Aqueous extracts of Cimicifuga racemosa and phenolcarboxylic constituents inhibit production of proinflammatory cytokines in LPS-stimulated human whole blood

Cimicifuga racemosa (black cohosh) is commonly used in traditional medicines as treatment for menopausal symptoms and as an antiinflammatory remedy. To clarify the mechanism of action and active principle for the antiinflammatory action, the effects of aqueous C. racemosa root extracts (CRE) and its major constituents on the release of the proinflammatory cytokines IL-6, TNF-α, IFN-γ, and the chemokine IL-8 were investigated in lipopolysaccharide (LPS)stimulated whole blood of healthy volunteers. CRE (3 µg/µL and 6 µg/µL) reduced LPS-induced release of IL- 6 and TNF-α in a concentration- and time-dependent manner and almost completely blocked release of IFN-γ into the plasma supernatant. Except for IFN-γ, these effects were attenuated at longer incubation periods. IL-8 secretion was stimulated by CRE. As shown by quantitative real-time RT-PCR, effects on cytokines were based on preceding changes in mRNA levels except for IL-8. According to their content in CRE, the phenolcarboxylic compounds caffeic acid, ferulic acid, and isoferulic acid, as well as the triterpene glycosides 23-epi-26-deoxyactein and cimigenol-3-O-xyloside, were tested at representative concentrations. Among these, isoferulic acid was the prominent active principle in CRE, responsible for the observed inhibition of IL-6, TNF-α, and IFN-γ, but not for IL-8 stimulation. The effect of this compound may explain the antiinflammatory activities of CRE and its beneficial actions in rheumatism and other inflammatory diseases. Key words: Cimicifuga racemosa, black cohosh, endotoxinaemia, lipopolysaccharide, proinflammatory cytokines, IL-6, IL-8, TNF-alpha, interferon-gamma, human whole blood, inflammation, monocytes, lymphocytes, caffeic acid, ferulic acid, isoferulic acid, cimigenol-3-O-xyloside, 23-epi-26-deoxyactein, rheumatism. Cimicifuga racemosa (cimicaire a grappes) est couramment utiliseeeenmedecine traditionnelle pour le traitement des symptomes de la menopause et comme remede anti-inflammatoire. Pour clarifier le mecanisme d'action et le principe actif de l'action anti-inflammatoire, nous avons examine; les effets d'extraits aqueux de racines de C. racemosa (ECR) et de leurs principaux constituants sur la liberation des cytokines proinflammatoires IL-6, TNF-α, IFN-γ et de la chimiokine IL-8 dans le sang total stimule par un lipopolysaccharide (LPS), chez des volontaires en sante. Les CRE (3 mg/mLet 6 µg/µL) ont reduit en fonction de la concentration et du temps la liberation d'IL-6 et de TNF-α induite par LPS, et bloque presque completement la liberation d'IFN-γ dans le surnageant plasmatique. Ces effets ont ete attends lors de periodes d'incubation de plus longue duree, sauf dans le cas d'IFN-g. Les CRE ont stimule; la secretion d'IL-8. La RT-PCR quantitative en temps reel a montree que les effets sur les cytokine etaient liees aux modifications anterieures des taux d'ARNm, sauf pour ce qui est d'IL-8. Selon leur teneur en CRE, nous avons examinee les composes phenolcarboxyliques, acide cafeique, acide ferulique et acide isoferulique, ainsi que les glycosides triterpeenes, 23-epi-26-deeoxyacteeine et cimigenol-3-O-xyloside, aux concentrations representatives. L'acide isoferulique a ete le principe actif dominant dans les CRE, responsable de l'inhibition observeee d'IL-6, de TNF-α et d'IFN-γ, mais pas de la stimulation d'IL-8. L'effet de ce compose pourrait expliquer les activitees anti-inflammatoires des CRE et les actions beneefiques sur le rhumatisme et d'autres maladies inflammatoires. Mots-cles: Cimicifuga racemosa, cimicaire a grappes, endotoxeemie, lipopolysaccharide, cytokines proinflammatoires, IL-6, IL-8, TNF-alpha, interferon gamma, sang humain, inflammation, monocytes, lymphocytes, acide cafeique, acide feerulique, acide isofeerulique, cimigeenol-3-O-xyloside, 23-epi-26-deesoxyacteine, rhumatisme. [Traduit par la Redaction] 10.1139/Y09-091
Introduction Cimicifuga racemosa (L.) Nutt. (Ranunculaceae; common name, black cohosh) is a medicinal herb found in the wild in eastern North America. Native Americans used black cohosh (also called 'rheumatism [...]