PCR), real time PCR, chromatin immunoprecipitation (ChIP) assay, and immunoblot analysis. Results: Cellular TG content was increased when HepG2 were cultured in the presence of oleic acid, and this increase was prevented by guggulsterone treatment. Guggulsterone prevented LXRα agonist (T0901317) induced activation of SREBP-1c, inhibited its mRNA and protein induction, thereby resulting in the down-regulation of SREBP-1c target genes. This inhibitory effect of guggulsterone was blocked by the protein kinase C (PKC) inhibitor. Moreover, guggulsterone enhanced LXRα phosphorylation at threonine residue and decreased phosphorylation at serine residue, which caused impaired DNA binding activity, leading to inhibition of LXRα transactivation and expression. Conclusion: These results show that guggulsterone prevents LXRα mediated SREBP-1c dependent hepatic steatosis through PKC dependent pathway, and suggests that guggulsterone can therapeutically be used to treat nonalcoholic fatty liver disease.
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