[Effects of TJN-101, a lignan compound isolated from Schisandra fruits, on liver fibrosis and on liver regeneration after partial hepatectomy in rats with chronic liver injury induced by CCl4].
TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.
Takeda
S
S
Tsumura Research Institute for Pharmacology, Ibaraki, Japan.
Kase
Y
Y
Arai
I
I
Ohkura
Y
Y
Hasegawa
M
M
Sekiguchi
Y
Y
Tatsugi
A
A
Funo
S
S
Aburada
M
M
Hosoya
E
E
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology* / Q000503:physiopathology; D034242:Cyclooctanes; D004149:Dioxoles; D006498:Hepatectomy; D017705:Lignans; D008106:Liver Cirrhosis, Experimental / Q000473:pathology* / Q000503:physiopathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000972:Antineoplastic Agents, Phytogenic; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D010936:Plant Extracts; D011083:Polycyclic Compounds; C033585:schizandrol B