Biochemical mechanism underlying hypertriglyceridemia and hepatic steatosis/hepatomegaly induced by acute schisandrin B treatment in mice
It has been demonstrated thatacute oral administration ofschisandrin B (Sch B) , an activedibenzocyclooctadiene isolatedfromSchisandrae Fructus (a commonly used traditional Chinese herb) , increased serum and hepatic triglyceride (TG) levels, as well as hepatic massin mice.The present studyaimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia andhepatomegaly.In this study, male ICR micewere given a single oral dose of Sch B (0.25-2 g/kg).Serum levels of biomarkersand hepatic lipids, as well as weights and histological changes of epididymal adipose tissue (EAT) andthe liverwere assessed over a period of 12-120h post-dosing.Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h post-Sch B administration, respectively.Sch B treatment elevated serum level of apolipoprotein B48 (up to 12%) , a marker of chylomicron or exogenous TG, but not the level of very-low-density lipoprotein, a major secretory product from the liver that transports endogenously synthesized TG, when compared with the vehicle treatment.Treatment withsch B caused a time-/dose-dependent reduction inEAT index (up to 39%) and elevation in serum non-esterified fatty acid level (up to 55%) at 48 and 24 h post-dosing, respectively.Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs.the vehicle control) and lipid positive staining area (up to 17.5 × 103 μm2) in liver tissues.Hepatic index and hepatic growth factor (HGF) levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively.In addition, ultrastructural changes,such as increase in size and disruption of cristae,in hepatic mitochondria were observed inSch B-treated mice.Our findingssuggestthat lipolysis and exogenoussources of lipidsmay mainly contribute to hypertriglyceridemia and hepatic steatosis in Sch B-treated mice.Hepatomegaly caused by Sch B may result from fat accumulation and mitochondrial damage in liver tissue.
schisandrin B hypertriglyceridemia lipolysis chylomicron hepatomegaly fat mass
Si-Yuan Pan YiZhang Jing Zhao Xiao-Yan Wang Pei-Li Zhu Zhu-Sheng Chu Zhi-Ling Yu Shu-Feng Zhou Ming Xie Kam-Ming Ko
Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
国内会议
北京
英文
254-265
2016-08-01（万方平台首次上网日期，不代表论文的发表时间）