Viscum album Exerts Anti-Inflammatory Effect by Selectively Inhibiting Cytokine-Induced Expression of Cyclooxygenase-2

Abstract

Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

Traditionally used Veronica officinalis inhibits proinflammatory mediators via the NF-κB signalling pathway in a human lung cell line

“…Biosynthesis of PGE 2 is largely dependent upon generation of arachidonic acid from membrane phospholipids catalyzed by phospolipase A2, which is further metabolized to prostaglandin H2 (PGH2), an active precursor for synthesis of various prostanoids, by COX-2 (Sastre et al, 2012). COX-2 is thus considered an important target for designing antiinflammatory molecules such as non-steroidal anti-inflammatory drugs and also for conception of novel phytotherapeutics (Chell et al, 2006;Chun and Surh, 2004;Hegde et al, 2011). Because PGE 2 has such an important impact on inflammation, we analyzed the influence of Veronica officinalis on this molecule, and demonstrated a concentration-dependent inhibitory effect of the used extract on PGE 2 release from human lung epithelial cells.…”

Phytochemical profile and therapeutic potential ofViscum albumL.

“…The water extract demonstrated a dosedependent anti-inflammatory effect by inhibiting IL-1b-induced prostaglandin E2 (PGE2) biosynthesis and a post-transcriptional regulatory effect on COX-2 expression, without influencing cyclooxigenase-1 (COX-1) expression (Hegde et al 2011).…”

Evaluation of seasonal changes of triterpenic acid contents in Viscum album from different host trees

“…There are many reports about its anti-inflammatory (Hegde et al 2011), antinociceptive, hypotensive (Ofem et al 2007), antidiabetic (Orhan et al 2005), anticancer (Burger et al 2001), immunomodulatory (Lavastre et al 2004), antioxidant (Orhan et al 2005), antimicrobial (Orhue et al 2014), antiepileptic, sedative, antipsychotic (Gupta et al 2012) and cytotoxic activities (Cebovi c et al 2008). V. album is used in contemporary pharmacy and medicine in a form of commercially available extracts and preparations mostly for treatment of hypertension and some cases of cancer.…”