Naringin / p27/CDKN1B 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)
p27/CDKN1B, p27kip1: Click to Expand ⟱
Source:
Type:
The cyclin-dependent kinase (Cdk) inhibitor p27 regulates cell proliferation, cell motility and apoptosis, and is inactivated through various means in many types of human cancer.

CDKN1B - Cyclin-Dependent Kinase Inhibitor 1B / p27

Abbreviation: CDKN1B, p27, p27Kip1

Type: Cyclin-dependent kinase inhibitor / cell-cycle regulator

Function: CDKN1B/p27 inhibits cyclin-CDK complexes, particularly cyclin E-CDK2 and cyclin A-CDK2, thereby restricting G1/S cell-cycle progression. It also regulates differentiation, transcription, cytoskeletal organization, cell migration, and cellular responses to growth-factor signaling.

Cancer: ↕ Context-dependent, but predominantly tumor-suppressive. Reduced nuclear p27 expression or functional loss can promote uncontrolled proliferation, tumor progression, and treatment resistance. However, cytoplasmic p27 can acquire CDK-independent pro-oncogenic functions that promote cell motility, invasion, and aggressive tumor behavior.
Scientific Papers found: Click to Expand⟱
1015- NarG,    Naringin induces endoplasmic reticulum stress-mediated apoptosis, inhibits β-catenin pathway and arrests cell cycle in cervical cancer cells
- in-vitro, Cerv, SiHa - in-vitro, Cerv, HeLa - in-vitro, Cerv, C33A
ER Stress↑, p‑eIF2α↑, CHOP/DDIT3↑, PARP1↑, Casp3↑, β-catenin/ZEB1↓, GSK‐3β↓, p‑β-catenin/ZEB1↓, p‑GSK‐3β↓, TumCCA↑, P21↑, p27/CDKN1B↑,

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:


Cell Death(tgid=5) ⓘ

Casp3↑, 1,   p27/CDKN1B↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

PARP1↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

P21↑, 1,   TumCCA↑, 1,  

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

GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,  

Migration(tgid=13) ⓘ

β-catenin/ZEB1↓, 1,   p‑β-catenin/ZEB1↓, 1,  
Total Targets: 12

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: p27/CDKN1B, p27kip1
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#:468  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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