Fenofibrate, an anti-hyperlipidemic drug and its phase-I biotransformed metabolite fenofibric acid, was studied for COX-1 (PDB ID: 3N8Y) and COX-2 (PDB ID: 1PXX) inhibition potentials in silico and in vitro for their effects on human recombinant COX-2 enzyme isolated from a Baculovirus expression system in sf21 cells (EC 1.14.99.1) using a conventional spectrophotometric assay. Furthermore, the compounds were also screened for their anti-inflammatory potentials in vivo using carrageenan-induced paw oedema method in Wistar rats. The test compounds fenofibric acid, fenofibrate, and the standard drug diclofenac exhibited binding energies of - 9.0, - 7.2, and - 8.0 kcal mol, respectively, against COX-2 and - 7.2, - 7.0, and - 6.5 kcal mol, respectively, against COX-1. In in vitro studies, both the test compounds inhibited COX-2 enzyme activity. Fenofibric acid showed an IC value of 48 nM followed by fenofibrate (82 nM), while diclofenac showed an IC value of 58 nM. Furthermore, under in vivo conditions in carrageenan-induced paw oedema rodent model, fenofibric acid exhibited relatively potent anti-inflammatory activity compared with fenofibrate. Hence, we conclude that fenofibric acid and fenofibrate are not only anti-hyperlipidemic but also shows potent anti-inflammatory activity, which may have an additional impact in the treatment of diabetic complications, viz., hyperlipidemia and inflammation leading to atherosclerosis.

The study was aimed to evaluate the analgesic and anti-inflammatory activity (by both in-vitro and in-vivo) of both chloroform and methanol root extracts of Andrographis serpyllifolia (Rottl. Ex Vahl.) Wt. Methods used for the studies were In-vitro 5-Lipoxygenase inhibition assay and In-vivo measurement of rat paw edema and ear edema in rats, acetic acid induced writhing response and hot plate method in albino mice. Chloroform and methanolic extracts of A. serpyllifolia root have shown moderate potency in inhibiting 5-LOX and shown significant anti-inflammatory activity. Despite the IC50 values are little higher, anti-inflammatory efficacy of these extracts possibly due to other mechanisms apart of 5-LOX inhibition. However, In-vivo anti-inflammatory studies revealed that A. serpyllifolia methanolic extract has shown higher degree of efficacy when compared to the chloroform extract. In terms of analgesic activity in writhing test, methanolic extract has shown more efficacy than chloroform extract. Hence, it is important to isolate the active principles for further testing the anti-inflammatory efficacy.DOI: http://dx.doi.org/10.3329/icpj.v1i8.11250 International Current Pharmaceutical Journal 2012, 1(8): 199-204

Different fungi viz. Aspergillus niger NCIM 589, A.ochraceous NCIM 1140, Cunninghamella blakesleeana NCIM 687, C. echinulata NCIM 691, Rhizopus stolonifer NCIM 880, Mucor rouxi MTCC 386, Trichothecium roseum NCIM 1147 were screened for their potential to biotransform anti-hyperlipidemia and anti-hypertriglyceridemia drug, fenofibrate to fenofibric acid, the active metabolite and other mammalian metabolites. Among the fungi screened C. blakesleeana transformed fenofibrate to fenofibric acid and other three metabolites. HPLC, LC-MS/MS analysis and previous reports confirmed the transformation of fenofibrate and metabolites as fenofibric acid (M1), reduced fenofibric acid (M2), reduced fenofibric acid taurine conjugate (M3), reduced fenofibric acid ester glucuronide (M4), the mammalian metabolites reported previously. The results proved the potential of C.blakesleeana NCIM 687 in the production of mammalian phase I (M1 and M2) and phase II (M3 and M4) metabolites in large quantities and also as an in vitro model for drug metabolism studies.