Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma

MA Guiping; ZHANG Yuanjie; ZHOU Yichi; LYU Jinzhen; WANG Conghui; LU Fenping; LIU Bowen; RAN Yun; HU Shiping

doi:10.6039/j.issn.1001-0408.2026.05.12

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Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma

更新时间：2026-03-10

- Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma
- ZHONGGUO YAOFANG Vol. 37, Issue 5, Pages: 620-625(2026)
- 作者机构：
  
  北京中医药大学深圳医院（龙岗）中心实验室，广东深圳　518172
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.05.12
  CLC： R965
- Received：20 August 2025，
  
  Revised：2026-02-11，
  
  Accepted：11 February 2026，
  
  Published：15 March 2026
- 稿件说明：
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马贵萍,张远杰,周怡驰,等.柴芪益肝颗粒改善肝细胞癌的作用机制预测及验证 ^Δ[J].中国药房,2026,37(05):620-625.

MA Guiping,ZHANG Yuanjie,ZHOU Yichi,et al.Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma[J].ZHONGGUO YAOFANG,2026,37(05):620-625.
马贵萍,张远杰,周怡驰,等.柴芪益肝颗粒改善肝细胞癌的作用机制预测及验证 ^Δ[J].中国药房,2026,37(05):620-625. DOI： 10.6039/j.issn.1001-0408.2026.05.12.

MA Guiping,ZHANG Yuanjie,ZHOU Yichi,et al.Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma[J].ZHONGGUO YAOFANG,2026,37(05):620-625. DOI： 10.6039/j.issn.1001-0408.2026.05.12.

摘要

目的

预测柴芪益肝颗粒改善肝细胞癌（HCC）的作用机制，并进行验证。

方法

采用网络药理学方法预测柴芪益肝颗粒改善HCC的信号通路。采用腋下注射肝癌细胞H22的方法构建肝癌移植瘤模型小鼠，将造模成功的小鼠随机分为模型组（生理盐水）、索拉非尼组（阳性对照，50 mg/kg）和柴芪益肝颗粒低、中、高剂量组（24.83、49.66、99.32 g/kg），每组10只。各组小鼠灌胃相应药液或生理盐水，每日1次，连续14 d。末次给药后，观察小鼠肿瘤组织病理学形态，采用免疫组化法检测小鼠肿瘤组织中细胞核增殖抗原Ki-67表达，采用Western blot法检测小鼠肿瘤组织中上皮间质转化[N-钙黏蛋白（N-cadherin）、E-钙黏蛋白（E-cadherin）、波形蛋白（Vimentin）、基质金属蛋白酶7（MMP7）]和丝裂原活化蛋白激酶（MAPK）信号通路[p38 MAPK、磷酸化p38 MAPK、c-Jun 氨基末端激酶（JNK）、磷酸化JNK、细胞外调节蛋白激酶1/2（ERK1/2）、磷酸化ERK1/2]相关蛋白表达。

结果

网络药理学结果显示，代谢通路、癌症通路、MAPK信号通路等可能是柴芪益肝颗粒改善HCC的关键信号通路。动物实验验证结果显示，模型组小鼠肿瘤组织中肿瘤细胞密集、生长状态旺盛；与模型组比较，柴芪益肝颗粒高剂量组小鼠肿瘤组织中肿瘤细胞密度降低，肿瘤组织中Ki-67、N-cadherin、MMP7、Vimentin蛋白表达水平和ERK1/2、JNK蛋白磷酸化水平均显著降低（

＜0.05），E-cadherin蛋白表达水平显著升高（

＜0.05），p38 MAPK蛋白磷酸化水平升高但差异无统计学意义（

＞0.05）。

结论

柴芪益肝颗粒可通过调控MAPK信号通路，抑制上皮间质转化，从而抑制肿瘤细胞侵袭和转移，进而发挥改善HCC的作用。

Abstract

OBJECTIVE

To predict and validate the mechanisms of Chaiqi yigan granules （CQYG） improving hepatocellular carcinoma （HCC）.

METHODS

The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group （normal saline）， sorafenib group （positive control， 50 mg/kg）， and CQYG low-， medium- and high-dose groups （24.83， 49.66， 99.32 g/kg）， with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， for 14 consecutive days. After last administration， pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition （EMT） [N-cadherin， E-cadherin， Vimentin， matrix metalloproteinase 7 （MMP7）] and the mitogen-activated protein kinase （MAPK） signaling pathway [p38 MAPK， phosphorylated p38 MAPK， c-Jun N-terminal kinase （JNK）， phosphorylated JNK， extracellular regulated protein kinase 1/2 （ERK1/2）， phosphorylated ERK1/2] in tumor tissue of mice.

RESULTS

Network pharmacology analysis revealed that metabolic pathways， pathways in cancer， and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments， the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group， CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover， the expression levels of Ki-67， N-cadherin， MMP7 and Vimentin proteins， along with the phosphorylation levels of ERK1/2 and JNK proteins， were all significantly reduced （

＜0.05）. The expression level of E-cadherin protein was significantly increased （

＜0.05）， the phosphorylation level of p38 MAPK protein was increased， the difference was not statistically significant （

＞0.05）.

CONCLUSIONS

CQYG can inhibit EMT by regulating the MAPK signaling pathway， thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.

关键词

Keywords

references

BRAY F ， LAVERSANNE M ， SUNG H ， et al . Global cancer statistics 2022：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin ， 2024 ， 74 （ 3 ）： 229 - 263 .

HAN B F ， ZHENG R S ， ZENG H M ， et al . Cancer incidence and mortality in China，2022 [J ] . J Natl Cancer Cent ， 2024 ， 4 （ 1 ）： 47 - 53 .

DOPAZO C ， SØREIDE K ， RANGELOVA E ， et al . Hepatocellular carcinoma [J ] . Eur J Surg Oncol ， 2024 ， 50 （ 1 ）： 107313 .

FENG F ， ZHAO Y . Hepatocellular carcinoma：prevention，diagnosis，and treatment [J ] . Med Princ Pract ， 2024 ， 33 （ 5 ）： 414 - 423 .

童光东，王宇新，邢宇锋，等 . 从 “虚、毒、瘀、积” 论慢性乙型肝炎及相关肝硬化、肝癌的治疗 [J ] . 中医杂志， 2021 ， 62 （ 16 ）： 1404 - 1407 .

李晓斌，苏晓鹏，马贵萍，等 . 柴芪益肝方治疗乙型病毒性肝炎相关性原发性肝癌正虚毒瘀证患者的临床回顾性分析 [J ] . 中医学报， 2024 ， 39 （ 4 ）： 845 - 853 .

XU X ， ZHANG W X ， HUANG C ， et al . A novel chemometric method for the prediction of human oral bioavailability [J ] . Int J Mol Sci ， 2012 ， 13 （ 6 ）： 6964 - 6982 .

JIA C Y ， LI J Y ， HAO G F ， et al . A drug-likeness toolbox facilitates ADMET study in drug discovery [J ] . Drug Discov Today ， 2020 ， 25 （ 1 ）： 248 - 258 .

ZHOU C F ， BASNET R ， ZHEN C X ， et al . Trimethylamine N-oxide promotes the proliferation and migration of hepatocellular carcinoma cell through the MAPK pathway [J ] . Discov Oncol ， 2024 ， 15 （ 1 ）： 346 .

KE J F ， HAN W Z ， MENG F W ， et al . CTI-2 inhibits metastasis and epithelial-mesenchymal transition of breast cancer cells by modulating MAPK signaling pathway [J ] . Int J Mol Sci ， 2021 ， 22 （ 22 ）： 12229 .

国家卫生健康委员会 . 原发性肝癌诊疗指南：2024年版 [J ] . 肿瘤综合治疗电子杂志， 2024 ， 10 （ 3 ）： 17 - 68 .

MOUSTARDAS P ， ABERDAM D ， LAGALI N . MAPK pathways in ocular pathophysiology：potential therapeutic drugs and challenges [J ] . Cells ， 2023 ， 12 （ 4 ）： 617 .

CARGNELLO M ， ROUX P P . Activation and function of the MAPKs and their substrates，the MAPK- activated protein kinases [J ] . Microbiol Mol Biol Rev ， 2011 ， 75 （ 1 ）： 50 - 83 .

LI M ， LI Z W ， SONG J Y ， et al . KLK7 involvement in thyroid papillary carcinoma cell migration and invasion by EMT via MAPK/ERK pathways [J ] . J Cancer ， 2025 ， 16 （ 5 ）： 1709 - 1725 .

SUN P H ， XIA S Y ， YUAN R Z ， et al . TMEM176B promotes EMT via FGFR/JNK signalling in development and tumourigenesis of lung adenocarcinoma [J ] . Cancers ， 2024 ， 16 （ 13 ）： 2447 .

JANTA S ， PRANWEERAPAIBOON K ， VIVITHANAPORN P ， et al . Holothurin A inhibits RUNX1- enhanced EMT in metastasis prostate cancer via the Akt/JNK and P38 MAPK signaling pathway [J ] . Mar Drugs ， 2023 ， 21 （ 6 ）： 345 .

KHAN A Q ， HASAN A ， MIR S S ， et al . Exploiting trans- cription factors to target EMT and cancer stem cells for tumor modulation and therapy [J ] . Semin Cancer Biol ， 2024 ， 100 ： 1 - 16 .

MI K ， ZENG L Z ， CHEN Y ， et al . DHX38 enhances proliferation，metastasis，and EMT progression in NSCLC through the G3BP1-mediated MAPK pathway [J ] . Cell Signal ， 2024 ， 113 ： 110962 .

CELIÀ-TERRASSA T ， KANG Y B . How important is EMT for cancer metastasis? [J ] . PLoS Biol ， 2024 ， 22 （ 2 ）： e3002487 .

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