Effects of bisbenzylisoquinoline alkaloids on alveolar macrophages: correlation between binding affinity, inhibitory potency, and antifibrotic potential.
The Chinese have conducted extensive studies concerning the medicinal properties of plant products. In this investigation the ability of three bisbenzylisoquinoline alkaloids to inhibit particle-induced activation of alveolar macrophages was evaluated and this inhibitory potential was correlated with the ability of those drugs to bind to membrane components. Tetrandrine, i.e., an herbal medicine used as an antifibrotic agent in China, was a potent inhibitor of particle-stimulated oxygen consumption, superoxide release, and hydrogen peroxide secretion by alveolar macrophages. Tetrandrine also exhibited substantial binding affinity for membrane lipids and alveolar macrophages. In contrast, tubocurine, an analogue with little antifibrotic potential, exhibited low binding affinity and had little effect on macrophage activation. Methoxyadiantifoline, an alkaloid of unknown antifibrotic potential, exhibited inhibitory and binding properties similar to those of tetrandrine. The data indicate that a strong relationship exists between the antifibrotic potential of these alkaloids and their ability to bind to alveolar macrophages and inhibit particle-induced activation of these phagocytes. These drugs should serve as useful probes to evaluate the role of alveolar macrophages in pulmonary fibrosis.
Castranova
V
V
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia.
Kang
J H
JH
Ma
J K
JK
Mo
C G
CG
Malanga
C J
CJ
Moore
M D
MD
Schwegler-Berry
D
D
Ma
J Y
JY
D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D044182:Benzylisoquinolines; D007546:Isoquinolines / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008854:Microscopy, Electron; D010100:Oxygen / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology; D011658:Pulmonary Fibrosis / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D015054:Zymosan / Q000494:pharmacology
D000470:Alkaloids; D001593:Benzyl Compounds; D044182:Benzylisoquinolines; D007546:Isoquinolines; D008563:Membrane Lipids; C068324:methoxyadiantifoline; C009438:tetrandrine; C067639:chondocurine; D015054:Zymosan; D010100:Oxygen