Dose-dependent Antioxidant Properties Research Articles

Evaluation of ZnO nanoparticles from ‘Monsooned Malabar Robusta Coffee’ husk as a potential antioxidant and biocidal candidate: A sustainable valorization approach

Nanotechnology has become a sustainable strategy to combat drug resistance. As agro-waste management has become a concern, efficient management of produced waste has been an imposing global issue. This study evaluated antioxidant, as well as antibacterial and antibiofilm potential of zinc oxide nanoparticles (ZnO NPs) synthesized by hydrothermal approach using ethanolic extract of ‘Monsooned Malabar Robusta coffee’ husk against multi-drug-resistant (MDR) strains of enteroaggregative Escherichia coli, Salmonella Enteritidis, S. Typhimurium and methicillin-resistant Staphylococcus aureus. The fabrication of ZnO NPs was confirmed by spectroscopy, whereas thermogravimetric analysis-differential thermogravimetric analysis confirmed stability of ZnO NPs, while the X-ray diffraction pattern confirmed the wurtzite crystalline structure. The agglomerated nature of ZnO NPs with a nearly spherical shape was evident with scanning electron microscopy, whereas transmission electron microscopy revealed a poly-crystalline nature with a mean diameter of 26.33 ± 3.778 nm. The microbroth dilution technique revealed a minimum inhibitory concentration (MIC) of 250 μg/mL and a minimum bactericidal concentration (MBC) of 500 μg/mL for the ZnO NPs. Furthermore, ZnO NPs exhibited significant antibiofilm activity against the MDR-test strains. Moreover, ZnO NPs were tested safe at MIC and MBC doses in chicken erythrocytes, and commensal gut microflora tested were not inhibited. Besides, a dose-dependent antioxidant property was exhibited by ZnO NPs. Additionally, in vitro time-kill kinetic assay of MDR-test strains treated with ZnO NPs revealed a complete bacterial clearance at 24 h. Overall, the synthesis of ZnO NPs from coffee husk demonstrated a simple, eco-friendly and valorization approach that could be devised as a potential delivery molecule.

Evaluation of the Reparative Effect of Sinomenine in an Acetaminophen-Induced Liver Injury Model.

Due to its rising global prevalence, liver failure treatments are urgently needed. Sinomenine (SIN), an alkaloid from sinomenium acutum, is being studied for its liver-repair properties due to Acetaminophen (APAP) overdose. SIN's effect on APAP-induced hepatotoxicity in rats was examined histologically and biochemically. Three groups of 30 adult male Wistar rats were created: control, APAP-only, and APAP + SIN. Histopathological and biochemical analyses were performed on liver samples after euthanasia. SIN is significantly protected against APAP damage. Compared to APAP-only, SIN reduced cellular injury and preserved hepatocellular architecture. The APAP + SIN Group had significantly lower ALT, MDA, and GSH levels, protecting against hepatocellular damage and oxidative stress. SIN also had dose-dependent antioxidant properties. When examining critical regulatory proteins, SIN partially restored Sirtuin 1 (SIRT1) levels. While BMP-7 levels were unaffected, histopathological evidence and hepatocyte damage percentages supported SIN's liver-restorative effect. SIN protected and repaired rats' livers from APAP-induced liver injury. This study suggests that SIN may treat acute liver damage, warranting further research into its long-term effects, optimal dosage, and clinical applications. These findings aid liver-related emergency department interventions and life-saving treatments.

Comparative Impact of Solvent Extracts of Spondias mombin Leaves on In-vitro Antioxidant and Acetylcholinesterase Inhibitory Activities

The underlying cause of a number of neurological disorders is oxidative stress. Given the dearth of medications now available to treat such disorders and their accompanying detrimental impacts, an urgent need exists for the global identification of brand-new antioxidants and acetylcholinesterase (AChE) inhibitors. This study evaluated the comparative impacts of the antioxidant and acetylcholinesterase activities of n-hexane, ethyl acetate, and methanol extracts of S. mombin leaves. The dried leaf samples of the plant were triturated. Following maceration of the powdered plant materials in each of the three extraction solvents (methanol, n-hexane, and ethyl acetate), the resulting solutions were separately subjected to lyophilization. The in-vitro antioxidant analysis was determined by employing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and lipid peroxidation (LPO) assays. Acetylcholinesterase (AChE) inhibitory abilities of the various extracts were also evaluated using a standard protocol. The methanol extract showed the greatest DPPH scavenging (75.91%) and AChE inhibitory (40.17%) properties in the DPPH and AChE inhibitory assays, respectively. The DPPH and lipid peroxidation assays also demonstrated that all extracts had dose-dependent antioxidant properties. In addition, evaluations of each extract's ability to inhibit lipid peroxidation revealed that, at initial concentrations of 0.05 mg/L and 0.1 mg/L, the methanol extract displayed stronger LPO inhibitory effects (5.90%, 6.15%) than the n-hexane (4.00%, 5.4%) and ethyl acetate (3.26%, 3.99%) extracts. Nonetheless, the n-hexane extract showed a greater LPO inhibitory effect (10.00%, 10.34%) at higher dosages of 0.2 mg/L and 0.5 mg/L respectively. The results of this study have shown that methanol is the best solvent for exploiting the pharmacological benefits of S. mombin leaves thereby reasserting the numerous applications of the plant in traditional medicine. It has also paved the way for the development of novel therapeutic alternatives for a range of neurodegenerative disorders and other health concerns.

Electrode Based on the MWCNTs and Electropolymerized Thymolphthalein for the Voltammetric Determination of Total Isopropylmethylphenols in Spices.

Isopropylmethylphenols, namely thymol and carvacrol, are natural phenolic monoterpenoids with a wide spectrum of bioactivity making them applicable in the cosmetic, pharmaceutical, and food industry. The dose-dependent antioxidant properties of isopropylmethylphenols require their quantification in real samples. Glassy carbon electrode (GCE) modified with multi-walled carbon nanotubes (MWCNTs) and electropolymerized thymolphthalein has been developed for the sensitive quantification of isopropylmethylphenols. Conditions of thymolphthalein electropolymerization (monomer concentration, number of cycles, and electrolysis parameters) providing the best response to thymol have been found. Scanning electron microscopy and electrochemical methods confirm the effectivity of the electrode developed. The linear dynamic ranges of 0.050-25 and 25-100 µM for thymol and 0.10-10 and 10-100 µM for carvacrol with detection limits of 0.037 and 0.063 µM, respectively, have been achieved in differential pulse mode in Britton-Robinson buffer pH 2.0. The selectivity of the isopropylmethylphenols response in the presence of typical interferences (inorganic ions, saccharides, ascorbic acid) and other phenolics (caffeic, chlorogenic, gallic and rosmarinic acids, and quercetin) is a significant advantage over other electrochemical methods. The electrode has been used in the analysis of oregano and thyme spices. Total isopropylmethylphenols contents have been evaluated after a single sonication-assisted extraction with methanol.

Ethnobotanical Survey, Physiochemical Composition and Preliminary Cytotoxic Evaluation of some Medicinal Plants with Anticancer Potential from Certain Areas in South-West Nigeria

Aims: Medicinal plants used by traditional medical practitioners (TMP) to treat cancers are considered safe when used alone or combined with conventional therapy to ensure their effectiveness and eliminate the toxic effects of orthodox medicines. Using cytotoxic and antioxidant studies, the study attempted to assess some of the commonly used medicinal plants used to cure cancer among Yoruba people in Ogun, Oyo, Osun, and Lagos (South-West, Nigeria).
 Study Design: Samples of commonly utilized anticancer plants obtained from the chosen areas using physical and virtual oral seminars were studied for physiochemical composition and a possible antioxidant and cytotoxic potential to validate the basis for the use of the selected anticancer plants.
 Methodology: Online academic literature searches were done on the cited plants to identify the already-exploited anticancer plants. The ethanolic extracts of the plant were examined for the presence of bioactive components and their total flavonoid content, with focusing on quercetin detection using thin layer bioautography (TLB) and brine shrimp lethality assay (BSLA) for cytotoxicity. In comparison to quercetin and ascorbic acid, the scavenging of superoxide radical (SOR), hydrogen peroxide, and 2, 2-Diphenyl-2-picrylhydrazyl (DPPH) radical activity by a model (most biologically active) of the anticancer plant was also evaluated.
 Results: There were only twelve anticancer species that were not used in related studies: Lannea egregia, Ficus exasperate, Croton zambesicus, Tetrapleurai tetraptera, Terminalia catappa, Zanthoxylum zanthoxyloides, Plumbago zelanica, Hilleria latifolia, Bryophyllum pinntum, Chromolena odorata, Brysocarpus coccineus and Spondias mombin. The anticancer plants contained bioactive and mineral substances like saponins, protein, lipids, magnesium, calcium, iron, zinc, and a decreased Na/K concentration. The plants had a fair amount of flavonoids and variable levels of cytotoxicity. L. egeregia was regarded as the prototype of the anticancer species due to its profound flavonoid concentration (85.40 µg/mL) and cytotoxicity (9.46 µg/mL) compared to other extracts. The TLB also demonstrated the presence of quercetin, with a dose-dependent antioxidant property. The anticancer model's overall antioxidant activity (34.72 µg/mL) was slightly lower than quercetin (30.44 µg/mL) but higher than ascorbic acid (41.68 µg/mL).
 Conclusion: The results support the traditional use of anticancer species as nutritional and dietary supplements, whose bioactive compounds are relevant in managing cancer patients. The plant’s bioactive principles need to be characterized in future research.

Switchable Nanozyme Activity of Porphyrins Intercalated in Layered Gadolinium Hydroxide

In this study, organo-inorganic nanohybrids LHGd-MTSPP with enzyme-like activity were prepared by in situ intercalation of anionic 5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin and its complexes with Zn(II) and Pd(II) (MTSPP, M = 2H, Zn(II) and Pd(II)) into gadolinium layered hydroxide (LHGd). The combination of powder XRD, CHNS analysis, FT-IR, EDX, and TG confirmed the layered structure of the reaction products. The basal interplanar distances in LHGd-MTSPP samples were 22.3-22.6 Å, corresponding to the size of an intercalated tetrapyrrole molecule. According to SEM data, LHGd-MTSPP hybrids consisted of individual lamellar nanoparticles 20-50 nm in thickness. The enzyme-like activity of individual constituents, LHGd-Cl and sulfoporphyrins TSPP, ZnTSPP and PdTSPP, and hybrid LHGd-MTSPP materials, was studied by chemiluminescence analysis using the ABAP/luminol system in phosphate buffer solution. All the individual porphyrins exhibited dose-dependent antioxidant properties with respect to alkylperoxyl radicals at pH 7.4. The intercalation of free base TSPP porphyrin into the LHGd preserved the radical scavenging properties of the product. Conversely, in LHGd-MTSPP samples containing Zn(II) and Pd(II) complexes, the antioxidant properties of the porphyrins changed to dose-dependent prooxidant activity. Thus, an efficient approach to the design and synthesis of advanced LHGd-MTSPP materials with switchable enzyme-like activity was developed.

Hypocholesterolemic, antidiabetic and bioactive properties of ultrasound-stimulated exopolysaccharide produced by Lactiplantibacillus plantarum strains

This study aimed to investigate the effects of ultrasound (US) pretreatment (100 W, 30 kHz; 0%, 25%, 50%, and 75% amplitudes, 15 min) on exopolysaccharide (EPS) production efficiency of L. plantarum LS5 and LU5 strains. Physicochemical (molecular weight and sugar composition) and bioactive properties of extracted EPSs such as antibiofilm, α-amylase inhibition, cholesterol-lowering, and antioxidant activities were investigated. The EPS production yield of strains was growth-associated and LS5 had more efficiency than LU5 but their molecular weights did not differ, significantly (p > 0.05). The predicted results were mathematically confirmed experimental data. The α and β values (EPS production constant) were obtained by the Elovich model (EM) using a genetic algorithm indicated that the highest EPS production was found for LS5 and an amplitude of 50%. Extracted EPSs were heteropolysaccharides and showed dose-dependent antioxidant properties. DPPH scavenging activity of LS5-EPS was higher than LU5-EPS but their Fe3+ reducing power did not differ markedly (p > 0.05). They had the highest and lowest antibiofilm activity against S.aureus and E. coli, respectively. The maximum α-amylase inhibition (35.13%) and Cholesterol-lowering activities (42.56%) were achieved by LU5-EPS and LS5-EPS, respectively. As a result, LS5-EPS was more bioactive than LU5-EPS, and ultrasound pretreatment at 50% amplitude is an efficient way for increasing LS5-EPS production, which has a great potential in the production of functional food and employment in pharmaceutical industries.

The effects of methanol extract of Galium verum L on cardiac redox state in hypertensive rats

The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.

Elaeagnus umbellata fruit - chemical composition, bioactive compounds, and kinetic of DPPH inhibition compared to standard antioxidants


 umbellata (Autumn Olive) is a medicinal plant used in traditional Asian medicine. In this study, we examine E. umbellata, which grows in central Europe (Poland). Despite significant climatic differences in both regions, we show that the fruits have a similar chemical composition and antioxidant activity to those observed in their native areas. For the first time, we examined the fatty acid composition of E. umbellata, showing that unsaturated fatty content for as much as 88.67% of total fat. Including the content of essential polyunsaturated fatty acids was over 50% of the total fat. We also examined proximate content, the content of fat-soluble vitamins, lycopene, beta carotene, and the mineral composition of the fruit. Moreover, using FT-IR spectrometry, we have shown that the fruits of the Autumn olive can change the distribution of chemical bonds when treated with hydrogen peroxide. The fruits of E. umbellata showed dose-dependent antioxidant properties with IC50 values of 76.27 µg / ml We also investigated the kinetic antioxidant activity of E. umbellata fruits based on DPPH radical inhibition compared to standard antioxidants (vitamin c and BHT). We have shown that using available protocols to spectrophotometrically study antioxidants' reaction with the DPPH radical may underestimate the effects of the Autumn Olive fruits.

Multivariate analysis of variance: An advanced chemometric approach to differentiate dose‐dependent antioxidant activities of grape ( Vitis labruscana ) skin extracts

Multivariate analysis of variance (MANOVA) was performed to differentiate dose-dependent antioxidant properties of grape skin extracts and compare the detailed analysis of MANOVA using 12 multivariate post hoc tests. The antioxidant activities were assessed by in vitro antioxidant activity assays, and data were processed using MANOVA statistical and post hoc tests. Wilks's Λ reported significant differences, F(20, 20.85) = 46.57 (p < .0001, Wilk's Λ = 0.03 × 10−3), between dose-dependent and radical scavenging activities of grape skin extracts. The results of post hoc analyses demonstrated that Tukey's (single-step) and Duncan's (step-down) multiple range tests were suitable methods for evaluating multiple mean comparisons. Tukey's and Duncan's multiple range methods were recommended for MANOVA post hoc analysis. The new findings revealed the use of statistical analysis in order to prove scientific hypotheses. Moreover, MANOVA statistical analysis is an alternative for choosing MANOVA for comparison of multiple variables. Practical applications The study was designed to differentiate dose-dependent antioxidant properties of grape skin extracts and compare the detailed analysis of MANOVA using 12 multivariate post hoc tests. MANOVA statistical tests and post hoc tests could be an alternate and easy statistical approach for evaluating the mean differences among the samples. Moreover, it is also provided a theoretical basis for the selection of best statistical methods in order to prove research hypotheses.

Food Potential and Antioxidant Property of Cassia auriculata Seed: A Nutritionally Unexploited Legume

Background: Seeds of Cassia auriculata are reported to be used for varying medicinal purposes; however, information on nutritive value and physical properties of seeds remains unexplored. Hence, this study is carried out to investigate the proximate, minerals, fatty acid profile, functional properties, phenolic profiling as well as antioxidant activities of seed in order to give adequate information on its suitability as a possible future food source. Methods: The proximate compositions were evaluated by AOAC, and other standard prescribed methods. Minerals and fatty acids compositions were determined using Atomic Absorption Spectrophotometer and UV-visible spectrophotometers, while anti-nutrient determinations were carried out using standard procedures. Antioxidant activity and phenolic profiles were also analyzed using UVvisible spectrophotometers and HPLC. Results: The results obtained from proximate analysis were: moisture content (9.74%), ash content (4.95%), protein (23.83%), lipid (6.68%), crude fiber (8.93%), total soluble sugars (53.4%) and energy value (412.6 Kcal/100g). The mineral analysis showed that nitrogen, potassium and phosphorus were the predominant elements present in the seeds. Calcium, zinc, sodium, magnesium, copper, and iron were also detected in appreciable amounts. The analyzed anti-nutritional factors were oxalate (1.38 μg/mg), phytate (0.12 μ g/mg), tannin (3.02 μg/mg), phenol (1.11 μg/mg) and saponins (0.0037%). In the seeds oils, palmitic acid (14.01%) was prominent saturated fatty acid followed by stearic acid (5.12%) and arachidic acid (2.17%), while oleic acid (21.31%) and linoleic acid (51.52%) constituted the dominant unsaturated fatty acids. The physicochemical and functional properties revealed that the seeds flour had excellent water absorption index, swelling index, foaming capacity and foam stability. In addition to that, the flour extracts revealed the dose-dependent antioxidant properties of tested extracts of the seed flour. Moreover, the HPLC analysis unveiled four phenolic compounds namely, benzoic acid (0.72 μg/mg), cinnamic acid (0.71 μg/mg), salicylic acid (0.65 μg/mg) and vanillic acid (0.61 μg/mg). Conclusion: The results of the present study revealed that Cassia auriculata seed flour is a good source of important nutrients such as fat, protein, fibre and minerals along with edible phenolics. So the seeds would be a valuable source of dietary supplements especially for growing population and could be used for industrial and pharmaceutical purposes.

ANTI-INFLAMMATORY ACTIVITY OF NIGELLA SATIVA SILVER NANOPARTICLES: BIOCHEMICAL STUDY

Objective: The aim of this study is to evaluate the anti-inflammatory activity of Nigella sativa silver nanoparticles (NS AgNPs).&#x0D; Methods: Fourier transform infrared analysis was used to characterize the NS AgNPs and the extract. 2,2-diphenylpicrylhydrazyl assay was done to test the antioxidant potency of NS AgNP. Furthermore, in vitro anti-inflammatory activity of the extract and the NS AgNP was determined by red blood cell (RBC) membrane stabilization assay, protein inhibition assay, and interleukin-1 (IL-1) beta assay.&#x0D; Results: The NS AgNP exhibited dose-dependent antioxidant property. At the concentration 0.01 mg/ml 80% of radical was scavenged by NS AgNP. Inhibition of protein denaturation assay also suggests that NS AgNP shows the highest activity (70%) when compared with the standard drug aspirin (65%). RBC assay suggests that NS AgNP stabilizes the RBC membrane and prevents leaking. In the enzyme-linked immunosorbent assay method the NS AgNP showed better IL-1 beta inhibition activity when compared to aqueous extract.&#x0D; Conclusion: From the study, it was inferred that NS AgNPs are more effective when compared to the extract. These results suggest that NS AgNP can be used to treat inflammatory disorders.

ANTI-INFLAMMATORY ACTIVITY OF SYZYGIUM AROMATICUM SILVER NANOPARTICLES: IN VITRO AND IN SILICO STUDY

Objective: In the present study, antioxidant and anti-inflammatory activity of Syzygium aromaticum (clove) silver nanoparticles (clove AgNP’s) was evaluated.Methods: Gas chromatography-mass spectrometry technique was used to identify the compounds present in the aqueous extract of clove. Fourier transform infrared (FT-IR) analysis was done to characterize the clove silver AgNP’s. 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was performed to evaluate the antioxidant property of nanoparticles (0.05 and 0.25 mg/ml) and aqueous extracts (0.05, 0.1, and 0.25 mg/ml) of clove. The anti-inflammatory property of the clove AgNP’s was determined by inhibition of protein denaturation and downregulation of interleukin-1 beta. In silico molecular docking studies was performed using Schrodinger Maestro software.Results: Eugenol was found to be highest with 16.27%. The AgNP’s exhibited dose-dependent antioxidant property. AgNP’s scavenged 80% of radical at the concentration of 0.25 mg/ml. The scavenging activity of AgNP’s markedly increased when compared to aqueous extract at the same concentration. Inhibition of protein denaturation assay also revealed AgNP’s showing the highest activity (66%) when compared with drug aspirin (55%) and aqueous extract (56%). In the enzyme-linked immunosorbent assay (ELISA) method, AgNP’s showed better inhibition (80%) when compared to aqueous extract (60%). Among 15 compounds, two compounds (eugenol and methyl 14-methylpentadecanoate) showed good glide energy, docking score, and hydrogen-bonded active site interactions with the protein interleukin-1 beta.Conclusion: As AgNP’s were more active than the aqueous extract, it may be considered for pharmacological activity against inflammatory disorders.

Antioxidant activities of ginger extract and its constituents toward lipids

Lipid oxidation—a major cause of food product deterioration—necessitates the use of food additives to inhibit food oxidation. Ginger extract (GE) has been reported to possess antioxidant properties. However, components isolated from ginger have been rarely reported to inhibit fat oxidation. Herein, antioxidant properties of GE and four pure components derived from it (6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol) were examined and their properties were compared to those of butylated hydroxytoluene. GE and the constituent components exhibited antioxidant properties that might be attributed to their hydroxyl groups and suitable solubilizing side chains. 6-Shogaol and 10-gingerol exhibited higher activity at 60°C than 6-gingerol and 8-gingerol. Low antioxidant activity was detected at high temperatures (120/180°C). Overall, GE displayed the strongest dose-dependent antioxidant properties, especially at high temperatures, thereby demonstrating that GE can be employed as a natural antioxidant in lipid-containing processed foods.

Influence of analgesic active 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one on the antioxidant status, glucose utilization and lipid accumulation in some in vitro and ex vivo assays

Purpose: Earlier we demonstrated that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) elevates nociceptive thresholds in the mouse model of diabetic neuropathic pain. Since drug-induced impairments of glucose and lipid metabolism and the oxidative stress might diminish benefits from analgesia achieved by analgesic drugs used in diabetic neuropathy, the effect of LPP1 on glucose utilization, lipid accumulation and its antioxidant and cytotoxic potential were assessed in some in vitro and ex vivo tests.Methods: Total antioxidant capacity was evaluated spectrophotometrically using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method, whereas the activities of glutathione (GSH) peroxidase and reductase were measured using methods based on the oxidation of NADPH to NADP. The spectrophotometric method for the evaluation of GSH level in mouse brain tissue homogenates involved the oxidation of GSH by the sulfhydryl reagent 5,5′-dithio-bis(2-nitrobenzoic acid) (DTNB) to form a yellow derivative, 5′-thio-2-nitrobenzoic acid (TNB), measurable at 412 nm. Cytotoxicity and glucose utilization were measured in hepatoma HepG2 cells and in 3T3-L1 adipocytes. Lipid accumulation was measured in 3T3-L1 cell lines.Results: LPP1 had dose-dependent antioxidant properties in DPPH radical assay (14–22% versus control; p < 0.001). Its single administration caused an increase in GSH concentration in brain tissue homogenates of mice by 34% (versus control group; p < 0.05). LPP1 was not cytotoxic and it did not increase glucose utilization or lipid accumulation in cell cultures.Conclusions: Previously demonstrated antinociceptive properties of LPP1 are accompanied by a lack of cytotoxicity. LPP1 does not impair glucose or lipid metabolism and is an antioxidant. All these properties might be advantageous for its use in diabetic neuropathy.

Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice

Recently we have shown that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride (LPP1) is an antinociceptive and local anesthetic agent in rodents. Below an extended study of the pharmacological activity of LPP1 is described. In vitro LPP1 has no affinity for GABAA, opioidergic μ and serotonergic 5-HT1A receptors. The total antioxidant capacity of LPP1 (1–10mM) measured as ABTS radical cation-scavenging activity showed that LPP1 has dose-dependent antioxidant properties in vitro. Low plasma concentration of this compound detected by means of HPLC method 30min after its intraperitoneal administration suggests a rapid conversion to metabolite(s) which may be responsible for its analgesic and anticonvulsant activities in vivo.In vivo the compound's influence on the electroconvulsive threshold and its activity in the maximal electroshock seizure test (MES) were evaluated. The results demonstrated that LPP1 had an anticonvulsant activity in the MES model (ED50=112mg/kg) and at a dose of 50mg/kg was able to elevate the electroconvulsive threshold for 8mA as compared to the vehicle-treated mice. The analgesic activity of LPP1 was investigated in the acetic acid-induced writhing test in two groups of mice: animals with sensory C-fibers ablated, and mice with C-fibers unimpaired. It proved the potent activity of this compound in both groups (approximately 85% as compared to the vehicle-treated mice). The adverse effects of LPP1 were evaluated as acute toxicity (LD50=747.8mg/kg) and motor coordination impairments in the rotarod and chimney tests. The results from these tests show that LPP1 at doses higher than 100mg/kg is likely to impair the motor performance of experimental animals. Concluding, LPP1 is an analgesic and anticonvulsant compound which has antioxidant properties in vitro. Further studies are necessary to assess whether the antioxidant activity and the receptor profiling demonstrated in vitro can be confirmed for its metabolite(s) that are formed in vivo.

Comparison of the antioxidant properties of wound dressing materials–carboxymethylcellulose, hyaluronan benzyl ester and hyaluronan, towards polymorphonuclear leukocyte-derived reactive oxygen species

In chronic wounds, factors are released which perpetuate inflammatory processes, including polymorphonuclear leukocyte (PMN)-derived reactive oxygen species (ROS), such as superoxide radical (O 2 − ) and hydroxyl radical ( OH) species. The glycosaminoglycan, hyaluronan, has established antioxidant properties towards ROS, although the antioxidant potential of wound dressing biomaterials, such as 75% benzyl esterified hyaluronan (BEHA) and carboxymethylcellulose (CMCH), are less characterised. This study compared the antioxidant properties of high and low molecular weight hyaluronan (HMWT HA and LMWT HA), BEHA and CMCH towards ROS, generated by stimulated PMN in vitro. The antioxidant capacities of each biomaterial were assessed by their inhibition of O 2 − -induced cytochrome C reduction, generated via PMN stimulation by phorbol myristyl acetate (PMA); and their inhibition of OH-induced 2-deoxy- d-ribose degradation, generated by PMA stimulated PMN in the presence of a ferric chloride-EDTA chelate. All biomaterials, except LMWT HA, possessed dose-dependent antioxidant properties against O 2 − , BEHA having greatest antioxidant potential, followed by HMWT HA and CMCH. HMWT HA exhibited the highest dose-dependent antioxidant properties towards OH, followed by BEHA and CMCH. LMWT HA demonstrated no antioxidant properties towards OH. These antioxidant activities, particularly towards O 2 − , may be beneficial in removing the initial source of ROS necessary for the secondary formation of OH, implicated as a causal factor for the extensive metabolic alterations observed in chronic wounds.

Comparison of the antioxidant properties of HYAFF ®-11p75, AQUACEL ® and hyaluronan towards reactive oxygen species in vitro

In chronic wounds, a number of host factors are released which perpetuate the inflammatory process, including polymorphonuclear leukocyte (PMN)-derived reactive oxygen species (ROS), such as superoxide radical (O 2 − ) and hydroxyl radical ( OH) species. The glycosaminoglycan, hyaluronan, has been shown to act as an antioxidant towards ROS, although the potential for biomaterials, such as HYAFF ®-11p75 (the 75% benzyl ester of hyaluronan) and AQUACEL ® (carboxymethylcellulose), to act in this manner has yet to be elucidated. This study compared the antioxidant properties of high and low molecular weight hyaluronan (HMWT HA and LMWT HA), HYAFF ®-11p75, AQUACEL ® and an AQUACEL ®/hyaluronan composite (AQUACEL ®/HA) against O 2 − and OH. The antioxidant capacities of each material were assessed by their ability to inhibit cytochrome C reduction by O 2 − fluxes, generated via the oxidation of hypoxanthine by xanthine oxidase, and their inhibition of 2-deoxy- d-ribose degradation by OH fluxes, generated by the reaction of hydrogen peroxide (H 2O 2) and iron (Fe 2+). All materials studied possessed dose dependent antioxidant properties towards O 2 − , with HYAFF ®-11p75 having the greatest antioxidant potential towards these species, followed by AQUACEL ®, HMWT HA, AQUACEL ®/HA and LMWT HA. Only HMWT HA exhibited dose dependent antioxidant properties towards OH at the fluxes examined. Gas chromatography/mass spectrometry analysis implied that ester bonds between the hyaluronan backbone and benzyl groups of HYAFF ®-11p75 are highly susceptible to O 2 − hydrolysis, with the de-esterified benzyl alcohol being rapidly degraded in the presence of OH. This data supports the hypothesis that HYAFF ®-11p75 has greater antioxidant capacity towards O 2 − , due to the esterified benzyl groups providing alternative sites for O 2 − attack other than the hyaluronan backbone of HYAFF ®-11p75 itself and explains the inability of HYAFF ®-11p75 to scavenge OH, due to benzyl alcohol degradation by OH. The antioxidant activities of these biomaterials, particularly HYAFF ®-11p75 and AQUACEL ®, towards O 2 − could be beneficial, as the scavenging of PMN-derived O 2 − may remove initial sources of O 2 − and further prevent the secondary formation of OH. These ROS are thought to be a primary causal factor for the extensive degradation and metabolic alterations observed in chronic wounds.