Publications by authors named "Francisco Valmor Macedo Cunha"

7 Publications

  • Page 1 of 1

Ethyl ferulate/β-cyclodextrin inclusion complex inhibits edema formation.

Mater Sci Eng C Mater Biol Appl 2020 Oct 13;115:111057. Epub 2020 May 13.

RENORBIO, Focal Point - Federal University of Piauí, Av. Nossa Senhora de Fátima s/n, 64049-550 Teresina, PI, Brazil. Electronic address:

Ethyl ferulate, a phenylpropanoid derived from rice hulls has aroused interest because of its antioxidant, anti-inflammatory and neuroprotective properties. However, it has low solubility in water which compromises the absorption in the gastrointestinal tract, decreases the bioavailability and compromises the reproducibility of the effects in vivo. To increase the solubility of ethyl ferulate, inclusion complexes were obtained by physical mixing, malaxing, lyophilization and spray drying and characterized using thermal analysis, XRD and FTIR. The complexes obtained were evaluated for ethyl ferulate content, stability, dissolution profile and evaluation of anti-inflammatory activity in vivo through carrageenan-induced paw edema model in rats. The inclusion complexes obtained resulted in increased solubility and stability compared to the isolated ethyl ferulate. In addition, the complexes obtained by malaxage, lyophilization and spray drying showed greater inhibition of the edema formation induced by carrageenan compared to ethyl ferulate 100 mg/kg v.o. The inclusion of ethyl ferulate in B-cyclodextrin resulted in the formation of stable inclusion complexes with potent antidematogenic activity possibly attributed to the increased solubility, dissolution profile of the active.
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October 2020

Systematic review and technological prospection: ethyl ferulate, a phenylpropanoid with antioxidant and neuroprotective actions.

Expert Opin Ther Pat 2019 02 25;29(2):73-83. Epub 2019 Jan 25.

c Federal University of Piauí , Teresina , Brazil.

Introduction: Ethyl ferulate is a phenylpropanoid with anti-inflammatory, antioxidant and neuroprotective activities of natural and synthetic origin with potential uses in the nutraceutical and pharmaceutical industry. Therefore, the aim of this study was to investigate the current scenario regarding patents and scientific articles available involving the substance in question, regarding aspects such as quantity, areas of knowledge and depositor countries.

Areas Covered: To do so, we conducted technological and scientific prospecting on the WIPO, EPO, USPTO and INPI and scientific databases in PubMed, Web of Science and Lilacs databases using the keywords 'ferulic acid ethyl ester' and 'ethyl ferulate' in English and Portuguese. A total of 16 articles and 17 patents of which 10 were Chinese and 11 claimed the use of ethyl ferulate or for the synthesis of other substances or synthetic methods of the same. Five of the patents selected claimed therapeutic applications related to the treatment of mycobacterial infections, use as a cosmetic and neuroprotective activity. The systematic review of the literature revealed antioxidant, neuroprotective, anti-inflammatory, antimutagenic, antiapoptotic, antimutagenic and antiproliferative activities.

Expert Opinion: The technological and scientific prospection highlighted ethyl ferulate, despite its known pharmacological activities, is little explored by the pharmaceutical and nutraceutical industries.
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February 2019

Inhibition of neutrophil migration and reduction of oxidative stress by ethyl p-coumarate in acute and chronic inflammatory models.

Phytomedicine 2019 Apr 27;57:9-17. Epub 2018 Sep 27.

Medicinal Plants Research Center, Federal University of Piauí, Av. Nossa Senhora de Fátima s/n, 64049-550 Teresina, Piauí, Brazil. Electronic address:

Background: It is well known that medicinal plants and their products are relevant candidates for the treatment of inflammatory conditions. Ethyl p-coumarate is a phenylpropanoid that has similar structure to others anti-inflammatory and antioxidant substances. However, these activities have never been tested.

Purpose: The aim of this study was to investigate the effect of ethyl p-coumarate on inflammatory and oxidative stress parameters.

Study Design: This is an experimental study to evaluate the anti-inflammatory and antioxidant activities of ethyl p-coumarate in acute and chronic models of inflammation.

Methods: The anti-inflammatory effect of ethyl p-coumarate was evaluated in Swiss mice by carrageenan-induced paw edema model (1%, 50 μl), followed by histological analysis, and edema induced by compound 48/80 (12 µg/paw), histamine (100  µg/paw), serotonin (100 µg/paw) and prostaglandin E2 (3 nmol/paw) in comparison to indomethacin treatment (10 mg/kg, p.o.). In addition, peritonitis was induced by carrageenan (500 μg/cavity) to neutrophil and total leukocytes counting, myeloperoxidase (MPO), interleukin 6 (IL-6) and 8 (IL-8), nitrite (NO), glutathione (GSH) and malondialdehyde (MDA) measurements. The arthritis model was induced with Freund's complete adjuvant (id. 0.1 ml) in female Wistar rats, with measurement of joint diameter and X-ray. Changes in gastric tissue of Swiss mice were analyzed in comparison to indomethacin (20  mg/kg, p.o.).

Results: After treatment with ethyl p-coumarate, the animals had no apparent toxic effects, and significantly inhibited paw edema induced by edematogenic agents, neutrophil (p < 0.001) and total leukocyte (p < 0.001) migration, MPO (p < 0.01), IL-6 (p < 0.05) and IL-8 (p < 0.5), MDA (p < 0.5), GSH (p < 0.5), NO (p < 0.001), joint thickness and bones changes. Furthermore, were not observed significant formation of gastric lesions.

Conclusion: Taken together, these results suggest that ethyl p-coumarate exhibits anti-inflammatory activity through the inhibition of inflammatory mediators and leukocyte migration without causing gastric lesions.
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April 2019

Hepatic function and antioxidant activity in diabetic rats subjected to diet supplemented with multimixture.

Nutr Hosp 2016 Sep 20;33(5):589. Epub 2016 Sep 20.

Hospital Santa Marcelina. São Paulo.

Introduction: Food and dietetic components have received considerable attention as auxiliary feeding resources on controlling of chronic non-transmissible diseases, among them diabetes. This study evaluated the effect of supplementary diet with multimixture based on linseed, sesame, oats and sunflower seeds on the hepatic function and antioxidant activity of diabetic rats.

Methods: Male rats were distributed on groups of seven animals: diabetic control (DC), diabetics subject to multimixture diet (DM), diabetic with insulin (DI), and normal control (NC). The treatment was started on the 5th day after diabetes induction with 40 mg/kg i.v. streptozotocin on tampon citrate and kept during 50 days.

Results: The ethereal extract of the supplemented diet showed a higher content of phenolics (p < 0.05) compared to other extracts of the supplemented diet and the ethereal extract of the standard diet. There was no difference in antioxidant in vitro activity of the utilized diets. Concerning to transaminases, significant bigger ALT levels (p < 0.05) were present on diabetic groups compared to NC. The relative liver weight on diabetic groups was significantly higher (p < 0.001) compared to NC group. Non-proteic sulfhydryl group levels were significantly higher (p < 0.05) on DM and I groups when compared to DM and NC. Only the treatment with insulin resulted in an improvement of antioxidant activity concerning to hepatic catalase. The supplementation with multimixture did not improve the metabolic control of diabetes.

Conclusion: The multimixture treatment showed an isolated improvement on antioxidant activity in the hepatic tissue, evidenced by the increasing on non-proteic sulfhydryl group levels.
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September 2016

Ferulic acid ethyl ester diminished Complete Freund's Adjuvant-induced incapacitation through antioxidant and anti-inflammatory activity.

Naunyn Schmiedebergs Arch Pharmacol 2016 Jan 24;389(1):117-30. Epub 2015 Oct 24.

Ferulic acid ethyl ester (FAEE) is a derivate from ferulic acid which reportedly has antioxidant effect; however, its role on inflammation was unknown. In this study, we investigated the orally administered FAEE anti-inflammatory activity on experimental inflammation models and Complete Freund's Adjuvant (CFA)-induced arthritis in rats. CFA-induced arthritis has been evaluated by incapacitation model and radiographic knee joint records at different observation time. FAEE (po) reduced carrageenan-induced paw edema (p < 0.001) within the 1st to 5th hours at 50 and 100 mg/kg doses. FAEE 50 and 100 mg/kg, po inhibited leukocyte migration into air pouch model (p < 0.001), and myeloperoxidase, superoxide dismutase, and catalase activities (p < 0.001) increased total thiol concentration and decreased the TNF-α and IL-1β concentrations, NO, and thiobarbituric acid reactive species. In the CFA-induced arthritis, FAEE 50 and 100 mg/kg significantly reduced the edema and the elevation paw time, a joint disability parameter, since second hour after arthritis induction (p < 0.001). FAEE presented rat joint protective activity in radiographic records (p < 0.001). The data suggest that the FAEE exerts anti-inflammatory activity by inhibiting leukocyte migration, oxidative stress reduction, and pro-inflammatory cytokines.
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January 2016

Hypoalbuminemia and oxidative stress in patients on renal hemodialysis program.

Nutr Hosp 2014 Oct 1;30(4):952-9. Epub 2014 Oct 1.

Graduate student in Medicine. Federal University of Piaui. Teresina-Piaui, Brazil..

Introduction: Albumin is considered an important extracellular antioxidant molecule. hypoalbuminemia is a strong and independent predictor of mortality in patients on hemodialysis. The present study evaluated the relation between hypoalbuminemia and oxidative stress by comparing superoxide dismutase activity, lipid peroxidation and antioxidant micronutrient consumption in chronic renal failure patients.

Methods: A case-control study was carried out with 64 patients of both sexes aged 18 to 59 years. The patients with hypoalbuminemia (ALB < 3,5 g/dL) were defined as case (n = 26) and control (n = 38) those with ALB ≥ 3.5 g/dL.Determinations of activity superoxide dismutase (SOD)and nitric oxide production by the contraction of nitrite in erythrocytes, concentration of malondialdehyde (MDA)in plasma, lipid profile and micronutrient antioxidants intake were performed. For comparisons between groups,the Student t test was used. Possible associations between variables were tested using the chi-square test and Pearson correlation test.

Results: Consumption of copper was significantly lower(p < 0.05) in the group with hypoalbuminemia. There was a positive correlation between the concentrations of albumin and intake copper (r = 0.280). Negative correlation was found between albumin and MDA concentrations.

Conclusion: Hypoalbuminemia is associated with increased lipid peroxidation, and can contribute to oxidative stress in chronic renal failure patients. Additionally, patients with chronic renal disease undergoing hemodialysis evaluated in this study had reduced consumption of cooper.
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October 2014

Chest and neck mobilization effects on spirometric responses in healthy subjects.

J Manipulative Physiol Ther 2011 Nov 23;34(9):622-6. Epub 2011 Sep 23.

PT Fellowship, Ciências Humanas e Tecnológicas do Piauí-Novafapi, Teresina, PI, Brazil.

Objectives: In this observational study, we evaluated the effects of chest and neck mobilization on spirometric parameters in healthy subjects.

Methods: We conducted an observational, quantitative, and experimental study in a sample of 100 healthy subjects. We evaluated spirometric parameters before and after pompage mobilization techniques. Three techniques were used, and each technique was performed 6 times.

Results: Forced vital capacity (3.4 ± 0.1 L vs 3.5 ± 0.1 L), forced expiratory volume at the first second (3.2 ± 0.09 L vs 3.3 ± 0.09 L), and peak expiratory flow (6.4 ± 0.27 L/s vs 6.6 ± 0.25 L/s) were significantly increased after mobilization (P < .0001), whereas Tiffeneau index (94% ± 1% vs 6% ± 0.2%) was decreased (P < .0001).

Conclusion: Chest and neck mobilization techniques used in this study improved spirometric parameters in a group of young and healthy subjects.
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November 2011