ABSTRACT

Background: Oxidative stress is implicated in the pathogenesis of many chronic diseases such as diabetes, cancer, and rheumatic arthritis.

Objectives: This study determined the bio-efficacy of methanol and chloroform extracts of B. brieyi root bark on inflammation-induced oxidative stress in Wistar rats.

Methods: Oxidative stress was induced in Wistar rats using cotton pellet-induced inflammatory model. The rats were treated with 50, 100, and 200 mg/kg body weight of methanol and chloroform extracts of B.brieyi and 50 mg/kg of indomethacin (standard drug) for 7 days. On day 8, their blood collected by cardiac puncture was used for the determination of biochemical parameters of oxidative stress such as the extent of lipid peroxidation, reduced glutathione, vitamins C and E as well as zinc, selenium, and iron concentrations along with antioxidant enzymes activities using standard methods. The bioactive compounds responsible for bioactivity were determined with Fourier transform infrared spectroscopic (FTIR) and Gas chromatography-mass spectrometry (GC-MS) techniques.

Results: There were significant (p < 0.05) decreases in malondialdehyde concentration, an increase in reduced glutathione, zinc, and selenium concentrations, superoxide dismutase, and catalase activities and a decrease in serum iron was observed in the extracts and indomethacin-treated groups when compared with the untreated group. A total of sixteen bioactive compounds with known antioxidant and anti-inflammatory activities were identified in the extracts with 9-Ocadecenoic acid being the most abundant.

Conclusion: The result of this study suggests that B. brieyi has antioxidant activities, and hence could be used in the management and treatment of oxidative stress-related diseases.

Oxidative stress is known to be the main factor involved in neurodegeneration and its aggravation is often associated to pro-oxidant molecules crossing blood-brain barrier. In this context, the investigation of the redox behavior of central acting drugs might provide relevant data to describe either if these compounds could end up promoting the genesis of reactive oxygen species (ROS), or scavenge them. Among the most commercialized central acting drugs in the marked is tramadol (TRA), whose biological activities are achieved by interaction with several bodily receptors such as μ-opioid receptor. The chronic intake of TRA is reported to enhance oxidative stress and promote neurodegeneration, what henceforth suggests this compound to exert pro-oxidant activities. This work therefore targeted the investigation of TRA redox behavior through electrochemical and quantum chemistry approaches (i.e. voltametry and Extended Hückel Method – EHM, respectively) in order to shed light on the thermodynamic and kinetic features associated to TRA pro-oxidant nature. Quantum chemistry results by EHM showcased that the energy gap between the highest occupied molecular orbitals (HOMO-n) and the lowest unoccupied molecular orbital (LUMO-n) as well as their displacements in the rendered model suggests that TRA tertiary amine and the aromatic ring moieties would be the most likely regions wherein oxidation and reduction would take place, respectively. Considering that previous outreaches showcase the correlation of HOMO-n and LUMO-n to various oxidation and reduction states in molecules, HOMO-0 therefore suggests the most thermodynamically feasible site for the first TRA oxidation (i.e. tertiary amine), whereas HOMO-1 and LUMO-0 suggests that the second oxidation and first reduction would most likely take place at TRA aromatic ring. The electrochemical results showcased that TRA presents two anodic peaks (1a and 2a) at electric potentials of +0.1 and +0.8 V, which are associated to the oxidation of electroactive moieties in TRA molecule. A cathodic process (1c) was also detected and it was seemingly associated to anodic peak 1a, hence suggesting a quasi-reversible reaction. Through these findings, an electro-oxidation pathway was proposed, depicting the oxidation of the tertiary amine, followed by demethylation and the formation of a catechol-quinone redox system, which was corroborated by the findings of other authors. The low kinetic associated to peaks 1a and 1c suggests that few molecules undergo this process. In this sense, considering that endogenous antioxidants are known to reduce ROS at electric potentials below +0.5 V due to favorable thermodynamic, TRA seemingly does not showcase noteworthy antioxidant potential. The second oxidation peak (2a) was seemingly irreversible, and taking into account that oxidation reactions are known to render highly energetic compounds (i.e. ROS), the voltammetric profile of TRA suggests pro-oxidant properties. Therefore, this work showcased how electrochemistry and EHM can be associated to readily investigate the redox behavior of central acting drugs under low cost, and shed light on their pro-oxidant or antioxidant potential.

The Hops (Humulus lupulus L.) are known worldwide as an essential flavor in the beer industry. Its compounds have been showing health benefits in terms of phytochemical, pharmacological and biological profiles, due to their antimicrobial, antioxidant, anti-inflammatory and anticancer activities. This study intends to develop a gel formulation incorporating hydroalcoholic extracts of different varieties of hops such as Cascade, Polaris and Spontaneous, from the cones and the vegetative plant parts, in different percentages. The essential oil of Thymus zygis was used as a natural conservative and the analysis of the composition was made by GC and GC-MS. Later evaluation of the physical-chemical parameters, stability and capacity to inhibit microbial growth was made . The pH measurement results of the formulations tend to be adjusted to the natural pH skin. The relative density obtained values ​​of 1 and 0.857. It was found that there were no changes in the phase separation in the centrifugation, vibration, stability and accelerated test. However, changes were observed in the UV-Visible spectra, in texture, consistency and viscosity, and in the color test. In the light test there was phase separation in the samples, which may be related to the manufacturing technique of the formulations. However, this formulations anti aging with phenols from Hop can be development in order to obtain formulations with relevant properties for the consumers and the cosmetic industry.

Zingiber officinale Roscoe (Zingiberaceae), common known as ginger, is extensively used as spice worldwide in cooking and to prepare beverage. Moreover, it was used to treat a wide range of diseases including metabolic syndrome (MetS). Mets is a group of risk factors, including insulin resistance and consequently impaired glucose tolerance, dyslipidaemia, obesity, and hypertension. It is estimated that that MetS affects 25% of the population [1]. The efficacy of natural products especially derived from vegetables and spice largely consumed worldwide is a topic of great interest not only to cure but also to prevent the onset of the disease. In this study the influence of organic (OR) and conventional (CONV) agricultural practices on chemical profile and nutraceutical properties of Zingiber officinale Roscoe spice was evaluated. A multi-target approach was used to test the antioxidant activity by using DPPH, ABTS, β-carotene bleaching, and FRAP assays. The anti-obesity effect was investigated through inhibition of lipase and carbohydrate hydrolyzing enzymes a-amylase and a-glucosidase [2]. Ginger bioactive compounds were extracted by ultrasound assisted maceration process with ethanol. OR Ginger (Z5) showed the highest TPC and TFC with values of 39.27 and 15.38 ug/g DW. This sample resulted the most active in all applied antioxidant test with particular reference to ABTS test where Z5 showed a stronger activity with IC₅₀ value of 0.81 ug/mL in comparison to the positive control ascorbic acid (1.70 mg/mL). RACI and GAS statistical approach confirmed the Z5 highest antioxidant potency. Moreover, Z5 exhibited a promising lipase inhibitory activity with IC₅₀ value quite similar to the positive control orlistat (IC₅₀ values of 34.48 vs 37.42 ug/mL). Collectively, our results demonstrated the impact of agricultural practices on ginger health properties. However, further in vivo studies will be needed to confirm the potential in humans and prove the safety of the products.

[1] Rochlani, Y.; Pothineni, N.V.; Kovelamudi, S.; Mehta, J.L. Metabolic syndrome: Pathophysiology, management, and modulation by natural compounds. Ther. Adv. Cardiovasc. Dis. 2017, 11, 215–225. [2] Leporini, M.; Loizzo, M.R.; Sicari, V.; Pellicanò, T.M.; Reitano, A.; Dugay, A.; Deguin, B.; Tundis, R. Citrus × Clementina Hort. Juice Enriched with Its By-Products (Peels and Leaves): Chemical composition, in vitro bioactivity, and impact of processing. Antioxidants 2020, 9, 298.

Daphne L. is one of the most diverse genera in the Thymelaeaceae family, with over 90 described species distributed in Asia, parts of North Africa, and Europe. Several species of this genus are used in traditional medicine for their antimicrobial, anticancer, anti-inflammatory, antitussive, and anti-rheumatic properties [1]. Terpenoids, phenols coumarins, lignans, and flavonoids are the most important classes of compounds identified in the genus Daphne [1].

Alzheimer’s Disease (AD) is the most common cause for dementia in ageing population. The primarily degenerative condition is characterized by the formation of amyloid plaques, neurofibrillary tangles and loss of neurons and synapses as well. Research revealed early a degeneration of cholinergic nuclei localised in the basal forebrain. Impairment of this cholinergic system is followed by disturbance of attentional processes and cognitive decline. AChE inhibitors are currently the best established treatment for this disease.

In this study, Daphne laureola L., a European-Mediterranean species [2] was investigated for its antioxidant properties using four bioassays, namely 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Activity Power (FRAP), and b-carotene bleaching assays, and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity using the in vitro Ellman’s method [3,4]. The aerial parts of D. laureola, collected in Sila, Calabria, S Italy (voucher in PI), were subjected to exhaustive and subsequent macerations with solvents at different polarity, such as methanol, dichloromethane, and n-hexane. Dichloromethane extract was the most promising in DPPH and FRAP tests with IC₅₀ values of 32.22 microg/ml and 71.50 microM Fe(II)/g, respectively. Methanol extract showed the most promising inhibition of lipid peroxidation evaluated by b-carotene bleaching test with an IC₅₀ value of 6.61 microg/ml after 30 min of incubation. This extract was the most active against AChE (IC₅₀ value of 56.7 microg/ml). An interesting result was obtained against BChE by the n-hexane extract, with an IC₅₀ value of 49.6 microg/ml. In conclusion, the results suggest that D. laureola may provide a substantial source of phytochemicals, which act as natural antioxidants and acetylcholinesterase inhibitors, and may be beneficial in the treatment of AD.

[1] Moshiashvilia, G.; Tabatadze, N.; Mshvildadze, V. The genus Daphne: a review of its traditional uses, phytochemistry and pharmacology. Fitoterapia 2020, 143, 104540. [2] Pignatti, S. Flora d'Italia ed. 2, 2017, 2, 1040-1045. New Business Media, Milano. [3] Tenuta, M.C.;, Brigitte Deguin, B.; Loizzo, M.R.; Dugay, A.; Acquaviva, R.; Malfa, G.A.; Bonesi, M.; Bouzidi, C.; Tundis, R. Contribution of flavonoids and iridoids to the hypoglycaemic, antioxidant, and nitric oxide (NO) inhibitory activities of Arbutus unedo L. Antioxidants 2020, 9, 184. [4] Loizzo, M.R.; Ben Jemia, M.; Senatore, F.; Bruno, M.; Menichini, F.; Tundis, R. Chemistry and functional properties in prevention of neurodegenerative disorders of five Cistus species essential oils. Food and Chemical Toxicology 2013, 59, 586.

Citrus fruits (Rutaceae) are an important source of bioactive compounds such as ascorbic and hydroxycinnamic acids. Citrus peels contain significant amounts of phenolic compounds especially phenolic acids and flavonoids.

The citrus fruit residues, which are usually discarded as waste can be used as nutraceutical resources. The utilization of these bioactive rich citrus residues can serve for the production of novel products or for the improvement of those already in use. Orange peel contains significant amounts of phenolic compounds especially phenolic acids and flavonoids, thus we can consider it a potential material for the formulation of nutraceuticals and food preservatives and may be used as a possible functional ingredient in alimentary products such as marmalade.

The industrial manufacture of fruit jams requires constant gel strength during production; consequently, commercial pectin is added to minimize the effect of the variability of native fruit pectin. Orange marmalade is generally prepared by boiling fruit pulp with sugar, pectin, acid and other ingredient (preservatives, coloring, and flavorings).

The aim of this study was to investigate the effect of adding dry (Citrus x sinensis) peel to orange marmalades as an alternative to pectin, and to evaluate product stability.

The product stability and the antioxidant effect on shelf life of this enriched marmalade were evaluated. In particular, the hydroxymethylfurfural formation in correlation with major bioactive compounds, antioxidant assay, total phenols and anthocyans were estimated during storage at 18 and 30 °C for 140 days. The level of phenols ranged from 70.27 to 152.01 mg/100 g for control samples and from 108.18–146.02 mg/100 g for enriched samples. Obtained data show that incorporation of orange peel in marmalade production can be a valid use of this by-product. After storage, the enriched samples at 18°C maintained the analytical parameters better than the samples stored at 30°C.

Oxidative stress has been implicated in many chronic diseases and the use of natural antioxidants has been suggested to be beneficial in the prevention and management of some chronic diseases. Deep Root^® herbal mixture (DRHM) is a branded Nigerian polyherbal drug composed of Cymbopogon citratus (17%), Carica papaya leaves (16%), Magnifera indica bark (15%), Moringa oleifera leaves (14%), Citrus limonia (12%), Psidium guajava (11%), Zingiber officinale root (9%) and Allium sativium (6%). Considering the bioactivities of the individual plant components in literature and the indications for managing chronic diseases, the potential of modulating hydrogen peroxide (H₂O₂)-induced oxidative stress in rats by DRHM was assessed. Thirty healthy male Wistar rats used for this study were divided into six groups of five rats each with group 1 serving as normal control - was neither intoxicated nor treated with any drug. Groups 2-6 were intoxicated (3 ml/kg b.w of 5% v/v of H₂O_2, i.p). Group 2 served as H₂O₂ control, groups 3-5 received 1, 2 and 3 ml/kg/d b.w. p.o of DRHM, respectively while group 6 was given silymarin (100 mg/kg/d. b.w. p.o) for 14 days. The hematological, liver, lipid peroxidation and antioxidant status of H₂O₂-intoxicated rats were evaluated. H₂O₂ elevated aspartate and alanine aminotransferases activities, and malondialdehyde and total bilirubin levels (p < 0.05). Conversely, H₂O₂ decreased superoxide dismutase, catalase and glutathione peroxidase activities, and antioxidant vitamins and reduced glutathione levels, hemoglobin concentration, packed cell volume, red blood cell, white blood cell and platelet counts (p < 0.05). However, in a dose-dependent manner, DRHM reversed the hematological status and attenuated oxidative damage to hepatic tissues likely by enhancing antioxidant defense system. This effect may be attributed to the phytoconstituents detected in DRHM. The polyherbal drug was shown to be tolerable up to 10 ml/kg. b.w. dose.

Italian gastronomy experiences have ever-enhancing fame around the world. It is due to the linkage between taste and salubriousness commonly related to Mediterranean foods. The market proposes many types of pizza to suit all palates. In this work, the antioxidant potential of the "pizza “marinara” included in the register of traditional specialties guaranteed (TSG) was determined. ABTS method evaluated the antioxidant activity of the pizza homogenized. In vitro digestion models estimated the intestinal and gastric bioaccessibility of the main antioxidant compounds (lycopene and phenolics). To our knowledge, this is the first study to provide the content, antioxidant potential, and bioaccessibility of the antioxidants (polyphenols and lycopene) contained in the traditional pizza “marinara TSG”. Our results showed that the "pizza marinara TSG" had polyphenols concentration, lycopene level, antioxidant activity, and bioaccessibility of phenolic compounds and lycopene better than other similar pizzas. They confirmed the nutritional importance of traditional preparations and established the functional potential of "pizza marinara TSG" as a food rich in bio-accessible antioxidants.

Intake of olive oil as the main source of fat in Mediterranean diet is related to positive effects on human health. The olive biophenol hydroxytyrosol (HT) is considered a promising cancer chemopreventive compound against different types of cancer. The aim of the present study was to compare the cytotoxic activity against prostate cancer (PCa) cell lines of HT, obtained from olive mill wastewaters, and five semisynthetic alkyl ether, ester, and nitro-derivatives. HT, hydroxytyrosyl acetate (HT-Ac) and ethyl hydroxytyrosyl ether (HT-Et) exerted higher cytotoxic effect against 22Rv1 and PC-3 PCa cell lines than in non-malignant RWPE-1 cells. These compounds also significantly decreased the migration rate of RWPE-1 and PC-3 cells and the colony and prostatosphere formation of 22Rv1 cells. However, HT-Ac and HT-Et, but not HT, were able to decrease p-AKT levels and colony and prostatosphere formation in PC-3. In sum, HT and its lipophilic derivatives could be considered as potential therapeutic tools in PCa.

Asthma is one of the most common respiratory diseases, with airway inflammation as the most prominent pathological feature. Although originally believed to be a single disease, it is now recognized as a complex of multiple phenotypes, with different degrees of severity and treatment responses. The severe inflammatory state becomes apparent when reactive oxygen species overwhelm the antioxidant defense. Thus the oxidant-antioxidant imbalance plays an important role in airway inflammation. It is well documented the role of oxidative stress (OS) in the increase of chromosome instability (CI), and, consequently, in cancer predisposition. So it is important to carry out studies in order to establish limits for harmful effects with carcinogenic potential.

The aim of this study was to evaluate cellular levels of OS-related CI in asthma patients and the possible protective effect of antioxidants. For that purpose, spontaneous and 1,2,3,4-diepoxybutane (DEB)-induced lymphocyte cultures from patients with mild and severe asthma were performed. Lymphocyte cultures from healthy donors, at the same conditions, were used as control. Antioxidant-enriched (N-Acetylcysteine+α-lipoic acid) lymphocyte cultures from severe patients were posteriorly performed. A hundred metaphases per culture were scored in order to estimate the relative frequency of CI.

Our results showed that lymphocytes from severe asthma patients had a significant increase of CI, both in spontaneous and DEB-induced cultures. However, in lymphocytes from mild asthma patients there were no significant differences compared to controls. This suggests that in patients with severe asthma, subjected to extreme OS conditions, a possible genotoxic effect may occur at the cellular level. When the lymphocytes from these patients were subjected to an antioxidant treatment, a significant and consistent decrease in levels of CI was observed.

Understanding how CI due to exposure to OS correlates to asthma patients clinical characteristics may be pivotal to the design of preventive measures or patient-specific treatments.