Research progress of the regulation of orphan nuclear receptors on chronic liver diseases / 生理学报

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

Effect of curcumin against capillarization of hepatic sinusoids and its mechanism / 中国组织工程研究

BACKGROUND: Capillarization of hepatic sinusoids is an inevitable part in liver fibrosis and cirrhosis, and is a characteristic lesion inducing portal hypertension. However, curcumin effects on the capillarization of hepatic sinusoids and the underlying mechanism remain unclear. OBJECTIVE: To observe the effect of curcumin (a natural polyphenolic compound derived from the rhizome of Curcuma longa)on the microstructure and secretion of hepatic sinusoidal endothelial cells(HSECs),and to further explore its intervention on sinusoidal capillarization and pharmacological action mechanism of anti-liver fibrosis and target sites. METHODS: The rat HSECs were cultured and divided into seven groups: blank control group received no intervention and cells in the other groups were activated by leptin, followed by treatment with nothing (model group), high-, medium- and low-dose of curcumin, colchicine and salvia miltiorrhiza phenolic acid B, respectively, for 48 hours. RESULTS AND CONCLUSION: Under scanning and transmission electron microscopes, with the increasing activation of leptin, the number of fenestrae in HSECs was increased and the aperture was decreased. Curcumin could increase and enlarge narrowed or disappeared fenestrae caused by leptin, attenuated the thickness and scope of extracellular basement membrane, and reduced the degree of capillarization of hepatic sinusoids in a dose-dependent manner. Real-time PCR and ELISA results showed that after activation of leptin, mRNA and protein expression levels of endothelin-1 and vascular endothelial growth factor in HSECs were significantly increased compared with the blank control group (P < 0.05), while the expressions showed a significant decrease after treatment with curcumin in a dose-dependent manner (P < 0.05). There was also a gradient reduction in the protein expression of endothelin-1 and vascular endothelial growth factor in HSECs treated with curcumin. Moreover, all above mRNA and protein expression levels in the high-dose curcumin group were significantly lower than those in the colchicine and salvia miltiorrhiza phenolic acid B groups. In summary, curcumin can significantly alleviate the sinusoidal capillarization, and thus delay the development of liver fibrosis, probably by down-regulating the expression levels of endothelin-1 and vascular endothelial growth factor.