Anti-inflammatory Effect of Spilanthol from Spilanthes acmella on Murine Macrophage by Down-Regulating LPS-Induced Inflammatory Mediators

Abstract

Spilanthes acmella (Paracress), a common spice, has been administered as a traditional folk medicine for years to cure toothaches, stammering, and stomatitis. Previous studies have demonstrated its diuretic, antibacterial, and anti-inflammatory activities. However, the active compounds contributing to the anti-inflammatory effect have seldom been addressed. This study isolates the active compound, spilanthol, by a bioactivity-guided approach and indicates significant anti-inflammatory activity on lipopolysaccharide-activated murine macrophage model, RAW 264.7. The anti-inflammatory mechanism of paracress is also investigated. Extracts of S. acmella are obtained by extraction with 85% ethanol, followed by liquid partition against hexane, chloroform, ethyl acetate, and butanol. The ethyl acetate extract exhibits a stronger free radical scavenging capacity than other fractions do, as determined by DPPH and ABTS radical scavenging assays. The chloroform extract significantly inhibits nitric oxide production ( p < 0.01) and is selected for further fractionation to yield the active compound, spilanthol. The diminished levels of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) mRNA and protein expression support the postulation that spilanthol inhibits proinflammatory mediator production at the transcriptional and translational levels. Additionally, the LPS-stimulated IL-1beta, IL-6, and TNF-alpha productions are dose-dependently reduced by spilanthol. The LPS-induced phosphorylation of cytoplasmic inhibitor-kappaB and the nuclear NF-kappaB DNA binding activity are both restrained by spilanthol. Results of this study suggest that spilanthol, isolated from S. acmella, attenuates the LPS-induced inflammatory responses in murine RAW 264.7 macrophages partly due to the inactivation of NF-kappaB, which negatively regulates the production of proinflammatory mediators.

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides

“…Spilanthol inactivates NF-kB, shows significant topical anti-inflammatory effects in the mouse ear edema test and is the only NAA that has a demonstrated influence on the transcription and translation of the COX enzymes Wu et al, 2008). All other investigated NAAs have no influence on transcriptional nor translational level of COX (Hinz et al, 2007), but their enzyme activity decreases in the presence of low concentrations of NAAs containing multiple alkyne groups in their fatty acid chain (Clifford et al, 2002).…”

“…However, also the, immune effects of Anacyclus pyrethrum and antiinflammatory effects of Spilanthes, Heliopsis, Piper and Achillea species are established Mullerjakic et al, 1994;Rimbau et al, 1996;Stöhr et al, 1999;Wu et al, 2008).…”

“…The production of the other pro-inflammatory (IL-1b, IL-2, IL-6, IL-8 IL-12) and the anti-inflammatory (IL-10) mediators is suppressed or enhanced, depending on the nature of chemical stimulation and the structural properties of the NAA (Cech et al, 2010;Matthias et al, 2007;Raduner et al, 2006;Stevenson et al, 2005;Wu et al, 2008).…”

Nitric oxide synthesis inhibition and cytotoxicity of Korean horse mussel Modiolus modiolus extracts on cancer cells in culture

“…The beneficial effect of the horse mussel extract and its solvent fractions on the inhibition of inflammatory mediators production in macrophages may be mediated by oxidative degradation of phagocytes products such as O 2-and HOCl (Loizzo et al 2009). The decline in NO production may be attributed to the decrease of inducible NO synthase (iNOS) at mRNA or protein level and the respective alterations of iNOS gene transcription (Wu et al 2008). New Zealand green-lipped mussel powder (lyprinol) had significant anti-inflammatory activity when given to animals and humans (Halpern 2000), where much of this activity was associated with lipid (omega-3 PUTAs) and carotenoids.…”

Concentração Das Atividades Antioxidantes Em Plantas De Jambu, Cultivadas Sob Adubação Orgânica E Mineral

“…Segundo BORGES et al (2013a) e BORGES et al (2012 dentre essas substâncias, tem-se o espilantol, trans-cariofileno, germacreno D, L-dodeceno e espatulenol, características bioquímicas essas que vem atraindo a atenção de empresas farmacêuticas e de cosméticos para as plantas de jambu. LI-CHEN et al (2008) realizando a análise da substância espilantol concluiram que esse composto possui efeito anti-inflamatório. Sendo assim esses autores recomendaram manipular essa substância para desenvolvimento de drogas antiinflamatórias.…”