Isovitexin / mTOR 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.


mTOR, mammalian target of rapamycin: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
mTOR (mechanistic target of rapamycin) is a central regulator of cell growth, proliferation, metabolism, and survival. It is a serine/threonine kinase that integrates signals from nutrients, growth factors, and cellular energy status.
mTOR promotes protein synthesis and cell growth by activating downstream targets such as S6 kinase and 4E-BP1. In cancer, this pathway can become hyperactivated, leading to uncontrolled cell proliferation.

mTor Inhibitors:
-rapamycin (Sirolimus): classic natural product mTOR inhibitor
-Curcumin
-Resveratrol
-Epigallocatechin Gallate (EGCG)
-Honokiol
Scientific Papers found: Click to Expand⟱
7912- IVT,    Isovitexin modulates autophagy in Alzheimer’s disease via miR-107 signalling
- in-vivo, AD, NA
*memory↑, IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ)
*Aβ↓,
*NeuroI↓, neuroinflammation
*PI3K↓, via the inhibition of PI3K/Akt/mTOR signalling axis.
*Akt↓,
*mTOR↓,
*miR-107↑, ascinatingly, we observed that miR-107 expression was significantly (P < 0.05) reinstated by the treatment with IVX against the downregulation of miR-107 expression in AD mice

7896- IVT,  VT,    Molecular targets of vitexin and isovitexin in cancer therapy: a critical review
- Review, Var, NA
chemoPv↑, Both in vitro and in vivo studies suggest that vitexin and isovitexin are chemopreventive compounds with activity against various cancers through proapoptotic processes and/or autophagy.
Dose↝, Vitexin and isovitexin are the main constituents of the fruits of Cucurbitaceae, mung beans (Vigna radiata), pigeon pea leaves (Cajanus cajan Millsp.), bamboo leave
ACE/ACE1↓, Experimental studies showed that flavone C-glycosides act as angiotensin-converting enzyme (ACE) inhibitors and have vasodilatory, -blocking, and/ or Ca 2+ channel-blocking activities.
Ca+2↓,
*iNOS↓, C-glycosides reduced lipopolysaccharide-induced proinflammatory cytokine secretion, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression
*COX2/PTGS2↓,
*ROS↓, and reactive oxygen species (ROS) generation
*Stroke↓, provide protective effects against myocardial ischemia–reperfusion injury.
Apoptosis↑, Vitexin-triggered apoptosis was generally accompanied by a decrease in mitochondrial membrane potential and Bcl-2 protein levels, as well as an increase in caspase-3 and caspase-9 protein expression.
MMP↓,
Bcl-2↓,
Casp3↑,
Casp9↑,
TumAuto↑, In heat stress–related research, vitexin promoted autophagy through the upregulation of Hsp90 expression and subsequent activation of endoplasmic reticulum stress.
HSP90↑,
ER Stress↑,
Hif1a↓, vitexin and isovitexin was found in PC12 and CORL-23 cells by inhibiting hypoxia-inducible factor 1 (HIF-1a)
TumMeta↓, resulting in the reduction of the metastatic prospective of PC12 and CORL-23 cells and angiogenesis.
angioG↓, They are prominent antiangiogenic potential agents
Tf↓, Isovitexin and vitexin were found to bind to transferrin (TF), 38 one type of iron-binding glycoprotein that is highly expressed in fast-growing cells, including cancer cells
MAPK↓, Molecular targets for flavone C-glycosides comprise the mitogenactivated protein kinase (MAPK), protein kinase C (PKC), PI3K-Akt, and -catenin pathways
PI3K↓,
Akt↓,
β-catenin/ZEB1↓,
TumCCA↑, Vitexin inhibited growth and induced cell cycle arrest at G1 /G0 by regulating the Akt/FOXO3a pathway
FOXO3↓,
mTOR↓, Vitexin inhibits choriocarcinoma via inducing cell apoptosis and suppressing the mTOR pathway

7892- IVT,    Isovitexin attenuates tumor growth in human colon cancer cells through the modulation of apoptosis and epithelial-mesenchymal transition via PI3K/Akt/mTOR signaling pathway
- in-vitro, Nor, HCEC 1CT - in-vivo, Colon, NA
TumCP↓, Isov inhibited cancer cell proliferation but had little cytotoxicity on HCECs.
selectivity↑,
TumCMig↓, Isov significantly attenuated cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and induced cell apoptosis.
TumCI↓,
EMT↓,
Apoptosis↑,
p‑PI3K↓, The expression levels of phosphorylated phosphatidylinositol 3-kinasep (p-PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and B cell lymphoma-2 (Bcl-2) decreased when treated with Isov
p‑Akt↓,
p‑mTOR↓,
Bcl-2↓,
BAX↑, while the levels of Bcl2-associated X (Bax) and caspase-3 significantly increased
Casp3↑,
TumVol↓, the tumor volume and weight were decreased, and the levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2 significantly decreased in tumor tissues.
TumW↓,

7824- MBS,  IVT,  VT,    Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review
- Review, AD, NA - Review, Stroke, NA - Review, Park, NA
*neuroP↑, it was speculated that vitexin, isovitexin, sinapic acid, and ferulic acid might be the major bioactive compounds for mung bean-mediated neuroprotection.
*Aβ↓, inhibition of β-amyloidogenesis, tau hyperphosphorylation, oxidative stress, and neuroinflammation, and promotion of autophagy and acetylcholinesterase enzyme activity.
*p‑tau↓,
*ROS↓,
*Inflam↓,
*AChE↓, vitexin significantly inhibited the activity of AChE in vitro, with an IC 50 of 12.16 μM.
*BBB↑, Notably, considerable levels of vitexin and isovitexin were detected in the brain, indicating their ability to cross the blood brain barrier (BBB)
*memory↑, Another study showed that mung bean sprout possessed anti-Alzheimer potential as evidenced by the improved short-term and long-term memory as well as inhibited AChE activity and oxidative stress after administering mung bean sprout for 15 days in mic
*hepatoP↑, That is, except for neuroprotection, mung bean can also provide several other health benefits, such as hepatoprotection, immunomodulation, antihyperglycemia, antihyperlipidemia, antihypertension, and anticancer
*Imm↑,
*hyperG↓,
*AntiCan↑,
*eff↑, neuroprotective potential of seed coat extract might be much stronger than that of cotyledon extract.
*Stroke↓, Vitexin showed great activities in improving CNS-related diseases, including AD, ischemic stroke, and Parkinson’s disease.
*BACE/β-secretase↓, vitexin suppressed the production of Aβ through downregulating the activity of β-secretase (BACE-1) with an IC 50 of 51.07 μM in vitro
*PI3K↓, Isovitexin was found to inhibit the activation of the PI3K/AKT/mTOR pathway, which might explain the molecular targets for isovitexin.
*Akt↓,
*mTOR↓,
*Dose↓, At the fifth day of sprouting, contents of vitexin and isovitexin decreased by 3.7 and 9.3 times, respectively


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Metal & Cofactor Biology(tgid=2) ⓘ

Tf↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 2,   BAX↑, 1,   Bcl-2↓, 2,   Casp3↑, 2,   Casp9↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 1,   p‑Akt↓, 1,   MAPK↓, 1,   mTOR↓, 1,   p‑mTOR↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

FOXO3↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 1,   HSP90↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

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

TumCP↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↓, 1,   EMT↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Barriers & Transport(tgid=15) ⓘ

MMP↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

ACE/ACE1↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,   selectivity↑, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoPv↑, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 34

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

hyperG↓, 1,   ROS↓, 2,  

Cell Death(tgid=5) ⓘ

iNOS↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 2,   mTOR↓, 2,   PI3K↓, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

miR-107↑, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   Imm↑, 1,   Inflam↓, 1,   NeuroI↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2,   BACE/β-secretase↓, 1,   p‑tau↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↓, 1,   eff↑, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   hepatoP↑, 1,   memory↑, 2,   neuroP↑, 1,   Stroke↓, 2,  
Total Targets: 23

Scientific Paper Hit Count for: mTOR, mammalian target of rapamycin
4 Isovitexin
2 Vitexin
1 Mung Bean Sprouts
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#:209  State#:%  Dir#:1
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