Biotransformation of malabaricone C by rat hepatic microsomes and cytotoxic activities against gastric cancer cells in vitro

Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investigated using rat hepatic microsomes for the first time and the main biotransformation product was elucidated as malabaricone B （2） according to the spectroscopic data. Further evaluation on human gastric cancer cell lines showed that the cytotoxic effects of malabaricone C and its metabolite malabaricone B were comparable to those of vinorelbine, with the values of IC50 of （42.62±3.10） and （19.80±1.70） μg/mL on NCI-N87, and （22.94±1.33） and （19.60±2.21） μg/mL on MGC803, respectively. Statistical analysis revealed that malabaricone B had significantly stronger cytotoxicity than the parent compound （P〈0.01 on NCI-N87 and P〈0.05 on MGC803）, which may indicate a bioactivation of malabaricone C by hepatic microsomes. These results suggest that malabaricone C has a simple biotransformation pathway by hepatic microsomes and provide valuable information for further investigation on both the parent compound and its biotransformation product as anti-gastric cancer agents or lead compounds.

Biotransformation of methyleugenol by rat hepatic microsomes

Methyleugenol （1）, one of the main bioactive constituents of the seeds of Myristicafragrans Houtt. （family： Myristicaceae）, was incubated with rat hepatic microsomes from rats pretreated with sodium phenobarbital. Eight biotransformation products named （R）-l＇-methoxymethyleugenol （2）, 3-（3,4-dimethoxyphenyl）-l-methoxyprop-2-ene （3）, cis-3,4-dimethoxycinnamyl acetate （4）, trans-3,4-dimethoxycinnamyl acetate （5）, （R）-I hydroxymethyleugenol （6）, trans-3,4-dimethoxycinnamyl alcohol （7）, cis-3,4-dimethoxycinnamyl alcohol （8）, and （R）-3-（3,4-dimethoxyphenyl）-propane-l,2-diol （9） were obtained and their structures were elucidated by NMR and MS data analysis and by comparison with the previously reported data. The biotransformation of 1 may provide valuable information for the use of methyleugenol. The NMR data of compounds 4 and 6 were reported for the first time.

Subacute Effect of Decabromodiphenyl Ethane on Hepatotoxicity and Hepatic Enzyme Activity in Rats

Information regarding decabromodiphenyl ethane （DBDPE） effects on hepatotoxicity and metabolism is limited. In the present study, Wistar rats were given oral DBDPE at different doses. DBDPE induced oxidative stress, elevated blood glucose levels, increased CYP2B2 mRNA, CYP2B1/2 protein, 7-pentoxyresorufin O-depentylase （PROD） activity, and induced CYP3A2 mRNA, CYP3A2 protein, and luciferin benzylether debenzylase （LBD） activity. UDPGT activity increased with its increasing exposure levels, suggesting that oral DBDPE exposure induces drug-metabolizing enzymes in rats via the CAR/PXR signaling pathway. The induction of CYPs and co-regulated enzymes of phase II biotransformation may affect the homeostasis of endogenous substrates, including thyroid hormones, which may, in turn, alter glucose metabolism.

Effect of Shengqing capsule on serum cholesterol content and hepatic scavenger receptor class B of rats with cholesterol calculus

Objective To observe the effect of Shengqing Capsule(SC)on serum contents of TC,LDL-C,and HDLC,hepatic scavenger receptor BⅠ(SRBⅠ),and CD36 in rats with cholesterol calculus.Methods