Estudo farmacológico da ternatina, um flavonóide isolado de Egletes viscosa, LESS

Abstract

Ternatin (5, 4’-dihydroxy-3, 7, 8, 3’-tetrametoxy-flavone), a flavonoid which was extracted and purified from Egletes viscosa, Less. (Compositae), was screened for various pharmacological effects in experimental animals. The compound (15 and 30 mg/kg, i.p.) demonstrated a dose-related significant anti- inflammatory effect in the carrageenan-induced rat hind paw test. In this model, indomethacin (5 mg/kg, p.o.), a known nonsteroidal anti-inflammatory drug (NASID), evidenced a much greater potency than to Ternatin. At similar doses, Ternatin effectively reduced the increase in vascular permeability induced by acetic acid in mice, a property common to many of the flavonoids. In mice, Ternatin (15 and 30 mg/kg, i.p.) failed to modify the reaction time in Eddy’s hot plate (55±1°C) test, but in writhing test induced by acetic acid, it significantly reduced the number of abdominal contractions (writhes) in a dose-dependent manner indicating a possible peripheral analgesic property. Ternatin also showed antipyretic activity in the rat model of pyrexia induced by Brewer’s Yeast. Its activity at 30 mg/kg, i.p., was almost equivalent to that produced by paracetamol (250 mg/kg, p.o.). The gastroprotective effect of Ternatin was evident in the model of acute gastric hyperemia provoked by ethanol 99% in mice. Ternatin at doses of 30 and 60 mg/kg, i.p., significantly reduced the development of ethanol induced hyperemic changes in the stomach. Besides, Ternatin (30 mg/kg, i.p.) demonstrated hepatoprotective property by causing significant inhibition of carbon tetrachloride (CCl4) – induced increases in serum alanina-aminotransferase (ALT) in rats. In rats treated with Ternatin (30 mg/kg, i.p.) for eight consecutive days, the pentobarbital-induced sleeping times was found to be significantly higher than vehicle treated controls what means signifies the possible depressant effect of the compound on drug metabolizable enzymes in liver and/or other organ systems. Ternatin (15 and 30 mg/kg, i.p.) inhibited, in a dose-dependent manner the gastrointestinal propulsion in mice. In addition, Ternatin (10 to 40 µg/mL in bath fluid) produced an effective reversible inhibition of contractile responses evoked by various agonists (acetylcholine, histamine, serotonin and barium chloride) in isolated guinea pig ileum. The inhibition was observed to be inespecific and could be overcome by an increase in the Ca++ concentration of bathing fluid implying that Ternatin affects cellular calcium dependent processes. In KB-cell lines, Ternatin evidenced low cytotoxicity. The effective drug concentration required to inhibit the growth of KB-cells (CyED50) was found to be 100 µg/mL. Ternatin and the crude extrats of Egletes viscosa evidenced low order of general toxicity. The present findings on Ternatin, together with the reported antiviral activity against polioviruses and adenoviruses suggest that it might be the unique active compound present in Egletes viscose and this may be the scientific basis for the extensive use of plant crude extracts in popular medicine for treating gastrointestinal disturbances.