Tabernaemontana catharinensis ethyl acetate fraction presents antinociceptive activity without causing toxicological effects in mice.
BACKGROUND
Tabernaemontana catharinensis (Apocynaceae) is a medicinal plant used for the treatment of painful and inflammatory disorders. Here, we investigated the antinociceptive potential of the ethyl acetate fraction (Eta) from T. catharinensis leaves and assessed its toxic effects in mice to validate its popular use.


METHODS
Adult male Swiss mice (30-35g) were used. The Eta antinociceptive effect (200-800mg/kg, oral route (p.o.)) was evaluated in the acetic acid, formalin, capsaicin and tail-immersion tests. Adverse effects were analyzed using rotarod and open-field tests, body temperature, biochemical analysis and gastric lesions assessment. To evaluate the acute (OECD 423) or sub-acute (OECD 407) toxicity of the Eta, it was administered orally at a single (2000mg/kg) or repeated doses (100-400mg/kg/day for 28 days), respectively. Mortality, behavioral changes, biochemical and hematological parameters were evaluated. The Eta effect on cellular viability also was evaluated.


RESULTS
Eta (200-800mg/kg) inhibited the nociception caused by acetic acid (93.9±1.5%), formalin (86.2±10.8%) or capsaicin (75.4±3.3%) without inducing gastric lesions. Moreover, Eta neither altered the body temperature, biochemical parameters, nor forced or spontaneous locomotor activity of mice. The acute administration of the Eta (2000mg/kg) promoted a decrease in blood glucose levels and alanine aminotransferase activity. In the sub-acute toxicity study, Eta increased the aspartate aminotransferase activity (400mg/kg) and platelet distribution width (200mg/kg). Furthermore, Eta did not alter the cellular viability in cortical slices.


CONCLUSIONS
Eta presents antinociceptive effects and mild toxicity in mice. These results support its traditional use as a potential analgesic.
Laboratory of Neurotoxicity and Psychopharmacology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Evelyne
E
da Silva Brum
Laboratory of Neurotoxicity and Psychopharmacology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Laís
L
da Rosa Moreira
Laboratory of Toxicological Analysis, Pharmaceutical Sciences Graduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Andreia Regina Haas
ARH
da Silva
Laboratory of Phytochemistry, Pharmaceutical Sciences Graduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Aline Augusti
AA
Boligon
Department of Biochemistry and Molecular Biology, Graduate Program in Biological Sciences: Biochemical Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Fabiano Barbosa
FB
Carvalho
Laboratory of Phytochemistry, Pharmaceutical Sciences Graduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Margareth Linde
ML
Athayde
Laboratory of Toxicological Analysis, Pharmaceutical Sciences Graduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Ricardo
R
Brandão
Laboratory of Neurotoxicity and Psychopharmacology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Department of Biochemistry and Molecular Biology, Graduate Program in Biological Sciences: Biochemical Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil. Electronic address: saramarchesan@hotmail.com.
Sara Marchesan
SM
Oliveira
D000085:Acetates / Q000737:chemistry*; D019342:Acetic Acid; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D029062:Apocynaceae / Q000737:chemistry*; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D008297:Male; D051379:Mice; D009043:Motor Activity; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D017288:Pain Threshold / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal; D018570:Risk Assessment; D045442:Rotarod Performance Test; D012997:Solvents / Q000737:chemistry*; D013997:Time Factors; D018675:Toxicity Tests
D000085:Acetates; D000700:Analgesics; D010936:Plant Extracts; D012997:Solvents; D005557:Formaldehyde; C007650:ethyl acetate; D019342:Acetic Acid; D002211:Capsaicin
Antinociception; Apocynaceae; Capsaicin (CID: 1548943); Cobrina; Inflammatory pain; MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (CID: 64965); ethyl acetate (CID: 8857); formalin (CID: 712); glutamate (CID: 33032); morphine (CID: 5288826); naloxone (CID: 5284596); sodium diclofenac (CID: 5018304)