Petasites hybridusExtractsin vitroInhibit COX-2 and PGE₂Release by Direct Interaction with the Enzyme and by Preventing p42/44 MAP Kinase Activation in Rat Primary Microglial Cells

Abstract

Rhizomes of butterbur, Petasites hybridus L. (Asteraceae), have been used since ancient times for the treatment of inflammatory diseases. In the present study, the effects of lipophilic extracts from rhizomes of Petasites hybridus on the formation and release of prostaglandin E2 were investigated. The extracts had different contents of petasin and isopetasin: A: 2.1 % and 0.4 %, B: 0.2 % and 0.1 %, C: 12.1 % and 6.1 % and D: 21.9 % and 9.4 %, respectively. Direct inhibition of cyclooxygenase (COX) -1 and -2 isoenzymes and inhibition of the expression of COX-2 and p42/44 MAP kinase in rat primary microglial cells were tested. All extracts were found to be only weak direct inhibitors of COX-1 (IC50> 400 microg/mL). However, most extracts revealed a strong inhibitory activity against the inducible isoform COX-2 ( A: IC50=30.4 microg/mL; B: IC50=60.6 microg/mL; C: IC50=22.6 microg/mL; D: IC50=20.0 microg/mL). This activity was not correlated to the content of petasin and isopetasin. Pure petasin and isopetasin neither inhibited COX-1 nor COX-2 (IC50 > 400 microM for both compounds and enzymes). Petasites extracts dose-dependently inhibited LPS-induced and thus COX-2-mediated PGE2 release in primary rat microglial cells (A: IC50= 2.4 microg/mL; C: IC50=5.8 microg/mL and D: IC50=4.6 microg/mL). Also this effect was independent from the petasin and isopetasin content. COX-2 synthesis in microglia was totally blocked with 5 microg/mL of C whereas COX-1 synthesis was not influenced. C and D did not affect the LPS-induced activation of p38 MAPK and IkappaBalpha, but they prevented the LPS-induced activation of p42/44 MAPK. Therefore, these Petasites hybridus extracts can be regarded as natural selective inhibitors of COX-2 and its expression, an effect which is independent from the petasin content.

Optimization of Extraction Conditions for Bakkenolide B from the Leaves of Petasites japonicus by Using Response Surface Methodology

“…Some pharmacological studies have suggested that petasin and s-petasin were active ingredients in this plant [1,5,16,17], furthermore, we found that bakkenolide B (Fig. 1), a major component in the leaves of Petasites japonicus, showed significant effects in an ovalbumin-induced asthma model in our previous studies [11].…”

“…Petasites genus has been reported to have many sesquiterpene lactones, especially petasin-type and bakkenolide type [4], and the extracts from this plant have been shown to have anti-allergic and anti-inflammatory effects [5,10,18] and to inhibit mast cell degranulation [15]. Some pharmacological studies have suggested that petasin and s-petasin were active ingredients in this plant [1,5,16,17], furthermore, we found that bakkenolide B (Fig.…”

Schizandra chinensis Alkaloids Inhibit Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells

“…It has been reported that toxic molecules released by activated neuroglial cells might be involved in the pathogenesis of various neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD) and HIV-associated dementia (Gonzalez-Scarano and Baltuch, 1999;McGeer and McGeer, 1995;Minghetti and Levi, 1998). Thus, many researchers have focused on the use of natural products to control the production of neuroinflammatory regulators, especially from microglia (Fiebich et al, 2005;Jung et al, 2007;Lau et al, 2007). The present study demonstrated that some compounds from S. chinensis suppressed microglial activation.…”

Phytotoxicity Assessment of Certain Phytochemical Products Containing Pyrrolizidine Alkaloids

“…Petasites hybridus root is used mainly for the antispastic, antiallergic and anti-infl ammatory eff ects [1]. Tussilago farfara leaves are used to relief dry caught [2] and the aerial parts of Senecio species are used especially for their antidiarrheal, diuretic, diaphoretic and expectorant properties [3].…”