# Research progress on mechanisms and applications of Chinese herbal pairs in treating hyperplasia of mammary gland

**Authors:** Lu Liu, Yuxuan Zhang, Wei Shen, Wanyu Li, Xudong Lei, Xiaoyan Dai

PMC · DOI: 10.3389/fphar.2025.1704606 · Frontiers in Pharmacology · 2026-02-11

## TL;DR

This paper reviews how traditional Chinese herbal pairs treat mammary gland hyperplasia by regulating hormones, inflammation, and cell balance.

## Contribution

The study systematically identifies four core pathways through which TCM herbal pairs treat HMG, combining multiple research methods.

## Key findings

- Herbal pairs regulate estrogen/progesterone signaling and reduce inflammation via NF-κB, IL-6, and TNF-α.
- They restore cell proliferation-apoptosis balance through PI3K/Akt, MAPK, and Bcl-2/Bax pathways.
- Clinically, they show 70–85% efficacy in reducing breast pain and lumps with fewer side effects than tamoxifen.

## Abstract

Hyperplasia of Mammary gland (HMG), a common gynecological disorder with potential malignant transformation risk, has been effectively treated using Traditional Chinese Medicine (TCM) herbal pairs. This systematic review explores the therapeutic effects and underlying mechanisms of eight classic Traditional Chinese Medicine (TCM) herbal pairs in treating hyperplasia of mammary glands (HMG). A systematic literature search was performed in PubMed (English) and CNKI (Chinese) from January 2010 to August 2025; peer-reviewed studies with clear designs (e.g., animal models, in vitro experiments, clinical case series) focusing on herbal pairs’ pharmacological mechanisms or clinical applications in the treatment of HMG were included. By integrating network pharmacology, molecular biology, preclinical experiments, and clinical evidence, we found that these herbal pairs exert combined regulatory effects through four core pathways: specifically, 1. hormonal regulation by modulating estrogen/progesterone signaling; 2. anti-inflammation by suppressing NF-κB, IL-6, and TNF-α; 3. restoring proliferation-apoptosis balance via PI3K/Akt, MAPK, and Bcl-2/Bax; 4. alleviating oxidative stress by enhancing SOD/GSH-Px activities. Preclinically, they inhibit mammary cell proliferation in a dose-dependent manner; clinically, they alleviate breast pain and reduce breast lumps with an efficacy rate of 70%–85% and fewer side effects than tamoxifen. These findings validate the scientific basis of TCM herbal pair compatibility and support future translational research (e.g., multi-center randomized controlled trials).

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], IL6 (interleukin 6) [NCBI Gene 3569], TNF (tumor necrosis factor) [NCBI Gene 7124], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], MAPK (mitogen activated kinase-like protein) [NCBI Gene 7446652], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], SOD1 (superoxide dismutase 1) [NCBI Gene 6647], Gpx1 (glutathione peroxidase 1) [NCBI Gene 24404]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, Prl (prolactin) [NCBI Gene 24683] {aka Gha1, PRLB, PRLSD1, Prl1a1, Prol, RATPRLSD1}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Rps6 (ribosomal protein S6) [NCBI Gene 29304], Faslg (Fas ligand) [NCBI Gene 25385] {aka Apt1Lg1, CD95-L, Fasl, Tnfsf6, Tnlg1a}, Hmox1 (heme oxygenase 1) [NCBI Gene 24451] {aka HEOXG, Heox, Hmox, Ho-1, Ho1, hsp32}, ESR2 (estrogen receptor 2) [NCBI Gene 2100] {aka ER-BETA, ESR-BETA, ESRB, ESTRB, Erb, NR3A2}, NOX4 (NADPH oxidase 4) [NCBI Gene 50507] {aka KOX, KOX-1, RENOX}, PRKCB (protein kinase C beta) [NCBI Gene 5579] {aka PKC-beta, PKCB, PKCI(2), PKCbeta, PRKCB1, PRKCB2}, Fgf2 (fibroblast growth factor 2) [NCBI Gene 54250] {aka Fgf-2, Fgf2a, bFGF}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, Bcl2l1 (Bcl2-like 1) [NCBI Gene 24888] {aka Bcl-xl, Bcl2l, Bclx, bcl-X}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], Tlr4 (toll-like receptor 4) [NCBI Gene 29260], Cdk6 (cyclin-dependent kinase 6) [NCBI Gene 114483], Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Hras (HRas proto-oncogene, GTPase) [NCBI Gene 293621] {aka HRAS1, c-H-ras}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, Gpx1 (glutathione peroxidase 1) [NCBI Gene 24404] {aka GSHPx, GSHPx-1}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], Il17a (interleukin 17A) [NCBI Gene 301289] {aka CTLA-8, IL-17, IL-17A, Il17}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Foxo3 (forkhead box O3) [NCBI Gene 294515] {aka Fkhrl1, Foxo3a}, Esr2 (estrogen receptor 2) [NCBI Gene 25149] {aka ER-beta, ERbeta, Erb2}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Pten (phosphatase and tensin homolog) [NCBI Gene 50557] {aka MMAC1, Mmac, TEP1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Casp9 (caspase 9) [NCBI Gene 58918] {aka Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Esr1 (estrogen receptor 1) [NCBI Gene 24890] {aka ER-alpha, Esr, RNESTROR}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, Egfr (epidermal growth factor receptor) [NCBI Gene 24329] {aka ERBB1, ErbB-1, Errp}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, Fdxr (ferredoxin reductase) [NCBI Gene 79122] {aka AR}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, PRLR (prolactin receptor) [NCBI Gene 5618] {aka HPRL, MFAB, RI-PRLR, hPRLrI}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], Pgr (progesterone receptor) [NCBI Gene 25154], Ccnd1 (cyclin D1) [NCBI Gene 58919], Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, Traf6 (TNF receptor associated factor 6) [NCBI Gene 311245], Cdk4 (cyclin-dependent kinase 4) [NCBI Gene 94201], Nqo1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 24314] {aka Dia4}
- **Diseases:** fibrosis (MESH:D005355), bitter taste (MESH:D013651), Chronic liver depression (MESH:D058625), metastasis (MESH:D009362), thrombotic (MESH:D013927), Inflammation (MESH:D007249), breast pain (MESH:D059373), atherosclerosis (MESH:D050197), scrofula (MESH:D014388), blood (MESH:D006402), pain (MESH:D010146), Breast Hyperplasia (MESH:D061325), cancer (MESH:D009369), endocrine dysfunction (MESH:D004700), lumps (MESH:C536531), phlegm coagulation (MESH:D001778), swelling (MESH:D004487), anxiety (MESH:D001007), cough (MESH:D003371), toxicity (MESH:D064420), endometrial hyperplasia (MESH:D004714), gynecological disorder (MESH:D005831), dry throat (MESH:C538390), depression (MESH:D003866), breast cancer (MESH:D001943), spleen deficiency (MESH:D013160), estrogen (MESH:D056828), hyperplastic (MESH:D000082242), uterine fibroids (MESH:D007889), sores (MESH:D063806), blood stasis (MESH:D014647), liver depression (MESH:D017093), TCM (MESH:C562377), SAM (OMIM:615508), fever (MESH:D005334), Mammary Gland Hyperplasia (MESH:D006965), goiter (MESH:D006042), kidney deficiency (MESH:D007680), Hyperplastic Diseases of the Breast (MESH:D001941), convulsions (MESH:D012640), chronic (MESH:D002908), accumulation syndromes (MESH:C579880), mass syndromes (MESH:C536030), microcirculation disorder (MESH:D009358)
- **Chemicals:** Curcumin (MESH:D003474), inosine (MESH:D007288), nandrolone (MESH:D009277), mansumbinoic acid (MESH:C079929), Angelicae Sinensis (-), naringin (MESH:C005274), Z-ligustilide (MESH:C027820), hesperidin (MESH:D006569), cortisol (MESH:D006854), saikosaponin C (MESH:C025759), Icariin (MESH:C056599), Quercetin (MESH:D011794), Amino acids (MESH:D000596), beta-sitosterol (MESH:C025473), Myrrh (MESH:C587573), polysaccharides (MESH:D011134), E2 (MESH:D004958), Tamoxifen (MESH:D013629), MDA (MESH:D008315), guggulsterone (MESH:C023617), Bergapten (MESH:D000078223), d-limonene (MESH:D000077222), kaempferol (MESH:C006552), steroid (MESH:D013256), neohesperidin (MESH:C546526), AGEs (MESH:D017127), Curcuminoids (MESH:D036381), tyrosine (MESH:D014443), Volatile oils (MESH:D009822), iodine (MESH:D007455), Ursolic Acid (MESH:C005466), nucleosides (MESH:D009705), PGE2 (MESH:D015232), Frankincense (MESH:D065260), sesquiterpenes (MESH:D012717), bromocriptine (MESH:D001971), lipid (MESH:D008055), boswellic acid (MESH:C054625), progesterone (MESH:D011374), beta-elemene (MESH:C445979), P4 (MESH:C015586), Isorhamnetin (MESH:C047368), luteolin (MESH:D047311), baicalin (MESH:C038044), ROS (MESH:D017382), borneol (MESH:C022871), curcumol (MESH:C022801), stigmasterol (MESH:D013265), flavonoids (MESH:D005419)
- **Species:** Sparganium stoloniferum (species) [taxon 203643], Atractylodes macrocephala (species) [taxon 265785], Bupleurum (genus) [taxon 46366], Curcuma (genus) [taxon 99568], Mus musculus (house mouse, species) [taxon 10090], Citrus x aurantium (bitter orange, species) [taxon 43166], Angelica sinensis (Chinese angelica, species) [taxon 165353], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Epimedium brevicornu (species) [taxon 253618], Cremastra appendiculata (species) [taxon 459596], Bupleurum chinense (species) [taxon 52451], Cervus elaphus (red deer, species) [taxon 9860], Myrrha (genus) [taxon 524508], Prunella vulgaris (common self-heal, species) [taxon 39358], Cyperus rotundus (species) [taxon 512623]
- **Cell lines:** MCF-10A — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0598), HBL-100 — Homo sapiens (Human), Transformed cell line (CVCL_4362)

## Full text

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## Figures

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## References

99 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932594/full.md

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Source: https://tomesphere.com/paper/PMC12932594