Dibenzylbutyrolactone Lignans from Forsythia koreana Fruits Attenuate Lipopolysaccharide-Induced Inducible Nitric Oxide Synthetase and Cyclooxygenase-2 Expressions through Activation of Nuclear Factor-κB and Mitogen-Activated Protein Kinase in RAW264.7 Ce

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概要

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• Previously, we reported that dibenzylbutyrolactone lignans (DBLLs) from the fruit of Forsythia koreana NAKAI (Oleaceae) has anti-inflammatory, antioxidant, and anti-asthmatic effects. In this study, to clarify the anti-inflammatory mechanisms of DBLL, we evaluated the effects of DBLLs on lipopolysaccharide-stimulated inducible nitric oxide synthetase (iNOS) and cyclooxygenase-2 (COX-2) expressions, nitric oxide (NO) and prostaglandin E2 (PGE2) productions, nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activations, inhibitor of κB (IκB) and inhibitor of κB kinase (IKK) phosphorylations in cytosolic proteins, and cytotoxicity in Raw264.7 cells. DBLLs potently suppressed both the enzyme expression and DNA-binding activity of NF-κB. Arctiin, arctigenin (1.0 μM) and matairesinol (10 μM) inhibited the expression of iNOS by 37.71±2.86%, 32.51±4.28%, and 27.44±2.65%, respectively, and arctiin, arctigenin (0.1 μM) and matairesinol (1.0 μM) inhibited COX-2 expression by 37.93±7.81%, 26.70±4.61% and 29.37±5.21%, respectively. The inhibitory effects of DBLLs on NO and PGE2 productions were the same patterns as those seen for the reductions in iNOS and COX-2 expression, respectively. Arctiin, arctigenin (1.0 μM) and matairesinol (10 μM) significantly (p<0.05) inhibited NF-κB DNA binding by 44.85±6.67%, 44.16±6.61%, and 44.79±5.62%, respectively, and arctiin (0.1 μM) and arctigenin (1.0 μM) significantly (p<0.05) inhibited the phosphorylation of IκB by 20.58±3.86% and 25.99±6.18%, respectively. Furthermore, arctiin, matairesinol (1.0 μM) and arctigenin (10 μM) inhibited the phosphorylation of IKK by 38.80±6.64%, 38.33±6.65%, and 38.57±8.14%, respectively. In addition, DBLLs potently inhibited the lipopolysaccharide (LPS)-induced activation of MAPKs (SAPK/c-Jun NH2-terminal kinase (JNK), p38, and extracellular signal receptor-activated kinase (ERK)1/2). Overall, arctiin was the most effective; its effect was nearly the same as that of 10 μM helenalin. These findings suggest that treatment with non-toxic DBLLs inhibits not only NF-κB and NF-κB-regulated protein activation, but also potently inhibits the activations of specific MAPKs.

• 日本薬学会の論文

著者

• Lee Ji

  Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University

• Kim Chang

  Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University

• Park Tae

  Division Of Gynecologic Oncology Department Of Obstetrics And Gynecology Catholic University Of Kore

• Kim Soo

  Division of Maternal-Feta Medicine, Department of Obstetrics and Gynecology, College of Medicine Cat

• Cho Bong

  Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University

• Park Byoung

  Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University

• Sim Sang

  Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University

• Kim Chang

  Division Of Insect Natural Enemies Institute Of Biological Control Faculty Of Agriculture Kyushu Uni

• Kim Soo

  Division Of Maternal-feta Medicine Department Of Obstetrics And Gynecology College Of Medicine Catho

• Lee Ji

  Division Of Endocrinology And Metabolism Department Of Medicine Samsung Medical Center Sungkyunkwan

• Kim Chang

  Division Of Hematology And Immunology Department Of Internal Medicine Kanazawa Medical University

• Kim Chang

  Division Of Computer Engineering Daejeon University

• Kim Soo

  Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University

• Park Tae

  Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University

• Lee Ji

  Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

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