Bauer ketones 23 and 24 from Echinacea paradoxa var. paradoxa inhibit lipopolysaccharide-induced nitric oxide, prostaglandin E2 and cytokines in RAW264.7 mouse macrophages

Abstract

Among the nine Echinacea species, E. purpurea, E. angustifolia and E. pallida, have been widely used to treat the common cold, flu and other infections. In our study, ethanol extracts of these three Echinacea species and E. paradoxa, including its typical variety, E. paradoxa var. paradoxa, were screened in lipopolysaccharide (LPS)-stimulated macrophage cells to assess potential anti-inflammatory activity. Echinacea paradoxa var. paradoxa, rich in polyenes/polyacetylenes, was an especially efficient inhibitor of LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) by 46%, 32%, 53% and 26%, respectively, when tested at 20 μg/ml in comparison to DMSO control. By bioactivity-guided fractionation, pentadeca-8Z-ene-11, 13-diyn-2-one (Bauer ketones 23, compound 1) and pentadeca-8Z, 13Z-dien-11-yn-2-one (Bauer ketone 24, compound 2) from E. paradoxa var. paradoxa were found primarily responsible for inhibitory effects on NO and PGE2 production. Moreover, Bauer ketone 24 (compound 2) was the major contributor to inhibition of inflammatory cytokine production in LPS-induced mouse macrophage cells. These results provide a rationale for exploring the medicinal effects of the Bauer ketone-rich taxon, E. paradoxa var. paradoxa, and confirm the anti-inflammatory properties of Bauer ketones 23 and 24.

A systematic review on the effects of Echinacea supplementation on cytokine levels: Is there a role in COVID-19?

“… Human peripheral blood mononuclear cells [from 16 subjects (9 males, 7 females, age 23.5 ± 3.8 years) who donated blood] LPS and PHA antigen E. laevigata, E. angustifolia, E. pallida, and E. purpurea Root tinctures of each species extracted in 50% EtOH/50% cell culture water at a ratio of 1:9 parts plant material:solvent. Dose: 50 μL/well DURATION: 24, 48 or 72 h Negative control: no treatment Positive control: LPS and PMA antigen Increased levels: IL-10 and TNF-α No change in levels: IL-2 1 Sharma, 2006 [ 109 ] Not stated The tracheo-bronchial line BEAS-2B and the rhinovirus-sensitive H-1 derivative of HeLa cells Rhinovirus type 14 E. purpurea Two extracts: E1: an expressed juice extract of the aerial parts of E. purpurea E2: a 50% alcoholic tincture, derived from E. purpurea roots (1:9 w/v) Dose: 100 μg/mL of E1 or 50 μg/mL of E2 DURATION: 24–96 h Negative control: no treatment on uninfected cells Positive control: no treatment on virally infected cells Increased secretion: IL-1β, IL-2, IL-3, and IL-7 Decreased secretion: IFN-γ, IL-1⍺, IL-1β, IL-2, IL-3, IL-5, IL-6, IL-7, IL-8, IL-15, IL-17, TNF-α, GM-CSF, CCL8, CCL10, CCL11, MIP-1α, MIP1β and MIP-4 3 Sharma, 2009 [ 110 ] Not stated The tracheo-bronchial line BEAS-2B, H-1 sub clone of HeLa cells, the lung-derived epithelial cell line A549, and human skin fibroblasts Rhinovirus types 1A and 14 E. purpurea Echinaforce by A. Vogel Bioforce AG, Switzerland: a 65% ethanol extract of freshly harvested aerial parts supplemented with 5% roots. Dose: dilutions of 1:20, 1:100, 1:200, and 1:400 DURATION: 48 h Negative control: no treatment on uninfected cells Positive control: no treatment on virally infected cells Decreased secretion: IL-6 and IL-8 3 Sharma, 2009 [ 111 ] Not stated Two human epithelial cell lines: the tracheo-bronchial line BEAS-2B and the lung-derived epithelial cell line A549 as well as human skin fibroblasts Viruses: RV1A, RV14, influenza, RSV, adenovirus types 3 and 11, and HSV E. purpure...…”

Effects of Cichoric Acid Extract fromEchinacea purpureaon Collagen-Induced Arthritis in Rats

“…The extract from E. paradoxa var. paradoxa showed an efficiently inhibitory effect on the LPS-induced production of nitric oxide, PGE2, IL-1β and IL-6 (Zhang et al, 2012). Echinacea extracts also exerted a dual action against several important respiratory bacteria (Sharma et al, 2010).…”

System-level Study on Synergism and Antagonism of Active Ingredients in Traditional Chinese Medicine by Using Molecular Imprinting Technology

“…Final volume and final concentration of each group was 500 μL and 1 µg mL −1 , respectively. Then cells of each group were incubated for another 18 h. Each group was performed in triplicate 43 44 45 .…”