A B S T R A C TObjective: To evaluate acute and subacute toxicity of methanol extract of Terminalia citrina leaves (family: Combretaceae) in Sprague Dawley rats. Methods: The acute toxicity studies were conducted where the limit test dose of 3 200 mg/kg body weight used. Observations were made and recorded systemically on 1, 2, 4, 24 and 48 h after dose administration for behavior, breathing, cutaneous effects, sensory nervous system response or gastrointestinal effects. For the subacute toxicity, four groups of 10 female rats were received; distilled water (control), 250, 500 and 1 000 mg/kg of extracts respectively every 24 h orally for 28 days. Results: No significant variation in the body and organ weights between the control and the treated group was observed after 28 days of treatment. Haematological analysis and biochemical parameters revealed no toxic effects of the extract. Pathologically, neither gross abnormalities nor histopathological changes were observed. No mortality was recorded in 28 days. Conclusions: It was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

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The present study was designed to investigate the in vitro anti-inflammatory, antimicrobial, cytotoxic and antioxidant effects of Naproxen metal complexes. Methodology: The anti-inflammatory activity was evaluated by HRBC membrane stabilization method while antimicrobial activity by disk diffusion method. The cytotoxicity was evaluated by brine shrimp lethality bioassay and compared with vincristine sulfate. Antioxidant potential was evaluated in terms of DPPH radical scavenging potential, ABTS scavenging potential, reducing power assay, superoxide dismutase assay and total antioxidant capacity by specific standard procedures. Results: The Naproxen metal chelates showed significant anti-inflammatory effects in dose dependent manner. Naproxen standard showed maximum inhibition occurred 73.21% at the dose of 2000 lg/ml. Among Naproxen metal chelates, Naproxen silver complex showed potent antimicrobial activity against most of the tested microorganisms while Naproxen zinc complex showed better activity against gram positive strains than gram negative. In brine shrimp lethality bioassay, varying degree of lethality to Naproxen metal chelates was observed showing Naproxen iron complex surprisingly very potent cytotoxic activity compared to vincristine sulfate where other metal complexes displayed reduced cytotoxicity than parent Naproxen while Naproxen exhibited the lowest antioxidant assay among all the metal complexes compared to the standard ascorbic acid. Conclusion: The present study demonstrated that Naproxen and its complexes possess in vitro anti-inflammatory activity while silver, zinc and iron complexes possess higher antimicrobial and cytotoxic properties than the parent ligand and possess very mild antioxidant activity.

Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand.