Studies on the in Vitro and in Vivo Interaction of Cold Water Extract of Azadirachta Indica (Neem) Leaves with Some Antibiotics

Abstract

The present study investigated herb-drug interactions involving cold water extract of Azadirachta indica (neem) leaves, with five classes of antibiotics, namely: Tetracyclines - Tetracycline (TET) and Doxycycline POX); I Penicillins - Penicillin G(PG) and Ampicillin (AMP); Cephalosporins – Cefuroxime (CF); Arninoglycosides -Gentamicycin (GEN) and Streptomycin (STREP) and Fluoroquinolones-Ciprofloxacin (CIP) and Norfloxacin (NF);. In vitro interactions between the neem leaf extract and the antibiotics were evaluated using Agar diffusion and checkerboard techniques. The in vivo interactions were evaluated using biological models in albino rats. The rats were infected with virulent strain of Klebsiella nreurnoniae and subsequently treated with Ciprofloxacin (100 mglkg), neem (70 mg/kg), neem-cip combinations (10 mg/kg of neem and 90 mg/kg of CIP). Immunological parameters were monitored by assessing changes in total and differential leucocytes I counts. In vitro results reveal that in the Agar diffusion method, 2 mg/ml and 5 mglml of the neem leaves cold water extracts showed mostly synergistic interactions with the antibiotics used. The enhanced activities of the antibiotics in the presence of neem were significant at p 0.05 levels of significance. In the checkerboard techniques, fractional inhibitory concentration (FIC) index showed that neem and either tetracycline, streptomycin, ciprofloxa&n, norfloxacin combinations produced synergistic effects against S. aureus, at the ratios (1:9), (1:9 and 9:1), (2:8 and 6:4) respectively. Neem and tetracycline produced a synergistic effect against E.coEi at the ratio (1:9). Neem and norfloxacin also produced synergistic effect against Bacillus subtilis at the ratio 6:4, 7:3 and 9:l respectively. The result of the in vivo interaction showed a reduction in the total, xiv leucocytes count below the normal range (Leucopoenia) after the infection of the animals. By the 5' day after treatment, there was a significant increase in leucocytes , count in the order: Neem + CIP >CIP>Neem at P<0.05 level of significant. The study Suggests a possible clinical use of the combination of cold-water extracts of neem and the antibiotics used against infections caused by these organisms. The neem extract can also be used to initiate or stimulate leucopoiesis through the interactions of T lymphocytes and the production of colony-stimulating activity (CSA) which is used to control proliferation of leucocytes.