Effect of Quzhi Ruangan prescription on the farnesoid X receptor-fibroblast growth factor 19 pathway in rats with nonalcoholic steatohepatitis

Enrui XIA; Gege TIAN; Suyan ZHANG; Shunzhen ZHANG

doi:10.3969/j.issn.1001-5256.2022.05.018

Volume 38 Issue 5

May 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(5): 1069-1074

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Effect of Quzhi Ruangan prescription on the farnesoid X receptor-fibroblast growth factor 19 pathway in rats with nonalcoholic steatohepatitis

DOI: 10.3969/j.issn.1001-5256.2022.05.018

School of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650000, China

Research funding:

The National Natural Science Foundation of China (81760818);

Key Laboratory of Microcosmic Syndrome Differentiation of TCM Syndrome in Yunnan Province (20190720);

Joint Special Project of Traditional Chinese Medicine of Yunnan Provincial Science and Technology Department (2018FF001(-042));

Joint Special Project of Traditional Chinese Medicine of Yunnan Provincial Science and Technology Department-Key Project (202101AZ070001-008)

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Corresponding author: ZHAGN Shunzhen, 694415176@qq.com(ORCID: 0000-0003-3908-6414)
Received Date: 2021-09-27
Accepted Date: 2021-11-01
Published Date: 2022-05-20

Abstract

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.
- Non-alcoholic Steatohepatitis,
- Farnesol X Receptor,
- Cytokines

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References

[1]	SHEKA AC, ADEYI O, THOMPSON J, et al. Nonalcoholic steatohepatitis: A review[J]. JAMA, 2020, 323(12): 1175-1183. DOI: 10.1001/jama.2020.2298.
[2]	XI Y, LI H. Role of farnesoid X receptor in hepatic steatosis in nonalcoholic fatty liver disease[J]. Biomed Pharmacother, 2020, 121: 109609. DOI: 10.1016/j.biopha.2019.109609.
[3]	KIR S, BEDDOW SA, SAMUEL VT, et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis[J]. Science, 2011, 331(6024): 1621-1624. DOI: 10.1126/science.1198363.
[4]	WANG RR, JI G. Interaction between intestinal flora and bile acid and non-alcoholic fatty liver disease[J]. Chin J Integr Tradit West Med Liver Dis, 2020, 30(4): 378-382. DOI: 10.3969/j.issn.1005-0264.2020.04.028. 王睿瑞, 季光. 肠道菌群和胆汁酸相互作用与非酒精性脂肪性肝病[J]. 中西医结合肝病杂志, 2020, 30(4): 378-382. DOI: 10.3969/j.issn.1005-0264.2020.04.028.
[5]	CHEN WH, LIU B, ZHANG C. Clinical observation on 126 cases of fatty liver treated with Quzhi Ruangan decoction[J]. Yunnan J Tradit Chin Med Mater Med, 2000, 21(5): 2-3. https://www.cnki.com.cn/Article/CJFDTOTAL-YZYY200005000.htm 陈文慧, 刘冰, 张超. 去脂软肝汤治疗脂肪肝126例疗效观察[J]. 云南中医中药杂志, 2000, 21(5): 2-3. https://www.cnki.com.cn/Article/CJFDTOTAL-YZYY200005000.htm
[6]	SUN LL, SHI J, HAO JH, et al. Effect of high-fat diet on establishment of a rat non-alcoholic steatohepatitis/liver fibrosis model[J]. J Clin Hepatol, 2011, 27(3): 254-257, 272. DOI: 10.3969/j.issn.1001-5256.2011.03.009. 孙林林, 石军, 郝菁华, 等. 高脂饮食致大鼠非酒精性脂肪性肝炎肝纤维化模型的建立[J]. 临床肝胆病杂志, 2011, 27(3): 254-257, 272. DOI: 10.3969/j.issn.1001-5256.2011.03.009.
[7]	HAO H, CAO L, JIANG C, et al. Farnesoid X receptor regulation of the NLRP3 inflammasome underlies cholestasis-associated sepsis[J]. Cell Metab, 2017, 25(4): 856-867. e5. DOI: 10.1016/j.cmet.2017.03.007.
[8]	CLIFFORD BL, SEDGEMAN LR, WILLIAMS KJ, et al. FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption[J]. Cell Metab, 2021, 33(8): 1671-1684. e4. DOI: 10.1016/j.cmet.2021.06.012.
[9]	HERNANDEZ GV, SMITH VA, MELNYK M, et al. Dysregulated FXR-FGF19 signaling and choline metabolism are associated with gut dysbiosis and hyperplasia in a novel pig model of pediatric NASH[J]. Am J Physiol Gastrointest Liver Physiol, 2020, 318(3): G582-G609. DOI: 10.1152/ajpgi.00344.2019.
[10]	LU X, HAN T, TIAN Y, et al. Research progress in roles of gut microbiota and bile acid metabolism in development and progression of NAFLD[J]. J Clin Hepatol, 2014, 30(11): 1225-1228. DOI: 10.3969/j.issn.1001-5256.2014.11.034. 鲁旭, 韩涛, 田垚, 等. 肠道菌群和胆汁酸代谢对非酒精性脂肪性肝病发生发展的作用[J]. 临床肝胆病杂志, 2014, 30(11): 1225-1228. DOI: 10.3969/j.issn.1001-5256.2014.11.034.
[11]	CHEN YY, LAN YM, WANG MG, et al. Mechanism of action of bile acid-farnesoid X receptor-intestinal microecological axis in the development of liver failure and liver regeneration[J]. J Clin Hepatol, 2021, 37(2): 480-484. DOI: 10.3969/j.issn.1001-5256.2021.02.049. 陈研焰, 蓝艳梅, 王明刚, 等. 胆汁酸-法尼醇核受体R-肠道微生态轴在肝衰竭发生及肝再生中的作用机制[J]. 临床肝胆病杂志, 2021, 37(2): 480-484. DOI: 10.3969/j.issn.1001-5256.2021.02.049.
[12]	SHI QR. Based on the research Quzhi Ruangan Decoction platelet active control rat early fatty liver mechanism[D]. Kunming: Yunnan University of Traditional Chinese Medicine, 2012. 施钦柔. 基于血小板活化研究去脂软肝方防治大鼠早期脂肪肝的作用机制[D]. 昆明: 云南中医学院, 2012.
[13]	ZHANG SZ, SHI AH, BIAN Y, et al. Influence of Quzhi Ruangan Formula on blood fat and hemorheology of rats with early fatty liver[J]. China J Tradit Chin Med Pharma, 2015, 30(3): 875-877. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201503069.htm 张顺贞, 石安华, 卞瑶, 等. 去脂软肝方对早期脂肪肝大鼠血脂及血液流变学的影响[J]. 中华中医药杂志, 2015, 30(3): 875-877. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201503069.htm
[14]	BIAN Y, HUANG WJ, YAO Z, et al. Experimental research of Quzhi Ruan'gan Prescription in effect of von Willebrand factor in rats with fatty liver caused by high fat[J]. China Med Herald, 2014, 11(1): 4-6. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201401003.htm 卞瑶, 黄文俊, 姚政, 等. 去脂软肝方对高脂诱导大鼠脂肪肝血管性血友病因子作用的实验研究[J]. 中国医药导报, 2014, 11(1): 4-6. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201401003.htm
[15]	ZHANG SY, XIA ER, ZHOU QL, et al. Effect of Quzhi Ruangan decoction on the mRNA and protein expression of organic anion transporting polypeptide 2B1 in the small intestine of rats with nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36(11): 2484-2488. DOI: 10.3969/j.issn.1001-5256.2020.11.017. 张素妍, 夏恩蕊, 周青丽, 等. 去脂软肝方对非酒精性脂肪性肝病大鼠模型小肠中有机阴离子转运多肽2B1 mRNA和蛋白表达水平的影响[J]. 临床肝胆病杂志, 2020, 36(11): 2484-2488. DOI: 10.3969/j.issn.1001-5256.2020.11.017.
[16]	ZHOU QL. Effect of Quzhi Ruangan Fang on the expression of NLRP3 inflammasome and related factors in rats with non-alcoholic steatohepatitis[D]. Kunming: Yunnan University of Traditional Chinese Medicine, 2020. 周青丽. 去脂软肝方对非酒精性脂肪性肝炎大鼠NLRP3炎症小体及相关因子表达的影响[D]. 昆明: 云南中医药大学, 2020.
[17]	YAO ZM, CHEN WD, YANG ZH, et al. Research progress in atractylodes macrocephala and predictive analysis on Q-marker[J]. Chin Tradit Herb Drug, 2019, 50(19): 4796-4807. DOI: 10.7501/j.issn.0253-2670.2019.19.031. 姚兆敏, 陈卫东, 仰忠华, 等. 白术研究进展及其质量标志物(Q-marker)的预测分析[J]. 中草药, 2019, 50(19): 4796-4807. DOI: 10.7501/j.issn.0253-2670.2019.19.031.
[18]	SHI J. Study on the classification of fortykinds of Chinese Herbal Pieces[D]. Beijing: China Academy of Chinese Medical Sciences, 2020. 石佳. 四十种中药饮片等级评价研究[D]. 北京: 中国中医科学院, 2020.
[19]	ZHOU HP, REN MX, GUAN JQ, et al. Research progress on chemical constituents and pharmacological effects of Chrysanthemum morifolium and predictive analysis on quality markers[J]. Chin Tradit Herb Drug, 2019, 50(19): 4785-4795. DOI: 10.7501/j.issn.0253-2670.2019.19.030. 周衡朴, 任敏霞, 管家齐, 等. 菊花化学成分、药理作用的研究进展及质量标志物预测分析[J]. 中草药, 2019, 50(19): 4785-4795. DOI: 10.7501/j.issn.0253-2670.2019.19.030.
[20]	CHEN H, LIU CY, LI CY. Advances in studies on chemical constituents and pharmacologic effects of Pericarpium Citri Reticulatae Viride[J]. Chin Tradit Herb Drug, 2001, 32(11): 93-95. DOI: 10.3321/j.issn:0253-2670.2001.11.039. 陈红, 刘传玉, 李承晏. 青皮的化学及药理作用研究进展[J]. 中草药, 2001, 32(11): 93-95. DOI: 10.3321/j.issn:0253-2670.2001.11.039.
[21]	PANG HT, LUO DS, GUO J. Study on chemical constituents of Notoginseng Radix et Rhizoma and network pharmacology of its anti-inflammatory mechanism[J]. Chin Tradit Herb Drug, 2020, 51(21): 5538-5547. DOI: 10.7501/j.issn.0253-2670.2020.21.018. 庞会婷, 罗朵生, 郭姣. 三七化学成分分析及其抗炎机制的网络药理学探讨[J]. 中草药, 2020, 51(21): 5538-5547. DOI: 10.7501/j.issn.0253-2670.2020.21.018.

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Effect of Quzhi Ruangan prescription on the farnesoid X receptor-fibroblast growth factor 19 pathway in rats with nonalcoholic steatohepatitis

DOI: 10.3969/j.issn.1001-5256.2022.05.018

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