In-vitro, in-vivo, and in-silico assessment of radical scavenging and cytotoxic activities of Oliveria decumbens essential oil and its main components

Abstract

We aimed to explore and compare new insights on the pharmacological potential of Oliveria decumbence essential oil (OEO) and its main components highlighting their antioxidant activity in-vitro, in-vivo, and in-silico and also cytotoxic effects of OEO against A549 lung cancer cells. At first, based on GC–MS analysis, thymol, carvacrol, p-cymene, and γ-terpinene were introduced as basic ingredients of OEO and their in-vitro antioxidant capacity was considered by standard methods. Collectively, OEO exhibited strong antioxidant properties even more than its components. In LPS-stimulated macrophages treated with OEO, the reduction of ROS (Reactive-oxygen-species) and NO (nitric-oxide) and down-regulation of iNOS (inducible nitric-oxide-synthase) and NOX (NADPH-oxidase) mRNA expression was observed and compared with that of OEO components. According to the results, OEO, thymol, and carvacrol exhibited the highest radical scavenging potency compared to p-cymene, and γ-terpinene. In-silico Molecular-Docking and Molecular-Dynamics simulation indicated that thymol and carvacrol but no p-cymene and γ-terpinene may establish coordinative bonds in iNOS active site and thereby inhibit iNOS. However, they did not show any evidence for NOX inhibition. In the following, MTT assay showed that OEO induces cytotoxicity in A549 cancer cells despite having a limited effect on L929 normal cells. Apoptotic death and its dependence on caspase-3 activity and Bax/Bcl2 ratio in OEO-treated cells were established by fluorescence microscopy, flow cytometry, colorimetric assay, and western blot analysis. Additionally, flow cytometry studies demonstrated increased levels of ROS in OEO-treated cells. Therefore, OEO, despite showing antioxidant properties, induces apoptosis in cancer cells by increasing ROS levels. Collectively, our results provided new insight into the usage of OEO and main components, thymol, and carvacrol, into the development of novel antioxidant and anti-cancer agents.

Hesperidin Inhibits Lung Cancer In Vitro and In Vivo Through PinX1

“…The pinX1 protein expression in normal lung epithelioid fibroblasts, L929 cell line, is higher than that in LLC cells, and hesperidin significantly increased the pinX1 protein expression in a concentration-dependent manner (Figure 4A). Hesperidin inhibits the cell viability of LLC cells in a concentration-dependent manner (in the first four columns) but does not affect the cell viability of L929 cells (Figure 4B), a normal epithelioid fibroblast cell line, which is employed to show that it has no cytotoxic effect on normal cells as indicated in the previous study (Rajamma et al, 2020;Jamali et al, 2021). The aforementioned results indicated that hesperidin is a potential anti-tumor candidate with less lethality on normal lung cells.…”

Thymol as a Potential Neuroprotective Agent: Mechanisms, Efficacy, and Future Prospects

“…Additionally, thymol has been reported to directly interact with NADPH oxidases (NOXs) and inhibit the expression of NOX subunits (including gp91phox, p67phox, p47phox, p40phox, and p22phox) in lipopolysaccharide (LPS)-treated macrophages, effectively reducing ROS production. 48 Consistently, Kavoosi et al found that thymol and carvacrol (an isomer of thymol) administrations could both effectively inhibit the increases in the activities of NOXs in high doses of glucose-treated human monocytes. 54 NOXs are the primary source of ROS production in animal cells, especially under pathological conditions.…”

The Essential Oil from Oliveria decumbens Vent. (Apiaceae) as Inhibitor of Breast Cancer Cell (MCF-7) Growth

“…Thymol is endowed with anti-inflammatory, anticancer, antioxidant, and antimicrobial properties [ 36 ]. This compound exerts its anticancer effects through the suppression of cell growth, induction of apoptosis, production of intracellular ROS, depolarization of mitochondrial membrane potential, and activation of various pro-apoptotic mitochondrial proteins in human gastric AGS and breast cancer cells [ 37 , 38 ]. Thus, the antitumor, antioxidant, and antimicrobial activities of OEO [ 19 , 20 , 21 ] may be related to the presence of thymol and carvacrol.…”