## 4 Discussion
Among the three tested bacterial species, _Camellia sinensis_ extract showed the highest antibacterial activity against _S. aureus_ (MRSA and MSSA), exhibiting the lowest MIC value (0.5 mg/mL) which is in agreement with the report of [22]. Additionally, _Camellia sinensis_ has anti-bacterial activity against MDR _P. aeruginosa_, which is similar to a previous report [32]. _Aloysia citrodora_ showed a MIC value of 1.3 mg/mL and 5.3 mg/mL against MRSA and _P. aeruginosa_, respectively, which is in agreement with [33], were essential oils of _Aloysia citrodora_ possessed significant antibacterial effect against both Gram negative and Gram positive bacteria, with MICs ranged between 2.84 and 8.37 mg/mL. Furthermore, there were no differences between the effects of plant extracts against MRSA and MSSA that is similar to the report of [34]. The infection severity of MRSA is due to lack of therapeutic options, but not due to it is virulence [34]. Gram negative bacteria (_E. coli_ and _P. aeruginosa_) were less susceptible to antibacterial plant extracts which may be due to their outer membrane lipopolysaccharidesaccharides, which is similar to the report of [35]. The antibacterial effects were higher against _S. aureus_ and comparatively lower in the case of _Salmonella_ and _E. coli_[35]. Results of this study are also consistent with many previous reports, which find a good indication for the potential of some plants to be applied as antimicrobial to treat bacterial infections [13; 19]. The toxicity of plant extract needs scientific validation to ensure it is safe to use by humans [19; 33]. Our results indicated that _Camellia sinensis_, _Aloysia citrodora_, _Hibiscus sabdariffa_, _Thymus vulgaris_, _Glycyrrhiz glabra_ did not have any toxicity at 100 mg/mL using erythrocyte hemolysis assay. This is similar to the report of [24; 36]. It is also worth mentioning that our results of the cytotoxicity assay are in agreement with many previous studies that investigated plants toxicity on human fibroblast and monkey Vero cell lines [24; 29; 33]. The results of the _in vitro_ MTT assay showed no cytotoxicity for all tested plants when compared with doxorubicin, which is used as a positive control [37]. Our challenge study demonstrated that MRSA-induced systemic infection after estimated acute cytotoxicity. All mice in the acute toxicity study were within normal limits. According to our results, _Camellia sinensis_, _Aloysia citrodora_, and _Hibiscus sabdariffa_ are safe to use as remedy which is in agreement with the results of [38; 39]. The previous three plants showed a significant decrease in the severity of the _in vivo_ MRSA infection compared to the positive control. _Camellia sinensis_ treated group has the most protective ability against MRSA infections among all groups including vancomycin, which is consistent with [35] results of the _Camellia sinensis_ seed saponins which possess strong antibacterial activities against infected chickens by _E. coli_, _S. aureus_, and _Salmonella_[35]. In recent years reduced vancomycin susceptibility of MRSA was noted [40] which is consistent with our results. The activity of _Aloysia citrodora_ extract was improved when combined with _Camellia sinensis_. Hence, the combination effects indicated synergistic efficacy. However, combinations of _Camellia sinensis_ with _Hibiscus sabdariffa_ were antagonists. In general, the synergistic effects of the combination of different herbs with various bioactive constituents have shown progressive protective effects [41; 42].