Synergistic Antioxidant Effect Research Articles

Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6) Mimicking Enzyme as Synergistic Antioxidant and Anti-Inflammatory Material for Periodontitis Therapy.

Periodontitis is an inflammatory disease induced by plaque microorganisms. In the clinic, antibiotic assistant periodontal mechanical therapy is the most effective therapy for the treatment of periodontitis. However, the drug resistance of the antibiotics and the repeated coming and diminishing of the disorder of oxidation-reduction balance in the inflammatory tissue could not meet the high requirements for periodontic health control in long periods. Deuterohemin-ala-his-thr-val-glu-lys (DhHP-6) is a biomimetic oxidase-mimicking enzyme that simulates the reactive oxygen radical scavenger function of heme by synthesizing the new molecular material following the key structure and amino acid sequence of heme. In this article, we report the antioxidant and anti-inflammatory properties of DhHP-6 by building a inflammatory model for human gingival fibroblasts (HGFs) stimulated by lipolysaccharide (LPS) and its effects on periodontitis in Wistar rats. DhHP-6 reduced the oxidative stress of HGFs by increasing the amount of the reductase species of glutathione (GSH) and catalase (CAT) while decreasing the amount of oxidase species of malonaldehyde (MDA) and reactive oxygen species (ROS). DhHP-6 had a dose-dependent protective effect on alveolar bone absorption in rats with periodontitis, enhanced antioxidant capacity, and reduced inflammation. As determined by Micro-CT scanning, DhHP-6 reduced alveolar bone loss and improved the bone structure of the left maxillary first molar of rats. There were no obvious morphological and histological differences in the rat organs with or without DhHP-6 treatment. These results suggest that DhHP-6 can be used to treat periodontitis by increasing the expression levels of antioxidant enzymes and antioxidants in systemic and local tissues, thereby reducing levels of oxidation products and cyto-inflammatory factors. The synergistic antioxidant and anti-inflammatory effects of DhHP-6 suggest that there are promising applications of this biomimetic enzyme molecular material for the next generation of agents for periodontitis therapy.

The synergistic antioxidant effect of polydopamine coating with amino-functionalized graphene quantum dots on osteoblast protection against oxidative stress

Oxidative stress is a major pathological feature in patients with metabolic bone diseases and isn’t conducive to postoperative osseointegration of implants. Although the free-radical scavenging activities of polydopamine (PDA) have been reported, its antioxidant-active catechol structure is susceptible to oxidation. Here, amino-functionalized graphene quantum dots (GQDs) were introduced into PDA to protect catechol structure from oxidation and expand its free-radical scavenging capacity. Compared to the clinically used hydroxyapatite (HAp) coating and the PDA-HAp coating, the GQD/PDA-HAp coating exhibited higher capacity to scavenge ABTS·+, DPPH and O2·-. The enhanced antioxidant effect of the GQD/PDA-HAp coating was ascribed to the combined effects of the sp2-hybridized carbon in GQDs and more catechol groups in PDA, indicating the synergistic antioxidant relationship between GQDs and PDA. In addition, the amino-functionalized GQDs increased the catechol content and the reducibility of the GQD/PDA coating as confirmed by Folin-Ciocalteu colorimetric assay and mediated electrochemical probing. In vitro studies showed that the GQD/PDA-HAp coating minimized intracellular reactive oxygen species production and protected osteoblast viability against H2O2-induced oxidative stress. Taken together, introducing amino groups in PDA is an efficient approach to preserve its structural related antioxidant properties which may broaden its application in treating oxidative stress-related diseases.

The protective effect of rivaroxaban with or without aspirin on inflammation, oxidative stress, and platelet reactivity in isoproterenol-induced cardiac injury in rats.

Coronary artery diseases are principal sources of mortality and disability in global human population. Progressively, rivaroxaban is being evaluated for the prevention of atherosclerotic thrombi, particularly with anti-platelet agents. Hence, the current report aimed to investigate the cardioprotective effect of rivaroxaban on isoproterenol (ISO)-induced cardiac injury model in rats and the possible synergistic effect when combined with aspirin. Male Wistar rats were randomly assigned into five different groups. Cardiac injury was induced by subcutaneous injection of ISO (85mg/kg) for 2 consecutive days. Rat tail bleeding time was performed prior to sacrifice. Cardiac enzymes, platelet activity, inflammatory, and oxidative stress biomarkers levels were measured using enzyme-linked immunoassay (ELISA). Pre-administration of rivaroxaban alone and on combination with aspirin prevented ISO-induced increase in cardiac thiobarbituric acid reactive substances (TBARS), interleukin 6 (IL-6), and thromboxane B2 (TXB2) levels. Moreover, a significant prolongation of bleeding time was demonstrated among aspirin, rivaroxaban, and aspirin plus rivaroxaban treated groups. On the other hand, the combination treatment of aspirin plus rivaroxaban showed no marked difference in these biomarkers and bleeding time relative to either drug administered separately. However, a prominent decrease of cardiac 6-keto prostaglandin F1α (6-Keto-PGF1α) level was displayed in the combination treatment when compared with ISO and rivaroxaban-treated groups, whereas no significant improvement was seen in cardiac glycoprotein V (GPV) levels except in aspirin-treated group. The study results demonstrated that rivaroxaban decreases cardiac oxidative stress, inflammation, and platelets reactivity. However, the addition of rivaroxaban to aspirin did not seem to show synergistic antioxidant, anti-inflammatory, or antiplatelet effect.

Safe by Design of nanomaterials in industrial production processes: nanomaterials in the cosmetic field

Cosmetic pleasantness of products containing inorganic UV filters depends on an unwanted whitening effect which is inversely correlated to their size. To overcome this effect, diameter has been reduced to nanosized but thus increasing the surface area and biological reactivity and carrying questions about the safety of humans and environment. Following a “safe and sustainability by design” approach, we designed a new class of optimized sunscreen UV filters by chemical functionalization of ZnO and TiO2 with Oxisol. If compared with the simple physical mixture, the new coated filters show different properties and benefits: a higher SPF (ISO 24443:2012), a better cytotoxic profile (MTT and NRU assay), a radical scavenging action (PCL assay) and an improved safety profile with a strong reduction of photocatalytic activity (Acid blue 9 test). In conclusion, our Safe by Design (acronym SbD) approach presents a new generation of UV filters bonded with booster molecules (by means of synergistic antioxidant effects) as the best compromise in the conscientious UV protection.

Mixture of Tomato and Lemon Extracts Synergistically Prevents PC12 Cell Death from Oxidative Stress and Improves Hippocampal Neurogenesis in Aged Mice.

Dietary habits have a great impact on one's health, especially in cognitive decline. Tomato and lemon contain diverse bioactive compounds and possess various effects, including the enhancement of cognitive function. We observed the protective effect of tomato, lemon extract and the mixture of them on H2O2-induced cytotoxicity of PC12 cells. To measure the in vivo effect in a murine model, each extract was orally administered to forty 1-year-old mice for 6 weeks, and a novel object recognition (NOR) test was performed to observe cognitive function, and hippocampal neurogenesis was observed through a doublecortin (DCX) stain. PC12 cell death by oxidative stress was reduced by pretreating with each extract, and a synergistic reduction was observed in the mixture. Newly generated DCX-positive neurons were synergistically increased in the hippocampus by the mixture. NOR test showed a tendency to significantly improve age-related cognitive dysfunction by consuming the mixture of tomato and lemon. In conclusion, tomato and lemon extracts can reduce cellular oxidative stress and increase NOR, likely due to enhanced neurogenesis, while the mixture of the two showed synergistic anti-oxidative effects and hippocampal neurogenesis.

Phytochemical Evaluation and Antioxidant Potential of Polyherbal Extract Mixture-an In Vitro and In Silico Study.

Standardisation of polyherbal formulations plays a key role in estimating the quality and safety of drugs. In this study, a novel polyherbal formulation was prepared for the treatment of diabetic nephropathy and it was attempted to evaluate for its safety and efficacy against free radicals. To ascertain the safety of the formulation, individual herbs and polyherbal formulation have been screened for microbial load, heavy metals, pesticide residues and aflatoxins according to Ayush guidelines. Phytochemical analysis was carried out using standard procedures and GCMS analysis to identify the bioactive compounds. Antioxidant methods such as DPPH, nitric oxide, hydrogen peroxide, hydroxyl and superoxide radical scavenging assays were undertaken. To predict the mechanism behind the antioxidant efficacy, a molecular docking analysis was performed against Keap1/Nrf2 (PDB ID: 2FLU) protein using AutoDock Vina software. Phytochemical analysis showed the presence of alkaloids, tannins, flavones, glycosides, polyphenols, phytosterols and saponins. The results of in vitro antioxidant studies showed increase in percentage inhibition with increase in concentration and found no significant difference compare with standards. Among the 15 bioactive compounds identified from GCMS analysis, guanosine showed high binding affinity with Keap1/Nrf2 and interacting with similar residues as that of standard ascorbic acid which is analysed through molecular docking. Based on the results, it has been concluded that the safety parameters of polyherbal formulation were found within specified limits of Ayush guidelines and its efficacy against oxidative stress plays an effective role to treat diabetic nephropathy due to its synergistic antioxidant effect.

Synergistic antioxidant effects of natural compounds on H2O2-induced cytotoxicity of human monocytes.

Natural compounds are endowed with a broad spectrum of biological activities, including protection against Toxins. Most of them are known for their antioxidant and radical scavenging activities. However, the synergistic combination of these natural molecules is not well studied. Therefore, the present study aims first to investigate the effect of four potent natural molecules [rosmarinic acid (Ros-A), ellagic acid (Ella-A), curcumin (Cur), and syringic acid (Syr-A)] on H2O2 -induced cell cytotoxicity and oxidative stress on the human monocytes (THP-1) and then to evaluate their combined action effect. Optimal combinations of these molecules were predicted using an augmented mixture design approach. In the first, as preliminary antioxidant activities screening, two in vitro assays were adopted to assess the single radicals scavenging activity of these natural compounds, DPPH• and ABTS• + tests. Based on the results obtained, the multitude of optimal formulas proposed by the mixture design study led to choosing four potent compositions (comp) in addition to ellagic acid, proposed as the most efficient when applied alone. The different molecules and mixtures were used to assess their cytoprotective effect on THP-1 cells in the presence and absence of H2O2. The most potent Comp-4, as well as the molecules forming this mixture, were exploited in a second experiment, aiming to understand the effect on oxidative stress via antioxidant enzyme activities analysis in the H2O2-induced oxidative stress in the THP-1 cell line. Interestingly, the natural molecules used for THP-1 cells treatment exhibited a significant increase in the antioxidant defense and glyoxalase system as well as suppression of ROS generation evaluated as MDA content. These results indicate that the natural compounds tested here, especially the synergistic effect of Cur and Ros-A (Comp-4), could serve as cytoprotective and immunostimulant agents against H2O2-induced cytotoxicity THP-1 cells, which makes them interesting for further investigations on the molecular mechanisms in preclinical animal models.

Inhibitive effect of cryoprotectants on the oxidative and structural changes in myofibrillar proteins of unwashed mince from silver carp during frozen storage

Silver carp is a type of Asian carp that poses a threat to the United States. Unfortunately, producing Asian carp surimi in the US has been unsuccessful due to the high cost. Thus, exporting Asian carp to China and other Asian countries in the form of frozen deboned fish mince (without washing) would be a new way to create commercial value. This study was to explore the effects of compound cryoprotectants CC (sucrose, sorbitol, and sodium tripolyphosphate) and CC + SD (salted egg white) on unwashed silver carp mince during frozen storage. In the presence of CC, unwashed mince exerted benefits on gel property and water holding property. CC was able to retard protein oxidation as indicated by the retarded carbonyl content and lower loss in sulfhydryl content. Based on indicators of content of salt-soluble protein, α-helix, myosin heavy chain and intrinsic fluorescence intensity, CC addition inhibited protein aggregation by protecting the protein structure. The inclusion of SD did not show a cryoprotective effect or synergistic antioxidant effect with sucrose-sorbitol, but SD improved the gel strength within 4 weeks of freezing. Thus, CC can provide cryoprotective protection during frozen storage of silver carp mince. CC + SD provides a reference for long-distance transport and off-site production of frozen silver carp mince.

Nanostructured Lipid Carrier-Based Codelivery of Raloxifene and Naringin: Formulation, Optimization, In Vitro, Ex Vivo, In Vivo Assessment, and Acute Toxicity Studies.

This work aimed to develop dual drug-loaded nanostructured lipid carriers of raloxifene and naringin (RLX/NRG NLCs) for breast cancer. RLX/NRG NLCs were prepared using Compritol 888 ATO and oleic acid using a hot homogenization–sonication method and optimized using central composite design (CCD). The optimized RLX/NRG NLCs were characterized and evaluated using multiple technological means. The optimized RLX/NRG NLCs exhibited a particle size of 137.12 nm, polydispersity index (PDI) of 0.266, zeta potential (ZP) of 25.9 mV, and entrapment efficiency (EE) of 91.05% (raloxifene) and 85.07% (naringin), respectively. In vitro release (81 ± 2.2% from RLX/NRG NLCs and 31 ± 1.9% from the RLX/NRG suspension for RLX and 93 ± 1.5% from RLX/NRG NLCs and 38 ± 2.01% from the RLX/NRG suspension for NRG within 24 h). Concurrently, an ex vivo permeation study exhibited nearly 2.3 and 2.1-fold improvement in the permeability profiles of RLX and NRG from RLX/NRG NLCs vis-à-vis the RLX/NRG suspension. The depth of permeation was proved with CLSM images which revealed significant permeation of the drug from the RLX/NRG NLCs formulation, 3.5-fold across the intestine, as compared with the RLX/NRG suspension. An in vitro DPPH antioxidant study displayed a better antioxidant potential of RLX/NRG in comparison to RLX and NRG alone due to the synergistic antioxidant effect of RLX and NRG. An acute toxicity study in Wistar rats showed the safety profile of the prepared nanoformulations and their excipients. Our findings shed new light on how poorly soluble and poorly permeable medicines can be codelivered using NLCs in an oral nanoformulation to improve their medicinal performance.

Nanoparticles of Lignins and Saccharides from Fishery Wastes as Sustainable UV-Shielding, Antioxidant, and Antimicrobial Biofillers.

Lignin nanoparticles containing saccharides from fishery wastes were prepared as sustainable biofillers for advanced materials. Organosolv lignin and Kraft lignin were used as polyphenol components in association with chitosan and chitooligosaccharides. The chemophysical and biological activities of lignin/saccharide nanoparticles, such as UV-shielding, antioxidant, and antimicrobial activities, were found to be dependent on both molecular weight and deacetylation degree of saccharides, with the best performance being obtained in the presence of low-molecular-weight and highly deacetylated chitooligosaccharides. In addition, chitooligosaccharides showed a synergistic antioxidant effect with lignins, associated with antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive).

Synergistic Antioxidant and Antimicrobial Effects of the Thymoquinone and Eugenol Combination

Synergistic Antioxidant and Antimicrobial Effects of the Thymoquinone and Eugenol Combination

Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress.

Chronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDefTM contained in the novel nutraceutical GlicefenTM (Mivell, Italy). In both yHUVEC and sHUVEC, the MIX significantly decreased the expression levels of inflammatory markers, such as MCP-1, IL-1β and IL-8, and ROS production. Importantly, in sHUVEC, a synergistic effect of the MIX was observed, suggesting its senomorphic activity. Moreover, the MIX was able to reduce the expression level of RAGE, a receptor involved in the activation of proinflammatory signaling. Overall, our data suggest that the consumption of nutraceuticals containing different natural compounds could be an adjuvant supplement to counteract proinflammatory and pro-oxidative signals induced by both hyperglycemic and senescence conditions.

Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO-1 signaling pathway in mice.

Stroke is the leading cause of disability and death. When blood flow is restored after prolonged ischemia and hypoxia, it leads to excessive production of reactive oxygen species (ROS), increased local inflammation, and apoptosis, which are the cause of most cerebral ischemia reperfusion injury (CIRI), leading to secondary brain tissue damage. Edaravone dexborneol is a novel neuroprotective agent consisting of edaravone and borneol. Studies have shown that it has synergistic antioxidant and anti‐inflammatory effects. However, whether Edaravone dexborneol stimulates the Nrf2/HO‐1 pathway to regulate NADPH oxidase 2 (NOX2) remains unclear. In this study, wild‐type (WT) mice and Nrf2 knockout (KO) mice were used to investigate the antioxidant, anti‐inflammatory, and anti‐apoptotic effects of Edaravone dexborneol on CIRI and its mechanism. The cognitive function of mice was evaluated with the Morris water maze (MWM), test and the cell structures of hippocampus were observed by hematoxylin and eosin (H&E) staining. Nrf2, HO‐1, and NOX2 proteins and apoptosis‐related proteins Bcl‐2, Bax, and Caspase 3 were detected by western blotting. Nrf2, HO‐1, NOX2, and inflammatory factors TNF‐α, IL‐1β, IL‐4, and IL‐10 were detected by real‐time polymerase chain reaction. The results showed that Edaravone dexborneol treatment improved learning and memory performance, neuronal damage, and enhanced antioxidant, inflammation, and apoptosis in CIRI mice. In addition, Edaravone dexborneol induced the activation Nrf2/HO‐1 signaling pathway activation while inhibiting NOX2 expression. Overall, these results indicate that Edaravone dexborneol ameliorates CIRI‐induced memory impairments by activating Nrf2/HO‐1 signaling pathway and inhibiting NOX2.

GC-MS-employed phytochemical characterization, synergistic antioxidant, and cytotoxic potential of Triphala methanol extract at non-equivalent ratios of its constituents

Triphala is a famous triherbal drug, comprising three herb fruits, including Terminalia chebula (Haritaki), Terminalia bellirica (Bibhitaki), and Phyllanthus emblica (Amalaki). It is enriched with vitamin C, polyphenols, flavonoids, sterols, saponins, etc., and is well-documented for its potent antioxidant, anticancer, chemoprotective, antimicrobial, and anti-inflammatory effects. This research was conducted to evaluate the synergistic antioxidative and cytotoxic potential of mixtures of the individual constituents of Triphala at their nonequivalent ratios along with the chemical characterization of individual constituents of Triphala to identify and quantify individual compounds. The antioxidative potential was measured using total antioxidant capacity (TAC), DPPH free radical scavenging assay, and total phenolic content (TPC) tests. The cytotoxic potential was assessed on brain cancer cells (N4X4) using MTT assay, and phytochemical characterization was performed by GS-MS analysis. Nonequivalent ratios of Triphala constituents exhibited significantly higher synergistic antioxidant and cytotoxic potential than the equivalent ratios of them. Moreover, the nonequivalent ratio where the quantity of Amalaki was doubled than the other two constituents showed the highest synergistic antioxidant and cytotoxic effect. GC-MS analysis of individual constituents of Triphala identified and quantified the presence of a wide array of compounds, and fatty acid, fatty acid ester, triterpene, and aminoglycoside remained the predominant class of compounds. Thus, it can be inferred that the observed bioactivities can be attributed to the phytocompounds characterized and extracts at the nonequivalent ratio of Triphala constituents where Amalaki is doubled can be more effective in treating oxidative degenerative diseases and glioblastoma.

A ternary system of α-tocopherol with phosphatidylethanolamine and l-ascorbyl palmitate in bulk oils provides antioxidant synergy through stabilization and regeneration of α-tocopherol

The stabilization of fats and oils against oxidative lipid deterioration is still a great challenge. The synergistic interaction between phospholipids, l-ascorbate, and tocopherols have not yet been comprehensively understood. The mechanism of the synergistic antioxidant effect of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (PE) in mixtures with l-ascorbyl palmitate (AP) and α-tocopherol (α-Toc) was investigated in an ethyl linoleate model and sunflower oil at 110 °C. The mixture of PE, AP, and α-Toc is stabilized through continuous regeneration of α-Toc from its oxidation product α-tocopherylquinone (α-TQ). This reaction is catalyzed by acids and proceeded through the formation of the α-tocopherone ion (T+) as an intermediate product. In addition to the direct reduction of T+ by AP, PE can also cause regeneration indirectly by reacting with dehydroascorbyl palmitate (DHAP) or other tricarbonyl compounds to form amino reductones. PE and AP undergo an amino-carbonyl reaction to form the condensate PE(AP)2.

Combination of Vitamin C and Curcumin Safeguards Against Methotrexate-Induced Acute Liver Injury in Mice by Synergistic Antioxidant Effects.

Methotrexate (MTX), an antineoplastic and immunosuppressive drug, widely used in the treatment of different types of cancers and the management of chronic inflammatory diseases. However, its use is associated with hepatotoxicity. Vitamin C (VC) and curcumin (CUR) exhibit anti-inflammatory and antioxidant effects. Thus, we aimed to investigate the potential hepatoprotective effects of VC and CUR pretreatment alone and in combination against MTX-induced hepatotoxicity. Albino mice were randomly divided into 7 groups: the control group, which received only normal saline; MTX group; VC group, pretreated with VC (100 or 200 mg/kg/day orally) for 10 days; CUR group, pretreated with CUR (10 or 20 mg/kg/day orally); and combination group, which received VC (100 mg/kg) and CUR (10 mg/kg). MTX was administered (20 mg/kg, intraperitoneally) to all the groups on the tenth day to induce hepatotoxicity. Forty eight hours after MTX administration, the mice were anesthetized. Blood samples were collected, the liver was removed for biochemical analysis, and a part of the tissue was preserved in formalin for histopathological analysis. The results indicated that pretreatment with a combination of VC and CUR induced a more significant decrease in the serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, and lactic dehydrogenase and a significant increase in the tissue level of superoxide dismutase and glutathione; furthermore, it induced a significant decrease in malondialdehyde levels and improvement in histopathological changes in the liver tissues, confirming the potential hepatoprotective effects of the combination therapy on MTX-induced liver injury. To conclude, MTX-induced hepatotoxicity is mediated by induction of oxidative stress as evident by increased lipid peroxidation and reduction of antioxidant enzyme activity. Pretreatment with VC, CUR or their combination reduces the MTX-induced hepatotoxicity by antioxidant and anti-inflammatory effects. However, the combined effect of VC and CUR provided a synergistic hepatoprotective effect that surpasses pretreatment with CUR alone but seems to be similar to that of VC 200 mg/kg/day. Therefore, VC and CUR combination or a large dose of VC could be effective against MTX-induced hepatotoxicity. In this regard, further studies are warranted to confirm the combined hepatoprotective effect of VC and CUR against MTX-induced hepatotoxicity.

The pan-JAK inhibitor LAS194046 reduces neutrophil activation from severe asthma and COPD patients in vitro

Non-T2 severe asthma and chronic obstructive pulmonary disease (COPD) are airway chronic inflammatory disorders with a poor response to corticosteroids. LAS194046, a novel pan-Janus kinase (JAK) inhibitor, shows inhibitory effects on T2 allergic lung inflammation in rats. In this work we analyze the effects of LAS194046, fluticasone propionate and their combination in neutrophils from non-T2 severe asthma and COPD patients in vitro. Neutrophils from 23 healthy subjects, 23 COPD and 21 non-T2 severe asthma patients were incubated with LAS194046 (0.01 nM–1 µM), fluticasone propionate (0.1 nM–1 µM) or their combination and stimulated with lipopolysaccharide (LPS 1 µM). LAS194046 shows similar maximal % inhibition and potency inhibiting IL-8, MMP-9 and superoxide anion release in neutrophils from healthy, COPD and asthma. Fluticasone propionate suppresses mediator release only in neutrophils from healthy patients. The combination of LAS194046 with fluticasone propionate shows synergistic anti-inflammatory and anti-oxidant effects. The mechanisms involved in the synergistic effects of this combination include the increase of MKP1 expression, decrease of PI3Kδ, the induction of glucocorticoid response element and the decrease of ERK1/2, P38 and JAK2/STAT3 phosphorylation compared with monotherapies. In summary, LAS194046 shows anti-inflammatory effects in neutrophils from COPD and severe non-T2 asthma patients and induces synergistic anti-inflammatory effects when combined with fluticasone propionate.

Estimation of Synergistic Antioxidant Effect of Methanolic Extracts of Some Medicinal Herbs

Antioxidant activity encompasses protection against cellular wear and tear by interfering in the formation of free radicals. The majority of the diseases are linked to oxidative stress generated due to these free radicals. It makes the basis for plants containing secondary metabolites showing antioxidant activity as the potential source for development of newer formulations showing action against diseases like infections, cancers and other degenerative diseases. The present study involves the study of methanolic extracts of three medicinal herbs cannabis (Cannabis sativa.), wheatgrass (Triticum aestivum) and carrot (Dascus carota L.) commonly available in Indian cultivation. The antioxidant potential of the combination of these extracts was also studied. The combinations showed a synergistic antioxidant activity suggesting that potential of natural plant extracts against any disease can be increased when used in combinations.

Amelioration of oxidative stress utilizing nanoemulsion loaded with bromocriptine and glutathione for the management of Parkinson's disease

Parkinson's disease (PD) is triggered by the formation of free radicals in dopaminergic neurons, which results in oxidative stress-induced neurodegeneration. The objective of the work was to relieve oxidative stress by employing intranasal delivery of Bromocriptine Mesylate (BRM) and Glutathione (GSH) loaded nanoemulsion for the better management of PD. The depth of permeation of the nanoemulsion was assessed through confocal laser scanning microscopy (CLSM) which revealed higher nanoemulsion permeation in contrast to suspension. Biocompatibility of nanoemulsion was confirmed by nasal cilio toxicity study. The DPPH study showed that the nanoemulsion had significant antioxidant activity. Biochemical estimation studies in Wistar rats were carried out in order to determine the effect of nanoemulsion on oxidative stress. The levels of GSH, superoxide dismutase (SOD), and catalase (CAT) were significantly enhanced; and the level of thiobarbituric acid reactive substances (TBARS) was significantly reduced after the intranasal administration of nanoemulsion in the haloperidol-induced model of PD. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also determined which reduced significantly after the administration of nanoemulsion. The oxidative stress levels were lowered with nanoemulsion, showing the combined antioxidant capability of BRM and GSH. The neuroprotective effect of the prepared nanoemulsion was confirmed by histopathological studies. Pharmacokinetic study revealed a higher concentration of BRM and GSH in the brain of Wistar rats after intranasal administration of nanoemulsion with a higher Brain/Plasma ratio. A higher value of AUC(0−8) of nanoemulsion in the brain after intranasal administration revealed that BRM and GSH remained in the brain for a longer period due to sustained release from nanoemulsion. According to the findings, BRM and GSH loaded nanoemulsion has the potential to provide a combined and synergistic anti-oxidant effect for efficient management of PD.

Synergistic effect of Lipophilic Antioxidants Extracted from Cloves (Syzygium aromaticum) with Vitamin E on the Stability of Cotton Seed Oil during Frying of Plantain Chips

Aims: This study was conducted in order to evaluate the synergistic effect of the ethanolic extract and powder of cloves buds (Syzygium aromaticum) with vitamin E in delaying cotton seed oil oxidation during frying of plantain chips.
 Study design: Purchase of clove buds, cleaning, preparation of clove buds ethanolic extract and powder, supplementation of cotton seed oil enriched with vitamin E with the extract and powder at different concentrations and evaluation of oil stability during frying of plantain chips.
 Place and Duration of Study: General Science Laboratory, School of Agriculture and Natural Resources, Catholic University Institute of Buea-Douala Campus, Littoral Region, Cameroon, from January to June 2019.
 Methodology: In refined cotton seed oil (2.5 L) containing vitamin E as preservative was respectively added 0.30, 0.60, 1.00 and 1.30% of Syzygium aromaticum (SA) buds ethanolic extract and 0.5, 1, 1.50% of buds powder. After ensuring the good dispersion of the antioxidants added, oil samples were used for the deep-frying of plantain chips for 10 and 20 min respectively. Oil sample without clove served as control. The stability of the various oil samples was evaluated through the determination of peroxide, thiobarbituric acid, iodine and acid acid (% oleic) values.
 Results: Results showed that the natural plant extract and powder increased the stability of the oil compared to the control. Oil samples supplemented with the extract at concentration 0.30 and 0.60% presented good stability compared to the control, while the same extract at higher concentrations (1.00 and 1.30%) tend to behave as prooxidant. Concerning the powder it exhibited better good preservative properties on the oil and at all levels.
 Conclusion: Clove ethanolic extract at concentration < 0.60% and its powder at concentration 0.50-1.5% can be used to delay cotton seed oil alteration during frying of plantain chips.