Antitumor, antiviral and immunopotentiating activities of pine cone extracts: potential medicinal efficacy of natural and synthetic lignin-related materials (review).
Several antitumor substances that effectively inhibited the growth of ascites and solid tumor cells transplanted in mice were isolated from pine cone NaOH extract by acid- and ethanol-precipitation. These antitumor substances were also potent antiviral agents against human immunodeficiency virus, herpes simplex virus and influenza virus; they induced antimicrobial activity against Staphylococcal aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and induced antiparasite activity against Hymenolepis nana in mice. Chemical analysis of these substances by IR, UV, NMR, ESR and partition chromatography on cellulose-TLC plate disclosed that they had lignin-related structures complexed with sugars or polysaccharides. Chlorinated decomposition of the lignin portion significantly reduced their antiviral activity. In agreement with this, the antiviral activity of synthesized lignins prepared by polymerization of phenylpropanoid precursors was comparable to that of the undecomposed counterparts of the pine cone extract. Acid hydrolysis of the polysaccharide portion significantly reduced the ability of the substances to induce antitumor and antimicrobial activities in mice. With an appropriate eliciting agent, intravenous administration of natural lignified substances transiently induced endogenous production of a cytotoxic factor (possibly tumor necrosis factor) in normal mice. Their priming activity was significantly higher than that of their component units or degradation products. These data suggest the importance of conjugating lignins with polysaccharides for in vivo expression of various kinds of immunopotentiating activity. As possible explanations for their induction of a variety of immunopotentiating activities, these natural and synthetic lignins stimulated macrophage NBT-reducing activity, polymorphonuclear cell (PMN) iodination and splenocyte DNA synthesis and inhibited poly (ADP-ribose) glycohydrolase, RNA-dependent DNA polymerase (reverse transcriptase) and RNA-dependent RNA polymerase activities.
Sakagami
H
H
First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
Kawazoe
Y
Y
Komatsu
N
N
Simpson
A
A
Nonoyama
M
M
Konno
K
K
Yoshida
T
T
Kuroiwa
Y
Y
Tanuma
S
S
D000276:Adjuvants, Immunologic; D000818:Animals; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006678:HIV / Q000187:drug effects; D008031:Lignin / Q000494:pharmacology* / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009975:Orthomyxoviridae / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D018139:Simplexvirus / Q000187:drug effects; D014197:Trees
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D010936:Plant Extracts; D008031:Lignin