Terpenoids isolated from Tunisian Nigella sativa L. essential oil with antioxidant activity and the ability to inhibit nitric oxide production

Fractionation of the essential oil from the seeds of Nigella sativa (Ranunculaceae) led to the isolation of four terpenoids: trans‐ (1), cis‐sabinene hydrate methyl ether (2), 1,2‐epoxy‐menth‐4‐ene (3) and 1,2‐epoxy‐menth‐4(8)‐ene (4). Structure elucidation was performed using NMR (1D and 2D NMR) experiments and mass spectral data. Compounds 3 and 4 are reported for the first time as natural products. Bioactivities of the compounds were assessed. The four compounds exhibit antioxidant activity in vitro, as assessed by the oxygen radical absorbance capacity test. Moreover, compounds 1, 2 and 4 displayed strong ability to inhibit oxidative stress in human skin WS‐1 fibroblasts cells, with IC50 values of 0.32, 0.005 and 0.43 µ m, respectively. In addition, the four tested compounds significantly inhibited nitric oxide release by lipopolysaccharide‐activated RAW 264.7 macrophages. The results show that the most effective compound was cis‐sabinene hydrate methyl ether (2). In addition, the cis‐configurated compound (2) exerted stronger activities in comparison with the trans‐configurated compound (1), suggesting geometric stereoselectivity for the biological activities