Sesquiterpene lactone fraction from Artemisia khorassanica inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression through the inactivation of NF-κB.
OBJECTIVE
Members of the Artemisia genus (Astraceae) are important medicinal plants throughout the world. Here, we prepared a sesquiterpene lactone fraction from Artemisia khorassanica (SLAK) and evaluated its effect on inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression, and nuclear factor-κB (NF-κB) activity.


METHODS
The effects of SLAK on lipopolysaccharide (LPS)-induced NO, prostaglandin E(2) (PGE(2)), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production was evaluated in mouse macrophage J774A.1 cells. Moreover, we evaluated SLAK modulation of iNOS and COX-2 enzyme expression by western blot analysis.


RESULTS
Our data revealed that SLAK (10-100 μg/mL), in a dose-dependent manner, inhibits NO, PGE(2), TNF-α, and IL-1β production induced by LPS in the J774A.1 cells. These data were consistent with the modulation of iNOS and COX-2 expressions. It was also showed that SLAK suppresses the iNOS and COX-2 enzyme expression through the inhibition of NF-κB activity.


CONCLUSIONS
In this study, we demonstrated that SLAK inhibits the production of NO, PGE2, TNF-α, and IL-1β in LPS-stimulated macrophages. This anti-inflammatory effect possibly occurs by inhibiting iNOS and COX-2 expression via the inactivation of NF-κB pathway.
Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Science, Mashhad, Iran.
Seyyed Ahmad
SA
Emami
Shahrzad Zamnai
SZ
Taghizadeh Rabe
Mehrdad
M
Iranshahi
Ali
A
Ahi
Mahmoud
M
Mahmoudi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019306:Artemisia / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D035261:Plant Components, Aerial / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone