The arachidonic acid pathway consists of several enzymes and targeting them is favored for developing anti-inflammatory drugs. However, till date the current drugs are generally active against a single target, leading to undesirable side-effects. Phytochemicals are known to inhibit multiple targets simultaneously and hence, an attempt is made here to investigate their suitability. A pharmacophore based study is performed with three sets of reported phytochemicals namely, dual 5-LOX/mPGES1, alkaloids and FLAP inhibitors. The analysis indicated that phenylpropanoids (including ferulic acid) and benzoic acids de-rivatives, and berberine mapped onto these pharmacophores with three hydrophobic centroids and an acceptor feature. 2,4,5-trimethoxy (7) and 3,4-dimethoxy cinnamic acids (8) mapped onto all the three pharmacophores. Expeiimental studies indicated that berberine inhibited 5-LOX (100 mu M) and PGE(2) (50 mu M) production by 72.2 and 72.0% and ferulic acid by 74.3 and 54.4% respectively. This approach offers a promising theoretical combined with experimental strategy for designing novel molecules against inflammatory enzymes. (C) 2017 Elsevier Inc. All rights reserved.