Chemical composition and in vivo/in silico anti-inflammatory activity of an antioxidant, non-toxic essential oil from Thymus algeriensis Boiss. & Reut.
Nadjat Righi, Amirouche Deghima, Ismail Daoud, Pedro A.R. Fernandes, Faiza Baali, Sabah Boumerfeg, Abderrahmane Baghiani, Manuel A. Coimbra, Elisabete Coelho
Abstract
Thymus algeriensis Reut & Boiss is an essential oil-bearing plant widely used in traditional medicine to treat digestive system disorders and numerous inflammatory diseases. The current work was designed to evaluate the anti-inflammatory properties of this species and its safety. Using in vivo models, the anti-inflammatory activity was examined by xylene-induced ear inflammation and the acute toxicity of T. algeriensis essential oil was orally tested at a limit dose of 2000 mg/kg bw. The essential oil was analyzed using gas chromatography coupled to mass spectrometry (GC-MS) and its antioxidant activity was also investigated in vitro. Molecular docking studies were performed to assess the binding efficiency of the essential oil major compounds with key inflammatory enzymes, cyclooxygenase-2 and phospholipase-A2. The GC-MS analysis of the essential oil revealed the presence of 33 terpenoids, with α-terpineol (19%), linalool (13%), geranyl acetate (12%), and methyl eugenol (8%) as major compounds. The essential oil exhibited substantial antioxidant activity and showed anti-inflammatory activity by reducing the xylene induced ear edema by 58% at 600 mg/ kg bw. Finally, T. algeriensis essential oil presented low toxicity with a median lethal dose (LD 50 ) higher than 2000 mg/kg bw. Molecular docking analysis and ADMET (Absorption, digestion, metabolism, excretion, and toxicity) properties revealed that the major compounds of T. algeriensis essential oil can be considered as lead candidates for the inhibition of both phospholipase-A2 and cyclooxygenase-2, with geranyl acetate as the best inhibitor against both targets. The potential anti-inflammatory effect combined with the relative safety of T. algeriensis essential oil makes it a good source of possible new anti-inflammatory agents. • Thymus algeriensis essential oil showed antioxidant and anti-inflammatory activities. • Acute toxicity study revealed that the essential oil can be used safely as pharmaceutical product. • The major compounds of T. algeriensis essential oils were α-terpineol, linalool , geranyl acetate, and methyl eugenol. • Major essential oil compounds presented potent cyclooxygenase-2 and phospholipase A2 inhibition ( in silico ).