Anti-ulcer mechanisms of polyphenols extract of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae).
BACKGROUND
Euphorbia umbellata (leitosinha) is used in southern Brazilian folk medicine to treat gastric problems, as well as for its analgesic and anti-inflammatory properties.


OBJECTIVE
To evaluate the anti-ulcer effects of methanolic bark fraction (MF) against in vivo and in vitro assays, as well as an antioxidant, antibacterial and chromatographic study of this fraction.


METHODS
In vivo anti-ulcer activity was performed using ethanol and indomethacin models with different MF concentrations (50, 100 or 200mg/Kg). The stomachs of the animals were applied to histological evaluation, and the serum to evaluate the ABTS(•+) radical capture. The 200mg/Kg dose was used to analyze the mechanisms involved in antiulcerogenic properties of methanolic fraction. The in vitro activity was performed using several different antioxidant assays, in addition to anti-Helicobacter pylori and anti-urease experiments. The chromatographic study was carried out by LC-MS analysis.


RESULTS
Pharmacological investigation of the MF showed an anti-ulcer potential in ethanol and indomethacin in vivo assays. The material presented a high antioxidant activity for several oxidant in vitro systems (DPPH(•), ABTS(•+), O2(•-), HOCl, TauCl and HRP), as well as an ABTS(•+) capture increasing (7.5%) by the treated animals serum (when compared to the negative control). Prostaglandins, nitric oxide/ cyclic guanosine monophosphate pathway and involvement of the protein components of the glutathione complex are some of the mechanisms related with this potential anti-ulcer action. The histological examination of the stomachs of the animals showed that the MF also prevents local action of offensive agents. Chemical analysis using LC-QTOF-MS revealed the presence of ellagic and gallic acid derivatives and flavonols.


CONCLUSIONS
The findings provide scientific basis to the ethnopharmacological purpose of the studied plant and the biological activities of MF of E. umbellata stem bark may be due to the presence of phenolic compounds.
Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil. Electronic address: brunominozzo@outlook.com.
Bruno Rodrigo
BR
Minozzo
Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
Bruna Mikulis
BM
Lemes
Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
Aline da Silva
ADS
Justo
Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
Jheniffer Ellen
JE
Lara
Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
Victor Emanuel Kubaski
VEK
Petry
Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
Daniel
D
Fernandes
Department of Clinical and Toxicological Analysis, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
Caroline
C
Belló
Department of Clinical and Toxicological Analysis, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
José Carlos Rebuglio
JCR
Vellosa
Department of Odontology, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil.
Eduardo Bauml
EB
Campagnoli
Department of Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória 29040-090, Espírito Santo, Brazil.
Otalíbio Castiglione
OC
Nunes
Department of Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória 29040-090, Espírito Santo, Brazil.
Rodrigo Rezende
RR
Kitagawa
National Center for Natural Products Research, University of Mississippi, Oxford 38677, MS, USA.
Bharathi
B
Avula
National Center for Natural Products Research, University of Mississippi, Oxford 38677, MS, USA.
Ikhlas Ahmad
IA
Khan
Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84900-030, Paraná, Brazil. Electronic address: flaviobeltra@gmail.com.
Flávio Luis
FL
Beltrame
D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000302:isolation & purification / Q000494:pharmacology; D000431:Ethanol; D020834:Ethnopharmacology; D028481:Euphorbia / Q000737:chemistry*; D005260:Female; D044948:Flavonols / Q000302:isolation & purification / Q000494:pharmacology; D005707:Gallic Acid / Q000302:isolation & purification / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects; D007213:Indomethacin; D000432:Methanol / Q000737:chemistry; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D059808:Polyphenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013451:Sulfonic Acids / Q000737:chemistry
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D052160:Benzothiazoles; D044948:Flavonols; D010936:Plant Extracts; D059808:Polyphenols; D012997:Solvents; D013451:Sulfonic Acids; D004610:Ellagic Acid; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D000431:Ethanol; D005707:Gallic Acid; D007213:Indomethacin; D000432:Methanol
Anti-ulcer; Antioxidant; Glutathione; Nitric oxide; Phenolic compounds; Prostaglandins