Sandra Regina Georgetti
@uel.br
Professor in Department of Pharmaceutical Sciences/State University of Londrina
State University of Londrina
RESEARCH INTERESTS
DEvelopement of topical formulations added natural antioxidant to prevent or delay UVB-induced skin damage
Scopus Publications
Scopus Publications
Carla F.S. Guazelli, Victor Fattori, Barbara B. Colombo, Isabela S. Ludwig, Laisa G. Vicente, Renata M. Martinez, Sandra R. Georgetti, Alexandre Urbano, Rubia Casagrande, Marcela M. Baracat,et al.
Elsevier BV
Cristina P. B. Melo, Priscila Saito, Renata M. Martinez, Larissa Staurengo-Ferrari, Ingrid C. Pinto, Camilla C. A. Rodrigues, Stephanie Badaro-Garcia, Josiane A. Vignoli, Marcela M. Baracat, Allan J. C. Bussmann,et al.
MDPI AG
Intense exposure to UVB radiation incites excessive production of reactive oxygen species (ROS) and inflammation. The resolution of inflammation is an active process orchestrated by a family of lipid molecules that includes AT-RvD1, a specialized proresolving lipid mediator (SPM). AT-RvD1 is derived from omega-3, which presents anti-inflammatory activity and reduces oxidative stress markers. The present work aims to investigate the protective effect of AT-RvD1 on UVB-induced inflammation and oxidative stress in hairless mice. Animals were first treated with 30, 100, and 300 pg/animal AT-RvD1 (i.v.) and then exposed to UVB (4.14 J/cm2). The results showed that 300 pg/animal of AT-RvD1 could restrict skin edema, neutrophil and mast cell infiltration, COX-2 mRNA expression, cytokine release, and MMP-9 activity and restore skin antioxidant capacity as per FRAP and ABTS assays and control O2•− production, lipoperoxidation, epidermal thickening, and sunburn cells development. AT-RvD1 could reverse the UVB-induced downregulation of Nrf2 and its downstream targets GSH, catalase, and NOQ-1. Our results suggest that by upregulating the Nrf2 pathway, AT-RvD1 promotes the expression of ARE genes, restoring the skin’s natural antioxidant defense against UVB exposition to avoid oxidative stress, inflammation, and tissue damage.
Marília F. Manchope, Mariana M. Bertozzi, Sergio M. Borghi, Cíntia L. Handa, Mariana A. Queiroz-Cancian, Camila R. Ferraz, Sandra S. Mizokami, Stephanie Badaró-Garcia, Ketlem C. Andrade, Tiago H. Zaninelli,et al.
MDPI AG
Background: Monascus purpureus and Aspergillus oryzae have been used to ferment defatted soybean flour (DSF: DSFF-Mp and DSSF-Ao, respectively) extract, improving antioxidant availability and conversion of the glycosylated isoflavones to aglycones. The aim of the present study was to evaluate the biological activity of fermented and non-fermented DSF extracts in pain and inflammation, which has not yet been explored. Methods: Phenolic compounds of extracts were determined. Non-fermented DSF (DSF-Non), DSFF-Mp, and DSFF-Ao (10–100 mg/kg) were administrated i.p., 30 min before i.pl. or i.p. carrageenan stimulus. Mechanical and thermal hyperalgesia, edema, histopathology, leukocyte recruitment, and oxidative stress in the paw tissue, and inflammatory cell recruitment, NFκB activation, and cytokine production were assessed in the peritoneum. Stomach and kidney toxicity were evaluated. Results: DSF-Non, DSFF-Mp, and DSFF-Ao extracts inhibited mechanical and thermal hyperalgesia, paw edema, histopathology, neutrophil recruitment, and oxidative stress, as well as inhibited peritoneal leukocyte recruitment. DSF-Non increased IL-10, and DSFF-Ao reduced IL-33 levels. DSFF-Mp increased IL-10 and reduced IL-33 production, and NFκB activation in CD45+ cells, without inducing toxicity. Conclusions: The present data reveal for the first time that fermented/non-fermented DSF extracts are analgesic and anti-inflammatory, showing differences in the mechanism of action depending on fungi applied for fermentation.
Sergio M. Borghi, Tiago H. Zaninelli, Jéssica B. Carra, Olivia K. Heintz, Marcela M. Baracat, Sandra R. Georgetti, Fabiana T. M. C. Vicentini, Waldiceu A. Verri, and Rubia Casagrande
MDPI AG
Asthma is a chronic disease with increasing prevalence and incidence, manifested by allergic inflammatory reactions, and is life-threatening for patients with severe disease. Repetitive challenges with the allergens and limitation of treatment efficacy greatly dampens successful management of asthma. The adverse events related to several drugs currently used, such as corticosteroids and β-agonists, and the low rigorous adherence to preconized protocols likely compromises a more assertive therapy. Flavonoids represent a class of natural compounds with extraordinary antioxidant and anti-inflammatory properties, with their potential benefits already demonstrated for several diseases, including asthma. Advanced technology has been used in the pharmaceutical field to improve the efficacy and safety of drugs. Notably, there is also an increasing interest for the application of these techniques using natural products as active molecules. Flavones, flavonols, flavanones, and chalcones are examples of flavonoid compounds that were tested in controlled delivery systems for asthma treatment, and which achieved better treatment results in comparison to their free forms. This review aims to provide a comprehensive understanding of the development of novel controlled delivery systems to enhance the therapeutic potential of flavonoids as active molecules for asthma treatment.
Jéssica Bassetto Carra, Ricardo Luís Nascimento de Matos, Ana Paula Novelli, Renê Oliveira do Couto, Fabio Yamashita, Marcos Alessandro dos Santos Ribeiro, Eduardo César Meurer, Waldiceu Aparecido Verri, Rubia Casagrande, Sandra Regina Georgetti,et al.
Elsevier BV
Novel microcapsules containing grape peel by-product extract were obtained. In this pursuit, complex coacervation of casein/pectin bioconjugate and spray-drying were combined. We have investigated the role of the dispersion feed rate (FR), drying air inlet temperature (IT) and drying air flow rate (AR) in the drying yield, microencapsulation efficiency, total polyphenols and anthocyanins contents, antioxidant activity, and morphology of the products. Also, the first-order degradation kinetics of the phytochemicals for both the extract and dried microcapsules was assessed and compared. The loss on the phytochemicals during spray-drying was attenuated in up to 88%, and the IT was the main factor affecting the particle properties. The polyphenols on the extract interacted with the polymers, influencing the assemble of the bioconjugate and the particle's features. Such microencapsulation strategy enhanced the thermal stability of the phytochemicals and rendered biocompatible and biodegradable products of which the nutraceutical and cosmeceutical application may have potential.
KÁTIA S. TAKAYAMA, MARIANA C. MONTEIRO, PRISCILA SAITO, INGRID C. PINTO, CLAUDIA T. NAKANO, RENATA M. MARTINEZ, DOUGLAS V. THOMAZ, WALDICEU A. VERRI JR, MARCELA M. BARACAT, NILTON S. ARAKAWA,et al.
FapUNIFESP (SciELO)
Cristiana F. G. Silva, Victor Fattori, Caroline R. Tonetti, Marcos A. S. Ribeiro, Ricardo L. N. Matos, Jéssica B. Carra, Eduardo C. Meurer, Elisa Y. Hirooka, Janice A. Rafael, Sandra R. Georgetti,et al.
Faculty of Food Technology and Biotechnology - University of Zagreb
Research background. Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach. A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a Vernier caliper, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions. In all wet winemaking residues peel mass fraction was 75 %, and in dry residues 59 %. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50 % of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution. This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.
Marília F. Manchope, Sandra S. Mizokami, Camila R. Ferraz, Sergio M. Borghi, Josiane A. Vignoli, Doumit Camilios-Neto, Nilton S. Arakawa, Sandra R. Georgetti, Waldiceu A. Verri, and Rubia Casagrande
Informa UK Limited
Pimenta pseudocaryophyllus (Gomes) Landrum is a Brazilian native plant. The mechanisms by which it promotes analgesia are unknown. We demonstrated the analgesic effect of P. pseudocaryophyllus dried extract (3 mg/kg; i.p.) in the following models of inflammatory pain (maximal inhibition): phenyl-p-benzoquinone (89%), formalin (72% - 1st phase and 96% - 2nd phase for flinches, and 50% - 1st phase and 71% - 2nd phase for licking behavior), complete Freund's adjuvant (95% - flinches and 33% - licking behavior), and carrageenin (56% - mechanical and 85% - thermal hyperalgesia) without motor impairment. Its analgesic effect depends on inhibiting neutrophil recruitment (95% - histopathology, 83% - myeloperoxidase activity, and 80% - LysM-eGFP mice), oxidative stress (86% - GSH and 98% - superoxide anion), and cytokine production (35% - IL-33, 80% - TNF-α, and 95% - IL-1β). The present study advances in understanding the analgesic mechanisms of P. pseudocaryophyllus.
Cristina P. B. Melo, Priscila Saito, David L. Vale, Camilla C. A. Rodrigues, Ingrid C. Pinto, Renata M. Martinez, Julia R. Bezerra, Marcela M. Baracat, Waldiceu A. Verri, Yris Maria Fonseca-Bazzo,et al.
Springer Science and Business Media LLC
Cordia verbenacea DC (Boraginaceae) is a flowering shrub found along the Brazilian Atlantic Forest, Brazilian coast, and low areas of the Amazon. The crude extract of its leaves is widely used in Brazilian folk medicine as an anti-inflammatory, both topically and orally. The aim of this study is to evaluate the activity of C. verbenacea ethanolic leaves extract (CVE) against UVB-triggered cutaneous inflammation and oxidative damage in hairless mice. CVE treatment recovered cutaneous antioxidant capacity demonstrated by scavenging ABTS+ free radical and iron-reducing antioxidant potential evaluated by FRAP. CVE also controlled the following UV-triggered events in the skin: reduced glutathione (GSH) depletion, catalase activity decrease, and superoxide anion (O⋅-) build-up. Furthermore, mice treated with CVE exhibited less inflammation, shown by the reduction in COX-2 expression, TNF-α, IL-1β, IL-6, edema, and neutrophil infiltration. CVE also regulated epidermal thickening and sunburn cells, reduced dermal mast cells, and preserved collagen integrity. The best results were obtained using 5% CVE-added emulsion. The present data demonstrate that topical administration of CVE presents photochemoprotective activity in a mouse model of UVB inflammation and oxidative stress. Because of the intricate network linking inflammation, oxidative stress, and skin cancer, these results also indicate the importance of further studies elucidating a possible role of C. verbenacea in the prevention of UVB-induced skin cancer and evaluating a potential synergy between CVE and sunscreens in topical products against UVB damaging effects to the skin.
Cristina P.B. Melo, Priscila Saito, David L. Vale, Camilla C.A. Rodrigues, Ingrid C. Pinto, Renata M. Martinez, Julia Rojo Bezerra, Marcela M. Baracat, Waldiceu A. Verri, Yris Maria Fonseca-Bazzo,et al.
Elsevier BV
Photochemoprotection of the skin can be achieved by inhibiting inflammation and oxidative stress, which we tested using Cordia verbenacea extract, a medicinal plant known for its rich content of antioxidant molecules and anti-inflammatory activity. In vitro antioxidant evaluation of Cordia verbenacea leaves ethanolic extract (CVE) presented the following results: ferric reducing antioxidant power (886.32 μM equivalent of Trolox/g extract); IC50 of 19.128 μg/ml for scavenging 2,2-diphenyl-1-picrylhydrazyl; IC50 of 12.48 μg/mL for scavenging 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); decrease of hydroperoxides from linoleic acid (IC50 of 10.20 μg/mL); inhibition of thiobarbituric acid reactive substances (IC50 8.90 μg/mL); iron-chelating ability in bathophenanthroline iron assay (IC50 47.35 μg/mL); chemiluminescence triggered by free radicals in the H2O2/horseradish peroxidase/luminol (IC50 0.286 μg/mL) and xanthine/xanthine oxidase/luminol (IC50 0.42 μg/mL) methods. CVE (10-100 mg per kg, 30 min before and immediately after UVB exposure) treatment was performed by gavage in hairless mice. CVE inhibited skin edema, neutrophil infiltration, and overproduction of MMP-9; reduced levels of TNF-α, IL-1β, and IL- 6; numbers of skin mast cells, epidermal thickening, number of epidermal apoptotic keratinocytes, and collagen degradation. CVE increased the skin's natural antioxidant defenses as observed by Nrf-2, NAD(P)H quinone oxidoreductase 1, and heme oxygenase 1 mRNA expression enhancement. Furthermore, CVE inhibited lipid peroxidation and superoxide anion production and recovered antioxidant reduced glutathione, catalase activity, and ROS scavenging capacity of the skin. Concluding, CVE downregulates the skin inflammatory and oxidative damages triggered by UVB, demonstrating its potentialities as a therapeutic approach.
Clovis M. Kumagai, Renata M. Martinez, Barbara B. Colombo, Priscila Saito, Ingrid C. Pinto, Camilla C. A. Rodrigues, David L. Vale, Ricardo L. N. Matos, Ana P. F. R. L. Bracarense, Marcela M. Baracat,et al.
Hindawi Limited
UVB radiation is certainly one of the most important environmental threats to which we are subjected to. This fact highlights the crucial protective role of the skin. However, the skin itself may not be capable of protecting against UVB depending on irradiation intensity and time of exposition. Sun blockers are used to protect our skin, but they fail to fully protect it against oxidative and inflammatory injuries initiated by UVB. To solve this issue, topical administration of active molecules is an option. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an arachidonic acid-derived lipid with proresolution and anti-inflammatory actions. However, as far as we are aware, there is no evidence of its therapeutic use in a topical formulation to treat the deleterious events initiated by UVB, which was the aim of the present study. We used a nonionic cream to vehiculate 15d-PGJ2 (30, 90, and 300 ng/mouse) (TFcPGJ2) in the skin of hairless mice. UVB increased skin edema, myeloperoxidase activity, metalloproteinase-9 activity, lipid peroxidation, superoxide anion production, gp91phox and COX-2 mRNA expression, cytokine production, sunburn and mast cells, thickening of the epidermis, and collagen degradation. UVB also diminished skin ability to reduce iron and scavenge free radicals, reduced glutathione (GSH), sulfhydryl proteins, and catalase activity. TFcPGJ2 inhibited all these pathological alterations in the skin caused by UVB. No activity was observed with the unloaded topical formulation. The protective outcome of TFcPGJ2 indicates it is a promising therapeutic approach against cutaneous inflammatory and oxidative pathological alterations.
David L. Vale, Renata M. Martinez, Daniela C. Medeiros, Camila da Rocha, Natália Sfeir, Renata F. V. Lopez, Fabiana T. M. C. Vicentini, Waldiceu A. Verri, Sandra R. Georgetti, Marcela M. Baracat,et al.
Informa UK Limited
Ultraviolet B (UVB) irradiation causes free radical production, increase inflammation and oxidative stress, thus, supporting the use of antioxidants by topical administration as therapeutic approaches. Quercetin (QC) is a flavonoid with antioxidant activity however high liposolubility makes it difficult to remain in the viable skin layer. Thus, this study evaluated whether microencapsulation of QC would enhance its activity in comparison with the same dose of free QC (non-active dose) and unloaded-microcapsules added in formulation for topical administration in a mouse model of UVB irradiation targeting the skin. Topical formulation containing Quercetin-loaded microcapsules (TFcQCMC) presents physico-chemical (color, consistence, phase separation and pH) and functional antioxidant stability at 4 °C, room temperature and 40 °C for 6 months. TFcQCMC inhibited the UVB-triggered depletion of antioxidants observed by GSH (reduced glutathione), ability to reduce iron, ability to scavenge 2,2´-azinobis radical and catalase activity. TFcQCMC also inhibited markers of oxidation (lipid hydroperoxides and superoxide anion production). Concerning inflammation, TFcQCMC reduced the production of inflammatory cytokines, matrix metalloproteinase-9 activity, skin edema, collagen fiber damage, myeloperoxidase activity/neutrophil recruitment, mast cell and sunburn cell counts. The pharmacological activity of TFcQCMC was not shared by the same pharmaceutical form containing the same dose of free QC or unloaded control microcapsules.
Renata M. Martinez, Miriam S. Hohmann, Daniela T. Longhi-Balbinot, Ana C. Zarpelon, Marcela M. Baracat, Sandra R. Georgetti, Fabiana T. M. C. Vicentini, Rogério Côrte Sassonia, Waldiceu A. Verri, and Rubia Casagrande
Inflammopharmacology Springer Science and Business Media LLC
Renata M. Martinez, Victor Fattori, Priscila Saito, Ingrid C. Pinto, Camilla C. A. Rodrigues, Cristina P. B. Melo, Allan J. C. Bussmann, Larissa Staurengo-Ferrari, Julia Rojo Bezerra, Josiane A. Vignoli,et al.
MDPI AG
Excessive exposure to UV, especially UVB, is the most important risk factor for skin cancer and premature skin aging. The identification of the specialized pro-resolving lipid mediators (SPMs) challenged the preexisting paradigm of how inflammation ends. Rather than a passive process, the resolution of inflammation relies on the active production of SPMs, such as Lipoxins (Lx), Maresins, protectins, and Resolvins. LXA4 is an SPM that exerts its action through ALX/FPR2 receptor. Stable ALX/FPR2 agonists are required because SPMs can be quickly metabolized within tissues near the site of formation. BML-111 is a commercially available synthetic ALX/FPR2 receptor agonist with analgesic, antioxidant, and anti-inflammatory properties. Based on that, we aimed to determine the effect of BML-111 in a model of UVB-induced skin inflammation in hairless mice. We demonstrated that BML-111 ameliorates the signs of UVB-induced skin inflammation by reducing neutrophil recruitment and mast cell activation. Reduction of these cells by BML-111 led to lower number of sunburn cells formation, decrease in epidermal thickness, collagen degradation, cytokine production (TNF-α, IL-1β, IL-6, TGF, and IL-10), and oxidative stress (observed by an increase in total antioxidant capacity and Nrf2 signaling pathway), indicating that BML-111 might be a promising drug to treat skin disorders.
Renata Micheli Martinez, Clara Ruiza de Souza, Cristina de Paula Barros de Melo, Marcela Maria Baracat, Nilton Syogo Arakawa, José Carlos Duarte, Waldiceu Aparecido Verri, Rúbia Casagrande, and Sandra Regina Georgetti
Editora Cubo
Neem tree (Azadirachta indica A. Juss. fam. Meliaceae) has been extensively employed to combat diverse pathologies. Moreover, it has been described that its leaf extract present anticarcinogenic action. Thus, the neem extract (NE) chemical and antioxidant properties was evaluated, and also, the capacity of two dermatological formulations incorporated with neem extract (F1 and F2) to avoid oxidative UVB-induced skin injury in hairless mice. NE constituents were investigated and free radical scavenging ability were determined by different methods in vitro. Skin from mice treated with F1 and F2 and submitted to UVB radiation were tested for different parameters of inflammation and oxidative injury. Results show that the NE polyphenol and flavonoid content were 135.30 and 37.12mg/g, respectively. High performance liquid chromatography (HPLC) results demonstrated the existence of azarachtin, rutin, ursolic acid and tannic acid. NE presented scavenging ability by ABTS radical, ferric-reducing antioxidant power (FRAP), inhibition of lipid peroxidation and iron chelation. In vivo, it was observed that mice treated with F1 and F2 showed amelioration of the inflammation by reducing UVB induced skin edema. However, only samples from animals treated with F1 had lower neutrophil recruitment (measured by myeloperoxidase activity), and returning the oxidative status to baseline levels in parameters such as reduced glutathione level, ferric reducing ability (FRAP), and scavenging of free radical (ABTS). Concluding, NE demonstrated a good antioxidant property in vitro, and the data suggest the use of NE added F1 to prevent skin damage caused by UVB irradiation.
Talita L. C. Cezar, Renata M. Martinez, Camila da Rocha, Cristina P. B. Melo, David L. Vale, Sergio M. Borghi, Victor Fattori, Josiane A. Vignoli, Doumit Camilios-Neto, Marcela M. Baracat,et al.
Springer Science and Business Media LLC
Acute exposure to UVB irradiation causes skin inflammation and oxidative stress, and long-term exposure to UVB irradiation may lead to carcinogenesis. Our organism has endogenous mechanisms to actively limit inflammation. Maresin 1 (MaR1; 7R,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid) is a pro-resolution lipid mediator derived from the docosahexaenoic acid, which presents anti-inflammatory and pro-resolution effects. However, it remains to be determined if treatment with MaR1 can inhibit inflammatory and oxidative alterations in the skin triggered by UVB. The treatment with MaR1 (0.1–10 ng/mice at −10 min relative to the UVB irradiation protocol) reduced UVB-induced skin edema, neutrophil recruitment (MPO; myeloperoxidase activity, and migration of LysM-eGFP+ cells), cytokine production, matrix metalloproteinase-9 activity, keratinocyte apoptosis, epidermal thickening, mast cells counts and degradation of skin collagen in hairless mice. UVB irradiation caused a decrease of GSH (reduced glutathione) levels, activity of the enzyme catalase, ferric reducing ability (FRAP), and ABTS radical scavenging capacity as well as induced lipid hydroperoxide, superoxide anion production, and gp91phox mRNA expression. These parameters that indicate oxidative stress were inhibited by MaR1 treatment. Therefore, these data suggest MaR1 as a promising pharmacological tool in controlling the deleterious effects related to UVB irradiation.
Daniela Cristina de Medeiros, Sandra Satie Mizokami, Natalia Sfeir, Sandra Regina Georgetti, Alexandre Urbano, Rubia Casagrande, Waldiceu A. Verri, and Marcela Maria Baracat
American Chemical Society (ACS)
This study aimed to develop and characterize microparticles containing rutin to improve the analgesic activity of the flavonoid. Rutin-loaded microparticles were produced with casein and pectin using the complex coacervation physicochemical method, resulting in an average particle size of 4.903 μm ± 4.421 (mean ± standard deviation), round shape, and irregular surfaces, and rutin crystals can be observed to be adsorbed on the outer surface of microparticles. The encapsulation efficiency was 76.9% as quantified by the antioxidant activity. In vivo, rutin-loaded microparticles showed greater inhibition of carrageenan-induced mechanical hyperalgesia (64%) than nonmicroencapsulated rutin (28%). The X-ray diffraction showed that rutin was dispersed in an amorphous matrix, and its crystallographic structure and crystal size did not exhibit changes. Differential scanning calorimetric studies confirmed that rutin was dispersed in the amorphous matrix within microparticles. The fact that rutin was dispersed in an ...
Cíntia Ladeira Handa, Fernando Sanches de Lima, Marcela Fernanda Geton Guelfi, Meg da Silva Fernandes, Sandra Regina Georgetti, and Elza Iouko Ida
Elsevier BV
The objective of this work was to evaluate the effects the solid-state fermentation parameters of defatted soybean flour (DSF) by Monascus purpureus or Aspergillus oryzae on the bioactive compounds. Central composite rotatable design, multi-response optimization, and Pearson's correlation were used. The fermentation parameters as initial pH (X1), DSF-to-water ratio (X2), and incubation temperature (X3) were taken as independent variables. The function responses were isoflavone content, total phenolic content (TPC), and antioxidant activity. All fermentation parameters affected the isoflavone content when fermented by Monascus purpureus, whereas the TPC or antioxidant activities remained almost unchanged. For the fermentation by Aspergillus oryzae, all the function responses were influenced by X2 and X3 and were independent of the X1. Estimated optimum conditions were found as x1 = 6.0, x2 = 1:1, and x3 = 30 °C for both fungi. Achieving suitable fermentation parameters is essential to increase bioactive compounds in the DSF that makes it promising for food industrial applications.
Vitória Ribeiro Garcia de Figueiredo, Ariana Justus, Dafne Garcia Pereira, Sandra Regina Georgetti, Elza Iouko Ida, and Louise Emy Kurozawa
FapUNIFESP (SciELO)
R. M. Martinez, Jenifer Freitas da Silva, L. R. Jorge, Rhye Lessa Ishikawa, Ana Paula Novelli, Tálita, Laiane Cardoso Cezar, S. R. Georgetti, M. Baracat and R. Casagrande
Journal of Applied Pharmaceutical Science
The amlodipine besylate is indicated as a first choice in the treatment of hypertension. Many similar and generic drug products companies were able to bring out to the market dosage forms containing amlodipine besylate with lower prices. In this context, the aim of this work was to validate a simple method for the determination of amlodipine content in tablets by ultraviolet spectrophotometry and to perform pharmaceutical equivalence and dissolution profile studies for three similar and one generic drug products and their respective innovator tablet containing amlodipine (5 mg). The developed method for the determination of amlodipine content proved to be linear, precise, accurate, robust, and appropriate for employment in the quality control of tablets containing amlodipine besylate. The reference (R), similar (S1, S2, and S3), and generic (G) drug products all fulfilled the specifications for the tests of identification, average weight, hardness, friability, disintegration, drug content, content uniformity, and dissolution. However, in comparative dissolution profile studies, the dissolution efficiency of products G and S2 was statistically different from product R, which may indirectly lead to the unsuitable bioavailability and therapeutic inefficacy. Thus, there is a need for tighter legislation and inspection regarding the quality of pharmaceutical products already on the market.
Renata M. Martinez, Ana L. M. Ivan, David L. Vale, Marcela Z. Campanini, Vitor S. Ferreira, Vinicius S. Steffen, Fabiana T. M. C. Vicentini, Fernanda M. P. Vilela, Maria J. V. Fonseca, Marcela M. Baracat,et al.
Oxford University Press (OUP)
To evaluate the effects of a topical emulsion containing pyrrolidine dithiocarbamate (PDTC) (EcPDTC) in skin oxidative stress and inflammation triggered by ultraviolet B (UVB) irradiation (dose of 4.14 J/cm2).
Priscila Saito, Cristina P. B. Melo, Renata M. Martinez, Victor Fattori, Talita L. C. Cezar, Ingrid C. Pinto, Allan J. C. Bussmann, Josiane A. Vignoli, Sandra R. Georgetti, Marcela M. Baracat,et al.
Frontiers Media SA
UV irradiation-induced oxidative stress and inflammation contribute to the development of skin diseases. Therefore, targeting oxidative stress and inflammation might contribute to reduce skin diseases. Resolvin D1 (RvD1) is a bioactive metabolite generated during inflammation to actively orchestrate the resolution of inflammation. However, the therapeutic potential of RvD1 in UVB skin inflammation remains undetermined, which was, therefore, the aim of the present study. The intraperitoneal treatment with RvD1 (3-100 ng/mouse) reduced UVB irradiation-induced skin edema, myeloperoxidase activity, matrix metalloproteinase 9 activity, and reduced glutathione depletion with consistent effects observed with the dose of 30 ng/mouse, which was selected to the following experiments. RvD1 inhibited UVB reduction of catalase activity, and hydroperoxide formation, superoxide anion production, and gp91phox mRNA expression. RvD1 also increased the Nrf2 and its downstream targets NQO1 and HO-1 mRNA expression. Regarding cytokines, RvD1 inhibited UVB-induced production of IL-1β, IL-6, IL-33, TNF-α, TGF-β, and IL-10. These immuno-biochemical alterations by RvD1 treatment had as consequence the reduction of UVB-induced epidermal thickness, sunburn and mast cell counts, and collagen degradation. Therefore, RvD1 inhibited UVB-induced skin oxidative stress and inflammation, rendering this resolving lipid mediator as a promising therapeutic agent.
Bruna R Böger, Aroldo Salviato, Daniel F Valezi, Eduardo Di Mauro, Sandra R Georgetti, and Louise E Kurozawa
Wiley
BACKGROUND
Grape seeds are a relatively abundant source of oil and bioactive compounds. To use this byproduct, the current work aimed to optimize the ultrasound-assisted extraction (UAE) of grape-seed oil to obtain greater process yield and minimize free radical formation in the oil.
RESULTS
The optimal condition was 15 °C with an ultrasonic wave amplitude of 42 µm, leading to a process yield of 82.9% and content of free radicals of 14.7 × 1017 kg-1 and 3.4 × 1018 kg-1 for samples stored for 7 and 30 days, respectively. No significant differences in fatty acid composition and acidity and iodine values were observed between samples. The oil obtained by ultrasound had greater phenolic compound content and antioxidant activity by ferric reduction than the control sample (without ultrasound application). However, higher content of free radicals and peroxide value was observed.
CONCLUSION
Sonication improved extraction yield when compared to the process without ultrasound application. Moreover, UAE favored the extraction of phenolic compounds. As it enhanced process yield with the minimum formation of free radicals, UAE is a promising oil-extraction technology. © 2018 Society of Chemical Industry.
R.M. Martinez, V. Fattori, P. Saito, C.B.P. Melo, S.M. Borghi, I.C. Pinto, A.J.C. Bussmann, M.M. Baracat, S.R. Georgetti, W.A. Verri,et al.
Elsevier BV
BACKGROUND
Lipoxin A4 (LXA4) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA4 has effect on ultraviolet (UV) radiation-induced skin inflammation.
OBJECTIVE
To investigate the effects of systemic administration with LXA4 on UV radiation-induced inflammation and oxidative damage in the skin of mice.
METHODS
Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm2).
RESULTS
Pretreatment with LXA4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP+ cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-33). Depending on the time point, LXA4 increased the levels of anti-inflammatory cytokines (TGF-β and IL-10). LXA4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA4 also reduced UV radiation-induced gp91phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression.
CONCLUSION
LXA4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2.
Carla F.S. Guazelli, Larissa Staurengo-Ferrari, Ana C. Zarpelon, Felipe A. Pinho-Ribeiro, Kenji W. Ruiz-Miyazawa, Fabiana T.M.C. Vicentini, Josiane A. Vignoli, Doumit Camilios-Neto, Sandra R. Georgetti, Marcela M. Baracat,et al.
Elsevier BV
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular lesions, recruitment of inflammatory cells and increased levels of pro-inflammatory cytokine. The intra-articular administration of zymosan is an experimental model that promotes inflammatory parameters resembling RA. Therefore, this model was used to investigate the efficacy of quercetin as a treatment of articular inflammation. Treatment with quercetin dose-dependently reduced zymosan-induced hyperalgesia, articular edema and the recruitment of neutrophils to the knee joint cavity. Histological analysis confirmed that quercetin inhibited zymosan-induced arthritis. The treatment with quercetin also inhibited zymosan-induced depletion of reduced glutathione (GSH) levels, TNFα and IL-1β production, and gp91phox, prepro-endothelin-1 (preproET-1), and cyclooxygenase-2 mRNA expression. These molecular effects of quercetin were related to the inhibition of the nuclear factor kappa-B and induction of Nuclear factor erythroid 2- related factor (Nrf2)/home oxygenase (HO-1) pathway. Thus, quercetin exerted anti-inflammatory, analgesic and antioxidant effects in experimental arthritis, suggesting quercetin is a possible candidate for arthritis treatment.