Experimental AA amyloidosis in mice is inhibited by treatment with triptolide, a purified traditional Chinese medicine.
The effect of triptolide, which is isolated from Tripterygium Wilfordii, on induction and development of murine AA amyloidosis was studied. In the first experiment, we examined the ability of triptolide to inhibit initiation of amyloidosis. Oral or intraperitoneal administration of 480 microg/kg/day triptolide inhibited splenic amyloid deposition in both rapid and chronic induction models of mouse AA amyloidosis. Moreover, serum amyloid A (SAA) and interleukin (IL)-6 levels were also suppressed remarkably. Triptolide also immediately decreased SAA levels and reduced the incidence of amyloidosis even under conditions of high SAA levels. In the second experiment, we evaluated the influence of triptolide on development and resorption of amyloid deposition. Amyloid deposition was induced in mice by 28 daily injections of casein. After splenic and hepatic biopsies to confirm the presence of amyloid deposits, the mice immediately started to receive daily injections of 480 microg/kg/day triptolide with or without casein. Treatment with triptolide for 35 days and 105 days prevented deposition of amyloid and promoted resorption of splenic amyloid deposits. In conclusion, we show for the first time that triptolide inhibits induction and development of experimental murine amyloidosis. These results suggest that through suppression of IL-6, triptolide can reduce production of SAA. Amyloid deposition is prevented when levels of the amyloid-forming precursor protein SAA are decreased significantly.
Cui
Dan
D
First Department of Pathology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. cuidan@yamaguchi-u.ac.jp
Hoshii
Yoshinobu
Y
Kawano
Hiroo
H
Sugiyama
Shinichi
S
Gondo
Toshikazu
T
Liu
Ye
Y
Ishihara
Tokuhiro
T
D000686:Amyloidosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D010616:Phenanthrenes / Q000494:pharmacology*; D000685:Serum Amyloid A Protein / Q000378:metabolism; D029757:Tripterygium
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D010616:Phenanthrenes; D000685:Serum Amyloid A Protein; C001899:triptolide