Naringin / P53 Cancer Research Results

NarG, Naringin: Click to Expand ⟱
Features:
Flavonoid glycoside. Responsible for the bitterness of grapefruit.
Naringin is a flavonoid glycoside predominantly found in citrus fruits such as grapefruit and oranges. It is known for its antioxidant, anti-inflammatory, and potential anticancer properties.
It is hydrolyzed in vivo to naringenin, which exhibits antioxidant and anti-inflammatory activities and modulates signaling pathways (e.g., Nrf2 and NF-κB). In preclinical cancer models, naringin/naringenin is associated with cell-cycle arrest, apoptosis, and reduced invasion/metastasis, often linked to upstream modulation of survival pathways (PI3K/AKT) and stress MAPKs. Oral systemic exposure is limited due to metabolism and conjugation.
-Antioxidant Activity
-Induction of Apoptosis
-Cell Cycle Arrest (often G1 or G2/M)
-Anti-inflammatory Effects

-**a natural bioenhancer(effects vary) and reported to enhance the bioavailability of drugs by inhibiting cytochrome P450 (CYP3A4 especially grape fruit juice) and P-glycoprotein (P-gp). Naringin/naringenin can inhibit CYP3A4 and P-glycoprotein, contributing to grapefruit–drug interactions and potentially increasing exposure of certain medications.
-Usually paired with other bioflavonoids such as quercetin, hesperidin and rutin.

-Mainly obtained from grapefruit
-Including enhanced solubility, improved bioavailability and targeted delivery.
-Antioxidant
-Inhibition of CYP19(weak/modest). Naringin suppresses the PI3K/AKT signalling pathway
-Wnt/β-catenin, PI3K/Akt, NF-ĸB, and TGF-β pathways
-Up-regulation of adenosine monophosphate-activated protein kinase (AMPK), and inhibition of gluconeogenesis
-Antioxidant effects, by modulating reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD)
-Naringenin can reduce carcinogenesis through pleiotropic processes such as antioxidative, apoptotic-inducing ROS generation, and cell cycle arrest
-Revealed new mechanisms underlying the hypolipidemic effects of naringin and naringenin, including regulation of lipid digestion, reverse cholesterol transport, and low-density lipoprotein receptor expression
-Low bioavailability (approximately 8.8%) when administered orally. Bioavailability: citrus flavonoid glycosides are hydrolyzed in the gut; systemic plasma levels are often much lower than in vitro MICs.

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Nrf2/ARE antioxidant response Stress adaptation modulation (context-dependent) Nrf2 ↑; antioxidant enzymes ↑ R, G Endogenous antioxidant upshift Naringin and its aglycone naringenin are widely reported to activate Nrf2, elevate HO-1 and other antioxidant defenses, and reduce oxidative injury in many models.
2 NF-κB inflammatory signaling NF-κB ↓; pro-inflammatory cytokines ↓ (reported) Inflammation tone ↓ R, G Anti-inflammatory signaling Consistent evidence shows naringin/naringenin reduces pro-inflammatory signaling and cytokine expression in tumor and non-tumor contexts.
3 PI3K/AKT/mTOR survival axis PI3K/AKT ↓ (reported; model-dependent) R, G Growth/survival modulation Modulation of survival pathways is observed in various cancer‐cell studies, but effects vary by cell type and context.
4 Cell cycle control (Cyclins/CDKs) Cell-cycle arrest ↑ (G1/S or G2/M; reported) G Cytostasis Often reported as reduced proliferation and cell cycle arrest following upstream signaling changes.
5 Intrinsic apoptosis (mitochondrial/caspase linked) Apoptosis ↑; caspase activation ↑ (reported) G Execution of cell death Observed in many in vitro models, usually downstream of signaling modulation and stress pathways.
6 MAPK re-wiring (ERK / JNK / p38) MAPK modulation (context-dependent) P, R, G Stress/mitogenic signaling adjustment MAPK effects vary by assay and cell type; avoid fixed up/down arrows without a specific citation.
7 Invasion / metastasis programs (MMPs/EMT) MMPs ↓; migration/invasion ↓ (reported) G Anti-invasive phenotype Downstream phenotype changes reported in some models; linked to NF-κB/MAPK modulation.
8 Angiogenesis signaling (VEGF & related) Angiogenic outputs ↓ (reported) G Anti-angiogenic support Later phenotype outcomes; direction is often model-dependent.
9 Reactive oxygen species modulation Redox buffering; ROS direction variable P, R, G Redox modulation (context-dependent) Naringin is classically antioxidant; ROS changes in cancer models vary and are not reliably pro-oxidant under typical conditions.
10 Bioavailability / metabolism constraint Systemic exposure limited; rapid metabolism/conjugation Translation constraint Naringin’s glycoside form is hydrolyzed to naringenin; phase II conjugates circulate. Native systemic levels are often low compared with in vitro effective concentrations.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (rapid biochemical/signaling interactions)
  • R: 30 min–3 hr (acute signaling and transcription modulation)
  • G: >3 hr (gene-regulatory adaptation and phenotype outcomes)


P53, P53-Guardian of the Genome: Click to Expand ⟱
Source: TCGA
Type: Proapototic
TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures.
p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers.
Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53.
In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein.
Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.


Scientific Papers found: Click to Expand⟱
1807- NarG,    A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies
- Review, NA, NA
AntiTum↑, TumCP↓, tumCV↓, TumCCA↑, Mcl-1↓, RAS↓, e-Raf↓, VEGF↓, AntiAg↑, MMP2↓, MMP9↓, TIMP2↑, TIMP1↑, p38↓, Wnt↓, β-catenin/ZEB1↑, Casp↑, P53↑, BAX↑, COX2↓, GLO-I↓, CYP1A1↑, lipid-P↓, p‑Akt↓, p‑mTOR↓, VCAM-1↓, P-gp↓, survivin↓, Bcl-2↓, ROS↑, ROS↑, MAPK↑, STAT3↓, chemoP↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

CYP1A1↑, 1,   lipid-P↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics

e-Raf↓, 1,  

Core Metabolism/Glycolysis

GLO-I↓, 1,  

Cell Death

p‑Akt↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp↑, 1,   MAPK↑, 1,   Mcl-1↓, 1,   p38↓, 1,   survivin↓, 1,  

Transcription & Epigenetics

tumCV↓, 1,  

DNA Damage & Repair

P53↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

p‑mTOR↓, 1,   RAS↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration

AntiAg↑, 1,   MMP2↓, 1,   MMP9↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCP↓, 1,   VCAM-1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature

VEGF↓, 1,  

Barriers & Transport

P-gp↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,  

Functional Outcomes

AntiTum↑, 1,   chemoP↑, 1,  
Total Targets: 33

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: P53, P53-Guardian of the Genome
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#:128  Target#:236  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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