ABSTRACT
The global burden of Salmonella infections remains high due to the emergence of multidrug resistance to all recommended treatment antibiotics. Tetrahydroisoquinolines (THIQs) have demonstrated promising activity against multidrug-resistant (MDR) Salmonella Typhi. Hence, their interaction with treatment antibiotics was investigated for possible synergy. Twenty combinations of five THIQs (1, 2, 3, 4, and 5) and four antibiotics were tested against each of 7 Salmonella isolates by the checkerboard method giving a total of 140 assays performed. Fractional inhibitory concentration indices (FICIs) were calculated, and isobolograms were plotted. In terms of FICI, synergism ranged from 0.078 to 0.5 and the highest magnitude (0.078) was recorded for chloramphenicol-THIQ 1 combination. In a total of 140 antibiotics-THIQs combination assays, 27 were synergistic (17%), 42 were additive (30%), 11 were antagonistic (7.8%), and 60 were indifferent (42%). The synergistic activity recorded for each antibiotic class in combination based on the total of 7 bacterial isolates tested ranged from 14.29% to 71.43%; the highest percentage was recorded for two combinations (chloramphenicol or sulphamethoxazole with THIQ 1). Ciprofloxacin-THIQ 1 combination showed additivity on all bacteria isolates tested (100%). Overall, THIQ 1 was the most synergistic and most additive in combination with three antibiotics (ampicillin, chloramphenicol, or sulphamethoxazole-trimethoprim). Some combinations of the THIQs and treatment antibiotics have shown high synergism which could potentially be efficacious against multidrug-resistant S. Typhi, hence this interaction should be further studied in vivo.
ABSTRACT
The treatment of Salmonella infections is threatened by multidrug resistance necessitating the search for alternative treatments, such as from medicinal plants. There are several reports on the antibacterial activity of Annona muricata. This study assessed the activity against multidrug-resistant (MDR) Salmonella and also the toxicity of the leaves of this plant. The hexane and methanol extracts of the leaves were screened against characterized MDR isolates by disc diffusion and microdilution methods. A cytotoxicity test was performed on monkey kidney epithelial cells; an acute toxicity test was conducted in BALB/c mice and the liver and kidney functions were assessed at the end of the test. Both extracts recorded weak activity in the disc test. Conversely, the extracts showed a wide range of activity against specific Salmonella isolates in the microdilution assay, and the lowest minimum inhibitory concentration value recorded was 0.0625 mg/mL. The hexane extract (ANOHEX) was not cytotoxic (CC50 = 57.7 µg/mL) and was also not toxic to the mice at 2000 mg/Kg bodyweight, while the methanol extract (ANOMET) was cytotoxic (CC50 = 18.44 µg/mL), and mortality was recorded at 2000 mg/Kg but not at 300 mg/Kg. There were no significant changes in biomarkers of the liver (alanine aminotransferase and aspartate aminotransferase) and kidney (creatinine and urea) functions (P > 0.05), except for ANOHEX which significantly decreased creatinine (P = 0.01), in the test mice which was not considered a toxic effect. In conclusion, this study has demonstrated high bacteriostatic activity against MDR Salmonella and a low risk of toxicity of A. muricata leaves. Hence, the leaves are a potential alternative treatment for resistant Salmonella infection. The natural products should be further investigated in vitro and in vivo.
ABSTRACT
Onchocerciasis is a parasitic infection affecting a relatively small population globally but has very devastating pathological outcomes. Ivermectin and recently moxidectin are the only drugs approved for clinical management of the disease, both of which have several limitations. In particular, they are efficacious against microfilariae (microfilaricidal) with no activity against adult worms (nonmacrofilaricidal). Promising anthelmintic activity has been reported in some lichens. This study investigated three lichens, Usnea articulata, Parmotrema tinctorum, and Heterodermia obscurata, found on Mount Cameroon, for potential macrofilaricidal activity. Organic extracts were screened for anti-Onchocerca activity against Onchocerca ochengi isolated from cattle skin using worm motility and MTT formazan assays. Toxicity of highly active extracts was investigated on monkey kidney epithelial (LLCMK2) cells and in BALB/c mice (2000 mg/kg body weight) including effects on liver enzymes. The methanol extract of P. tinctorum (Pammet) was the most active against adult male worms (IC50 = 8.1 µg/mL) with the highest selectivity index (SI = 21.3). U. articulata was the most active against the adult female (IC50 = 36.3 µg/mL) but had a low SI value (3.4). No mortality and no adverse effects were recorded in the acute toxicity test. These two most active extracts had no significant effect on liver enzymes, alanine aminotransferase, and aspartate (P values < 0.05), but a high AST : ALT ratio (2.59) for Pammet indicates likely reversible adverse hepatic toxicity. The high macrofilaricidal activity and selectivity of P. tinctorum suggest it is a potential source of new macrofilaricides which should be further investigated to identify its bioactive constituents.
ABSTRACT
BACKGROUND: Traditional medicine remedies are commonly used for treatment of diverse ailments including bacterial infections. The activity against resistant bacteria and safety of some remedies sold as anti-infective treatments in market places in Buea, Southwest Cameroon were investigated as potential alternative treatment to counter increasing antibiotic resistance. METHODS: Ten remedies were purchased, their components documented and microbial load estimated. Methanol extracts of the remedies were tested for antibacterial activity by disc diffusion and microdilution. Cytotoxicity was evaluated on monkey kidney epithelial cells (LLC-MK2) while acute oral toxicity was done in BALB/c mice for the bactericidal extract. Extracts were further analysed using phytochemical tests. RESULTS: All the remedies had microbial loads above the acceptable limit of 105 CFU/g. The highest activity was produced by extracts of four remedies (TP 1, 2, 4, 6a, 6b) against all clinical isolates among which three were active against four control strains. Zones of inhibition ranged from 8 to 27 mm. Two of the four extracts produced zones ≥20 mm against multidrug resistant clinical isolates of Citrobacter freundii and Escherichia coli but were less active compared to Gentamycin positive control (P < 0.0001-0.0014). The most active extracts also recorded minimum inhibitory concentrations of 1 to 4 mg/mL. One of them (TP2) was bactericidal against a clinical isolate of methicillin-resistant Staphylococcus aureus with a minimum bactericidal concentration of 8 mg/mL. Extracts of six remedies did not show cytotoxicity and no mortality or adverse effect was recorded in the acute oral toxicity test. Phytochemical screening showed the most active extracts contained relatively high amounts of alkaloids and flavonoids. CONCLUSION: Only four of the eight remedies tested showed activity against multidrug resistant bacteria suggesting some of these remedies may not be effective against bacterial infections. Production and handling methods should be improved and the product quality controlled to ensure biosecurity. The remedies which were both active and non-toxic should be further investigated including in vivo experiments to assess their efficacy.
