Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice

Objective:To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus(FSS)and Schisandra chinensis Fructus(FSC)oils in mice.Methods:Mice were orally administered a single dose of SchisandraeFructusoils.Serumandhepatictriglyceride(TG),triglyceridetransferprotein(TTP),apolipoproteinB48(Apo B48),very-low-densitylipoprotein(VLDL),hepatocytegrowth factor(HGF),alanine aminotransfease(ALT)and liver index were measured at 6-120 h post-dosing.Results:FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels,with maximum increases in the liver(by 297%and 340%)at 12 h post-dosing and serum(244%and 439%)at 24-h post-dosing,respectively.Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51%and63%,Apo B48 by 152%and 425%,and VLDL by 67%and 38%in mice,respectively.FSS and FSC oil treatments also increased liver mass by 53%and 55%and HGF by 106%and 174%,but lowered serum ALT activity by 38%and 22%,respectively.Fenofibrate pre/co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41%and 49%at 48 h post-dosing,respectively,but increased hepatic TG contents(by 38%and 33%,respectively)at 12 h post-dosing.Conclusions:Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil(mainly increasing endogenous TG)and FSC oil(mainly elevating exogenous TG).

Schisandra chinensis Oil Attenuates Aristolochic Acid Ⅰ-Induced Nephrotoxicity in vivo and in vitro

Objective: To investigate the protective effects of Schisandra chinensis oil(SCEO) against aristolochic acid Ⅰ(AAⅠ)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.Methods: C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AAⅠ group, and AAⅠ+SCEO(0.25, 0.5 and 1 g/kg) groups(n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AAⅠ groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AAⅠ(5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling(TUNEL) staining, respectively. The levels of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), and serum creatinine(SCr), as well as renal malondialdehyde(MDA), glutathione, r-glutamyl cysteingl+glycine(GSH), and superoxide dismutase(SOD) were analyzed using enzyme-linked immunosorbent assay(ELISA).Expressions of hepatic cytochrome P450 1A1(CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1(NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction(qPCR) and Western blot,respectively. In vitro, SCEO(40 μg/mL) was added 12 h before treatment with AAⅠ(40 μmol/mL for 48 h) in human renal proximal tubule cell line(HK-2), then apoptosis and reactive oxygen species(ROS) were analyzed by flow cytometry. Results: SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AAⅠ-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr(P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA,GSH and SOD(P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues(P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 μg/mL inhibited apoptosis and ROS generation(P<0.05 or P<0.01). Conclusions: SCEO can alleviate AAⅠ-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.