Hepatoprotective dibenzylbutyrolactone lignans of Torreya nucifera against CCl4-induced toxicity in primary cultured rat hepatocytes.
Three dibenzylbutyrolactone lignans, (-)-arctigenin, (-)-traxillagenin, and (-)-4'-demethyltraxillagenin, isolated from the bark of Torreya nucifera SIEB. et ZUCC. (Taxaceae) showed significant hepatoprotective activity in primary cultures of rat hepatocytes injured by carbon tetrachloride (CCl(4)). These lignans reduced the release of glutamic pyruvic transaminase into the culture medium from the CCl(4)-injured primary cultures of rat hepatocytes. Further investigation revealed that the three lignans significantly preserved the level of glutathione (GSH) and activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the CCl(4)-injured rat hepatocytes. The lignans also ameliorated lipid peroxidation as demonstrated by a reduction in malondialdehyde-related products. Moreover, these lignans significantly attenuated the GSH reduction caused by diethylmaleate which depletes GSH through the formation of stable conjugates. However, these lignans showed no effect on the GSH synthesis inhibited by buthionine sulfoximine. From these results, it can be concluded that arctigenin, traxillagenin, and 4'-demethyltraxillagenin may protect hepatocytes from CCl(4) injury by maintaining the GSH level.
Kim
Seung Hyun
SH
College of Pharmacy, Seoul National University, Seoul, Korea.
Jang
Young Pyo
YP
Sung
Sang Hyun
SH
Kim
Chang Jong
CJ
Kim
Jin Woong
JW
Kim
Young Choong
YC
D000818:Animals; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002478:Cells, Cultured; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D032490:Taxaceae
C439406:4,4',9-trihydroxy-3,3'-dimethoxy-9,9'-epoxylignan; D005663:Furans; D017705:Lignans; D010936:Plant Extracts; D002251:Carbon Tetrachloride