PGE2 production inhibition

The plant is strongly aromatic on account of an essential oil which comprises cis-a-ocimene (25.11%), 3,7-dimethyl-l,6-octadien-3 ol (16.85%), and trans-nerolidol (13.89%), hence the use of the plant in aromatherapy. A methanolic extract of bark of Litsea cubeba (Lour.) Pers. and its fractions (0.01 mg/mL) from bark inhibit NO and PGE2 production in LPS-activated RAW 264.7 macrophages without significant cytotoxicity at less than 0.01 mg/mL concentration. The methanol extract decreased the enzymatic activity of myeloperoxidase (0.05 mg/mL). These findings suggest that L. cubeba is beneficial for inflammatory conditions and may contain compound(s) with anti-inflammatory properties (63). Can we expect the vasorelaxant laurotetanine (64) isolated from the plant to exert such activity ... 

JP-8-induced systemic immunosuppression is explained in part by modulation of cytokine and inflammatory pathways. Within 48 hours of a single dermal application of JP-8 (300 pL), serum IL-10 levels increase significantly to nearly 3000 pg/mL [36], As IL-10 is known to suppress DTH responses [64,65], it is likely that modulation of this cytokine contributes to JP-8 s immunotoxicity. Furthermore, splenic T-cell proliferative responses are significantly decreased in JP-8 exposed mice, yet this effect is reversed following neutralization of IL-10, administration of IL-12, or inhibition of prostaglandin E2 (PGE2) production [60], Additional studies demonstrated suppression... 

Jaksic, A. et al., Cis-urocanic acid synergizes with histamine for increased PGE2 production by human keratinocytes Link to indomethacin-inhibitable UVB-induced immunosuppression, Photochem. Photobiol. 61, 303-309, 1995. 

Several fatty acids and derivatives were isolated from the dichloromethane extract of Angelica pubescens Maxim f. biserrata Shan et Yuan (Umbelliferae) by following in vitro 5-LOX and COX-1 inhibitory assays. Linoleic acid showed potent inhibition against PGE2 production from purified COX-1 enzyme. Falcarindiol, which is an acetylenic alcohol, showed higher potency against LOX than COX (Table 3) [122]. Linolenic acid is an... 

Nonsteroidal anti-inflammatory drugs (NSAlDs) nonselectively inhibit the activities of both COX-1 and COX-2. Out of concern for the gastrointestinal side effects of NSAID, scientists have discovered and developed many specific COX-2 inhibitors that facilitate a safer choice for controlling inflammatory diseases (73). Eor example, NS-398, a selective COX-2 inhibitor, has been shown to reduce tension (mechanical stress)-induced PGE2 production from periodontal ligament cell cultures (74). 

Vedaprofen is a propionic acid derivative that, like carprofen and ketoprofen, exists as two enantiomers with different pharmacokinetic profiles in the horse. For example, the plasma disposition of S(-t-)-vedaprofen is characterized by a very rapid decline with a plasma half-life of less than 1 h while R(-)-vedaprofen has a more prolonged elimination phase with a plasma half-life of over 2h (Lees et al 1999). Both enantiomers also accumulate in and exhibit a delayed elimination from inflammatory exudates. In horses, vedaprofen appears to be slightly selective for the COXl enzyme. For example, the median effective concentration for inhibition of serum TXB2 production, which is assumed to be a reflection of COXl activity, was much lower than that for inhibition of inflammatory infiltrate PGE2 production, which is assumed to be a reflection of COX2 activity. Although the results of these studies are promising, there are no published data on the clinical effectiveness and safety of vedaprofen in horses. 

Some flavonoids have been shown both to inhibit and to stimulate production of prostaglandins in vitro [28, 212]. Flavone and flavanone induced PGE2 production in isolated gastric mucosal cells, but since these compounds did not stimulate the prostanoid production in gastric cells exposed to arachidonic acid, it is likely that both flavonoids enhance prostaglandin formation by acting as cofactors of cyclooxygenase [142]. 

The dichloromethane extract from Wilbrandia ebracteata (p.o.) significantly reduced the paw elevation time (1 mg/kg) and cell influx (10 mg/kg) in zymosan-induced arthritis in rats. The same extract inhibited COX-2 activity, as measured by PGE2 production, without affecting that of COX-1. Moreover, nitrite release was clearly and significantly reduced at a dose of 10 mg/kg (p.o.). The analysis of the pharmacological data, together with the HPLC analysis of the extracts, points to an anti-inflammatory effect based on an associated reduction in nitric oxide (NO) release and COX-2 inhibition by the cucurbitacins... 

Tn the case of the extract of Kageneckia oblonga, the authors established a relationship between cucurbitacins present in the extract and its antipyretic and analgesic activities, justifying a potential mechanism in which a decrease in PGE2 production through the inhibition of COX activity is implicated [13]. 

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