Isovitexin / HO-1 Cancer Research Results

IVT, Isovitexin: Click to Expand ⟱
Features:

Isovitexin - Apigenin-6-C-Glucoside

Alternative Names: Apigenin-6-C-glucoside, apigenin-6-C-β-D-glucopyranoside

Type: Flavone C-glycoside / apigenin derivative

Function: Isovitexin is a naturally occurring C-glycosylated flavone and positional isomer of vitexin, with glucose attached to apigenin at the C-6 position. It exhibits antioxidant, anti-inflammatory, metabolic, neuroprotective, and antiproliferative activities and can influence NF-κB, Nrf2, MAPK, PI3K/AKT, AMPK, apoptotic, and oxidative-stress signaling.

-similar to Vitexin

Isovitexin — Isovitexin (IVT; ISV; IVX), also known as apigenin-6-C-glucoside or 6-C-β-D-glucopyranosylapigenin, is a naturally occurring C-glycosylated flavone and positional isomer of vitexin, in which glucose is attached to apigenin at carbon 6 rather than carbon 8. It occurs in food and medicinal plants including mung bean, rice, passionflower, and other botanical sources. It is formally classified as a flavone C-glycoside / apigenin derivative. Compared with vitexin, isovitexin has a smaller but distinct experimental literature and should be maintained as a separate compound. Anticancer activity remains preclinical.
-buckwheat sprouts contain orientin, isoorientin, vitexin, isovitexin, and rutin

Primary mechanisms (ranked):

  1. Suppression of PI3K/AKT/mTOR survival signaling, associated with reduced proliferation, migration, invasion, EMT, and increased apoptosis.
  2. Mitochondrial apoptosis through Bax induction, Bcl-2/Mcl-1 suppression, cytochrome-c release, caspase-3 activation, and PARP cleavage.
  3. ER-stress-driven apoptosis and pro-death autophagy involving IRE1α/XBP1s, GRP78, CHOP, Beclin-1, ATG3/ATG5, and LC3-II.
  4. Suppression of cancer stemness, including miR-34a induction and reduction of CD44, ABCG2, ALDH1, and NANOG.
  5. Inhibition of EMT, migration, and invasion, substantially linked to PI3K/AKT/mTOR suppression in colorectal cancer models.
  6. ROS/NRF2 modulation is strongly context-dependent: isovitexin generally decreases ROS and activates NRF2/HO-1 in nonmalignant oxidative-injury models; a generalized pro-oxidant anticancer mechanism has not been established for isovitexin.
  7. Suppression of inflammatory MAPK/NF-κB signaling in nonmalignant inflammatory models.
  8. CYP17A1 inhibition has recently been proposed in breast cancer, but current evidence is substantially less mature than the apoptosis and PI3K/AKT/mTOR evidence.

Bioavailability / PK relevance: Oral exposure is a significant translational limitation. C-glycosylation gives isovitexin greater chemical stability than many O-glycosides, but direct intestinal absorption is limited and substantial material reaches the intestine for microbial metabolism. Rat studies demonstrate absorption and broad tissue distribution after oral plant-extract administration, while intravenous isovitexin has a plasma half-life of approximately 1 hour and distributes particularly to kidney, intestine, and liver. Human isovitexin-specific PK data are not established.

In-vitro vs systemic exposure relevance: Many mechanistic experiments use micromolar concentrations that may be difficult to reproduce as circulating unchanged isovitexin after ordinary dietary or oral exposure. Consequently, high-concentration cell-culture findings should not be interpreted as demonstrating clinically achievable anticancer activity. Intestinal exposure and metabolites may be more pharmacologically relevant after oral administration.

Clinical evidence status: Preclinical. Anticancer evidence consists primarily of cell studies and rodent/xenograft experiments. No established human anticancer efficacy, randomized clinical trial evidence, or approved oncology indication was identified. Isovitexin has an FDA substance identifier but this does not constitute drug approval. Long-term human safety, therapeutic dosing, drug interactions, and cancer-specific pharmacokinetics remain insufficiently defined.

Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 PI3K AKT mTOR survival signaling ↓ p-PI3K, ↓ p-AKT, ↓ p-mTOR Context-dependent ↓ proliferation, ↓ survival, ↓ invasion, ↑ apoptosis Strong direct evidence in colon cancer and also implicated in experimental AD. IGF-1 partially reverses anticancer effects, supporting pathway involvement.
2 Mitochondrial apoptosis ↑ Bax, ↑ cytochrome-c release, ↑ caspase-3, ↑ PARP cleavage, ↓ Bcl-2, ↓ Mcl-1 ↓ apoptosis during oxidative injury ↑ cancer-cell apoptosis Direction differs appropriately by cellular context: pro-apoptotic in malignant cells but cytoprotective in several nonmalignant injury models.
3 ER stress and unfolded protein response ↑ IRE1α, ↑ XBP1s, ↑ GRP78, ↑ CHOP Not established ↑ apoptosis and autophagy ER-stress inhibition substantially reverses isovitexin-induced apoptosis and autophagy in liver cancer cells, supporting a causal mechanism.
4 Autophagy ↑ Beclin-1, ↑ ATG3, ↑ ATG5, ↑ LC3-II Context-dependent ↑ pro-death autophagy In hepatoma models, autophagy facilitates rather than protects against isovitexin-induced apoptosis. Autophagy can be protective in neurological injury models.
5 Cancer stemness and miR-34a ↑ miR-34a, ↓ CD44, ↓ ABCG2, ↓ ALDH1, ↓ NANOG Not established ↓ stemness and apoptosis resistance Demonstrated in SK-Hep-1 hepatocellular carcinoma spheroids. miR-34a inhibition attenuates isovitexin activity.
6 EMT migration and invasion ↓ EMT, ↓ migration, ↓ invasion Little cytotoxicity reported in normal colonic epithelial cells ↓ metastatic phenotype Closely linked to PI3K/AKT/mTOR inhibition in colorectal cancer models.
7 ROS and oxidative stress Context-dependent ↓ ROS, ↓ MDA, ↑ GSH, ↑ SOD Antioxidant cytoprotection Unlike isoorientin, a robust ROS↑ anticancer mechanism should not currently be assigned to isovitexin. Most direct isovitexin evidence supports ROS↓ in nonmalignant oxidative-stress models.
8 NRF2 HO-1 antioxidant response Not established as a core anticancer mechanism ↑ NRF2, ↑ HO-1 ↑ antioxidant defense Secondary/contextual mechanism demonstrated in lung, liver, kidney, ageing, and oxidative-injury models.
9 NF-κB and MAPK inflammatory signaling Context-dependent ↓ NF-κB, ↓ MAPK activation ↓ inflammatory signaling Well supported in inflammatory injury models but substantially less established as a direct cancer-cell mechanism.
10 CYP17A1 ↓ CYP17A1 activity Not established Potential ↓ steroidogenic growth signaling Recent breast-cancer evidence combines computational target identification with experimental MCF-7 evaluation. Treat as emerging rather than core.
11 Clinical Translation Constraint High experimental concentrations; no demonstrated therapeutic human exposure Human systemic PK and long-term safety insufficiently characterized Limits clinical extrapolation Low gastrointestinal absorption, extensive intestinal disposition and metabolism, lack of cancer trials, and absence of validated clinical dosing are major constraints.


Alzheimer's disease relevance: Isovitexin has meaningful but entirely preclinical AD relevance. Direct evidence includes inhibition of AChE and BChE in biochemical assays, protection against Aβ-induced neuronal toxicity, and improvement of cognition, Aβ burden, neuroinflammation, and autophagic dysfunction in an STZ-induced mouse model. The latter study links benefit to miR-107-mediated suppression of PI3K/AKT/mTOR signaling. These findings justify retaining AD as a disease category, but they do not establish clinical efficacy.

Primary mechanisms (ranked):

  1. miR-107-mediated suppression of PI3K/AKT/mTOR and restoration of autophagic regulation.
  2. Reduction of experimental Aβ burden and Aβ-associated neuronal toxicity.
  3. Reduction of neuroinflammation, including TNF-α, IL-6, and caspase-1 signaling.
  4. AChE and BChE inhibition in biochemical assays.
  5. Antioxidant/neuroprotective activity and protection from excitotoxic injury.

Clinical evidence status: Preclinical only. No human Alzheimer's disease efficacy data or validated therapeutic dosing were identified.

Alzheimer's Disease Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 miR-107 PI3K AKT mTOR ↑ miR-107, ↓ PI3K/AKT/mTOR Improved autophagic regulation and cognition Mechanistically supported in an STZ-induced mouse AD model using antagomiR-107.
2 Amyloid beta pathology ↓ Aβ ↓ amyloid burden and toxicity Reduced Aβ burden in the mouse AD model and protected PC12 cells from Aβ25-35 toxicity.
3 Autophagy Normalization of LC3-II, ATG7 and Beclin-1 Improved proteostatic function Direction is better represented as normalization rather than simply ↑ or ↓ because AD-associated autophagic dysfunction is model-dependent.
4 Neuroinflammation ↓ TNF-α, ↓ IL-6, ↓ caspase-1 ↓ inflammatory neuronal injury Demonstrated in the STZ mouse model.
5 Cholinesterases ↓ AChE, ↓ BChE Potential preservation of cholinergic signaling Direct biochemical inhibition; clinical relevance and achievable brain concentration are unknown.
6 Excitotoxic neuronal injury ↓ glutamate-induced neurotoxicity ↑ neuronal survival Observed in mouse hippocampal slice experiments.
7 Clinical Translation Constraint Human efficacy and CNS exposure not established Limits AD translation Oral bioavailability and human brain exposure are uncertain; all disease-specific evidence remains experimental.


HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
Scientific Papers found: Click to Expand⟱
7890- IVT,    Isovitexin protects against cisplatin-induced kidney injury in mice through inhibiting inflammatory and oxidative responses
- in-vivo, Nor, NA
RenoP↑, *BUN↓, *creat↓, *TNF-α↓, *IL1β↓, *IL6↓, *MDA↓, *ROS↓, *NF-kB↓, *NRF2↑, *HO-1↑,
7888- IVT,    Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways
- vitro+vivo, Nor, NA
*Inflam↓, *iNOS↓, *COX2/PTGS2↓, *ROS↓, *Apoptosis↓, *p‑MAPK↓, *NF-kB↓, *NRF2↑, *HO-1↑, *ICAM-1↓, *VCAM-1↓, *MPO↓, *MDA↓, *GSH↑, *SOD↑,
7887- VT,  IVT,    Dietary Flavonoids Vitexin and Isovitexin: New Insights into Their Functional Roles in Human Health and Disease Prevention
- Review, AD, NA - Review, Var, NA
*antiOx↑, *Inflam↓, *AntiCan↑, *Bacteria↓, *neuroP↑, *Obesity↓, *cardioP↑, *ROS↓, *MMP↑, *ATP↑, *MFN2↑, *DRP1/DNM1L↓, *FOXO3↑, *NRF2↑, *Ferroptosis↓, *GPx4↑, TumCP↓, HMGB1↓, PI3K↓, Akt↓, Hif1a↓, CDK1↓, CycB/CCNB1↓, TumCCA↑, Apoptosis↑, P53↑, NF-kB↓, ERK↓, p‑PI3K↓, miR-34a↑, Apoptosis↑, CSCs?, *MAPK↓, *HO-1↑, *hepatoP↑, *AMPK↑, *Akt↑, *GSK‐3β↑, *chemoP↑, *Casp3↓, *IRes↝, *GlucoseCon↑, ChemoSen↑, *GSH↑, *SOD↑, *ATF2↑, *GPx↑, *GSTs↑, *AntiAge↑, *Stroke↓, *AChE↓, *ACE/ACE1↓, *ACE2↓, *GutMicro↑, *MPO↓, *H+/K+-ATPase↓, *AntiDiabetic↑, *GLUT4↑, *Obesity↓, *HH↓, *RenoP↑, *BioAv↓, *BioAv↝, *BioAv↑,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 1,   CycB/CCNB1↓, 1,   TumCCA↑, 1,  

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

CSCs?, 1,   ERK↓, 1,   miR-34a↑, 1,   PI3K↓, 1,   p‑PI3K↓, 1,  

Migration(tgid=13) ⓘ

TumCP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

HMGB1↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,  

Functional Outcomes(tgid=23) ⓘ

RenoP↑, 1,  
Total Targets: 17

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

ACE/ACE1↓, 1,   ACE2↓, 1,   H+/K+-ATPase↓, 1,   IRes↝, 1,   Stroke↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Ferroptosis↓, 1,   GPx↑, 1,   GPx4↑, 1,   GSH↑, 2,   GSTs↑, 1,   HO-1↑, 3,   MDA↓, 2,   MFN2↑, 1,   MPO↓, 2,   NRF2↑, 3,   ROS↓, 3,   SOD↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,   DRP1/DNM1L↓, 1,   MMP↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,   BUN↓, 1,   GlucoseCon↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↑, 1,   Apoptosis↓, 1,   ATF2↑, 1,   Casp3↓, 1,   Ferroptosis↓, 1,   iNOS↓, 1,   MAPK↓, 1,   p‑MAPK↓, 1,  

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

FOXO3↑, 1,   GSK‐3β↑, 1,   HH↓, 1,  

Migration(tgid=13) ⓘ

VCAM-1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT4↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   ICAM-1↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 2,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioAv↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

creat↓, 1,   GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1,   AntiCan↑, 1,   AntiDiabetic↑, 1,   cardioP↑, 1,   chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   Obesity↓, 2,   RenoP↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,  
Total Targets: 61

Scientific Paper Hit Count for: HO-1, HMOX1
3 Isovitexin
1 Vitexin
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#:463  Target#:597  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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