Palmatine attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice.
Palmatine is an isoquinoline alkaloid from Coptis chinensis, an herbal medicine used to treat various inflammatory diseases such as gastritis, edema and dermatitis. The present study examined the cytoprotective properties of palmatine on d(+)-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were intraperitoneally given GalN (700 mg/kg)/LPS (10 microg/kg). Palmatine (25, 50, 100, and 200mg/kg) was administered 1h before GalN/LPS. GalN/LPS increased the mortality and serum aminotransferase activities. These increases were attenuated by palmatine. GalN/LPS increased hepatic lipid peroxidation and decreased the contents of reduced glutathione. Palmatine did not affect the lipid peroxidation and glutathione content. GalN/LPS increased the circulating levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and IL-10. Palmatine prevented the increase of serum TNF-alpha and augmented that of serum IL-10. GalN/LPS treatment also increased the levels of TNF-alpha, IL-6 and IL-10 mRNA expression in liver tissue. Palmatine decreased the TNF-alpha mRNA expression and increased the IL-10 mRNA expression. Palmatine attenuated the apoptosis of hepatocytes, as evidenced by the TUNEL method and capase-3 analysis. Our data suggest that palmatine alleviates GalN/LPS-induced liver injury by modulating the cytokine response and inhibiting apoptosis.
Lee
Woo-Cheol
WC
College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
Kim
Joon-Ki
JK
Kang
Jung-Woo
JW
Oh
Woo-Yong
WY
Jung
Joo-Yeon
JY
Kim
Yeong Shik
YS
Jung
Hyun Ah
HA
Choi
Jae Sue
JS
Lee
Sun-Mee
SM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D001600:Berberine Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D039323:Coptis / Q000737:chemistry; D016207:Cytokines / Q000097:blood; D005688:Galactosamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018517:Plant Roots / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D001600:Berberine Alkaloids; D016207:Cytokines; D008070:Lipopolysaccharides; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; C005413:palmatine; D005978:Glutathione