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SARAGHINA MARIA DONATO DA CUNHA
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BIOPROSPECTION OF ANTIGUNGEAL ACTIVITY AND CYTOXICITY OF PATCHOULI ESSENTIAL OIL (POGOSTEMON CABLIN BENTH)
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Fecha: 28-oct-2022
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Hora: 14:00
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Mostrar Resumen
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The incidence of infections caused by Candida has increased worldwide and these strains are
becoming resistant to their respective drugs. The search for new drugs with greater efficacy and
safety is necessary and in this logic, essential oils (EOs) stand out, which are a complex mixture
of volatile compounds and present several relevant biological activities, but there are few
studies on the potential beneficial and/or adverse effects. In this sense, the objective of this
study was to evaluate the antifungal and cytotoxic activities of Patchouli (Pogostemon cablin
Benth) essential oil. In the evaluation of the antifungal activity it was used different strains of
Candida genus and it was determined the Minimum Inhibitory Concentration (MIC) and the
minimum fungicidal concentration (MFC), by microdilution technique. The interference of the
EO on the cell wall and its potential for rupture was done by MIC in the presence of sorbitol,
and the interference on the cell membrane was done by MIC with ergosterol. Also, the
interference of EO on the resistance to standard antifungal drugs was evaluated, in the absence
and in the presence of EO at subinhibitory concentrations. For cytotoxic activity studies, human
RBCs of blood types A, B and O were used and the hemolytic and antihemolytic activity was
evaluated. The analyses revealed that the EO showed excellent antifungal activity against
clinical strains of C. parapsilosis and C. albicans with a MIC and MIC between 4 and 16 μg/mL,
this effect being fungicidal in nature. Its mechanism of action involves no effect on the cell wall
as well as on the plasma membrane. It promoted a synergistic effect when associated with
amphotericin B. The effect on red blood cells showed a low percentage of hemolysis for red
blood cells of the ABO system at a concentration of 50 to 100 μg/mL. In addition, it shows
moderate anti-hemolytic effect at concentrations of 500 to 1000 μg/mL for blood types B and
O. Considering the results obtained in the in vitro cytotoxicity study and the pharmacological
activity, it can be seen that Patchouli OE becomes a promising candidate for use of its bioactive
properties in herbal medicines, but auxiliary studies are needed as in vivo toxicity and
pharmacological to better elucidate the mechanisms of action of this compound.
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ALESON PEREIRA DE SOUSA
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Toxicity assessment and determination of biological activities of flavonoids vitexin, tylyroside and 5,7-dihydroxy-3,8,4'-trimethoxy: studies in silico, in vitro and ex vivo.
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Fecha: 17-ago-2022
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Hora: 14:00
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Mostrar Resumen
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Alternative therapies using medicinal plants and herbal medicines are quite common in
Brazil. Among several Brazilian plant species used in such therapies, the species of the
Malvaceae family stand out. The present study aimed to investigate the bioavailability,
toxicity and determination of the antimicrobial and genotoxic potential of the flavonoids
vitexin, tiliroside and 5,7-dihydroxy-3,8,4'-trimethoxy (Pg-1), isolated from species of the
Malvaceae family, using in silico, in vitro and ex vivo studies. The chemical structure and
predicted bioactive properties were analyzed in silico using software. The in vitro and ex-
vivo assays using human samples were performed in accordance to the Ethics Code of the
World Medical Association and were approved by the Ethics Committee (protocol number:
3.621.284). The in silico analysis of the chemical structure of the molecules and the
expected bioactive properties shows that vitexin and Pg-1 have oral bioavailability and
good absorption owing to their balanced lipophilicity/hydrosolubility, while tiliroside has
increased lipophilicity resulting in increased permeability of biological membranes. The in
silico toxicity tests revealed the potential efficacy of these molecules in cellular protection
against free radicals, in addition to possible antimutagenic, anticarcinogenic, antioxidant,
antineoplastic, anti-inflammatory, anti-hemorrhagic and apoptosis agonist activity. The in
vitro cytotoxic and ex-vivo genotoxic evaluation detected low rates of hemolysis in human
red blood cells and no cellular toxicity against oral mucosa cells. The reduction in
cytotoxic activity is indicative of the safety of the concentrations used (500-1000 μg/mL)
and demonstrates different forms of interaction of the molecules with the types of cells
analyzed. The MIC showed a strong effect of the flavonoids vitexin, tiliroside and Pg-1
against K. pneumoniae, E. coli and E. fecalis. The MBC revealed that vitexin has a
bacteriostatic effect for strains of K. pneumoniae and E. fecalis, tiliroside had a bactericidal
effect against a strain of K. Pneumoniae, Pg-1 was considered bactericidal for strains of E.
fecalis and E. coli, and bacteriostatic in the K. Pneumoniae strain. The data suggest that
vitexin, tiliroside and Pg-1 are safe molecules for possible therapeutic applications and
their toxicity profile indicates that they are promising targets for future studies.
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HUMBERTO DE CARVALHO ARAGÃO NETO
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Investigation of the antinociceptive and anti-inflammatory activities of coumarin-3-carboxylic acid.
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Fecha: 15-jul-2022
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Hora: 09:00
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Mostrar Resumen
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Pain is an unpleasant sensory and emotional experience either associated with actual
or potential harm, or described in terms of such harm. Estimates suggest that 20% of
adults suffer from some form of pain worldwide. Pain therapy is currently one of the
challenges of modern medicine. Orofacial pain disorders are frequent in the general
population and their pharmacological treatment is difficult and controversial. The
therapeutic use of non-steroidal anti-inflammatory drugs as analgesics is associated
with a wide spectrum of adverse effects, including gastrointestinal injuries,
cardiovascular events, and renal toxicity. In this context, coumarins comprise an
important class of phenolic compounds, exhibiting several pharmacological effects.
Their therapeutic applications depend on the central chemical structure and the
substitution patterns in the aromatic ring of these compounds. Simple coumarins
represent the main subclass with anti-inflammatory properties. Studies demonstrate
that the insertion of functional groups at carbon 3 of the coumarin basic skeleton results
in pharmacological agents with potent anti-inflammatory effects. In this context,
coumarin-3-carboxylic acid (A3CC) is a substituted derivative of simple coumarins,
whose effects on pain and inflammation models have not yet been explored. The
present study aimed at investigating, for the first time, the antinociceptive and anti-
inflammatory effects of A3CC using in silico, in vitro and in vivo approaches. PASS,
Molinspiration, Volsurf+, OSIRIS DataWarrior and MetaSite 6 software were used to
establish data on spectrum of activity, bioavailability, toxicity, blood-brain permeability,
and metabolic profile. The effect on human erythrocytes was investigated through
hemolysis and osmotic fragility assays. The antinociceptive activity was evaluated in
models of acetic acidinduced abdominal writhing test, orofacial glutamate and
formalin, and the latter was used to investigate the participation of the opioid pathway
and K+
ATP channels. The anti-inflammatory activity was analyzed using the
carrageenan-induced paw edema model and confirmed by molecular docking studies
with the enzyme cyclooxygenase (COX). The A3CC demonstrated viability in the blood
circulation by showing a low percentage of hemolysis against human erythrocytes, in
addition to being able to protect the erythrocyte membrane in the osmotic fragility test
(p<0.001). It also exhibited analgesic properties, significantly inhibiting nociceptive
behavior in the formalin-induced (p<0.001) and glutamate (p<0.001) orofacial
nociception tests, as well as in the acetic acid-induced writhing test (p<0.0001). A3CC
has been shown to exert its effect peripherally, by exhibiting anti-inflammatory
properties to reduce carrageenan-induced paw edema (p<0.05). This effect was
confirmed by molecular docking and may be related to COX-2 inhibition by interactions
with Tyr385 and Ser530 residues.
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LUIZA TOSCANO DE ALMEIDA
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Evaluation of non-clinical and ophthalmologic toxicity of Waltheria viscosíssima A. St. Hill Malvaceae in mammals"
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Asesor : MARGARETH DE FATIMA FORMIGA MELO DINIZ
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Fecha: 03-jun-2022
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Hora: 14:00
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Mostrar Resumen
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Among the various plant species used in the cure of ills, those belonging to the Malvaceae
family stand out, both from the phytochemical point of view and for their use in folk
medicine. The species Waltheria viscosíssima A.St. Hill. has reports about its use in popular
medicine as an expectorant, antitussive and antihypertensive, emollient, tumor maturation, in
addition to healing old ulcers. Its wide use in popular medicine justifies toxicity studies that
guarantee its use´s safety. In this sense, we performed a non-clinical toxicological evaluation
and acute eye irritation test of the crude ethanolic extract of aerial parts of Waltheria
viscosissima A.St. Hil., based on the Guide for the Conduct of Non-Clinical Studies of
Toxicology and Pharmacological Safety required for drug development and on OECDs 423
and 407. For acute toxicological assessment, female Wistar rats were used and a single dose
of 2000 mg/kg was orally used. After treatment, the following parameters were observed for
14 days: behavioral effects for 240 minutes; water and food intake daily; weight evolution
weekly. All animals survived and were sacrificed for analysis of biochemical and
hematological parameters, macroscopic evaluation of the organs and histopathological exams
in altered organs. In the subchronic toxicological study, fractionated doses of crude ethanolic
extract from aerial parts of Waltheria viscosissima A.St. Hil. Were administered during 28
days in male and female rats and the following parameters were evalueted: blood glucose,
water and feed consumption, body weight, exploratory activity of the animals, hematological
and biochemical parameters and histopathological exams of the organs of the rats under study.
The methodology used to evaluate the single dose eye irritability of crude ethanolic extract
from aerial parts of Waltheria viscosissima A.St. Hil., was based on the work developed by
Draize et al. (1944), with some modifications based on the Guide for conducting non-clinical
toxicology and pharmacological safety studies necessary for drug development (BRASIL,
2013). By the class method, the ethanolic extract of aerial parts of Waltheria viscosissima
A.St. Hill. falls into Class 5 (substance with LD50 greater than 2000 mg/kg and less than
5000 mg/kg), being considered of low toxicity. Regarding eye irritability, the 9% extract can
be considered non-irritating.
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CAROLINE UCHÔA SOUZA CARVALHO
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Antimicrobial solution development and evaluation
for incorporation into surgical suture thread based on
essential oil of Lippia sidoides Cham. associated with
antimicrobials
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Fecha: 29-abr-2022
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Hora: 14:00
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Mostrar Resumen
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Bacterial infections are a worldwide public health problem, the so-called
Healthcare-Related Infections (HAIs), transcend the hospital environment, occurring
anywhere where patient care is provided. Among the HAIs we have the Surgical Site
Infections (SSI), characterized by microbial infestation in wounds from surgical
procedures, and the microorganisms involved originate from the skin, environmental
microbiota or even from the hands of health professionals. The suture procedure aims
to repair tissues and prevent pathogens from contaminating the site, however, the
suture material works as a foreign body and can potentiate the infection, depending on
the material used for the procedure and the problem of bacterial adhesion both in the
suture material and in the injured tissue. Antimicrobial drugs are used to reduce
infections, which leads to the problem of resistance of microorganisms to the antibiotics
used in therapy. Polyglactin suture coated with triclosan antiseptic has the property of
reducing virulence at the surgical site, indicating that antibacterial coatings are a
valuable tool to reduce wound infection rates. In the search for greater effectiveness
in therapy, the concept of antimicrobial synergism arises, where the combination of
two compounds has a potentiated activity, the synergistic interaction between essential
oils and antibiotics has proven its efficiency in reducing bacterial growth. In view of this
tool, the following work associated the essential oil of the Lippia Sidoides Cham. plant
with the antimicrobials ciprofloxacin and ampicillin, obtaining synergistic
concentrations from which a new antimicrobial coating for Polyglactin sutures was
developed. The associations of the oil with the respective antimicrobials were
synergistic, and when tested in association, they demonstrated to inhibit bacterial
growth and also reduce the formation of bacterial biofilm. The synergistic
concentrations were used to produce a solution that was incorporated into the
polyglactin suture. The thread incorporated with the antimicrobial associations was
tested for bacterial biofilm growth, showing positive results with reduced microbial
growth, when compared with Vicryl Plus®, proving to be a future alternative for a new
health product with antimicrobial properties, optimizing the procedure suture,
consequently reducing the rates of Surgical Site Infections (SSIs).
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SUSIANY PEREIRA LOPES
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Synthetic p-Cumarate Derivatives: Antiparasitic, Antimicrobial,
anti-enzymatic and in silico Study.
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Fecha: 30-mar-2022
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Hora: 13:30
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Mostrar Resumen
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p-Coumaric acid is a naturally abundant phenolic compound that has generated great
interest among researchers in the discovery and development of new drugs, due to its
beneficial effects against various pathologies. In the present study, the trypanocidal
effect was tested on epimastigote and trypomastigote forms of T. cruzi, leishmanicidal
activities on the amastigote form of L. braziliensis, antiplasmodic on P. falciparum, all
using the microdilution technique in 96-well plates, in addition to the inhibitory activity
of AChE and BChE enzymes using the spectrophotometric method and antifungal
activity evaluating MIC and CFM as well as the mechanisms of action of p-coumaric
acid derivatives.Among the 23 compounds obtained via Fisher esterification,
Mitsunobu esterification and SN2 nucleophilic substitution reactions with halides in the
presence of a base, 8 of them were unpublished in the literature and identified by
infrared spectroscopic methods and 1H and 13C magnetic resonance as well as by high
resolution mass spectroscopy. Of these, pentyl p-coumarate (7) (5.16 ± 1.28 μM; 61.63
± 28.59 μM) showed the best trypanocidal activity against epimastigote and
trypomastigote forms, respectively. Flow cytometry analysis revealed an increase in
the percentage of 7-AAD-labeled cells, an increase in reactive oxygen species, and a
loss of mitochondrial membrane potential; indicating cell death by necrosis. This
mechanism was confirmed by scanning electron microscopy, observing the loss of
cellular integrity.The molecular docking data indicated that, of the chemical compounds
tested, compound 7 potentially acts through two mechanisms of action, either by
binding to aldo-keto reductase (AKR) or comprising cruzain (CZ), which is a major
developmental enzyme of Trypanosoma cruzi. The results indicate that for both
enzymes, van der Waals interactions between ligand and receptors favor binding and
hydrophobic interactions with the phenolic and aliphatic parts of the ligand. However,
hexyl p-coumarate (9) (4.14 ± 0.55 μg/mL; IS=2.72) showed the best leishmanicidal
activity against the Leishmania braziliensis amastigotes form. The molecular docking
results on compound 9 indicate that ALDH, MPK4 and TOP2 are potentially promising
targets to guide future investigations into the possible mechanisms of action. Of the
compounds analyzed against Plasmodium falciparum, methyl p-coumarate (1) (64.59
± 2.89 μg/mL; IS= 0.1) showed reasonable activity against the other derivatives.
However, three derivatives showed enzymatic activity against butyrylcholinesterase,
4-chlorobenzyl p-coumarate (14) (75.17 ± 1.81; IC50=19.08 ± 0.70 μM), 4-
bromobenzyl p-coumarate (15) (76.09 ± 2.16; IC50=22.22 ± 1.50 μM) and naphthalene
p-coumarate (19) (65.39 ± 3.88; IC50=22.69 ± 2.15 μM). However, compounds 9
(62.90; 31.45 and 125.85 μM) and 14 (27.05; 54.09 and 54.09 μM) were bioactive
against Candida species. Therefore, the study shows that p-coumaric derivatives are
promising molecules for the planning of new drugs with various activities.
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CLAUDENISE CALDAS DA SILVA DANTAS VIEGAS
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ANTINOCICEPTIVE, ANTI-INFLAMMATORY AND ANTI-INFLAMMATORY ACTIVITY
GROSS ETHANOL EXTRACT ANTIOXIDANT AND
ALKALOID FRACTION OF Waltheria viscosissima A. St. Hil -
malvaceae
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Fecha: 18-mar-2022
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Hora: 14:00
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Mostrar Resumen
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The Waltheria viscosissima A. St.- Hil (Malvaceae) is also known as Malva branca,
has been reported ethnopharmacologically to have antinociceptive and antiinflammatory properties. The objective of this study is to lucidate the antinociceptive,
anti-inflammatory and antioxidant activity of the crude ethanol extract (EEBWa.v) and
alkaloid fraction (FAWa.v) of aerial parts of the W. viscosissima in Swiss mice. Initially,
the acute toxicity test of the EEBWa.v and FAWa.v was performed at a dose of 2000
mg/kg, intraperitoneally (i.p.), and the behavioral screening through the Rota rod test
with EEBWa.v and FAWa.v (50, 100 e 200 mg/kg), Diazepam (4 mg/kg). EEBWa.v and
FAWa.v (50, 100 and 200 mg/kg) and morphine (10 mg /kg) were used in vivo tests of
chemical nociception induced by acetic acid (0.6%; 10 mg/kg) and formalin (2.5%) in
Swiss male mice. Acute inflammation was assessed by the prostaglandin induced paw
edema model and induced peritonitis by carrageenan (1%), in vivo tests, whose groups
were the control (inflammation induced without treatment) and the groups treated with
EEBWa.v (100 mg/kg), FAWa.v (100 mg/kg) and indomethacin (10 mg/kg) or
dexamethasone (2 mg/kg). After the carrageenan induced peritonitis procedure, the
animals were euthanized and the peritoneal fluid was collected to evaluate cell
migration and redox balance (malondialdehyde - MDA and Total Antioxidant Capacity
- TAC). The mechanism of action was evaluated by the formalin test with caffeine (10
mg/kg, i.p.), naloxone (5 mg/kg, i.p.) and glibenclamide (10 mg/kg, i.p.). The morphine,
EEBWa.v (50 and 100 mg/kg) and FAWa.v (100 mg/kg) significantly reduced the
number of abdominal contortions when compared to the control group and FAWa.v
(100 mg/kg) was superior to FAWa.v (200 mg/kg). In the formalin-induced nociception
model, in the neurogenic phase EEBWa.v (50 and 200 mg/kg) significantly reduced the
number of paw licks. In the inflammatory phase FAWa.v (100 mg/kg) was superior to
EEBWa.v (200 mg/kg). EEBWa.v and FAWa.v (100 mg/kg) proved to be significant for
the next experiments. Both samples showed reduction in paw edema and cell migration,
as well as those treated with indomethacin and dexamethasone, in animals with
inflammation induced by prostaglandin and carrageenan, when compared to the control
group. The redox balance (TAC and MDA) revealed that only EEBWa.v (100 mg/kg)
had higher antioxidant potential than the untreated group and the dexamethasone group,
p<0.005 and p<0.001, respectively. FAWa.v (100 mg/kg) did not show antioxidant
activity superior to EEBWa.v. It was also detected that EEBWa.v and FAWa.v (100
mg/kg) failed to inhibit lipid peroxidation and present a possible antinociceptive
mechanism of action by opioid receptors and K+
ATP channels. The W. viscosissima
stimulates pain control, which can be mediated by both central and peripheral action.
These bioactive compounds showed promising and bioactive effect is statistically
similar to morphine, indomethacin and dexamethasone, standard drugs on the market,
but with the advantage of antioxidant activity.
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LARISSA RODRIGUES BERNARDO
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EVALUATION OF THE MECHANISM OF ACTION OF MILONIN IN THE MODEL ACUTE PULMONARY INJURY MURINE AND ITS STUDY PHARMACOKINETIC IN SILICO
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Fecha: 16-feb-2022
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Hora: 09:00
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Mostrar Resumen
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Acute lung injury (ALI) is a pathology of inflammatory background with neutrophil
infiltration, alveolar-capillary barrier damage, cytokine production leading to acute
respiratory failure. The complexity of physiological/immunological events makes
it difficult to develop an effective pharmacotherapy. Thus, therapeutic strategies
that promote the resolution of inflammation have been developed, using natural
products as sources of new anti-inflammatory molecules. In this context, the aim
of this study was to evaluate the anti-inflammatory potential of milonine, a
morphine alkaloid from Cissampelos sympodialis Eichl (Menispermaceae) in the
murine ALI model. For this purpose, BALB/c mice were lipopolysaccharide (LPS)-
challenged and treated with milonine at 2.0 mg/kg. Twenty-four hours after the
challenge, the animals were euthanized, and the bronchoalveolar lavage (BAL),
blood and lungs were collected for cellular and molecular analysis. For the
prediction of molecular targets and pharmacokinetic profile, in silico studies were
performed. Treatment with milonine inhibited the migration of inflammatory cells
to the lung, mainly neutrophils, reduced protein exudate, pulmonary edema, and
cytokines, IL-1β, IL-6 and TNF-α in the BAL, however, only IL-6 has been reduced
to the systemic level. Histological changes were attenuated with treatment with
milonine, with a reduction in leukocytes and maintenance of the bronchial
alveolar architecture, confirmed by morphometric data. The anti-inflammatory
effect of milonine is associated with inhibition of kinase B (or Akt) and nuclear
factor κB (NFκB). In silico molecular docking studies showed that the alkaloid had
a binding energy of -43.96 kcal/mol and formed hydrophobic interactions with
amino acids Ile124 and Phe126 in the MD-2 receptor associated with the Toll
Like-4 receptor. The alkaloid showed a promising ADMET profile (absorption,
distribution, metabolism, excretion and toxicity) related to safety pharmacokinetic
parameters and good availability. Therefore, milonine had an immunomodulatory
effect on the inflammatory process of acute lung injury associated with regulatory
factors of inflammatory cytokine genes, as well as pharmacokinetics with good
safety and availability, making it a potential molecule for the treatment of lung
inflammation.
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DAVIDSON BARBOSA ASSIS
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EVALUATION OF ANTIOXIDANT ACTIVITY AND MECHANISMS INVOLVED IN THE ANTINOCICEPTIVE AND ANTI-INFLAMMATORY EFFECT OF 2-ALLYLPHENOL.
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Fecha: 04-feb-2022
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Hora: 08:00
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Mostrar Resumen
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ASSIS, D.B. Evaluation of antioxidant activity and mechanisms involved in the antinociceptive and anti-inflammatory effects of 2-allylphenol. 2021. 106p. Tese (Pós-graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos) UFPB / CCS, João Pessoa.
2-Allylphenol (2-AF) is a phenylpropanoid widely marketed in China under the name Yinguo. Extracted from the exosperm of the Ginkgo biloba fruit, 2-AF has previously reported antibacterial, antitumor, antifungal and antinociceptive activities. However, it is necessary to elucidate in more detail the mechanism by which 2-AF promotes its antinociceptive effect, so this study aims to evaluate a possible antioxidant and anti-inflammatory activity exerted by 2-AF in mice, evaluating the mechanisms involved in these effects. The administration of 2-FA was carried out at doses of 50, 75 and 100 mg/kg (i.p.) always thirty minutes before the performance of pharmacological tests. The experiments started with the investigation of the antinociceptive mechanism of 2-AF. To study the participation of the nitroxidergic, GABAergic and dopaminergic systems, respectively, L-NNA, flumazenil and sulpiride were administered fifteen minutes before the treatment with 2-AF in the test of abdominal writhing induced by acetic acid. In order to increase the evidence of the action of 2-AF in the adenosinergic pathway, previously reported, a study of molecular docking was carried out. The carrageenan-induced peritonitis test was used to assess the anti-inflammatory effect of 2-AF by evaluating cell migration and levels of pro-inflammatory cytokines TNF-α and IL-1β in peritoneal fluid. Finally, the antioxidant activity of 2-allylphenol was determined by tests of total antioxidant capacity, DPPH scavenging activity, hydroxyl radical scavenging activity test, superoxide scavenging activity test. Treatment with L-NNA, flumazenil and sulpiride did not reverse the antinociceptive effect of 2-AF, ruling out the participation of the nitroxidergic, GABAergic and dopaminergic systems in the antinociceptive effect. Docking studies confirmed an affinity between 2-AF and the A2a receptor, this interaction may be related to the reduction in the production of pro-inflammatory cytokines. In anti-inflammatory tests, 2-AF inhibited leukocyte migration via reduced levels of TNF-α and IL-1β in the peritonitis test. It presented a high total antioxidant capacity, this activity being provided through the scavenging of superoxide radicals, demonstrating that its antioxidant activity may also be helping in the anti-inflammatory and antinociceptive effect. In view of the results, the clinical potential of 2-AF for the treatment of pain and inflammation becomes evident.
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