# Atlas‐Based Mapping of Traditional Chinese Medicine Effects on Tumor Microcirculation Regulation

**Authors:** I Ho, Yijie Xie, Zhipeng Liu, Dingjun Cai

PMC · DOI: 10.1002/iid3.70347 · 2026-02-04

## TL;DR

This paper explores how Traditional Chinese Medicine affects tumor microcirculation, identifying key formulations and mechanisms that could aid cancer treatment.

## Contribution

The study provides a systematic analysis of TCM's effects on tumor microcirculation using bibliometric and knowledge-map approaches.

## Key findings

- TCM formulations like Tao Hong Si Wu Decoction modulate angiogenesis via VEGF, PI3K/AKT, and HIF-1α pathways.
- Non-pharmacological TCM methods normalize vascular structure and reshape immune polarization.
- Network pharmacology and molecular docking are increasingly used to understand TCM mechanisms.

## Abstract

Tumor microcirculation plays a central role in the onset and progression of hypoxia, therapeutic resistance, and immune evasion within the tumor microenvironment. Traditional Chinese Medicine (TCM), characterized by its multi‐targeted and systemic regulatory properties, has garnered increasing attention for its potential to modulate this complex milieu.

We systematically retrieved core literature published between 2003 and 2025 and conducted a comprehensive bibliometric and knowledge‐map analysis of 300 representative publications using CiteSpace and VOSviewer. This approach enabled the identification of key modulatory factors, underlying mechanisms, and evolving research trajectories related to TCM‐mediated regulation of tumor microcirculation.

Our findings reveal that TCM formulations and their active constituents—such as Tao Hong Si Wu Decoction, ginsenoside Rg3, and tanshinone IIA—modulate angiogenesis and enhance immune cell infiltration through signaling pathways including VEGF, PI3K/AKT, and HIF‐1α. Additionally, non‐pharmacological interventions such as acupuncture, electroacupuncture, and moxibustion have been shown to normalize vascular structure, modulate glycolytic activity, and reshape immune polarization. Emerging methodologies such as network pharmacology and molecular docking are increasingly utilized to unravel the complex mechanisms of TCM, facilitating the integration of traditional theories with modern scientific frameworks.

TCM exhibits a remarkable capacity for multidimensional regulation of tumor microcirculation. Future efforts should focus on rigorous experimental validation and systems‐level modeling to accelerate its clinical translation and incorporation into integrative cancer therapy.

## Linked entities

- **Proteins:** VEGFA (vascular endothelial growth factor A), HIF1A (hypoxia inducible factor 1 subunit alpha)
- **Chemicals:** ginsenoside Rg3 (PubChem CID 9918693), tanshinone IIA (PubChem CID 164676)

## Full-text entities

- **Genes:** ENO1 (enolase 1) [NCBI Gene 2023] {aka ENO1-IT1, ENO1L1, HEL-S-17, MPB1, NNE, PPH}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, NRP1 (neuropilin 1) [NCBI Gene 8829] {aka BDCA4, CD304, NP1, NRP, VEGF165R}, GLO1 (glyoxalase I) [NCBI Gene 2739] {aka GLOD1, GLYI, HEL-S-74}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}
- **Diseases:** Cell lung cancer (MESH:D055752), hypoxic (MESH:D002534), lung cancer (MESH:D008175), Metastasis (MESH:D009362), vascular abnormalities (MESH:D014652), hepatocellular carcinoma (MESH:D006528), Cancer (MESH:D009369), toxicity (MESH:D064420), breast cancer (MESH:D001943), gastric cancer (MESH:D013274), Hypoxia (MESH:D000860), phlegm syndrome (MESH:D013577), Inflammation (MESH:D007249)
- **Chemicals:** astragaloside IV (MESH:C052064), curcumin (MESH:D003474), myricetin (MESH:C040015), indirubin (MESH:C027185), Bevacizumab (MESH:D000068258), Tanshinone IIA (MESH:C021751), Bai Zhu lactone I (-), ginsenosides (MESH:D036145), ginsenoside Rg3 (MESH:C097367), cisplatin (MESH:D002945), glucose (MESH:D005947), artemisinin (MESH:C031327), lactate (MESH:D019344)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12872975/full.md

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Source: https://tomesphere.com/paper/PMC12872975