Antioxidant Properties of Lippia alba Essential Oil: A Potential Treatment for Oxidative Stress-Related Conditions in Plants and Cancer Cells

Abstract

Lippia alba (Mill.) N.E.Br. ex Britton and P. Wilson is used in folk medicine of Central and South America for its biological activities: i.e., antifungal, antibacterial, antiviral, and anti-inflammatory. Based on ethnopharmacological information and the increasing interest in this species, this work aimed to test a possible wide use of its essential oil (EO) in pharmaceutical and horticultural applications. Therefore, we focused the attention on the antioxidant activity of the oil as a possible tool to overcome the oxidative stress in both applications. For this purpose, we have chosen three aggressive breast cancer cell lines and two horticultural species (Solanum lycopersicum L. and Phaseolus acutifolius L.) that are very sensitive to salt stress. We determined the antioxidant activity of L. alba EO through the quantification of phenols and flavonoids. Regarding tomato and bean plants under salt stress, L. alba EO was used for the first time as a seed priming agent to enhance plant salt tolerance. In this case, the seed treatment enhanced the content of phenolic compounds, reduced power and scavenger activity, and decreased membrane lipid peroxidation, thus mitigating the oxidative stress induced by salt. While in breast cancer cells the EO treatment showed different responses according to the cell lines, i.e., in SUM149 and MDA-MB-231 the EO decreased proliferation and increased antioxidant activity and lipid peroxidation, showing high cytotoxic effects associated with the release of lactate dehydrogenase, vice versa no effect was observed in MDA-MB-468. Such antioxidant activity opens a new perspective about this essential oil as a possible tool to counteract proliferation in some cancer cell lines and in horticulture as a seed priming agent to protect from oxidative damage in crops sensitive to salinity.

Keywords: Lippia alba; ROS; antioxidant activity; breast cancer cells; essential oil; glycophytes; phenolic compounds; salt stress.

Figure 1

Habit of Lippia alba (Mill.) N.E.Br. ex Britton and P. Wilson.

Figure 2

DPPH free radical inhibiting activity (%) at various concentration of EO (% v/v) (a) and estimation of IC₅₀ value of EO (b). The dotted line represents 50% inhibition. The values are compared with ascorbic acid.

Figure 3

Phenolic compounds of bean (a) and tomato (b) plants. Data are expressed as mean ± SE (n = 6). Mean values in the column marked by different letters are significantly different within the same group (p < 0.05; ANOVA and Tukey–Kramer test). Significant differences to CTRL are reported as * p < 0.05; ** p < 0.01.

Figure 4

Flavonoids of bean (a) and tomato (b) plants. Data are expressed as mean ± SE (n = 6). Mean values in the column marked by different letters are significantly different within the same group (p < 0.05; ANOVA and Tukey–Kramer test). Significant differences to CTRL are reported as *** p < 0.001.

Figure 5

Estimation of IC₅₀ value of bean (a) and tomato plants (b) expressed as mg·mL⁻¹.

Figure 6

Thiobarbituric acid reactive products in bean (a) and tomato (b) samples. Data are expressed as mean ± SE (n = 6). Mean values in the column marked by different letters are significantly different within the same group (p < 0.05; ANOVA and Tukey–Kramer test). Significant differences to CTRL are reported as ** p < 0.01; *** p < 0.001.

Figure 7

Proliferation and Cytotoxicity (%) of MDA-MB-231 cell lines. Data are expressed as mean ± SE (n = 6). Significant differences to control (CTRL) were calculated by t-student test and reported as * p < 0.05; ** p < 0.01.

Figure 8

Proliferation and Cytotoxicity (%) of SUM149 cell lines. Data are expressed as mean ± SE (n = 6). Significant differences to control (CTRL) were calculated by t-student test and reported as *** p < 0.001.

Figure 9

Proliferation (%) MDA-MB-468 cell lines. Data are expressed as mean ± SE (n = 6). Significant differences to control (CTRL) were calculated by t-student test and reported as ** p < 0.01; *** p < 0.001.

Figure 10

Estimation of IC₅₀ value from MDA-MB-231 (a) and SUM149 (b) cell lines expressed as % v/v.

Figure 11

Ferric reducing antioxidant power of MDA-MB-231 (a) and SUM149 (b) cell lines. Data are expressed as mean ± SE (n = 6). Significant differences to control (CTRL) were calculated by t-student test and reported as * p < 0.05; *** p < 0.001.

Figure 12

Potassium ferricyanide reducing antioxidant power of MDA-MB-231 (a) and SUM149 (b) cell lines. Data are expressed as mean ± SE (n = 6). Significant differences to control (CTRL) were calculated by t-student test and reported as ** p < 0.01; *** p < 0.001.

Figure 13

Thiobarbituric acid reactive products of MDA-MB-231 (a) and SUM149 (b) cell lines. Data are expressed as mean ± SE (n = 6). Significant differences to control (CTRL) were calculated by t-student test and reported as * p < 0.05; *** p < 0.001.

Figure 14

Lactate dehydrogenase activity of MDA-MB-231 (a) and SUM149 (b) cell lines. Data are expressed as mean ± SE (n = 6). Significant differences to control (CTRL) were calculated by t-student test and reported as * p < 0.05; *** p < 0.001.

Figure 15

Possible mechanism of action of L. alba EO on bean and tomato cells under salt stress. In the presence of high salt concentration, primed plants increase the synthesis of intracellular phenolic compounds, enhancing their antioxidant activity, inhibiting ROS overproduction. Furthermore, flavonoids prevent lipid peroxidation, avoiding the interaction between ROS and PUFAs, which cause severe damage to the plasma membrane by producing new radical species. Created by BioRender.com (accessed on 23 July 2023).

Figure 16

Possible mechanism of action of L. alba EO on breast cancer cells. The dotted line represents the threshold value of antioxidant capacity of the cells to overcome ROS toxicity. Above this threshold, the cells are unable to overcome the damage caused by the accumulation of ROS. (Image based and modified from [5,14]). Created in BioRender.com (accessed on 23 July 2023).