Endogenous levels of echinacea alkylamides and ketones are important contributors to the inhibition of prostaglandin E2 and nitric oxide production in cultured macrophages

Carlie A. Lalone; Ludmila Rizshsky; Kimberly D.P. Hammer; Lankun Wu; Avery K.S. Solco; Manyu Yum; Basil J. Nikolau; Eve S. Wurtele; Patricia A. Murphy; Meehye Kim; Diane F. Birt

doi:10.1021/jf901202y

Endogenous levels of echinacea alkylamides and ketones are important contributors to the inhibition of prostaglandin E2 and nitric oxide production in cultured macrophages

Carlie A. Lalone, Ludmila Rizshsky, Kimberly D.P. Hammer, Lankun Wu, Avery K.S. Solco, Manyu Yum, Basil J. Nikolau, Eve S. Wurtele, Patricia A. Murphy, Meehye Kim, Diane F. Birt

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Because of the popularity of Echinacea as a dietary supplement, researchers have been actively investigating which Echinacea constituent or groups of constituents are necessary for immunemodulating bioactivities. Our prior studies indicate that alkylamides may play an important role in the inhibition of prostaglandin E2 (PGE ₂) production. High-performance liquid chromatography fractionation, employed to elucidate interacting anti-inflammatory constituents from ethanol extracts of Echinacea purpurea, Echinacea angustifolia, Echinacea pallida, and Echinacea tennesseensis, identified fractions containing alkylamides and ketones as key anti-inflammatory contributors using lipopolysaccharideinduced PGE ₂ production in RAW264.7 mouse macrophage cells. Nitric oxide (NO) production and parallel cytotoxicity screens were also employed to substantiate an anti-inflammatory response. E pallida showed significant inhibition of PGE ₂ with a first round fraction, containing gas chromatography-mass spectrometry (GC-MS) peaks for Bauer ketones 20, 21, 22, 23, and 24, with 23 and 24 identified as significant contributors to this PGE ₂ inhibition. Chemically synthesized Bauer ketones 21 and 23 at 1 μM each significantly inhibited both PGE ₂ and NO production. Three rounds of fractionation were produced from an E angustifolia extract. GC-MS analysis identified the presence of Bauer ketone 23 in third round fraction 3D32 and Bauer alkylamide 11 making up 96% of third round fraction 3E40. Synthetic Bauer ketone 23 inhibited PGE ₂ production to 83% of control, and synthetic Bauer alkylamide 11 significantly inhibited PGE ₂ and NO production at the endogenous concentrations determined to be present in their respective fraction; thus, each constituent partially explained the in vitro anti-inflammatory activity of their respective fraction. From this study, two key contributors to the anti-inflammatory properties of E angustifolia were identified as Bauer alkylamide 11 and Bauer ketone 23.

Original language	English (US)
Pages (from-to)	8820-8830
Number of pages	11
Journal	Journal of agricultural and food chemistry
Volume	57
Issue number	19
DOIs	https://doi.org/10.1021/jf901202y
State	Published - 2009
Externally published	Yes

Keywords

Anti-inflammatory
Bauer alkylamides
Bauer ketones
Echinacea angustifolia
Echinacea pallida
Echinacea purpurea
Fractionation
Nitric oxide
Prostaglandin e2

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10.1021/jf901202y

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Lalone, C. A., Rizshsky, L., Hammer, K. D. P., Wu, L., Solco, A. K. S., Yum, M., Nikolau, B. J., Wurtele, E. S., Murphy, P. A., Kim, M., & Birt, D. F. (2009). Endogenous levels of echinacea alkylamides and ketones are important contributors to the inhibition of prostaglandin E2 and nitric oxide production in cultured macrophages. Journal of agricultural and food chemistry, 57(19), 8820-8830. https://doi.org/10.1021/jf901202y

Endogenous levels of echinacea alkylamides and ketones are important contributors to the inhibition of prostaglandin E2 and nitric oxide production in cultured macrophages. / Lalone, Carlie A.; Rizshsky, Ludmila; Hammer, Kimberly D.P. et al.
In: Journal of agricultural and food chemistry, Vol. 57, No. 19, 2009, p. 8820-8830.

Research output: Contribution to journal › Article › peer-review

Lalone, CA, Rizshsky, L, Hammer, KDP, Wu, L, Solco, AKS, Yum, M, Nikolau, BJ, Wurtele, ES, Murphy, PA, Kim, M & Birt, DF 2009, 'Endogenous levels of echinacea alkylamides and ketones are important contributors to the inhibition of prostaglandin E2 and nitric oxide production in cultured macrophages', Journal of agricultural and food chemistry, vol. 57, no. 19, pp. 8820-8830. https://doi.org/10.1021/jf901202y

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abstract = "Because of the popularity of Echinacea as a dietary supplement, researchers have been actively investigating which Echinacea constituent or groups of constituents are necessary for immunemodulating bioactivities. Our prior studies indicate that alkylamides may play an important role in the inhibition of prostaglandin E2 (PGE 2) production. High-performance liquid chromatography fractionation, employed to elucidate interacting anti-inflammatory constituents from ethanol extracts of Echinacea purpurea, Echinacea angustifolia, Echinacea pallida, and Echinacea tennesseensis, identified fractions containing alkylamides and ketones as key anti-inflammatory contributors using lipopolysaccharideinduced PGE 2 production in RAW264.7 mouse macrophage cells. Nitric oxide (NO) production and parallel cytotoxicity screens were also employed to substantiate an anti-inflammatory response. E pallida showed significant inhibition of PGE 2 with a first round fraction, containing gas chromatography-mass spectrometry (GC-MS) peaks for Bauer ketones 20, 21, 22, 23, and 24, with 23 and 24 identified as significant contributors to this PGE 2 inhibition. Chemically synthesized Bauer ketones 21 and 23 at 1 μM each significantly inhibited both PGE 2 and NO production. Three rounds of fractionation were produced from an E angustifolia extract. GC-MS analysis identified the presence of Bauer ketone 23 in third round fraction 3D32 and Bauer alkylamide 11 making up 96% of third round fraction 3E40. Synthetic Bauer ketone 23 inhibited PGE 2 production to 83% of control, and synthetic Bauer alkylamide 11 significantly inhibited PGE 2 and NO production at the endogenous concentrations determined to be present in their respective fraction; thus, each constituent partially explained the in vitro anti-inflammatory activity of their respective fraction. From this study, two key contributors to the anti-inflammatory properties of E angustifolia were identified as Bauer alkylamide 11 and Bauer ketone 23.",

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author = "Lalone, {Carlie A.} and Ludmila Rizshsky and Hammer, {Kimberly D.P.} and Lankun Wu and Solco, {Avery K.S.} and Manyu Yum and Nikolau, {Basil J.} and Wurtele, {Eve S.} and Murphy, {Patricia A.} and Meehye Kim and Birt, {Diane F.}",

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doi = "10.1021/jf901202y",

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AU - Lalone, Carlie A.

AU - Rizshsky, Ludmila

AU - Hammer, Kimberly D.P.

AU - Wu, Lankun

AU - Solco, Avery K.S.

AU - Yum, Manyu

AU - Nikolau, Basil J.

AU - Wurtele, Eve S.

AU - Murphy, Patricia A.

AU - Kim, Meehye

AU - Birt, Diane F.

PY - 2009

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AB - Because of the popularity of Echinacea as a dietary supplement, researchers have been actively investigating which Echinacea constituent or groups of constituents are necessary for immunemodulating bioactivities. Our prior studies indicate that alkylamides may play an important role in the inhibition of prostaglandin E2 (PGE 2) production. High-performance liquid chromatography fractionation, employed to elucidate interacting anti-inflammatory constituents from ethanol extracts of Echinacea purpurea, Echinacea angustifolia, Echinacea pallida, and Echinacea tennesseensis, identified fractions containing alkylamides and ketones as key anti-inflammatory contributors using lipopolysaccharideinduced PGE 2 production in RAW264.7 mouse macrophage cells. Nitric oxide (NO) production and parallel cytotoxicity screens were also employed to substantiate an anti-inflammatory response. E pallida showed significant inhibition of PGE 2 with a first round fraction, containing gas chromatography-mass spectrometry (GC-MS) peaks for Bauer ketones 20, 21, 22, 23, and 24, with 23 and 24 identified as significant contributors to this PGE 2 inhibition. Chemically synthesized Bauer ketones 21 and 23 at 1 μM each significantly inhibited both PGE 2 and NO production. Three rounds of fractionation were produced from an E angustifolia extract. GC-MS analysis identified the presence of Bauer ketone 23 in third round fraction 3D32 and Bauer alkylamide 11 making up 96% of third round fraction 3E40. Synthetic Bauer ketone 23 inhibited PGE 2 production to 83% of control, and synthetic Bauer alkylamide 11 significantly inhibited PGE 2 and NO production at the endogenous concentrations determined to be present in their respective fraction; thus, each constituent partially explained the in vitro anti-inflammatory activity of their respective fraction. From this study, two key contributors to the anti-inflammatory properties of E angustifolia were identified as Bauer alkylamide 11 and Bauer ketone 23.

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KW - Nitric oxide

KW - Prostaglandin e2

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Endogenous levels of echinacea alkylamides and ketones are important contributors to the inhibition of prostaglandin E2 and nitric oxide production in cultured macrophages

Abstract

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