Effect of Huatan Qushi Huoxue prescription on macrophage efferocytosis mediated by a disintegrin and metalloproteinase 17 and triggering receptor expressed on myeloid cells 2 in rats with metabolic dysfunction-associated steatohepatitis

Lihui ZHANG; Sutong LIU; Qing ZHAO; Shanzheng LI; Minghao LIU; Wenxia ZHAO

doi:10.12449/JCH260214

Volume 42 Issue 2

Feb. 2026

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2026 > 42(2): 345-355

PDF( 61455 KB)

Effect of Huatan Qushi Huoxue prescription on macrophage efferocytosis mediated by a disintegrin and metalloproteinase 17 and triggering receptor expressed on myeloid cells 2 in rats with metabolic dysfunction-associated steatohepatitis

DOI: 10.12449/JCH260214

Lihui ZHANG^{1, 2},
Sutong LIU^{1, 2},
Qing ZHAO^{1, 2},
Shanzheng LI³,
Minghao LIU^{1, 2},
Wenxia ZHAO^{1, 2
,
,
,}

1.
Liver Disease （Spleen and Stomach） Regional Diagnosis and Treatment Center，The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China
2.
Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine，Zhengzhou 450046，China
3.
The First Clinical Medical College of Henan University of Chinese Medicine，Zhengzhou 450046，China

Research funding:

Natural Science Foundation of Henan Province (252300420622);

Special Project for Scientific Research of Traditional Chinese Medicine in Henan Province (2022JDZX098);

Special Project for Scientific Research of Traditional Chinese Medicine in Henan Province (2022JDZX006);

Special Project for Scientific Research of Traditional Chinese Medicine in Henan Province (2023ZXZX1051);

National Natural Science Foundation of China (82205086);

Henan Province Traditional Chinese Medicine “Double First Class” Creation Scientific Research Special Project (HSRP-DFCTCM-2023-7-23)

More Information

Corresponding author: ZHAO Wenxia， zhao-wenxia@163.com （ORCID： 0000-0001-6666-9469）
Received Date: 2025-09-01
Accepted Date: 2025-10-29
Published Date: 2026-02-25

Abstract

Abstract

Objective To investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis （MASH）. Methods A total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group， model A group， model B group， Western medicine group （polyene phosphatidylcholine， 143.64 mg/kg）， high-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 20.16 g/kg）， and middle-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 10.08 g/kg）. All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8， and since week 12， the other groups were given the corresponding drug once a day for 8 consecutive weeks， with samples collected at week 20. Body weight， liver wet weight， and liver index were measured for all rats； the microplate method was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acids （FFA）； ELISA was used to measure the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and soluble triggering receptor expressed on myeloid cells 2 （sTREM2）； HE staining and oil red O staining were performed to observe liver histopathological changes； immunofluorescence assay was used to measure CD68⁺TREM2⁺ cells in liver tissue and calculate the phagocytosis rate of macrophages； quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate （S1P）， sphingosine 1-phosphate receptor 1 （S1PR1）， a disintegrin and metalloproteinase 17 （ADAM17）， and triggering receptor expressed on myeloid cells 2 （TREM2） in liver tissue， and immunohistochemistry was used to measure the protein expression levels of S1P， S1PR1， ADAM17， and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups， and the least significant difference t-test was used for further comparison between two groups； the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups， and the Tamhane’s 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 groups， and the Dunn’s test was used for further comparison between two groups. Results Compared with the blank control group， the model A group and the model B group had significant increases in body weight and liver wet weight， and the model B group had a significant increase in liver index （all P<0.05）. HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B， with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group， the model A group and the model B group had significant increases in NAS score and oil red O-positive area （all P<0.05）， and the model B group had significant increases in these two indicators than the model A group （both P<0.05）. Compared with the blank control group， the model A group and the model B group had significant increases in the serum levels of TC， TG， LDL-C， FFA， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C， and the model B group had significant increases in the serum levels of ALT， AST， and TNF-α （all P<0.05）； compared with the model A group， the model B group had significant increases in the serum levels of ALT， AST， TC， TG， FFA， TNF-α， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C （all P<0.05）. Immunofluorescence assay showed that compared with the blank control group， the model A group had a significant increase in the phagocytosis rate of macrophages （P<0.05）， while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group （P<0.05）. Quantitative real-time PCR showed that compared with the blank control group， the model A group and the model B group had a significant increase in the mRNA expression level of TREM2， and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 （both P<0.05）； moreover， compared with the model A group， the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 （both P<0.05）. Immunohistochemistry showed that compared with the blank control group， the model A group and the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17， and the model A group had a significant increase in the protein expression level of TREM2 （all P<0.05）； compared with the model A group， the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17 and a significant reduction in the protein expression level of TREM2 （all P<0.05）. Compared with the model B group， each medication group had significant reductions in body weight， liver wet weight， and liver index （all P<0.05）； each medication group had significant improvements in hepatic steatosis and inflammatory damage， with significant reductions in NAS score and oil red O-positive area （all P<0.05）； each medication group had significant reductions in the serum levels of ALT， AST， TC， TG， FFA， IL-1β， and IL-6 （all P<0.05） and a significant increase in the serum level of HDL-C （P<0.05）， and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α （P<0.05）； each medication group had a significant increase in the phagocytosis rate of macrophages （all P<0.05）； the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17， and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 （all P<0.05）. Conclusion Huatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.
- Huatan Qushi Huoxue Formula,
- Metabolic Dysfunction-Associated Steatohepatitis,
- Macrophage,
- Efferocytosis

FullText(HTML)

References(20)

References

[1]	GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet Gastroenterol Hepatol, 2020, 5( 3): 245- 266. DOI: 10.1016/S2468-1253(19)30349-8.
[2]	XIAO J, WANG F, WONG NK, et al. Global liver disease burdens and research trends: Analysis from a Chinese perspective[J]. J Hepatol, 2019, 71( 1): 212- 221. DOI: 10.1016/j.jhep.2019.03.004.
[3]	The Lancet Gastroenterology Hepatology. Resmetirom for NASH: Balancing promise and prudence[J]. Lancet Gastroenterol Hepatol, 2024, 9( 4): 273. DOI: 10.1016/S2468-1253(24)00049-9.
[4]	LIU XY, SHANG DF, ZHANG LH, et al. Clinical study on treatment of non-alcoholic steatohepatitis patients with dyslipidemia by Dizhuo Huayu prescription with catgut embedding therapy[J]. Chin J Exp Tradit Med Formulae, 2025, 31( 20): 152- 159. DOI: 10.13422/j.cnki.syfjx.20251591. 刘晓彦, 尚东方, 张丽慧, 等. 涤浊化瘀方联合穴位埋线治疗非酒精性脂肪性肝炎合并血脂异常患者的临床疗效[J]. 中国实验方剂学杂志, 2025, 31( 20): 152- 159. DOI: 10.13422/j.cnki.syfjx.20251591.
[5]	LIU XY, MA SP, MA QL, et al. Clinical effect of Xiaozhi Hugan capsules in treatment of patients with non-alcoholic steatohepatitis and its impact on serum IL-6 and MCP-1[J]. Chin J Exp Tradit Med Formulae, 2025, 31( 12): 185- 192. DOI: 10.13422/j.cnki.syfjx.20251198. 刘晓彦, 马素平, 马庆亮, 等. 消脂护肝胶囊治疗非酒精性脂肪性肝炎患者的临床疗效及对血清IL-6、MCP-1的影响[J]. 中国实验方剂学杂志, 2025, 31( 12): 185- 192. DOI: 10.13422/j.cnki.syfjx.20251198.
[6]	Branch of Hepatobiliary Diseases, China Association of Chinese Medicine. Diagnosis and treatment guideline for Chinese Medicine on non-alcoholic steatohepatitis[J]. J Clin Hepatol, 2023, 39( 5): 1041- 1048. DOI: 10.3969/j.issn.1001-5256.2023.05.007. 中华中医药学会肝胆病分会. 非酒精性脂肪性肝炎中医诊疗指南[J]. 临床肝胆病杂志, 2023, 39( 5): 1041- 1048. DOI: 10.3969/j.issn.1001-5256.2023.05.007.
[7]	ZHAO WX, LIU QZ, LIU JY, et al. Clinical observation of Huatan Lishi Houxue formula for 96 patients with non-alcoholic steatohepatitis[J]. J Tradit Chin Med, 2012, 53( 12): 1025- 1027. DOI: 10.13288/j.11-2166/r.2012.12.002. 赵文霞, 刘全忠, 刘君颖, 等. 化痰利湿活血方加减治疗非酒精性脂肪性肝炎患者96例临床观察[J]. 中医杂志, 2012, 53( 12): 1025- 1027. DOI: 10.13288/j.11-2166/r.2012.12.002.
[8]	SHI HX, MOORE MP, WANG XB, et al. Efferocytosis in liver disease[J]. JHEP Rep, 2024, 6( 1): 100960. DOI: 10.1016/j.jhepr.2023.100960.
[9]	WANG XC, HE QF, ZHOU CL, et al. Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development[J]. Immunity, 2023, 56( 1): 58- 77.e11. DOI: 10.1016/j.immuni.2022.11.013.
[10]	TAVAGLIONE F, JAMIALAHMADI O, de VINCENTIS A, et al. Development and validation of a score for fibrotic nonalcoholic steatohepatitis[J]. Clin Gastroenterol Hepatol, 2023, 21( 6): 1523- 1532.e1. DOI: 10.1016/j.cgh.2022.03.044.
[11]	BIAO YN, CHU XQ, ZHANG MQ, et al. Regulation of Danshen Zexie decoction on AMPK/Nrf2 signaling pathway in rats with metabolic-associated fatty liver disease[J]. Chin J Exp Tradit Med Formulae, 2023, 29( 1): 67- 74. DOI: 10.13422/j.cnki.syfjx.20222244. 彪雅宁, 储心乔, 张睦清, 等. 丹参泽泻汤对代谢相关脂肪性肝病大鼠AMPK/Nrf2信号通路的调节作用[J]. 中国实验方剂学杂志, 2023, 29( 1): 67- 74. DOI: 10.13422/j.cnki.syfjx.20222244.
[12]	HAO JH, WANG HJ, CAO YX, et al. Network analysis and experimental validation of tanshinone ⅡA in the treatment of non-alcoholic fatty liver disease[J]. Chin J Gerontol, 2024, 44( 21): 5243- 5249. DOI: 10.3969/j.issn.1005-9202.2024.21.033. 郝健亨, 王海军, 曹玉霞, 等. 丹参酮ⅡA治疗非酒精性脂肪性肝病的网络分析及实验验证[J]. 中国老年学杂志, 2024, 44( 21): 5243- 5249. DOI: 10.3969/j.issn.1005-9202.2024.21.033.
[13]	HAI J, CHEN ZD, ZHANG ZB, et al. Research progress on the mechanism of total flavonoids from hawthorn leaves in intervening nonalcoholic fatty liver disease[J]. Chin Tradit Pat Med, 2025, 47( 6): 1937- 1942. DOI: 10.3969/j.issn.1001-1528.2025.06.024. 海杰, 陈振东, 张宗博, 等. 山楂叶总黄酮干预非酒精性脂肪性肝病作用机制的研究进展[J]. 中成药, 2025, 47( 6): 1937- 1942. DOI: 10.3969/j.issn.1001-1528.2025.06.024.
[14]	XUE JL, TAN LF, LI LC, et al. Exploring the mechanism of action of aqueous extract of Cassia seed-hawthorn-Lotus leaf to improve hyperlipidemia based on network pharmacology[J]. Asia Pac Tradit Med, 2025, 21( 11): 18- 27. DOI: 10.11954/ytctyy.202511004. 薛佳丽, 谭兰芳, 李连春, 等. 基于网络药理学探究决明子-山楂-荷叶水提物改善高脂血症作用机制[J]. 亚太传统医药, 2025, 21( 11): 18- 27. DOI: 10.11954/ytctyy.202511004.
[15]	ZHANG LH, LIU ST, ZHANG WJ, et al. Mechanism of Huatan Qushi Huoxue Formula in improving the inflammatory injury of rats with nonalcoholic steatohepatitis based on ADPN/PI3K/AKT signal pathway[J]. China J Tradit Chin Med Pharm, 2021, 36( 10): 5832- 5837. 张丽慧, 刘素彤, 张文娟, 等. 基于ADPN/PI3K/AKT信号通路探讨化痰祛湿活血方改善非酒精性脂肪性肝炎大鼠炎症损伤的机制[J]. 中华中医药杂志, 2021, 36( 10): 5832- 5837.
[16]	BOADA-ROMERO E, MARTINEZ J, HECKMANN BL, et al. The clearance of dead cells by efferocytosis[J]. Nat Rev Mol Cell Biol, 2020, 21( 7): 398- 414. DOI: 10.1038/s41580-020-0232-1.
[17]	GERLACH BD, AMPOMAH PB, YURDAGUL A Jr, et al. Efferocytosis induces macrophage proliferation to help resolve tissue injury[J]. Cell Metab, 2021, 33( 12): 2445- 2463.e8. DOI: 10.1016/j.cmet.2021.10.015.
[18]	INDIRA CHANDRAN V, WERNBERG CW, LAURIDSEN MM, et al. Circulating TREM2 as a noninvasive diagnostic biomarker for NASH in patients with elevated liver stiffness[J]. Hepatology, 2023, 77( 2): 558- 572. DOI: 10.1002/hep.32620.
[19]	HENDRIKX T, PORSCH F, KISS MG, et al. Soluble TREM2 levels reflect the recruitment and expansion of TREM2⁺ macrophages that localize to fibrotic areas and limit NASH[J]. J Hepatol, 2022, 77( 5): 1373- 1385. DOI: 10.1016/j.jhep.2022.06.004.
[20]	LEE YS, OLEFSKY J. Eating macrophages for a healthy anti-NASH meal[J]. Immunity, 2023, 56( 1): 3- 5. DOI: 10.1016/j.immuni.2022.12.011.

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(3) / Tables(8)

Get Citation

PDF

XML

Article Metrics

Article views (28) PDF downloads(12)

Effect of Huatan Qushi Huoxue prescription on macrophage efferocytosis mediated by a disintegrin and metalloproteinase 17 and triggering receptor expressed on myeloid cells 2 in rats with metabolic dysfunction-associated steatohepatitis

DOI: 10.12449/JCH260214

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Effect of Huatan Qushi Huoxue prescription on macrophage efferocytosis mediated by a disintegrin and metalloproteinase 17 and triggering receptor expressed on myeloid cells 2 in rats with metabolic dysfunction-associated steatohepatitis

DOI: 10.12449/JCH260214

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