Anti-inflammatory activity of arctigenin from Forsythiae Fructus.
Oleaceae Forsythiae Fructus has been used for anti-inflammatory, diuretics, antidote, and antibacterials in traditional herbal medicine. Our previous screening of medicinal plants showed that methanol (MeOH) extract of Forsythiae Fructus had significant anti-inflammatory activity, but the active ingredients remain unclear. For isolation of active ingredient of MeOH extract of Forsythiae Fructus, it was partitioned with n-hexane and ethylacetate (EtOAc), and arctigenin was isolated from EtOAc fraction by column chromatography with anti-inflammatory activity-guided separation. Its activity was evaluated in the animal models of inflammation including myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activities in the edematous tissues homogenate, and silica-induced reactive oxygen species (ROS) production in the RAW 264.7 cell line. It was shown that arctigenin (100 mg/kg) had significantly decreased not only carrageenan-induced paw edema 3 and 4h after injection of carrageenan, arachidonic acid (AA)-induced ear edema at a painting dose of 0.1-1.0mg/ear, and acetic acid-induced writhing response and acetic acid-induced capillary permeability accentuation at an oral dose of 25-100, and 100 mg/kg, respectively, but also MPO and EPO activities at a painting dose of 0.1-1.0mg/ear in the AA-induced edematous tissues homogenate as indicators of neutrophils and eosinophils recruitment into the inflamed tissue. Further, arctigenin (0.1-10 microM) also significantly inhibited the intracellular ROS production by silica. These results indicate that arctigenin is a bioactive agent of Forsythiae Fructus having significant anti-inflammatory action by inhibition of the exudation, and leukocytes recruitment into the inflamed tissues. The pharmacologic mechanism of action of arctigenin may be due to the inhibition of release/production of inflammatory mediators such as AA metabolites and free radicals.
Kang
Hyo Sook
HS
Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University, 221 Huksuk-dong, Dongjak-Ku, Seoul 156-756, Republic of Korea.
Lee
Ji Yun
JY
Kim
Chang Jong
CJ
D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002853:Chromatography, Liquid; D047209:Eosinophil Peroxidase / Q000378:metabolism; D031657:Forsythia / Q000737:chemistry*; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013057:Spectrum Analysis
D000893:Anti-Inflammatory Agents; D005663:Furans; D017705:Lignans; D017382:Reactive Oxygen Species; D047209:Eosinophil Peroxidase; D009195:Peroxidase; D019342:Acetic Acid; C071942:arctigenin