The inhibitory effect of phenylpropanoid glycosides and iridoid glucosides on free radical production and beta2 integrin expression in human leucocytes.
Rapid production of reactive oxygen species (ROS) and upregulation of beta2 integrin by leucocytes are two important inflammatory responses in human leucocytes. To evaluate whether three phenylpropanoid glycosides (acteoside, crenatoside, and rossicaside B) and two iridoid glucosides (boschnaloside and 8-epideoxyloganic acid) identified from two medicinal plants with similar indications (Orobanche caerulescens and Boschniakia rossica) exhibited anti-inflammatory activity, their effects on N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol-12-myristate-13-acetate (PMA)-activated peripheral human neutrophils (PMNs) and mononuclear cells were examined. Pretreatment with 1-50 microM phenylpropanoid glycoside concentration-dependently diminished PMA- and fMLP-induced ROS production with IC50 values of approximately 6.8-23.9 and 3.0-8.8 muM, respectively. Iridoid glucoside was less effective than phenylpropanoid glycoside with an IC50 value of approximately 8.9-28.4 microM in PMA-activated PMNs and 19.1-21.1 microM in fMLP-activated mononuclear cells. Phenylpropanoid glycosides also effectively inhibited NADPH oxidase (NOX) and displayed potent free radical-scavenging activity, but did not interfere with pan-protein kinase C (PKC) activity. Furthermore, all compounds, except rossicaside B, significantly inhibited PMA- and fMLP-induced Mac-1 (a beta2 integrin) upregulation at 50 microM but not that of fMLP-induced intracellular calcium mobilization. These drugs had no significant cytotoxicity as compared with the vehicle control. Our data suggested that inhibition of ROS production, possibly through modulation of NOX activity and/or the radical scavenging effect, and beta2 integrin expression in leucocytes indicated that these compounds had the potential to serve as anti-inflammatory agents during oxidative stress.
Lin
Lie-Chwen
LC
National Research Institute of Chinese Medicine, Taipei, Taiwan.
Wang
Yea-Hwey
YH
Hou
Yu-Chang
YC
Chang
Shiou
S
Liou
Kuo-Tong
KT
Chou
Yueh-Ching
YC
Wang
Wen-Yen
WY
Shen
Yuh-Chiang
YC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D005609:Free Radicals / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D006834:Hydrazines / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010851:Picrates; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives; D059808:Polyphenols
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D018821:CD18 Antigens; D002109:Caffeic Acids; D005609:Free Radicals; D005960:Glucosides; D006834:Hydrazines; D039823:Iridoids; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; D010636:Phenols; D010851:Picrates; D011493:Protein Kinase C; D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate; C083069:crenatoside; C058956:acteoside; D059808:Polyphenols; C016658:phorbolol myristate acetate; C004931:1,1-diphenyl-2-picrylhydrazyl