Inhibition of Interleukin-12 Production in Lipopolysaccharide-Activated Mouse Macrophages by Hpyericin, an Active Component of Hypericum perforatum

Abstract

Hypericin, an active component of Hypericum perforatum, was evaluated for the regulation of interleukin-12 (IL-12) production in mouse macrophages. Hypericin significantly inhibited IL-12 production in lipopolysaccharide-activated macrophages in a dose-dependent manner (IC₅₀ = 1.45 μg/ml). Furthermore, hypericin potently inhibited the activation of IL-12 gene promoter, suggesting that hypericin negatively regulated IL-12 production at the transcription level. These results may explain some known biological activities of hypericin including its anti-rheumatic effect.

References

• 1 Trinchieri G, Scott P. Interleukin-12: basic principles and clinical applications.  Current Topics in Microbiology and Immunology. 1999;  238 57-78
• 2 Kim W U, Min S Y, Cho M L, Youn J, Min D J, Lee S H, Park S H, Cho C S, Kim H Y. The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis.  Clinical and Experimental Immunology. 2000;  119 175-81
• 3 Schwarting A, Tesch G, Kinoshita K, Maron R, Weiner H L, Kelley V R. IL-12 drives IFN-γ-dependent autoimmune kidney disease in MRL-Fas(lpr) mice.  Journal of Immunology. 1999;  163 6884-91
• 4 Mattner F, Smiroldo S, Galbiati F, Muller M, Di Lucia P, Poliani P L, Martino G, Panina-Bordignon P, Adorini L. Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hyercalcemic analogue of 1,25-dihydroxyvitamin D₃ .  European Journal of Immunology. 2000;  30 498-508
• 5 Butterweck V, Petereit F, Winterhoff H, Nahrstedt A. Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test.  Planta Medica. 1998;  64 291-4
• 6 Lavie G, Mazur Y, Lavie D, Meruelo D. The chemical and biological properties of hypericin: a compound with a broad spectrum of biological activities.  Medicinal Research Reviews. 1995;  15 111-9
• 7 Fox F E, Niu Z, Tobia A, Rook A H. Photoactivated hypericin is an anti-proliferative agent that induces a high rate of apoptotic death of normal, transformed, and malignant T lymphocytes: implications for the treatment of cutaneous lymphoproliferative and inflammatory disorders.  Journal of Investigative Dermatology. 1998;  111 327-32
• 8 Kang K, Kubin M, Cooper K D, Lessin S R, Trinchieri G, Rook A H. IL-12 synthesis by human Langerhans cells.  Journal of Immunology. 1996;  156 1402-7
• 9 Chung S W, Kang B Y, Kim S H, Pak Y K, Cho D, Trinchieri G, Kim T S. Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-γ and nuclear factor-κB.  Journal of Biological Chemistry. 2000;  275 32681-7
• 10 Ammon H P, Wahl M A. Pharmacology of Curcuma longa .  Planta Medica. 1991;  57 1-7
• 11 Kang B Y, Song Y J, Kim K M, Choe Y K, Hwang S Y, Kim T S. Curcumin inhibits Th1 cytokine profile in CD4⁺ T cells by suppressing interleukin-12 production in macrophages.  British Journal of Pharmacology. 1999;  128 380-4