ABSTRACT
Objective To investigate the effect of Quzhi Ruangan prescription on the farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) pathway in rats with nonalcoholic steatohepatitis (NASH). Methods Male Sprague-Dawley rats were randomly divided into normal group (Control group with 8 rats), model group (HFD group with 12 rats), simvastatin group with 8 rats, high-dose Quzhi Ruangan prescription group (QH group with 8 rats), and low-dose Quzhi Ruangan prescription group (QL group with 8 rats). The rats in the Control group were fed with a normal diet and those in the other groups were fed with a high-fat diet. Related samples were collected at the end of week 10 to observe liver pathological changes and measure the serum levels of liver function parameters, the level of FGF19 in the liver and the small intestine, and the level of bile acid (BA) in the liver. The expression levels of FXR in the small intestine and cholesterol 7α-hydroxylase (CYP7A1) in the liver were also measured. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison bewteen two groups. Results Compared with the Control group, the HFD group showed the pathological manifestations of marked inflammatory lesions and steatosis. Compared with the HFD group, all administration groups had a significant increase in high-density lipoprotein cholesterol and significant reductions in alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, and low-density lipoprotein cholesterol (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in FGF19 in the small intestine and a significant increase in BA in the liver (both P < 0.05). Compared with the HFD group, all administration groups had a significant increase in FGF19 in the small intestine and a significant reduction in BA in the liver (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the mRNA expression of FXR in the small intestine and a significant increase in the mRNA expression of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the QH group had a significant increase in the mRNA expression of FXR in the small intestine, while the QL group had a significant reduction (both P < 0.05), and the QH group had a significant reduction in the mRNA expression of CYP7A1 in the liver ( P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the positive rate of FXR in the small intestine and a significant increase in the positive rate of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the simvastatin group and the QH group had a significant increase in the positive rate of FXR in the small intestine (both P < 0.05), and the simvastatin group, the QH group, and the QL group had a significant reduction in the positive rate of CYP7A1 in the liver (all P < 0.05). Conclusion Quzhi Ruangan prescription can activate the FXR-FGF19 pathway in NASH rats and may exert a preventive and therapeutic effect on NASH through this pathway.
ABSTRACT
Nonalcoholic steatohepatitis (NASH) is a serious type of nonalcoholic fatty liver disease (NAFLD) and can develop into life-threatening liver cirrhosis and liver cancer. Toll-like receptor 4 (TLR4) is a type of pattern recognition receptor in innate immunity, and after being activated, it can trigger a cascade reaction and activate nuclear factor-κB (NF-κB) which mediates inflammatory response. The TLR4/NF-κB signaling pathway is a classic inflammatory pathway. In clinical practice, traditional Chinese medicine has achieved a good effect in the treatment of NASH, and the TLR4/NF-κB signaling pathway is one of the approaches for traditional Chinese medicine to treat NASH. By searching the relevant literature, this article summarizes the active components and compounds of traditional Chinese medicine that can regulate the TLR4/NF-κB signaling pathway to alleviate NASH, so as to provide ideas for future research and medication.
ABSTRACT
ObjectiveTo investigate the effect of Quzhi Ruangan decoction on the mRNA and protein expression of organic anion transporting polypeptide 2B1 (OATP2B1) in the small intestine of rats with nonalcoholic fatty liver disease (NAFLD). MethodsAfter 1 week of adaptive feeding, 36 male Sprague-Dawley rats were randomly divided into normal group, model group, simvastatin group, and high-, middle-, and low-dose Quzhi Ruangan decoction groups, with 6 rats in each group. Liver tissue was collected and HE staining was used to observe hepatic steatosis; an automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), and cholesterol (CHOL); RT-PCR and Western blot were used to measure the mRNA and protein expression of OATP2B1 in the small intestine of rats. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results There were significant differences in liver index, GLU, and CHOL between groups (F=10.814, 12.298, and 5.024, all P＜0.05), and there were also significant differences in the mRNA and protein expression of OATP2B1 in the small intestine (F=13.384 and 73.025, both P＜0.05). Compared with the normal group, the model group had significant increases in the mRNA and protein expression of OATP2B1 (both P＜0.05); compared with the model group, the simvastatin group and the high- and middle-dose Quzhi Ruangan groups had a significant reduction in the mRNA expression of OATP2B1 (all P＜0.05); compared with the simvastatin group, the middle- and low-dose Quzhi Ruangan groups had a significant reduction in the mRNA expression of OATP2B1 (both P＜0.05). Compared with the normal group, the model group had a significant increase in the protein expression of OATP2B1 (P＜0.05); compared with the model group, all treatment groups had a significant reduction in the protein expression of OATP2B1 (all P＜0.001); compared with the simvastatin group, the high-, middle-, and low-dose Quzhi Ruangan groups had a significant reduction in the protein expression of OATP2B1 (all P＜0.05). ConclusionQuzhi Ruangan decoction may alleviate the pathological changes of NAFLD by reducing the overexpression of OATP2B1.