The objective of this current study was to analyze the biochemical compositions of three Malaysian Channa spp. fish. The proximate analysis revealed that the protein content of Channa lucius, Channa micropeltes and Channa striatus was 19.9%, 22.1%, 23.0% (% of dry weight), respectively. The total lipid content was generally high, ranging from 5.7% to 11.9% and crude ash ranged from 1.0% to 1.8%. The major amino acids were glutamic acid, aspartic acid and lysine, ranging from 9.7% to 21.7%, and the most abundant fatty acid in Channa spp. was C16:0, ranging from 25.6% to 30.4%. The other major fatty acids detected were C22:6, C18:1 and C18:0. The level of arachidonic acid (C20:4) was unusually high in C. striatus (19.02%). The levels of DHA in these fish would also explain the use of Channa spp., especially C. striatus, which has been used for centuries for reducing pain, inflammation and promote wound healing in Malaysia.

The non-steroidal anti-inflammatory drug ketoprofen (KTP) was administered as the racemate to cats intravenously (IV) and orally at clinically recommended dose rates of 2 and 1 mg/kg, respectively, to establish its chiral pharmacokinetic and pharmacodynamic properties. After IV dosing, clearance was more than five times greater and elimination half-life and mean residence time were approximately three times shorter for R(-) KTP than for S(+) KTP. Absorption of both S(+) and R(-) enantiomers was rapid after oral dosing and enantioselective pharmacokinetics was demonstrated by the predominance of S(+) KTP, as indicated by plasma AUC of 20.25 (S(+)KTP) and 4.09 (R(-)KTP) microg h/mL after IV and 6.36 (S(+)KTP) and 1.83 (R(-)KTP) microg h/mL after oral dosing. Bioavailability after oral dosing was virtually complete. Reduction in ex vivo serum thromboxane (TX)B(2) concentrations indicated marked inhibition of platelet cyclo-oxygenase (COX)-1 for 24 h after both oral and IV dosing and inhibition was statistically significant for 72 h after IV dosing. Both oral and IV rac-KTP failed to affect wheal volume produced by intradermal injection of the mild irritant carrageenan but wheal skin temperature was significantly inhibited by IV rac-KTP at some recording times. Possible reasons for the disparity between marked COX-1 inhibition and the limited effect on the cardinal signs of inflammation are considered. In a second experiment, the separate enantiomers of KTP were administered IV, each at the dose rate of 1mg/kg. S(+)KTP again predominated in plasma and there was unidirectional chiral inversion of R(-) to S(+)KTP. Administration of both enantiomers again produced marked and prolonged inhibition of platelet COX-1 and, in the case of R(-)KTP, this was probably attributable to S(+)KTP formed by chiral inversion.

There have been few studies of the pharmacodynamics of nonsteroidal antiinflammatory drugs (NSAIDs) using PK-PD modelling, yet this approach offers the advantage of defining the whole concentration-effect relationship, as well as its time course and sensitivity. In this study, ketoprofen (KTP) was administered intravenously to goats as the racemate (3.0 mg/kg total dose) and as the single enantiomers, S(+) KTP and R(-) KTP (1.5 mg/kg of each). The pharmacokinetics and pharmacodynamics of KTP were investigated using a tissue cage model of acute inflammation. The pharmacokinetics of both KTP enantiomers was characterized by rapid clearance, short mean residence time (MRT) and low volume of distribution. The penetration of R(-) KTP into inflamed (exudate) and noninflamed (transudate) tissue cage fluids was delayed but area under the curve values were only slightly less than those in plasma, whereas MRT was much longer. The S(+) enantiomer of KTP penetrated less readily into exudate and transudate. Unidirectional inversion of R(-) to S(+) KTP occurred. Both rac-KTP and the separate enantiomers produced marked inhibition of serum thromboxane B2 (TxB2) synthesis (ex vivo) and moderate inhibition of exudate prostaglandin E2 (PGE2) synthesis (in vivo); pharmacodynamic variables for S(+) KTP were Emax (%) = 94 and 100; IC50 (microg/mL) = 0.0033 and 0.0030; N = 0.45 and 0.58, respectively, where Emax is the maximal effect, IC50 the plasma drug concentration producing 50% of Emax and N the slope of log concentration/effect relationship. The IC50 ratio, serum TxB2:exudate PGE2 was 1.10. Neither rac-KTP nor the individual enantiomers suppressed skin temperature rise at, or leucocyte infiltration into, the site of acute inflammation. These data illustrate for KTP shallow concentration-response relationships, probable nonselectivity of KTP for cyclooxygenase (COX)-1 and COX-2 inhibition and lack of measurable effect on components of inflammation.

Inhibition of serum TXB2 concentration and exudate PGE2 synthesis for similar time courses after S(+) KTP administration indicates that it is a nonselective inhibitor of COX in sheep.

The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC). TNF-α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)-dextran. Asiaticoside pretreatment significantly suppressed TNF-α-induced increased permeability. Asiaticoside also prevented TNF-α-induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF-α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti-hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D-induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF-α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F-actin organization.