Hyperoside / TumCI Cancer Research Results

HYP, Hyperoside: Click to Expand ⟱
Features:
Hyperoside is a chemical compound and a quercetin galactoside. It is found in various plants and has antibacterial, antifungal and UV blocking properties.
Hyperoside is an active ingredient in plants, such as Hypericum monogynum in Hypericaceae, Crataegus pinnatifida in Rosaceae and Polygonum aviculare in Polygonaceae.
Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam.
**-Note NRF2 up in normal cells and down in cancer cells**
-not currently available as supplement, but it is in Hawthorn Extract. (Natural factors lists it as hyperoside equilvalents 6.6mg/300mg)

Hyperoside — also known as hyperin and quercetin-3-O-β-D-galactoside, is a naturally occurring flavonol glycoside consisting of quercetin conjugated at the 3-position to β-D-galactose. It is found in numerous medicinal and dietary plants including species of Hypericum, Crataegus, Polygonum, and Rhododendron. It is classified as a plant-derived flavonoid/polyphenolic small molecule. Hyperoside has antioxidant and cytoprotective activity in many normal-cell models but can produce cancer-selective stress responses, apoptosis, autophagy, and ferroptosis depending on tumor type and concentration. Its aglycone is quercetin.

Primary mechanisms (ranked):

  1. Apoptosis induction through mitochondrial dysfunction, Bax/Bcl-2 modulation, cytochrome-c release, and caspase-9/caspase-3 activation.
  2. PI3K/AKT/mTOR suppression with autophagy induction; ATG13-mediated autophagy has recently been identified as an important mechanism in NSCLC.
  3. NF-κB pathway inhibition, reducing prosurvival and inflammatory signaling and promoting apoptotic susceptibility.
  4. Redox modulation with strong context dependence: hyperoside can suppress excessive ROS in breast-cancer and normal-cell models, while in other tumor contexts oxidative stress contributes to cytotoxicity.
  5. NRF2/SLC7A11/GPX4 suppression and ferroptosis induction in chronic myeloid leukemia; this contrasts with NRF2 activation and antioxidant cytoprotection in many normal-cell models.
  6. MAPK modulation including p38/JNK-mediated mitochondrial apoptosis and context-dependent ERK regulation.
  7. Cell-cycle arrest through p53/p21 and related regulatory pathways.
  8. Suppression of tumor-cell migration, invasion, EMT, and inflammatory signaling.
  9. Radiosensitization through suppression of STAT3/AKT/ERK signaling demonstrated preclinically in esophageal carcinoma.

Bioavailability / PK relevance: Oral bioavailability of intact hyperoside appears poor. Rat studies found very low systemic exposure after intragastric administration, with substantially greater exposure after parenteral administration. Hyperoside is relatively resistant to gastrointestinal hydrolysis compared with isoquercitrin, which may limit absorption of its quercetin aglycone. Distribution studies indicate preferential accumulation in kidney relative to several other organs. Nanoparticle and liposomal formulations have therefore been investigated to improve delivery and tumor or mitochondrial accumulation. Long-term high-dose exposure warrants caution because renal toxicity has been reported preclinically.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM hyperoside, while some autophagy studies have used 0.5–2 mM. These concentrations, particularly the millimolar experiments, are unlikely to represent achievable concentrations of unchanged hyperoside following conventional oral administration. Consequently, direct translation of many in-vitro anticancer effects to oral supplementation is weak without an exposure-enhancing formulation.

Clinical evidence status: Preclinical. Anticancer activity has been demonstrated in multiple cancer-cell systems and several mouse xenograft or chemically induced tumor models, including lung, breast, pancreatic, skin, liver, colorectal, esophageal, and hematologic malignancy models. There is currently no established human anticancer efficacy, approved oncology indication, or convincing interventional clinical evidence for purified hyperoside. FDA substance registration identifies hyperoside chemically but does not constitute drug approval.

Hyperoside Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 Mitochondrial apoptosis ↑ Bax/Bcl-2; ↑ cytochrome c; ↑ caspase-9; ↑ caspase-3; ↓ mitochondrial membrane potential Often ↔ or cytoprotective at lower concentrations Apoptotic cell death Observed across lung, pancreatic and colorectal models; one of the most reproducible anticancer effects.
2 PI3K/AKT/mTOR signaling ↓ PI3K; ↓ AKT; ↓ mTOR; ↓ p70S6K; ↓ 4E-BP1 Context-dependent ↓ survival signaling; ↑ autophagy and apoptosis Strongly demonstrated in NSCLC and skin-cancer models.
3 Autophagy and ATG13 ↑ ATG13; ↑ LC3-II; ↑ autophagosomes ↔ in some comparative epithelial-cell experiments Autophagy-associated tumor suppression Recent NSCLC data support ATG13-mediated autophagy as an upstream contributor to apoptosis.
4 NF-κB inflammatory and survival signaling ↓ NF-κB activation; ↓ inflammatory cytokines; ↓ prosurvival signaling ↓ excessive inflammatory activation (context-dependent) ↑ apoptosis; ↓ inflammation and tumor progression Repeatedly reported in lung, pancreatic and breast models.
5 NRF2/SLC7A11/GPX4 ferroptosis axis ↓ NRF2; ↓ SLC7A11; ↓ GPX4; ↑ lipid oxidative stress ↑ NRF2/HO-1 in oxidative-stress models ↑ ferroptosis Important context-dependent differential effect. Direct NRF2 targeting has been reported in chronic myeloid leukemia, whereas normal cells commonly show NRF2 activation.
6 Redox regulation ↑ or ↓ ROS (context-dependent) ↓ excessive ROS; ↑ antioxidant defenses Context-dependent oxidative stress or antioxidant protection ROS direction is not uniform across cancer types. Breast-cancer studies report ↓ ROS, whereas some colorectal and ferroptotic models depend on increased oxidative stress.
7 p38/JNK mitochondrial stress signaling ↑ p38; ↑ JNK (model-dependent) Context-dependent ↑ mitochondrial apoptosis Particularly demonstrated in A549 NSCLC cells.
8 p53/p21 cell-cycle control ↑ p53; ↑ p21; ↑ G1 or G2/M arrest (model-dependent) Context-dependent ↓ proliferation Reported in colorectal and lung models; exact arrest point varies with model.
9 EGFR/ERK/FOXO1 signaling ↓ EGFR/ERK signaling; ↑ FOXO1 Unclear ↓ proliferation; ↑ apoptosis Recent NSCLC work identifies this axis as a potential therapeutic mechanism; T790M-positive NSCLC also shows FOXO1 upregulation.
10 Migration invasion and EMT ↓ migration; ↓ invasion; ↓ mesenchymal phenotype; ↑ E-cadherin Unclear ↓ metastatic phenotype Observed across several solid-tumor models including lung and esophageal carcinoma.
11 Radiosensitization ↑ radiation sensitivity; ↓ STAT3/AKT/ERK Insufficient evidence ↑ radiation-induced tumor control Demonstrated preclinically in esophageal carcinoma cells and mouse tumors; not clinically validated.
12 Clinical Translation Constraint Low oral exposure Potential renal accumulation with prolonged high-dose exposure Limits systemic translation Poor oral bioavailability and frequent use of high micromolar to millimolar experimental concentrations are major limitations. Targeted nanoparticles and liposomes may improve exposure.


Hyperoside and Alzheimer's disease: Hyperoside has significant preclinical neuroprotective evidence in Alzheimer's disease models. Long-term administration in APP/PS1 transgenic mice improved spatial learning and memory and reduced amyloid plaque deposition, tau phosphorylation, activated microglia and astrocytes, neuroinflammation, and oxidative stress. Mechanistic evidence implicates suppression of BACE1 and GSK-3β, protection of the blood-brain barrier, inhibition of mitochondrial and caspase-dependent apoptosis, and broader antioxidant/anti-inflammatory effects. Evidence remains preclinical; clinical efficacy in human Alzheimer's disease has not been established.

Hyperoside Alzheimer's-Relevant Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Amyloid and BACE1 ↓ BACE1; ↓ Aβ deposition ↓ amyloid pathology Demonstrated in APP/PS1 mice following chronic treatment.
2 GSK-3β and tau ↓ GSK-3β activity/signaling; ↓ tau phosphorylation ↓ tau pathology Provides a mechanistic connection between hyperoside treatment and reduced pathological tau phosphorylation.
3 Neuroinflammation ↓ activated microglia; ↓ activated astrocytes; ↓ inflammatory signaling ↓ neuroinflammation Observed in chronic APP/PS1 treatment studies.
4 Oxidative stress and NRF2 ↓ ROS; ↑ NRF2/HO-1 antioxidant defenses (context-dependent) Neuronal protection NRF2 activation is well established in non-cancer oxidative-stress models and is mechanistically consistent with hyperoside's neuroprotective phenotype.
5 Blood-brain barrier integrity ↑ ZO-1; ↑ claudin-5; ↑ occludin; ↓ MMP-2; ↓ MMP-9 ↓ Aβ-induced BBB disruption Demonstrated primarily in Aβ-exposed brain endothelial-cell models.
6 Mitochondrial apoptosis ↓ Bax/Bcl-2; ↓ cytochrome c release; ↓ caspase activation ↓ neuronal and endothelial apoptosis Opposite therapeutic direction to its pro-apoptotic action in cancer cells.
7 Clinical Translation Constraint Low oral bioavailability; uncertain human CNS exposure Limits clinical inference No established human AD efficacy; brain exposure and therapeutically relevant human dosing remain poorly defined.


TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
Scientific Papers found: Click to Expand⟱
7569- HYP,    Inhibitory effects of hyperoside on lung cancer by inducing apoptosis and suppressing inflammatory response via caspase-3 and NF-κB signaling pathway
- vitro+vivo, Lung, A549
TumCP↓, TumCMig↓, TumCI↓, Casp3↑, Apoptosis↑, NF-kB↓, TNF-α↓, IL6↓, IL1β↓, IL18↓, TumVol↓, TumW↓,
7568- HYP,  PacT,    Administration with hyperoside sensitizes breast cancer cells to paclitaxel by blocking the TLR4 signaling
- in-vitro, BC, MDA-MB-231
Inflam↓, AntiTum↑, selectivity↑, chemoP↑, TumCI↓, ChemoSen↑, tumCV↓, Apoptosis↑, Casp3↑, TLR4↓, NF-kB↓,
7567- HYP,    Hyperoside: A review on its sources, biological activities, and molecular mechanisms
- Review, Var, NA
*AntiCan↑, *Bacteria↓, *AntiViral↑, *antiD↓, *RenoP↑, *hepatoP↑, *eff↑, *Sepsis↓, *AntiArt↑, *Stroke↓, TumCMig↓, TumCI↓, MTA1↓, TIMP2↓, MMP2↓, MMP↓, Cyt‑c↑, Akt↓, mTOR↓, P70S6K↓, TumAuto↑, PD-L1↓, TNF-α↓, IL1β↓, IL6↓, IL8↓, Bcl-2↓, Bcl-xL↓, BAX↑, BAD↑, Bak↑, VEGF↓, Casp3↑, Casp8↑, P53↑, GSH↓, SOD↓, Catalase↓, TAC↓, XIAP↓, ROS↓, NF-kB↓, TLR4↓, P-gp/ABCB1↓, LRP1↓, Fas↑, p27/CDKN1B↑, *cardioP↑, *AntiThr↑, *PAI-1/SERPINE1↓, *BUN↓, *ALAT↓, *AST↓, *neuroP?,
7549- HYP,  Rad,    Study on the mechanism of hyperoside in affecting the biological progression and radiosensitivity of esophageal carcinoma by modulating the STAT3/AKT/ERK pathway
- vitro+vivo, ESCC, TE1 - vitro+vivo, ESCC, KYSE150
TumCP↓, TumCI↓, TumCMig↓, EMT↓, Apoptosis↑, RadioS↑, p‑STAT3↓, p‑Akt↓, p‑ERK↓,
90- QC,  HYP,    Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA‑21
- in-vitro, Pca, PC3
ROS↑, cl‑Casp3↑, cl‑PARP↑, miR-21↓, PDCD4↑, TAC↑, tumCV↓, TumCI↓,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

MTA1↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   GSH↓, 1,   ROS↓, 1,   ROS↑, 1,   SOD↓, 1,   TAC↓, 1,   TAC↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,   XIAP↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 3,   BAD↑, 1,   Bak↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 1,   Cyt‑c↑, 1,   Fas↑, 1,   p27/CDKN1B↑, 1,   PDCD4↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

miR-21↓, 1,   tumCV↓, 2,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,   cl‑PARP↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

EMT↓, 1,   p‑ERK↓, 1,   mTOR↓, 1,   P70S6K↓, 1,   p‑STAT3↓, 1,  

Migration(tgid=13) ⓘ

LRP1↓, 1,   MMP2↓, 1,   TIMP2↓, 1,   TumCI↓, 5,   TumCMig↓, 3,   TumCP↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL18↓, 1,   IL1β↓, 2,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 3,   PD-L1↓, 1,   TLR4↓, 2,   TNF-α↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 2,   PD-L1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiTum↑, 1,   chemoP↑, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 61

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiArt↑, 1,   antiD↓, 1,   Stroke↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   BUN↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

AntiThr↑, 1,  

Migration(tgid=13) ⓘ

PAI-1/SERPINE1↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cardioP↑, 1,   hepatoP↑, 1,   neuroP?, 1,   RenoP↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1,   Bacteria↓, 1,   Sepsis↓, 1,  
Total Targets: 18

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
5 Hyperoside
1 Paclitaxel/Taxol
1 Radiotherapy/Radiation
1 Quercetin
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:97  Target#:324  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

Home Page