging activity at any time point, though to a minor extent. The highest salivary polyphenol concentration was reached 30 min after wine drinking, followed by a steady decrease up to 240 min. Wine drinking was not associated to a reduced salivary antiradical capacity. However, wine extract greatly improved the salivary antioxidant status.     

Mechanisms involved in the in vitro contractile dysfunction induced by different concentrations of ferrous iron in the rat myocardium

Iron intoxication is related to reactive oxygen species (ROS) production and organic damage including the cardiovascular system, and is a leading cause of poisoning deaths in children. In this study we examined whether a range of ferrous iron (Fe(2 +)) concentrations can interfere differently on the myocardial mechanics, investigating the ROS-mediated effects. Developed force of isolated rat papillary muscles was depressed with a concentration- and time-dependency by Fe(2 +) 100–1000 μM. The contractile response to Ca(2 +) was reduced, but it was partially reversed by co-incubation with catalase and DMSO, but not TEMPOL. In agreement, in situ detection of OH was increased by Fe(2 +) whereas O₂⁻ was unchanged. The myosin-ATPase activity was significantly decreased. Contractions dependent on the sarcolemal Ca(2 +) influx were impaired only by Fe(2 +) 1000 μM, and antioxidants had no effect. In skinned fibers, Fe(2 +) reduced the pCa-force relationship, and pCa50 was right-shifted by 0.55. In conclusion, iron overload can acutely impair myocardial contractility by reducing myosin-ATPase activity and myofibrillar Ca(2 +) sensitivity. These effects are mediated by local production of OH and H₂O₂. Nevertheless, in a such high concentration as 1000 μM, Fe(2 +) appears to depress force also by reducing Ca(2 +) influx, probably due to a competition at Ca(2 +) channels.     

The co-application effects of fullerene and ascorbic acid on UV-B irradiated mouse skin

The role of fullerene as a pro-oxidant or anti-oxidant in Ultraviolet B ray (UV-B)-induced disorders in mouse skin was investigated. Fullerene gave no photo-toxic effect to UV-B-irradiated mouse skin. Since erythema was concentrated at the pore circumference in a UV-B irradiation experiment in mouse skin, the sebaceous gland pairs was strongly implicated as a site for the generation of reactive oxygen species (ROS). In a histological evaluation of the skin stained with CH₃MDFDA (ROS index) and YO-Pro-1 (apoptosis index), the fluorescence intensity of a sebaceous gland significantly increased with UV-B irradiation. With the application of fullerene to UV-irradiated mouse skin, no toxicity was recognized in comparison with the control, and erythema, the ROS index, and the apoptosis index decrease with the application of fullerene. Ascorbyl radical (AA) increased with the application of ascorbate (AA) to UV-B-irradiated mouse skin, and AA decreased with the application of fullerene. The co-application of AA and fullerene, which suppressed AA in vitro, significantly suppressed erythema, and also suppressed both the ROS index and apoptosis index in mouse skin after UV-B irradiation. In both mouse skin at 48 h after UV-B irradiation and in an attempt to reproduce this phenomenon artificially in vitro, a similar high AA peak (AA/H > 4) was observed in electron spin resonance (ESR) charts. The binding of fullerene with AA impairs the Fenton reaction between AA and Fe-protein based on the observation of ascorbate-specific UV absorption and a linear equation for the calibration curve. Therefore, fullerene may impair the intercalation of AA to a heme pocket by binding with AA. These results suggest that the co-application of AA and fullerene is effective against oxidative skin damage caused by UV-B irradiation, and the development of an AA inhibitor such as fullerene should be useful for reducing organ damage associated with Fe-protein oxidation.     

Effect of non-steroidal anti-inflammatory drugs and new fenamate analogues on TRPC4 and TRPC5 channels

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used anti-inflammatory therapeutic agents, among which the fenamate analogues play important roles in regulating intracellular Ca²⁺ transient and ion channels. However, the effect of NSAIDs on TRPC4 and TRPC5 is still unknown. To understand the structure–activity of fenamate analogues on TRPC channels, we have synthesized a series of fenamate analogues and investigated their effects on TRPC4 and TRPC5 channels.Human TRPC4 and TRPC5 cDNAs in tetracycline-regulated vectors were transfected into HEK293 T-REx cells. The whole cell current and Ca²⁺ movement were recorded by patch clamp and calcium imaging, respectively.Flufenamic acid (FFA), mefenamic acid (MFA), niflumic acid (NFA) and diclofenac sodium (DFS) showed inhibition on TRPC4 and TRPC5 channels in a concentration-dependent manner. The potency was FFA > MFA > NFA > DFS. Modification of 2-phenylamino ring by substitution of the trifluoromethyl group in FFA with F, CH₃, OCH₃, OCH₂CH₃, COOH, and NO₂ led to the changes in their channel blocking activity. However, 2-(2′-methoxy-5′-methylphenyl)aminobenzoic acid stimulated TRPC4 and TRPC5 channels. Selective COX1-3 inhibitors (aspirin, celecoxib, acetaminophen, and indomethacin) had no effect on the channels. Longer perfusion (>5 min) with FFA (100 μM) and MFA (100 μM) caused a potentiation of TRPC4 and TRPC5 currents after their initial blocking effects that appeared to be partially mediated by the mitochondrial Ca²⁺ release.Our results suggest that fenamate analogues are direct modulators of TRPC4 and TRPC5 channels. The substitution pattern and conformation of the 2-phenylamino ring could alter their blocking activity, which is important for understanding fenamate pharmacology and new drug development targeting the TRPC channels.     

Polyphenolic constituents of methanolic and aqueous extracts of Vitex negundo render protection to Hep3B cells against oxidative cytotoxicity

This study was aimed at investigating the phenolic constituents of methanolic and aqueous extracts of Vitex negundo in context of antioxidant potential and inhibition of oxidative stress-induced cytotoxicity. Antioxidant efficacies of both extracts were estimated by their abilities to scavenge DPPH and to reduce Fe⁺³ to Fe⁺². Their protective potential against H₂O₂-driven oxidative damage to cells were evaluated by XTT assay in Hep3B (human hepatoma) cells. Total phenolic content of both extracts were estimated, and were tested for correlation with antioxidant potential and protection against oxidative cytotoxicity. Polyphenolic levels in both extracts showed significant (P < 0.05) positive correlations with DPPH scavenging, Fe⁺³–Fe⁺² reduction and percentage decrease in H₂O₂-induced cytotoxicity. Major phenolic compounds in the extracts were identified by HPLC. It was concluded that both V. negundo extracts hold considerable potential as antitheses of free radical toxicity by virtue of their polyphenolic constituents, and might have significant clinical roles in prospect.     

Nine compounds from the Root Bark of Lycium chinense and their anti-inflammatory activities

Two new compounds, named lyciumlignan D (1) and lyciumphenyl propanoid A (2), along with seven known compounds, were isolated from the root bark of Lycium chinense. Their structures were elucidated using spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the literature. Compounds 39 were isolated from this genus for the first time. In the in vitro assay, compounds 3, 6, and 7 exhibited stronger anti-inflammatory effects than the positive control curcumin at a concentration of 10 μmol/L.     

In vitro cellular responses to silicon carbide particles manufactured through the Acheson process: Impact of physico-chemical features on pro-inflammatory and pro-oxidative effects

Silicon carbide (SiC) an industrial-scale product manufactured through the Acheson process, is largely employed in various applications. Its toxicity has been poorly investigated. Our study aims at characterizing the physico-chemical features and the in vitro impact on biological activity of five manufactured SiC powders: two coarse powders (SiC C1/C2), two fine powders (SiC F1/F2) and a powder rich in iron impurities (SiC I). RAW 264.7 macrophages were exposed to the different SiC particles and the cellular responses were evaluated. Contrary to what happens with silica, no SiC cytotoxicity was observed but pro-oxidative and pro-inflammatory responses of variable intensity were evidenced. Oxidative stress (H₂O₂ production) appeared related to SiC particle size, while iron level regulated pro-inflammatory response (TNFα production). To investigate the impact of surface reactivity on the biological responses, coarse SiC C1 and fine SiC F1 powders were submitted to different thermal treatments (650–1400 °C) in order to alter the oxidation state of the particle surface. At 1400 °C a decrease in TNFα production and an increase in HO, COO⁻ radicals production were observed in correlation with the formation of a surface layer of crystalline silica. Finally, a strong correlation was observed between surface oxidation state and in vitro toxicity.     

Acute iron overload and oxidative stress in brain

An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A)/ascorbate (AH^?) ratio, taken as oxidative stress index, was assessed. The A/AH^? ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increased after 8 h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR generation rate after 6 h of Fe overload. This information has potential clinical relevance, as it could be the key to understand specific brain damage occurring in conditions of Fe overload.     

Increased glutathione levels contribute to the beneficial effects of hydrogen sulfide and inducible nitric oxide inhibition in allergic lung inflammation

ObjectiveThe interaction between nitric oxide (NO) and hydrogen sulfide (H₂S) in the airways could have significant implications for the pathogenesis and therapeutic effects of both on lung diseases. In this study we investigated whether the beneficial effects of H₂S on asthma could be comparable to that inhibition of inducible NO synthase (iNOS).MethodsFemale BALB/C mice sensitized with ovalbumin (OVA) received either the H₂S donor sodium hydrosulfide (NaHS, 14 μmol/kg) or the iNOS inhibitor 1400 W (1 mg/kg), 30 min before each OVA challenge during six days. On the first, second and sixth days, the leucocyte infiltration in lung parenchyma and bronchoalveolar lavage was evaluated. The aconitase activity (a sensor of O₂ formation) and lipid peroxidation, as well as levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were determined in the lung tissues.ResultsOVA-challenge caused a significant and time-dependent increase in the eosinophil number in the airways, which was accompanied by a significant decrease of aconitase activity and GSH/GSSG ratio along with enhanced lipid peroxidation in the lungs. Treatment with NaHS or 1400 W significantly attenuated the airways eosinophilia that was paralleled by an increase in aconitase activity and decrease of lipid peroxidation. NaHS or 1400 W treatments also reversed the decreased GSH/GSSG ratio seen after OVA-challenge.ConclusionsThe present study shows for the first time that the increased GSH/GSSG ratio caused by either H₂S supplementation or iNOS-inhibition is a potential mechanism protecting airways against oxidative stress and inflammatory lung diseases.     

Semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1 protects against gamma radiation-induced oxidative stress

In the present study, radioprotective potential of Semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 was evaluated. γ-Radiation induced protein carbonylation, plasmid DNA damage, enzyme functional impairment, lipid peroxidation, HO radicals generation and their protection by SQGD was assessed. As a result of SQGD treatment, significant inhibition (p < 0.05) in protein carbonylation was observed with BSA. SQGD treatment was found to restore supercoiled (∼70 ± 3.21%) form of irradiated plasmid DNA against γ-irradiation. SQGD protects enzymes (EcoR1 and BamH1) against radiation-induced dysfunctioning. SQGD significantly inhibited (p < 0.05) lipid peroxidation in liposomes, brain and liver homogenate. Higher HO^• radicals-averting activity of SQGD was observed in the serum and liver homogenate of C57BL/6 mice against H₂O₂-induced oxidative stress. In conclusion, SQGD demonstrates excellent radical-scavenging activity towards bio-macromolecules in irradiated environment and can be developed as an ideal radioprotector against radiation-induced oxidative stress in future.     

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

The aim of this study was to characterize alterations in vascular structure and mechanics in murine mesenteric arteries from obese non-hypertensive mice, as well as their relationship with adipokines. Four-week old C57BL/6J male mice were assigned either to a control (C, 10% kcal from fat) or a high-fat diet (HFD, 45% kcal from fat) for 32 weeks. HFD animals weighed 30% more than controls (p < 0.001), exhibited similar blood pressure, increased leptin, insulin and superoxide anion (O₂⁻⁾ levels, and reduced adiponectin levels and nitric oxide (NO) bioavailability. Arterial structure showed an outward remodeling with an increase in total number of both adventitial and smooth muscle cells in HFD. Moreover, HFD mice exhibited an increased arterial stiffness assessed by β-values (C = 2.4 ± 0.5 vs HFD = 5.3 ± 0.8; p < 0.05) and aortic pulse wave velocity (PWV, C = 3.4 ± 0.1 vs HFD = 3.9 ± 0.1; p < 0.05). β-Values and PWV positively correlated with leptin, insulin or O₂⁻ levels, whereas they negatively correlated with adiponectin levels and NO bioavailability (p < 0.01). A reduction in fenestrae number together with an increase in type-I collagen amount (p < 0.05) were observed in HFD. These data demonstrate that HFD accounts for the development of vascular remodeling and arterial stiffness associated with adipokine dysregulation and oxidative stress, independently of hypertension development.