FR177391, a new anti-hyperlipidemic agent from Serratia. II. Pharmacological activity of FR177391.
The pharmacological effect of FR177391, isolated from Serratia liquefaciens No. 1821, was studied in normal animals and various types of animal models of hypertriglyceridemia. Treatment of normal mice with FR177391 resulted in an increase in heparin-releasable lipoprotein lipase (LPL) activity in the blood and epididymal fat tissue. FR177391 treatment decreased triglyceride (TG) and increased high-density lipoprotein cholesterol in the blood in normal rats following 7 days treatment, suggesting potent LPL activating properties of FR177391. Both Triton WR1339-induced severe and fructose-induced mild hypertriglyceridemia in rats were attenuated by FR177391 treatment. Severely elevated levels of TG in db/db mice, an insulin resistant diabetic animal model, also significantly decreased from 14 days of treatment with FR177391. FR177391 treatment for 9 days caused a decrease in the elevated levels of TG in mice induced by intraperitoneal inoculation of murine lymphoma EL-4. Overall, this study demonstrated that FR177391 can be possibly a LPL activating agent and that FR177391 treatment improved hypertriglyceridemia in various rat and mouse animal models. These results suggest that FR177391 is a promising candidate compound for the management of hypertriglyceridemia.
Inami
Masamichi
M
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co Ltd, Yodogawa-ku, Osaka, Japan. masamichi.inami@jp.astellas.com
Kawamura
Ikuo
I
Tsujimoto
Susumu
S
Yasuno
Tohru
T
Lacey
Elizabeth
E
Hirosumi
Jiro
J
Takakura
Shoji
S
Nishigaki
Fusako
F
Naoe
Yoshinori
Y
Manda
Toshitaka
T
Mutoh
Seitaro
S
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D012705:Serratia / Q000737:chemistry*; D014280:Triglycerides / Q000097:blood*
D000085:Acetates; C508031:FR177391; D006571:Heterocyclic Compounds; D000960:Hypolipidemic Agents; D014280:Triglycerides