Naringin / CYP19 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)
CYP19, aromatase: Click to Expand ⟱
Source:
Type:
CYP19, also known as aromatase, is an enzyme that plays a crucial role in the biosynthesis of estrogens by converting androgens (such as testosterone and androstenedione) into estrogens (such as estradiol and estrone). The activity of CYP19 is significant in various tissues, including the ovaries, testes, adipose tissue, and the brain.

-Estrogen Production: Elevated levels of estrogens, which can result from increased CYP19 activity, are associated with the development and progression of certain cancers, particularly estrogen receptor--positive breast cancer.
-Aromatase Inhibitors: In the treatment of hormone-sensitive breast cancer, aromatase inhibitors (such as anastrozole, letrozole, and exemestane) are commonly used. These drugs work by inhibiting the activity of CYP19, thereby reducing estrogen levels and slowing the growth of estrogen-dependent tumors.
Scientific Papers found: Click to Expand⟱
1801- NarG,    A Narrative Review on Naringin and Naringenin as a Possible Bioenhancer in Various Drug-Delivery Formulations
- Review, Var, NA
AntiCan↓, CYP19↓, PI3K↓, Akt↓, TumAuto↑, eff↑, BioEnh↑,
1800- NarG,    Naringenin
- Human, Nor, NA
CYP19↓,
981- NarG,  QC,    Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer
- in-vivo, NA, NA
TumVol↓, CYP19↓,

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 ⓘ

Akt↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CYP19↓, 3,  

Drug Metabolism & Resistance ⓘ

BioEnh↑, 1,   eff↑, 1,  

Functional Outcomes ⓘ

AntiCan↓, 1,   TumVol↓, 1,  
Total Targets: 8

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CYP19, aromatase
3 Naringin
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#:128  Target#:75  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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