In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential Oil and Its Main Component for Promoting Their Use in Clinical Practice

Abstract

Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its possible use in clinical practice with regards to its cytotoxic, anti-herpes simplex virus type 2 (HSV-2), and antihypertensive (through inhibition of human angiotensin-converting enzyme; ACE) properties. The phytochemical profile of EO (99.9%) was analyzed by Gas Chromatography with Flame-Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). In this study, all biological methods were performed at the level of in vitro studies. The results showed that TB-EO exerted remarked cytotoxic properties against human cervical carcinoma cells, colon cancer cells, and lung adenocarcinoma cells with the half-maximal inhibitory concentration (IC50) values of 7.22, 9.30, and 8.62 µg/mL, respectively, in comparison with that of standard anticancer drug cisplatin with IC50 values of 4.24, 5.21, and 5.43 µg/mL, respectively. Fascinatingly, TB-EO showed very weak cytotoxicity on the healthy human fetal lung fibroblast cells with an IC50 value of 118.34 µg/mL compared with that of cisplatin (IC50 = 10.08 µg/mL). TB-EO, its main component geraniol, TB-EO combined with acyclovir (ACV) along with standard ACV, have displayed pronounced inhibitory properties against the replication of HSV-2 with the half-maximal effective concentration (EC50) values of 2.13, 1.92, 0.81 and 1.94 µg/mL, respectively, with corresponding selectivity indices (SI) 98.59, 109.38, 259.26 and 108.25, respectively. TB-EO and geraniol at a concentration of 15 µg/mL showed prominent inhibitory activities against ACE with % of inhibition 95.4% and 92.2%, respectively, compared with that of standard inhibitor captopril (99.8%; 15 µg/mL). Molecular docking studies were performed to unveil the mechanism of action of geraniol as well as structural parameters necessary for anti-HSV-2 activity (through the inhibition of HSV-2 protease) and ACE inhibition. This is the first report on the chemical composition of Egyptian TB-EO along with the above-mentioned biological activities. Our results may be considered as novel findings in the course of a search for new and active anticancer, anti-HSV-2 and antihypertensive agents, and expand the medicinal value of this plant and its phytochemicals in clinical practice.

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development

“…Each group of terpenoids-monoterpenes, sesquiterpenes, diterpenes and triterpenes (including steroidal compounds)-gave us at least one positive hint in the search. The least abundant are monoterpenes, that are represented only by cypellocarpin C (63) isolated from E. globulus (63, arising from the combination of monocyclic monoterpene with a methylchromone), geraniol (64), here obtained from T. bovei essential oil [57], showing effects against HSV-2, both IC 50 and SI, greater than acyclovir [58], and (+)-rhodonoid C (64) (a cross-metabolite of monoterpene and polyketide [59]). In comparison to acyclovir, positive results were also obtained for cucurbitacin B (94) [73], meroditerpenes from Brazilian seaweed Stypopodium zonale 79 and 80 [67], dollabene diterpenes (85 and 86) from brown alga Dictyota pfaffi [70], which were inhibiting reverse transcriptase of HSV-1, as well as for halistanol derivatives (95)(96)(97), a steroidal type compound obtained from Brazilian marine sponge Petromica citrina [74] which, interestingly, showed a synergistic effect when tested together with acyclovir, but a lower selectivity index when tested alone.…”

“…essential oil has shown to possess obvious inhibitory effects on HSV-2 replication (EC50 = 1.92 μg/mL; SI = 109.38) compared with that of standard ACV (EC50 = 1.94 μg/mL; SI = 108.25). This substance, in a molecular docking analysis, has proved to bind to the active site of HSV-2 protease as a competitive inhibitor, and hence uncovered the potential mechanism of action behind the antiherpetic properties against HSV-2 ( Figure 6) [57]. In another study, psoromic acid (45), a bioactive, lichen-derived molecule, was tested for its inhibitory action against HSV-1 and HSV-2 [46].…”

“…Hydrogen bonding and several substantial interactions with amino acid residues are displayed. This figure and its description have been adapted from Hassan et al[57] with permission, as the article has been published by an MDPI publisher and licensed under an open access Creative Commons CC BY 4.0 license.…”

Brassicasterol with Dual Anti-Infective Properties against HSV-1 and Mycobacterium tuberculosis, and Cardiovascular Protective Effect: Nonclinical In Vitro and In Silico Assessments

“…Brassicasterol and standard captopril were investigated for their anti-ACE properties. ACE inhibition activities of test compounds were determined by a spectrophotometric method based on the production of hippuric acid from hippuryl-L -histidyl-L -leucine (HHL; substrate) [15]. Concisely, the assay was performed by incubating the test substances at a fixed concentration of 12.3 µg/mL with 120 mU/mL of human ACE (Sigma-Aldrich, Prague, Czech Republic) prepared in Tris Buffer (50 mM, pH = 8.3) for 80 min at 37 • C. After incubation, ACE activity was initiated by adding 110 µL of HHL (10 mM; Sigma-Aldrich, Prague, Czech Republic) to the mixture.…”

“…Angiotensin-converting enzyme (ACE) is a key enzyme in the regulation of the reninangiotensin system, with the ability to cleave angiotensin-I to angiotensin-II and hydrolyze several peptides [15]. It is known that angiotensin-II mainly circulates in the blood and triggers the muscles surrounding blood vessels to contract, thus narrowing the vessels, leading to an increase in blood pressure (hypertension) [16].…”