## 3 Results and Discussion
Non-Cytotoxic Effect of Polyphenol Extract of Mexican Oregano L. gravelens on Normal Human Cells CCD-18 Co  
The results obtained from the evaluation of the cytotoxicity of the polyphenol extract of _L. gravelens_ are shown in Figure 2. The lactate dehydrogenase enzyme (LDH) activity indicated cell membrane integrity or cell death. In normal conditions, a lysis control can be seen on the left side of Figure 2, with a 100% activity of the LDH enzyme and a cellular control (cells without polyphenol extract). In addition, 250 \(\upmu\)M of cisplatin was used as a reference drug to compare the extract's effect in treating breast cancer. We observed that the polyphenol extract did not show cytotoxicity in this type of normal human cells since the LDH enzyme activity was less than 10% after treatment with the extract for 24 h. Compared to the reference drug, there was a marked difference regarding the behavior of the extract, and cisplatin presented values above 40% of cell death. On the other hand, we also observed a lower percentage of cell death after the treatment with the polyphenol extract of _L. gravelens_ compared to the control cells. This may be because the antioxidant compounds present in the extract can form stable complexes, preventing the catabolic action of the free radicals in the membrane and protecting DNA from oxidative damage, thereby contributing to increased cell viability [31; 58]. On the other hand, the behavior observed in the cytotoxicity results for cell line MDA-MB-231 shows a marked selectivity of the extract on these cells, because, at the same conditions and the same concentration of polyphenic extract of _L. gravelens_ evaluated, a percentage of LDH enzyme activity above 50% was obtained; the effect of the extract on these cancer cells can be seen in Figure 3. In previous work by our research group, we demonstrated that the polyphenol extract of _L. gravelens_ can inhibit the proliferation of breast cancer cells without cytotoxicity in normal mouse cells (NIH3T3) at a concentration of 150 \(\mu\)g/mL of the extract [29], behavior that coincides with the results obtained with these cell lines for the LDH cytotoxicity assay. According to results, it could be observed that the extract did not cause cytotoxicity in normal human CCD-18 Co cells, an important characteristic of this extract to highlight since many of the drugs currently used for the treatment of breast cancer lack cell specificity, causing significant damage in normal cells which leads to the presence of serious side effects for patients, for example, the cisplatin. In addition, another work showed that this oregano species presented cytotoxicity in SK-LU-1 lung cancer cells without causing damage in normal HFF-1 cells [43]. Also, similar behavior was observed in the extract of the _Origanum vulgare_ species, presenting activity against B16-F10 and A375 melanoma cells without cytotoxicity or mutagenicity in normal C2C12 myoblast cells [48]. Following this context, we can find more evidence of the selectivity of flavonoids to inhibit cancer cells than normal cells in the literature. For example, in a study conducted  
Figure 3: MDA-MB-231 cells exposed to different treatments during 24 h incubation. Cell control represents cells without treatment. LG: polyphenol extract of Mexican oregano _Lippia graveolens_. Images obtained under the microscope (40\(\times\)). Figure 2: Cytotoxicity of polyphenol extract of Mexican oregano _Lippia graveolens_ (LG) on normal CCD-18 Co cells and MDA-MB-231 cancer cells, expressed as a percentage of lactate dehydrogenase activity (LDH). Results are expressed as means (n = 3) \(\pm\) standard deviation (bars). The ANOVA was evaluated with the Dunnett test with lysis control for each cell type. Values without letters are statistically different (\(p\leq 0.05\)).