The purpose of the present study was to evaluate the antibacterial, anti-inflammatory, and cytotoxic properties of Melia azedarach leaf. The phytoconstituents found in the leaves were extracted with four different solvent systems based on their polarity index. Antimicrobial activity of selected plant extracts was evaluated using disc diffusion and micro-broth dilution methods against four different pathogenic bacterial strains. The ethanolic extract of M. azedarach leaf showed a significant inhibitory effect on the growth of Escherichia coli (15.07 mm) and Staphylococcus aureus (18.23 mm) (P < 0.005), followed by Bacillus subtilis and Salmonella typhi. Further, the mechanism of action was confirmed by live/dead cells analysis, which revealed the death of E. coli and S. aureus upon treatment with ethanolic extract. In vivo anti-inflammatory test conducted using carrageenan-induced rat paw edema model revealed that the 300 mg/kg ethanolic extract exhibited a significant anti-inflammatory activity of 51.78% compared with that of standard drug diclofenac (P < 0.001). Further, the cytotoxicity of ethanolic extract against human hepatocarcinoma cell lines (HepG2) was evaluated by MTT assay, and the findings showed a moderate level of toxicity against the HepG2 cell line with an IC50 value of 540.00 &plusmn; 0.6 &mu;g/mL compared to doxorubicin. HepG2 cells treated with doxorubicin (2 &mu;g/mL) and ethanolic extract showed a 2.33- and 1.35-fold increase in p53 gene expression, respectively. Apoptosis activity was measured in terms of DNA laddering, which indicated the late stage of apoptosis. The results showed that the extract-treated cell lines induced DNA fragmentation, which was found to be a potent anti-cancer mechanism in HepG2 cells. This study corroborated that the leaf extract of M. azedarach is a good source of active phytochemicals, with promising biological activities.
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