Chen Minhu

Effect of silybin on high-fat-induced fatty liver in rats

Silybin, a natural antioxidant, has been traditionally used against a variety of liver ailments. To investigate its effect and the underlying mechanisms of action on non-alcoholic fatty liver in rats, we used 60 4-6-week-old male Sprague-Dawley rats to establish fatty liver models by feeding a high-fat diet for 6 weeks. Hepatic enzyme, serum lipid levels, oxidative production, mitochondrial membrane fluidity, homeostasis model assessment-insulin resistance index (HOMA-IR), gene and protein expression of adiponectin, and resistin were evaluated by biochemical, reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Compared with the model group, silybin treatment (26.25 mg·kg(-1)·day(-1), started at the beginning of the protocol) significantly protected against high-fat-induced fatty liver by stabilizing mitochondrial membrane fluidity, reducing serum content of alanine aminotransferase (ALT) from 450 to 304 U/L, decreasing hepatic malondialdehyde (MDA) from 1.24 to 0.93 nmol/mg protein, but increasing superoxide dismutase (SOD) and glutathione (GSH) levels from 8.03 to 9.31 U/mg protein and from 3.65 to 4.52 nmol/mg protein, respectively. Moreover, silybin enhanced the gene and protein expression of adiponectin from 215.95 to 552.40, but inhibited that of resistin from 0.118 to 0.018. Compared to rosiglitazone (0.5 mg·kg(-1)·day(-1), started at the beginning of the protocol), silybin was effective in stabilizing mitochondrial membrane fluidity, reducing SOD as well as ALT, and regulating gene and protein expression of adiponectin (P < 0.05). These results suggest that mitochondrial membrane stabilization, oxidative stress inhibition, as well as improved insulin resistance, may be the essential mechanisms for the hepatoprotective effect of silybin on non-alcoholic fatty liver disease in rats. Silybin was more effective than rosiglitazone in terms of maintaining mitochondrial membrane fluidity and reducing oxidative stress.

Contribution of rs11465788 in IL23R gene to Crohn’s disease susceptibility and phenotype in Chinese population

Multiple studies have shown that IL23 cytokine plays an essential role in the development of autoimmune diseases by activating IL17-producing helper T (Th17) cells. Given that the susceptibility loci in IL23R for Crohn’s disease (CD) is present in Western population and not in Asian population; we screened the IL23R gene by DNA sequencing to identify susceptibility loci in a selected CD cohort and confirmed it in all our subjects (134 CD and 131 controls). A novel nonsynonymous SNP (p.Gly149Arg, c.445G>A) and 35 single nucleotide polymorphisms (SNPs) were identified. Among them, only rs11465788 was implicated in CD susceptibility (P = 4.9 × 10−4, OR = 0.30). Genotype-phenotypic interaction analysis showed that rs11465788 is associated with nonstricturing and nonpenetrating disease behaviour in CD patients (P = 0.015). Our results provide the evidence that rs11465788 may influence the susceptibility and clinical features of CD in Chinese population.