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Some of the widely used plants for the treatment of eye diseases, especially animals, include Lepidium sativium and Rumex nervosus. Therefore, the phytochemical screening and antimicrobial activities of the crude extracts of the seeds L. sativium and leaves of R. nervosus were investigated. Freshly matured seeds of L. sativium and leaves of R. nervosus were collected, and sequentially extracted by soxhlet extractor using different polarity solvents including n-hexane, methanol, ethanol and water. The extracts were thus screened for the presence of the prominent secondary metabolites which display characteristic bioactivities. Comparatively, the methanol and ethanol extracts displayed most of the metabolites including alkaloids, flavonoids, tannins, phenols, glycosides and steroids. Moreover, the antimicrobial activities of the extracts were tested against Staphylococcus aureus, Escherichia coli and Candida albicans using agar well diffusion method. The ethanolic extracts of R. nervosus leaves showed the highest activity (18.00 mm) against S. aureus and the water extracts gave the lowest zone of inhibition (6.00 mm) against E. coli. In all the extracts, the growths of the two bacterial and fungus strains were inhibited by the methanol and ethanol extracts. The best antifungal activity was observed in the methanol extract of the seeds of L. sativium against Candida albicans (20.00 mm). The results revealed that, the ethanol and methanol extracts of both plants were the two best extractive solvents with potential inhibitory activity against microbial growth. The observed activities were related to the presence of the noticeable phytochemicals in those plants. Therefore, this finding strongly supports the claim of the local community to use L. sativium and R. nervosus for the treatment of different pathogenic bacterial infections associated to eye diseases. However, the traditional aqueous extraction practice should be modified by addition of alcohol in order to maximize the extraction efficiency and thus the bioactivity of the plants.