中草药

基于数据挖掘、网络药理学和动物实验探究中药治疗癌症恶病质用药规律及作用机制

PDF下载

中草药 | 数据挖掘与循证医学 2026,57(6): 2216-2233

收起

中草药 |数据挖掘与循证医学 2026 , 57 (6) : 2216 -2233

基于数据挖掘、网络药理学和动物实验探究中药治疗癌症恶病质用药规律及作用机制

全屏

陈晟¹, 段熔辉¹, 刘正艺¹, 胡宇翔¹, 肖望重¹, 文静¹, 杨仁义², 孙银辉³, 王理槐¹

作者信息

作者简介:

陈晟: 陈晟,硕士研究生,从事中西医结合防治恶性肿瘤研究。Tel:13317355490 E-mail:20233042@stu.hnucm.edu.cn

Exploring medication patterns and mechanisms of traditional Chinese medicines in treatment of cancer cachexia based on data mining, network pharmacology, and animal experiments

CHEN Sheng, DUAN Ronghui, LIU Zhengyi, HU Yuxiang, XIAO Wangzhong, WEN Jing, YANG Renyi, SUN Yinhui, WANG Lihuai

Affiliations

doi: 10.7501/j.issn.0253-2670.2026.06.018

文章导航

摘要

收起

目的探讨中医药治疗癌症恶病质（cancer cachexia，CC）的用药规律、核心组方及其多维作用机制。方法通过数据挖掘，从211篇文献中筛选出高频药物和核心组方，随后利用网络药理学方法，筛选核心处方的活性成分和靶点，构建“药物-成分-靶点”网络和蛋白质-蛋白质相互作用网络，并进行基因本体论（gene ontology，GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析，并通过分子对接验证核心成分与靶点的结合能力。在A549荷瘤裸鼠CC模型上，通过检测体质量、摄食量、肌肉功能、炎症因子［白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）］水平和关键蛋白［肌肉萎缩F-box蛋白（muscle atrophy F-box protein，Atrogin-1）、肌肉环指蛋白1（muscle ring-finger protein-1，MuRF1）、蛋白激酶B1（protein kinase B1，Akt1）、缺氧诱导因子-1α（hypoxia-inducible factor-1α，HIF-1α）等］表达量进行体内药效验证。结果最终纳入方剂67首，涉及药物171味，确定核心组方为茯苓、白术、黄芪、山药、炙甘草。网络药理学预测出149个潜在靶点，涉及磷脂酰肌醇-3-羟激酶（phosphatidylinositol-3-hydroxykinase，PI3K）/蛋白激酶B（protein kinase B，Akt）、缺氧反应因子-1（hypoxia-inducible factor-1，HIF-1）、p53和凋亡等信号通路，分子对接显示槲皮素等核心成分与核心靶点结合良好。体内实验显示，核心处方高剂量组疗效最佳，显著改善了CC裸鼠的厌食症状、维持体质量、恢复握力峰值和股四头肌湿质量（均P＜0.05）。机制方面，核心组方显著降低了裸鼠血清IL-6和TNF-α水平；免疫荧光显示其显著抑制了腓肠肌中Atrogin-1和MuRF1的表达，同时上调了抗凋亡蛋白蛋白激酶B1（protein kinase B1，Akt1）和B淋巴细胞瘤-2（B-cell lymphoma-2，Bcl-2）的表达，并下调了HIF-1α、肿瘤蛋白p53（tumor protein p53，TP53）和原癌基因蛋白c-Myc（cellular-Myc，MYC）等促凋亡及代谢重编程蛋白的表达（均P＜0.05），调控结果与网络药理学预测的HIF-1α、PI3K-Akt信号通路调控一致。结论中医药治疗CC的核心组方以健脾渗湿、益气扶正为主要法则，其机制可能通过PI3K-Akt/HIF-1α等通路，实现对代谢重编程、炎症反应及细胞凋亡的综合调节，并有效抑制泛素-蛋白酶体途径，从而发挥多维度、整体性的抗恶病质作用。

关键词

癌症恶病质 / 数据挖掘 / 网络药理学 / 分子对接 / HIF-1α / 茯苓 / 白术 / 黄芪 / 山药 / 炙甘草 / 槲皮素

Abstract

收起

Objective To investigate the medication rules, core formula, and multi-dimensional mechanisms of traditional Chinese medicine (TCM) in the treatment of cancer cachexia (CC). Methods Medication rules and the core formula were screened from 211 publications through data mining. Network pharmacology was subsequently applied to identify the active components and potential targets of the core formula, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses and molecular docking validation. Finally, the therapeutic efficacy and mechanisms were validated in vivo using an A549 tumor-bearing nude mouse CC model. Evaluation indicators included tumor-free body weight, food intake, muscle function, inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], and key proteins [muscle atrophy F-box protein (Atrogin-1), muscle RING-finger protein-1 (MuRF1), protein kinase B1 (Akt1), and hypoxia-inducible factor-1α (HIF-1α)]. Results A total of 67 prescriptions involving 171 drugs were identified, and the core formula was determined as Fuling (Poria), Baizhu (Atractylodis Macrocephalae Rhizoma), Huangqi (Astragali Radix), Shanyao (Dioscoreae Rhizoma), and Zhigancao (Glycyrrhizae Radix et Rhizoma Praeparata cum Melle). Network pharmacology predicted 149 potential targets involved in the PI3K-Akt, HIF-1α, p53, and apoptosis signaling pathways. Molecular docking showed that core components, such as quercetin, exhibited strong binding affinities with key targets. In vivo experiments demonstrated that the high-dose core formula exhibited the best therapeutic effect, significantly improving anorexia, maintaining tumor-free body weight, and restoring peak grip strength and quadriceps wet weight (all P < 0.05). Mechanistically, the core formula significantly reduced serum levels of IL-6 and TNF-α. Furthermore, it markedly inhibited the expression of muscle-atrophy-related proteins Atrogin-1 and MuRF1 in the gastrocnemius muscle. It also upregulated the expression of the anabolic protein Akt1 and anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), while downregulating the expression of metabolic reprogramming and pro-apoptotic proteins, including HIF-1α, tumor protein p53 (TP53), and cellular-Myc (MYC) (all P < 0.05). These results were consistent with the regulatory patterns predicted for the HIF-1α and PI3K-Akt signaling pathways. Conclusion The core TCM formula for treating CC follows the therapeutic principles of invigorating the spleen, resolving dampness, supplementing qi, and strengthening healthy qi. Its mechanism likely involves the modulation of the PI3K-Akt/HIF-1α signaling axis to comprehensively regulate metabolic reprogramming, inflammatory response, and cell apoptosis while effectively inhibiting the ubiquitin-proteasome pathway, thereby exerting a multi-dimensional and holistic anti-cachexia effect.

Key words

cancer cachexia / data mining / network pharmacology / molecular docking / HIF-1α / Poria / Atractylodis Macrocephalae Rhizoma / Astragali Radix / Dioscoreae Rhizoma / Glycyrrhizae Radix et Rhizoma Praeparata cum Melle / quercetin

引用本文

陈晟, 段熔辉, 刘正艺, 胡宇翔, 肖望重, 文静, 杨仁义, 孙银辉, 王理槐. 基于数据挖掘、网络药理学和动物实验探究中药治疗癌症恶病质用药规律及作用机制. 中草药, 2026 , 57 (6) : 2216 -2233 . DOI: 10.7501/j.issn.0253-2670.2026.06.018

CHEN Sheng, DUAN Ronghui, LIU Zhengyi, HU Yuxiang, XIAO Wangzhong, WEN Jing, YANG Renyi, SUN Yinhui, WANG Lihuai. Exploring medication patterns and mechanisms of traditional Chinese medicines in treatment of cancer cachexia based on data mining, network pharmacology, and animal experiments[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (6) : 2216 -2233 . DOI: 10.7501/j.issn.0253-2670.2026.06.018

基金

收起

国家科技重大专项 (2024ZD0521301); 湖南省中医肿瘤临床研究中心平台项目 (2021SK4023); 2024年湖南中医药大学研究生创新课题项目 (2024CX111)

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

Muscaritoli M, Rossi Fanelli F, Molfino A. Perspectives of health care professionals on cancer cachexia: Results from three global surveys[J]. Ann Oncol, 2016, 27(12): 2230-2236.
Fearon K, Strasser F, Anker S D, et al. Definition and classification of cancer cachexia: An international consensus[J]. Lancet Oncol, 2011, 12(5): 489-495.
Zhang X Y, Qiu H, Li C S, et al. The positive role of traditional Chinese medicine as an adjunctive therapy for cancer[J]. Biosci Trends, 2021, 15(5): 283-298.
孙银辉, 何晓, 李涵宇, 等. 扶正口服液对诱导性癌症恶病质裸鼠骨骼肌中ERAD/ERSIA通路的影响[J]. 湖南中医药大学学报, 2022, 42(11): 1816-1822.
王理槐, 窦娴, 陈晟, 等. 扶正口服液通过内质网应激途径改善癌症恶病质肌肉萎缩的机制研究[J]. 湖南中医药大学学报, 2022, 42(11): 1809-1815.
Feng S Q, Wang G J, Zhang J W, et al. Combined treatment with apatinib and docetaxel in A549 xenograft mice and its cellular pharmacokinetic basis[J]. Acta Pharmacol Sin, 2018, 39(10): 1670-1680.
Li L, Wazir J, Huang Z Q, et al. A comprehensive review of animal models for cancer cachexia: Implications for translational research[J]. Genes Dis, 2023, 11(6): 101080.
Alves C, Goodyear L, Brum P. Muscle metabolic stress determines cancer cachexia severity in mice[J]. Front Physiol, 2022, 13: 1033932.
徐叔云. 药理实验方法学[M]. 第3版. 北京: 人民卫生出版社, 2002: 983.
Wang D L, Chen W Q, Bi Q Y, et al. Baoyuan Jiedu decoction alleviates cancer-induced myotube atrophy by regulating mitochondrial dynamics through p38 MAPK/PGC-1α signaling pathway[J]. Front Oncol, 2020, 10: 523577.
Kantarci A, Kansal S, Hasturk H, et al. Resolvin E1 reduces tumor growth in a xenograft model of lung cancer[J]. Am J Pathol, 2022, 192(10): 1470-1484.
Dodson S, Baracos V E, Jatoi A, et al. Muscle wasting in cancer cachexia: Clinical implications, diagnosis, and emerging treatment strategies[J]. Annu Rev Med, 2011, 62: 265-279.
Der-Torossian H, Wysong A, Shadfar S, et al. Metabolic derangements in the gastrocnemius and the effect of Compound A therapy in a murine model of cancer cachexia[J]. J Cachexia Sarcopenia Muscle, 2013, 4(2): 145-155.
Brown J L, Rosa-Caldwell M E, Lee D E, et al. Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice[J]. J Cachexia Sarcopenia Muscle, 2017, 8(6): 926-938.
Muthamil S, Kim H Y, Jang H J, et al. Understanding the relationship between cancer associated cachexia and hypoxia-inducible factor-1[J]. Biomed Pharmacother, 2023, 163: 114802.
Devine R D, Bicer S, Reiser P J, et al. Increased hypoxia-inducible factor-1α in striated muscle of tumor-bearing mice[J]. Am J Physiol Heart Circ Physiol, 2017, 312(6): H1154-H1162.
Schwarzkopf M, Coletti D, Sassoon D, et al. Muscle cachexia is regulated by a p53-PW1/Peg3-dependent pathway[J]. Genes Dev, 2006, 20(24): 3440-3452.
Robert F, Mills J R, Agenor A, et al. Targeting protein synthesis in a Myc/mTOR-driven model of anorexia- cachexia syndrome delays its onset and prolongs survival[J]. Cancer Res, 2012, 72(3): 747-756.
Geremia A, Sartori R, Baraldo M, et al. Activation of Akt-mTORC1 signalling reverts cancer-dependent muscle wasting[J]. J Cachexia Sarcopenia Muscle, 2022, 13(1): 648-661.
Minagawa K, Wakahashi K, Fukui C, et al. Tfl deletion induces extraordinary Cxcl13 secretion and cachexia in VavP-Bcl2 transgenic mice[J]. Front Immunol, 2023, 14: 1197112.
Trott O, Olson A J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading[J]. J Comput Chem, 2010, 31(2): 455-461.
陈海彬, 周红光, 李文婷, 等. 网络药理学: 中药复方作用机制研究新视角[J]. 中华中医药杂志, 2019, 34(7): 2873-2876.
Baracos V E, Martin L, Korc M, et al. Cancer-associated cachexia[J]. Nat Rev Dis Primers, 2018, 4: 17105.
张兆洲, 冯媛媛, 王炎. 癌毒传舍的中医病机探讨[J]. 中医肿瘤学杂志, 2024, 6(2): 8-16.
曲一玮, 李晓, 王怀哲, 等. 基于“虚则卫气不足, 劳则营气竭”论恶病质的中医防治[J]. 中国中医基础医学杂志, 2023, 29(12): 2001-2004.
王胜男, 孔智谦, 周智慧, 等. 基于数据挖掘、网络药理和分子对接分析中药组方治疗梅尼埃病的作用机制[J]. 中草药, 2025, 56(6): 2066-2078.
冯宇, 呼健. 肿瘤恶病质的中医分期诊治思路探析[J]. 中华中医药杂志, 2023, 38(11): 5333-5335.
Al-Khayri J M, Sahana G R, Nagella P, et al. Flavonoids as potential anti-inflammatory molecules: A review[J]. Molecules, 2022, 27(9): 2901.
Li X, Wei S Z, Niu S Q, et al. Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Huanglian Jiedu Decoction against sepsis[J]. Comput Biol Med, 2022, 144: 105389.
VanderVeen B N, Cardaci T D, Cunningham P, et al. Quercetin improved muscle mass and mitochondrial content in a murine model of cancer and chemotherapy-induced cachexia[J]. Nutrients, 2022, 15(1): 102.
Shibuya S, Watanabe K, Sakuraba D, et al. Natural compounds that enhance motor function in a mouse model of muscle fatigue[J]. Biomedicines, 2022, 10(12): 3073.
Chang X, Zhang T, Meng Q Y, et al. Quercetin improves cardiomyocyte vulnerability to hypoxia by regulating SIRT1/TMBIM6-related mitophagy and endoplasmic reticulum stress[J]. Oxid Med Cell Longev, 2021, 2021: 5529913.
Wang Y, Quan F, Cao Q H, et al. Quercetin alleviates acute kidney injury by inhibiting ferroptosis[J]. J Adv Res, 2020, 28: 231-243.
Liu L Y, Hu R, You H Y, et al. Formononetin ameliorates muscle atrophy by regulating myostatin-mediated PI3K/Akt/FoxO3a pathway and satellite cell function in chronic kidney disease[J]. J Cell Mol Med, 2021, 25(3): 1493-1506.
Boonmuen N, Gong P, Ali Z, et al. Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities[J]. Steroids, 2016, 105: 42-49.
Zhang Z X, Lin M, Wang J L, et al. Calycosin inhibits breast cancer cell migration and invasion by suppressing EMT via BATF/TGF-β1[J]. Aging, 2021, 13(12): 16009-16023.
Tian W, Wang Z W, Yuan B M, et al. Calycosin induces apoptosis in osteosarcoma cell line via ERβ-mediated PI3K/Akt signaling pathways[J]. Mol Med Rep, 2020, 21(6): 2349-2356.
Zhao X G, Li X, Ren Q Y, et al. Calycosin induces apoptosis in colorectal cancer cells, through modulating the ERβ/MiR-95 and IGF-1R, PI3K/Akt signaling pathways[J]. Gene, 2016, 591(1): 123-128.
Liu Y, Piao X J, Xu W T, et al. Calycosin induces mitochondrial-dependent apoptosis and cell cycle arrest, and inhibits cell migration through a ROS-mediated signaling pathway in HepG2 hepatocellular carcinoma cells[J]. Toxicol In Vitro, 2021, 70: 105052.
Mazumder S, Higgins P J, Samarakoon R. Downstream targets of VHL/HIF-α signaling in renal clear cell carcinoma progression: Mechanisms and therapeutic relevance[J]. Cancers, 2023, 15(4): 1316.
Taneja N, Chauhan A, Kulshreshtha R, et al. HIF-1 mediated metabolic reprogramming in cancer: Mechanisms and therapeutic implications[J]. Life Sci, 2024, 352: 122890.
Nagao A, Kobayashi M, Koyasu S, et al. HIF-1-dependent reprogramming of glucose metabolic pathway of cancer cells and its therapeutic significance[J]. Int J Mol Sci, 2019, 20(2): 238.
Schönberger T, Fandrey J, Prost-Fingerle K. Ways into understanding HIF inhibition[J]. Cancers, 2021, 13(1): 159.
Infantino V, Santarsiero A, Convertini P, et al. Cancer cell metabolism in hypoxia: Role of HIF-1 as key regulator and therapeutic target[J]. Int J Mol Sci, 2021, 22(11): 5703.
Dong S H, Liang S, Cheng Z Q, et al. ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer[J]. J Exp Clin Cancer Res, 2022, 41(1): 15.
郝羚伦, 张艳, 彭梦薇, 等. 六君子汤改善肿瘤环境下C2C12成肌细胞分化的分子机制[J]. 中华中医药学刊, 2025, 43(1): 122-127.
张艳, 桑亚洲, 彭梦薇, 等. 六君子汤调控STAT3/泛素蛋白酶体途径防治肺癌恶病质小鼠肌肉萎缩的机制[J]. 中国实验方剂学杂志, 2022, 28(5): 8-15.
张俊荚, 赵家彬, 张同兴. 补中益气颗粒联合醋酸甲地孕酮改善晚期癌症患者恶液质临床观察[J]. 中国中医药信息杂志, 2009, 16(6): 77-78.
Xu B B, Cheng Q Q, So W K W. Review of the effects and safety of traditional Chinese medicine in the treatment of cancer cachexia[J]. Asia Pac J Oncol Nurs, 2021, 8(5): 471-486.
Stitt T N, Drujan D, Clarke B A, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors[J]. Mol Cell, 2004, 14(3): 395-403.
Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy[J]. Cell, 2004, 117(3): 399-412.
Nishimura Y, Chunthorng-Orn J, Lord S, et al. Ubiquitin E3 ligase Atrogin-1 protein is regulated via the rapamycin-sensitive mTOR-S6K1 signaling pathway in C2C12 muscle cells[J]. Am J Physiol Cell Physiol, 2022, 323(1): C215-C225.
Sartori R, Romanello V, Sandri M. Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease[J]. Nat Commun, 2021, 12(1): 330.

2026年第57卷第6期

PDF下载

引用本文

BibTeX

文章信息

doi: 10.7501/j.issn.0253-2670.2026.06.018

接收时间：2025-11-08
首发时间：2026-09-09

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2025-11-08

基金

作者信息

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/zcy/CN/10.7501/j.issn.0253-2670.2026.06.018

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

关闭全屏

BibTeX
EndNote
RefWorks
TxT