Anti-inflammatory action of phenolic compounds from Gastrodia elata root.
Previous screening of the pharmacological action of Gastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The anti-inflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4'-hydroxybenzyloxy)benzyl methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried out in vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determined in vitro. These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.
Lee
Ji Yun
JY
Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Jang
Young Woon
YW
Kang
Hyo Sook
HS
Moon
Hee
H
Sim
Sang Soo
SS
Kim
Chang Jong
CJ
D019342:Acetic Acid; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D016718:Arachidonic Acid; D001593:Benzyl Compounds / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004431:Ear, External / Q000187:drug effects / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D031668:Gastrodia / Q000737:chemistry*; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D000432:Methanol; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D001593:Benzyl Compounds; D016861:Cyclooxygenase Inhibitors; D010636:Phenols; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D002351:Carrageenan; D011451:Prostaglandin-Endoperoxide Synthases; D019342:Acetic Acid; D000432:Methanol