Effects of Xuefu Zhuyu decoction and its extracts on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet

Hao TANG; Yixiao YIN; Wei LIU; Yi FANG; Jun WANG; Yiyang HU; Jinghua PENG

doi:10.3969/j.issn.1001-5256.2022.12.010

Volume 38 Issue 12

Dec. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2022 > 38(12): 2728-2737

PDF( 4784 KB)

Effects of Xuefu Zhuyu decoction and its extracts on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet

DOI: 10.3969/j.issn.1001-5256.2022.12.010

Hao TANG^{1, 2, 3, 4},
Yixiao YIN^{1, 2, 3, 4},
Wei LIU^{1, 2, 3, 4},
Yi FANG^{1, 2, 3, 4},
Jun WANG^{1, 2, 3, 4},
Yiyang HU^{1, 2, 3, 4},
Jinghua PENG^{1, 2, 3, 4
,
,
,}

1.
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2.
Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
3.
Key Laboratory of Liver and Kidney Diseases of the Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
4.
Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China

Research funding:

General Project of National Natural Science Foundation of China (81673750);

Siming Scholar Foundation of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (SGXZ-201911)

More Information

Corresponding author: PENG Jinghua, pengjinghua2004@163.com (ORCID: 0000-0002-0665-7666)
Received Date: 2022-05-15
Accepted Date: 2022-06-20
Published Date: 2022-12-20

Abstract

Abstract

Objective To investigate the effect of Xuefu Zhuyu decoction on nonalcoholic fatty liver disease (NAFLD) and its material basis. Methods In experiment 1 for exploring the effect of Xuefu Zhuyu decoction on mice with NAFLD induced by high-fat diet, 50 healthy male C57BL/6J mice were randomly divided into normal group, model group, high- and low-dose Xuefu Zhuyu decoction groups, and obeticholic acid control group, with 10 mice in each group. The mice in the normal group were given control diet, and those in the other groups were given high-fat diet. Gastric administration was started at week 13, and related samples were collected at the end of week 16. Food intake and body weight were recorded, enzyme-linked immunosorbent assay was used to measure the serum level of fasting insulin, fasting blood glucose was measured, and insulin resistance index was calculated. HE staining and NAFLD activity score (NAS) were used to observe liver histopathology in mice, oil red O staining was used to observe lipid deposition, and triglyceride (TG) level in liver tissue and serum alanine aminotransferase (ALT) level were measured. In experiment 2 for exploring the effect of different extracts of Xuefu Zhuyu decoction on mice with NAFLD induced by high-fat diet, the methods of water decocting, water extraction and alcohol precipitation, and petroleum ether extraction were used to obtain the extracts 1, 2, and 3 of Xuefu Zhuyu decoction, and 54 healthy male C57BL/6J mice were randomly divided into normal group, model group, Xuefu Zhuyu decoction extract 1, 2, and 3 groups, and Xuefu Zhuyu decoction control group, with 9 mice in each group. The mice in the normal group were given control diet, and those in the other groups were given high-fat diet. Gastric administration was started at week 13, and related samples were collected at the end of week 16. Food intake and body weight were recorded, and enzyme-linked immunosorbent assay was used to measure the serum level of fasting insulin, fasting blood glucose was measured, and insulin resistance index was calculated. HE and NAS were used to observe liver histopathology in mice, oil red O staining was used to observe lipid deposition, and the levels of TG and gamma-glutamyl transpeptidase (GGT) in liver tissue and the serum level of ALT were measured. The t-test was used for comparison of normally distributed continuous data between two groups; 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 between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. Results In experiment 1, compared with the model group, the high- and low-dose Xuefu Zhuyu decoction groups and the obeticholic acid control group had significant reductions in body weight, insulin resistance index, the distribution of vacuolar lipid droplets in liver tissue, intralobular inflammation, the ballooning degeneration of hepatocytes, NAS score, the level of TG in liver tissue, and the serum level of ALT (all P < 0.05). Compared with obeticholic acid, high- and low-dose Xuefu Zhuyu decoction had a significantly better effect in reducing body weight, insulin resistance index, and total NAS score (all P < 0.05), and low-dose Xuefu Zhuyu decoction had a significantly better effect in improving serum ALT (P < 0.05). In experiment 2, compared with the model group, the Xuefu Zhuyu decoction extract 1, 2, and 3 groups had significant reductions in fasting blood glucose, insulin resistance index, the distribution of lipid droplets in liver tissue, intralobular inflammation lesions, the ballooning degeneration of hepatocytes, total NAS score, and the level of TG in the liver (all P < 0.05). Compared with the model group, the extract 1 group had a significant reduction in body weight (P < 0.05); the extract 2 and 3 groups had a significant reduction in the serum level of ALT (P < 0.05); the extract 2 group had a significant reduction in the level of GGT in liver tissue (P < 0.05). The extract 2 of Xuefu Zhuyu decoction had the closest effect to compound Xuefu Zhuyu decoction. Conclusion Xuefu Zhuyu decoction and its extracts can help to achieve varying degrees of improvement in NAFLD induced by high-fat diet in mice, and the extract 2 of Xuefu Zhuyu decoction might be the main material basis for Xuefu Zhuyu decoction.
- Non-alcoholic Fatty Liver Disease,
- XuefuZhuyu Decoction,
- Mice, Inbred C57BL

FullText(HTML)

References(38)

References

[1]	LOOMBA R, FRIEDMAN SL, SHULMAN GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease[J]. Cell, 2021, 184(10): 2537-2564. DOI: 10.1016/j.cell.2021.04.015.
[2]	GEIER A, TINIAKOS D, DENK H, et al. From the origin of NASH to the future of metabolic fatty liver disease[J]. Gut, 2021, 70(8): 1570-1579. DOI: 10.1136/gutjnl-2020-323202.
[3]	ZHOU J, ZHOU F, WANG W, et al. Epidemiological features of NAFLD from 1999 to 2018 in China[J]. Hepatology, 2020, 71(5): 1851-1864. DOI: 10.1002/hep.31150.
[4]	Branch of Gastrointestinal Diseases, China Association of Chinese Medicine. Expert consensus on TCM diagnosis and treatment of nonalcoholic fatty liver disease (2017)[J]. J Clin Hepatol, 2017, 33(12): 2270-2274. DOI: 10.3969/j.issn.1001-5256.2017.12.002. 中华中医药学会脾胃病分会. 非酒精性脂肪性肝病中医诊疗专家共识意见(2017)[J]. 临床肝胆病杂志, 2017, 33(12): 2270-2274. DOI: 10.3969/j.issn.1001-5256.2017.12.002.
[5]	DONG GF. Treatment of 50 cases of non-alcoholic fatty liver with Xuefu Zhuyu Decoction[J]. Guangming J Chin Med, 2013, 28(6): 1151-1152. DOI: 10.3969/j.issn.1003-8914.2013.06.034. 董桂芬. 血府逐瘀汤加减治疗非酒精性脂肪肝50例[J]. 光明中医, 2013, 28(6): 1151-1152. DOI: 10.3969/j.issn.1003-8914.2013.06.034.
[6]	YOUNOSSI ZM, RATZIU V, LOOMBA R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial[J]. Lancet, 2019, 394(10215): 2184-2196. DOI: 10.1016/S0140-6736(19)33041-7.
[7]	DUAN FJ. Traditional medical formulae[M]. Shanghai: Shanghai Scientific & Technical Publishers, 1995: 197. 段富津. 方剂学[M]. 上海: 上海科学技术出版社, 1995: 197.
[8]	RODRIGUES PM, AFONSO MB, SIMÃO AL, et al. miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice[J]. Cell Death Dis, 2017, 8(4): e2748. DOI: 10.1038/cddis.2017.172.
[9]	KLEINER DE, BRUNT EM, VAN NATTA M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease[J]. Hepatology, 2005, 41(6): 1313-1321. DOI: 10.1002/hep.20701.
[10]	WANG CE, XU WT, GONG J, et al. Advances in the treatment of nonalcoholic fatty liver disease[J]. Chin J Med Offic, 2022, 50(9): 897-899, 903. DOI: 10.16680/j.1671-3826.2022.09.06. 王彩娥, 许文涛, 宫建, 等. 非酒精性脂肪性肝病治疗研究进展[J]. 临床军医杂志, 2022, 50(9): 897-899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.
[11]	NEUSCHWANDER-TETRI BA. Therapeutic landscape for NAFLD in 2020[J]. Gastroenterology, 2020, 158(7): 1984-1998. DOI: 10.1053/j.gastro.2020.01.051.
[12]	Digestive Diseases Professional Committee of Chinese Association of Integrated Traditional Chineseand Western Medicine. Consensus on diagnosis and treatment of nonalcoholic fatty liver disease with integrated traditional Chinese and western medicine(2017)[J]. Chin J Integr Trad West Med Dig, 2017, 25(11): 805-811. DOI: 10.3969/j.issn.1671-038X.2017.11.02. 中国中西医结合学会消化系统疾病专业委员会. 非酒精性脂肪性肝病中西医结合诊疗共识意见(2017年)[J]. 中国中西医结合消化杂志, 2017, 25(11): 805-811. DOI: 10.3969/j.issn.1671-038X.2017.11.02.
[13]	SHEN H, SHAHZAD G, JAWAIRIA M, et al. Association between aspirin use and the prevalence of nonalcoholic fatty liver disease: a cross-sectional study from the Third National Health and Nutrition Examination Survey[J]. Aliment Pharmacol Ther, 2014, 40(9): 1066-1073. DOI: 10.1111/apt.12944.
[14]	XIE JW, LI HC, YANG SL, et al. Change of hemorheology indexes in non-alcoholic fatty liver patients of blood congestion type[J]. Chin J Integr Trad West Med Dig, 2004, 12(5): 284-285. DOI: 10.3969/j.issn.1671-038X.2004.05.010. 谢纪文, 李宏春, 杨胜兰, 等. 非酒精性脂肪肝血瘀证患者血液流变学变化[J]. 中国中西医结合消化杂志, 2004, 12(5): 284-285. DOI: 10.3969/j.issn.1671-038X.2004.05.010.
[15]	LIU JH, DAI XH. Application of Xuefu Zhuyu Decoction in modern medicine[J]. Fujian J Tradit Chin Med, 1988, 19(1): 58-60. 刘建华, 戴西湖. 血府逐淤汤在近代医学中的应用[J]. 福建中医药, 1988, 19(1): 58-60.
[16]	SONG L, TANG SQ, TONG JW, et al. Study on the mechanism of Xuefu Zhuyu Decoction in preventing and treating NAFLD[J]. Chin J Integr Trad West Med, 2020, 40(9): 1103-1106. DOI: 10.7661/j.cjim.20200315.132. 宋丽, 唐宋琪, 童继威, 等. 血府逐瘀汤防治非酒精性脂肪肝的效应机制研究[J]. 中国中西医结合杂志, 2020, 40(9): 1103-1106. DOI: 10.7661/j.cjim.20200315.132.
[17]	QI L, XU J, XIANG Y, et al. Clinical effect of xuefu zhuyu decoction for liver fibrosis of chronic hepatitis B: a Meta-analysis[J]. Chin J Integr Tradit West Med Liver Dis, 2019, 29(5): 437-442. DOI: 10.3969/j.issn.1005-0264.2019.05.017. 戚璐, 徐俊, 向阳, 等. 血府逐瘀汤治疗慢性乙型肝炎肝纤维化临床疗效的Meta分析[J]. 中西医结合肝病杂志, 2019, 29(5): 437-442. DOI: 10.3969/j.issn.1005-0264.2019.05.017.
[18]	ZHANG XH. Clinical Efficacy of Treatment of Non-alcoholic Steatohepatitis by Modified Xuefu Zhuyu Decoction[J]. Chin Arch Tradit Chin Med, 2012, 30(10): 2356-2357. DOI: 10.13193/j.archtcm.2012.10.214.zhangxh.037. 张兴宏. 加味血府逐瘀汤治疗非酒精性脂肪肝疗效分析[J]. 中华中医药学刊, 2012, 30(10): 2356-2357. DOI: 10.13193/j.archtcm.2012.10.214.zhangxh.037.
[19]	ZHANG YL, HUANG MF, WANG YM, et al. Identification of active compounds and potential targets of Xue-Fu-Zhu-Yu-Tang[J]. World Sci Technol Modern Tradit Chin Med, 2012, 14(4): 1793-1797. DOI: 10.3969/j.issn.1674-3849.2012.04.008. 张燕玲, 黄明峰, 王元明, 等. 基于中药有效成分族辨识的血府逐瘀汤配伍研究[J]. 世界科学技术-中医药现代化, 2012, 14(4): 1793-1797. DOI: 10.3969/j.issn.1674-3849.2012.04.008.
[20]	ZHANG P, DAI H. Pharmacodynamics engineering of Chinese herbal compound[M]. Beijing: China Medical Science Press, 2005: 90. 张骠, 大海. 中药复方药效工程学[M]. 北京: 中国医药科技出版社, 2005: 90.
[21]	CAI CC, WANG HX, WANG S. Therapeutic effect of reglynan on obese diabetic rat models and effects on serum GLP-1 and GIP levels[J]. Chin J Gerontol, 2013, 33(18): 4506-4507. DOI: 10.3969/j.issn.1005-9202.2013.18.060. 蔡春沉, 王洪玺, 王肃. 地黄多糖对肥胖糖尿病大鼠模型的治疗作用及对血清中GLP-1、GIP水平的影响[J]. 中国老年学杂志, 2013, 33(18): 4506-4507. DOI: 10.3969/j.issn.1005-9202.2013.18.060.
[22]	WU Q. Hepatoprotective effects of crude Glycyrrhiza uralensis polysaccharide on non-alcoholic fatty liver disease in rats[D]. Yinchuan: Ningxia Medical University, 2019. 吴琼. 甘草粗多糖对非酒精性脂肪肝大鼠的保护作用[D]. 银川: 宁夏医科大学, 2019.
[23]	LIU LH. Study on antioxidant effect of Angelica Polysaccharide[J]. Contemp Med Forum, 2014, 12(3): 284-285. DOI: 10.3969/j.issn.2095-7629.2014.03.258. 刘丽花. 当归多糖抗氧化作用的研究[J]. 当代医药论丛, 2014, 12(3): 284-285. DOI: 10.3969/j.issn.2095-7629.2014.03.258.
[24]	LI WY, YU YT, YANG BH. Protective effect of hydroxysafflor yellow A against nonalcoholic fatty liver in high-fat diet induced mice by targeting Sirt1 signaling pathway[J]. Central South Pharm, 2018, 16(11): 1538-1542. DOI: 10.7539/j.issn.1672-2981.2018.11.008. 李望云, 喻娅婷, 阳碧辉. 羟基红花黄色素A通过调节Sirt1抑制高脂诱导的非酒精性脂肪肝[J]. 中南药学, 2018, 16(11): 1538-1542. DOI: 10.7539/j.issn.1672-2981.2018.11.008.
[25]	WANG CY, LIU Q, HUANG QX, et al. Activation of PPARγ is required for hydroxysafflor yellow A of Carthamus tinctorius to attenuate hepatic fibrosis induced by oxidative stress[J]. Phytomedicine, 2013, 20(7): 592-599. DOI: 10.1016/j.phymed.2013.02.001.
[26]	LIU Q, WANG CY, LIU Z, et al. Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling[J]. Pharm Biol, 2014, 52(9): 1085-1093. DOI: 10.3109/13880209.2013.877491.
[27]	LI X, GE J, LI Y, et al. Integrative lipidomic and transcriptomic study unravels the therapeutic effects of saikosaponins A and D on non-alcoholic fatty liver disease[J]. Acta Pharm Sin B, 2021, 11(11): 3527-3541. DOI: 10.1016/j.apsb.2021.03.018.
[28]	HE Y, HU ZF, LI P, et al. Experimental study of saikosaponin-d (SSd) on lipid peroxidation of hepatic fibrosis on rat[J]. China J Chin Mater Med, 2008, 33(8): 915-919. DOI: 10.3321/j.issn:1001-5302.2008.08.013. 何燕, 胡志峰, 李平, 等. 柴胡皂苷d抗肝纤维化大鼠脂质过氧化作用的研究[J]. 中国中药杂志, 2008, 33(8): 915-919. DOI: 10.3321/j.issn:1001-5302.2008.08.013.
[29]	HWANG YP, CHOI JH, KIM HG, et al. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells[J]. Toxicol Appl Pharmacol, 2013, 267(2): 174-183. DOI: 10.1016/j.taap.2013.01.001.
[30]	CHOI JH, JIN SW, CHOI CY, et al. Saponins from the roots of Platycodon grandiflorum ameliorate high fat diet-induced non-alcoholic steatohepatitis[J]. Biomed Pharmacother, 2017, 86: 205-212. DOI: 10.1016/j.biopha.2016.11.107.
[31]	LI XX, XU Y, XU B, et al. Effects of hesperidin on nonalcoholic fatty liver rats induced by high fructose diet[J]. World Chin Med, 2021, 16(2): 249-253. DOI: 10.3969/j.issn.1673-7202.2021.02.011. 李晓霞, 许莹, 徐波, 等. 橙皮苷对果糖饮食诱导的非酒精性脂肪肝小鼠的作用研究[J]. 世界中医药, 2021, 16(2): 249-253. DOI: 10.3969/j.issn.1673-7202.2021.02.011.
[32]	LI XX, FANG CH, XU Y, et al. Effect of hesperidin on CYP2E1 expression in nonalcoholic fatty liver rats induced by high fructose diet[J]. Mod J Integr Tradit Chin West Med, 2020, 29(24): 2635-2639. DOI: 10.3969/j.issn.1008-8849.2020.24.003. 李晓霞, 方春华, 许莹, 等. 橙皮苷对果糖诱导的非酒精性脂肪肝病小鼠肝脏组织中CYP2E1表达的影响[J]. 现代中西医结合杂志, 2020, 29(24): 2635-2639. DOI: 10.3969/j.issn.1008-8849.2020.24.003.
[33]	LU KY, PRIMUS DASS KT, LIN SZ, et al. N-butylidenephthalide ameliorates high-fat diet-induced obesity in mice and promotes browning through adrenergic response/AMPK activation in mouse beige adipocytes[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2021, 1866(12): 159033. DOI: 10.1016/j.bbalip.2021.159033.
[34]	LI SW, WU Q, ZHAO SY, et al. Experimental study on antilipid effect of total flavonoids from Fructus aurantii[J]. Pract Clin J Integr Tradit Chin West Med, 2013, 13(3): 91, 94. DOI: 10.3969/j.issn.1671-4040.2013.03.063. 李顺文, 吴琦, 赵诗云, 等. 枳壳总黄酮降血脂作用的实验研究[J]. 实用中西医结合临床, 2013, 13(3): 91, 94. DOI: 10.3969/j.issn.1671-4040.2013.03.063.
[35]	LI T. Study on enzyme-assisted extraction, purification and hypoglycemic activity of glycyrrhizin[D]. Tianjin: Tianjin University of Science and Technology, 2019. 李婷. 甘草酸酶法提取、纯化及降血糖活性研究[D]. 天津: 天津科技大学, 2019.
[36]	YUAN DS, ZHOU LF, SHI L. Protective effect of total paeony glycoside on mice with liver injury induced by D-galactosamine[J]. J Trop Med, 2007, 7(2): 139-142. DOI: 10.3969/j.issn.1672-3619.2007.02.012. 袁冬生, 周兰芳, 石磊. 赤芍总苷对D-氨基半乳糖胺所致小鼠肝损伤的保护作用[J]. 热带医学杂志, 2007, 7(2): 139-142. DOI: 10.3969/j.issn.1672-3619.2007.02.012.
[37]	WU X, ZHANG F, XIONG X, et al. Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway[J]. IUBMB Life, 2015, 67(4): 312-321. DOI: 10.1002/iub.1348.
[38]	WU GT, LIU WZ, DU LD, et al. Protective effects of angelica sinensis volatile oil on levels of blood fats and vascular endothelial structure in hyperlipidemia rats[J]. Chin J Arteriosclerosis, 2016, 24(10): 989-993. https://www.cnki.com.cn/Article/CJFDTOTAL-KDYZ201610004.htm 吴国泰, 刘五州, 杜丽东, 等. 当归挥发油对高血脂模型大鼠的降血脂作用及血管内皮保护作用[J]. 中国动脉硬化杂志, 2016, 24(10): 989-993. https://www.cnki.com.cn/Article/CJFDTOTAL-KDYZ201610004.htm

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(2) / Tables(5)

Get Citation

PDF

XML

Article Metrics

Article views (1698) PDF downloads(86)

Effects of Xuefu Zhuyu decoction and its extracts on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet

DOI: 10.3969/j.issn.1001-5256.2022.12.010

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Effects of Xuefu Zhuyu decoction and its extracts on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet

DOI: 10.3969/j.issn.1001-5256.2022.12.010

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content