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Biochemical and Molecular Actions of Nutrients

Garlic (Allium sativum L.) Modulates Cytokine Expression in Lipopolysaccharide-Activated Human Blood Thereby Inhibiting NF-B Activity

Hans-Peter Keiss, Verena M. Dirsch², Thomas Hartung^*, Thomas Haffner, Laurence Trueman^**, Jacques Auger, Rémi Kahane and Angelika M. Vollmar

Department of Pharmacy, Center of Drug Research, University of Munich, D-81377 Munich, Germany; ^* Biochemical Pharmacology, University of Konstanz, D-78457 Konstanz, Germany; Lichtwer Pharma AG, D-13435 Berlin, Germany; ^** HRI Wellesbourne, Wellesbourne, Warwick, CV35 9EF, UK; Université François Rabelais, IRBI CNRS UMR 6035 37200 Tours, France; and CIRAD-FLHOR, PS4/TA50, 34398 Montpellier cedex 5, France

²To whom correspondence should be addressed. E-mail: Verena.Dirsch{at}cup.uni-muenchen.de.

Garlic is proposed to have immunomodulatory and anti-inflammatory properties. This paper shows that garlic powder extracts (GPE) and single garlic metabolites modulate lipopolysaccharide (LPS)-induced cytokine levels in human whole blood. GPE-altered cytokine levels in human blood sample supernatants reduced nuclear factor (NF)-B activity in human cells exposed to these samples. Pretreatment with GPE (100 mg/L) reduced LPS-induced production of proinflammatory cytokines interleukin (IL)-1ß from 15.7 ± 5.1 to 6.2 ± 1.2 µg/L and tumor necrosis factor (TNF)- from 8.8 ± 2.4 to 3.9 ± 0.8 µg/L, respectively, whereas the expression of the anti-inflammatory cytokine IL-10 was unchanged. The garlic metabolite diallydisulfide (1–100 µmol/L) also significantly reduced IL-1ß and TNF-. Interestingly, exposure of human embryonic kidney cell line (HEK293) cells to GPE-treated blood sample supernatants (10 or 100 mg/L) reduced NF-B activity compared with cells exposed to untreated blood supernatants as measured by a NF-B-driven luciferase reporter gene assay. Blood samples treated with extract obtained from unfertilized garlic (100 mg/L) reduced NF-B activity by 25%, whereas blood samples treated with sulfur-fertilized garlic extracts (100 mg/L) lowered NF-B activity by 41%. In summary, garlic may indeed promote an anti-inflammatory environment by cytokine modulation in human blood that leads to an overall inhibition of NF-B activity in the surrounding tissue.

KEY WORDS: • garlic • cytokines • nuclear factor-B

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