Database Query Results : Piperine, ,

PI, Piperine: Click to Expand ⟱
Features:
Compound of black pepper that boosts bioavailability of curcumin

piperine’s bioenhancing function, often more important than piperine’s direct anticancer activity
Mechanisms of bioenhancement
| Mechanism                     | Effect                             |
| ----------------------------- | ---------------------------------- |
| **↓ CYP3A4, CYP2C9**          | Slows metabolic clearance          |
| **↓ UGT (glucuronidation)**   | Increases parent compound exposure |
| **↓ P-glycoprotein (ABCB1)**  | Improves intracellular retention   |
| **↑ Intestinal permeability** | Better oral absorption             |

-Curcumin: ↑ bioavailability ~20–30×
-Resveratrol, EGCG, quercetin: ↑ exposure 2–10×

Primary pathways: NF-κB, STAT3, PI3K/Akt/mTOR, apoptosis, EMT
Direct anticancer potency: modest
Bioenhancing value: central and often dominant
Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 Wnt / β-catenin signaling ↓ Wnt/β-catenin (↓ β-catenin nuclear program) Growth & stemness suppression Piperine suppresses canonical Wnt signaling and shows anti-cancer effects in colorectal cancer cells (ref)
2 PI3K → AKT survival signaling ↓ PI3K/AKT signaling Reduced survival / increased apoptosis Gastric cancer study concludes piperine inhibits proliferation and induces apoptosis through inhibition of PI3K/Akt signaling (ref)
3 AKT → mTOR axis ↓ Akt/mTOR Anti-growth + anti-migration Piperine downregulates Akt/mTOR signaling with associated inhibition of migration and MMP-9 expression (ref)
4 NF-κB transcriptional program ↓ NF-κB activation Reduced inflammatory / pro-survival gene expression Piperine is reported as a potent inhibitor of NF-κB and related transcription factor activity in melanoma cells (ref)
5 STAT3 → Snail EMT axis ↓ STAT3 / ↓ Snail → ↓ EMT Anti-migration / anti-invasion Piperine inhibits colorectal cancer migration/invasion through a STAT3/Snail-mediated EMT mechanism (ref)
6 Multidrug resistance transporter ABCB1 (P-gp) ↓ P-gp-mediated efflux (chemosensitization) Improved chemo response (MDR reversal) Demonstrates piperine has chemosensitizing activity in P-gp–mediated MDR models (piperine characterized as P-gp substrate/modulator) (ref)
7 ROS / oxidative stress ↑ ROS Upstream stress trigger Piperine induces oxidative stress in cancer cells (ROS increase shown) and links it to growth inhibition/apoptosis (ref)
8 Intrinsic apoptosis (caspase activation) ↑ apoptosis Programmed cell death HeLa study: piperine induces apoptosis in a dose-dependent manner with apoptosis markers reported (ref)
9 Autophagy-dependent cell death (ROS–Akt/mTOR coupling) ↑ autophagy-dependent death (with ↓ Akt/mTOR) Stress-lethal program Colon cancer study: piperine induces autophagy-dependent cell death by increasing ROS and inhibiting Akt/mTOR signaling (ref)
10 Cell-cycle progression ↑ cell-cycle arrest (context-dependent) Proliferation blockade Rectal cancer cell study: piperine impairs cell-cycle progression and produces cytostatic/cytotoxic effects (ref)
11 Migration / invasion (MMP-9 axis) ↓ migration / ↓ MMP-9 Anti-metastatic phenotype Piperine suppresses migration with MMP-9 downregulation and Akt/mTOR inhibition (ref)
12 In vivo chemosensitization (doxorubicin) ↑ doxorubicin sensitivity Enhanced therapeutic efficacy Study evaluates piperine as an adjuvant to enhance doxorubicin sensitivity in triple-negative breast cancer models (ref)


Scientific Papers found: Click to Expand⟱
5212- CAP,  PI,  Chemo,    Capsaicin and Piperine Can Overcome Multidrug Resistance in Cancer Cells to Doxorubicin
- in-vitro, Colon, Caco-2
ChemoSen↑, P-gp↓, eff↑,
3586- CUR,  PI,    Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers
- in-vivo, NA, NA
*BioAv↑,
3582- CUR,  PI,    Therapeutic and Preventive Effects of Piperine and its Combination with Curcumin as a Bioenhancer Against Aluminum-Induced Damage in the Astrocyte Cells
*eff↑, *IL6↓, *TGF-β↓, *BioAv↑,
3750- CUR,  PI,    Synergistic Effects of Curcumin and Piperine as Potent Acetylcholine and Amyloidogenic Inhibitors With Significant Neuroprotective Activity in SH-SY5Y Cells via Computational Molecular Modeling and in vitro Assay
- in-vitro, AD, SH-SY5Y
*AChE↓, *neuroP↑,
3760- CUR,  GI,  CAP,  RosA,  PI  Extending the lore of curcumin as dipteran Butyrylcholine esterase (BChE) inhibitor: A holistic molecular interplay assessment
*AChE↓, *other↓, *other↓, *other↓, *other↓, *other↓, *other↓,
649- EGCG,  CUR,  PI,    Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
*BioEnh↑, EGFR↓, HER2/EBBR2↓, IGF-1↓, MAPK↓, ERK↓, RAS↓, Raf↓, NF-kB↓, p‑pRB↓, TumCCA↑, Glycolysis↓, Warburg↓, HK2↓, Pyruv↓,
646- EGCG,  PI,    Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice
- in-vivo, Nor, NA
*BioAv↑,
3597- PI,    Chronic diseases, inflammation, and spices: how are they linked?
- Review, AD, NA - Review, Park, NA - Review, Var, NA
*NF-kB↓, *MAPK↓, *AP-1↓, *COX2↓, *NOS2↓, *IL1β↓, *TNF-α↓, *PGE2↓, *STAT3↓, *IL10↑, *IL4↓, *IL5↓, P53↑, MMP9↓, MMP2↓, cMyc↓, VEGF↓, STAT3↓, survivin↓, p65↓,
5216- PI,  doxoR,    Piperine enhances doxorubicin sensitivity in triple-negative breast cancer by targeting the PI3K/Akt/mTOR pathway and cancer stem cells
- vitro+vivo, BC, MDA-MB-231
ChemoSen↑, necrosis↑, PTEN↓, PI3K↓, p‑Akt↓, mTOR↓, ALDH↓, TumVol↓, OS↑, cardioP↑, cl‑PARP↑,
3598- PI,    Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer's disease
- in-vivo, AD, NA
*ROS↓, *Inflam↓, *cognitive↑, *Aβ↓, *tau↓,
3599- PI,    Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's disease
- in-vivo, AD, NA
*memory↑, *neuroP↑, *lipid-P↓, *AChE↓,
3600- PI,    Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer's disease: optimization, biological efficacy, and potential toxicity
- in-vivo, AD, NA
*neuroP↑,
4220- PI,    Piperine ameliorated memory impairment and myelin damage in lysolecethin induced hippocampal demyelination
- in-vivo, AD, NA - in-vivo, MS, NA
*memory↑, *iNOS↓, *NRF2↑, *HO-1↑, *TAC↑, *TNF-α↓, *IL1β↓, *NF-kB↓, *IL10↑, *FOXP3↑, *BDNF↑, other↑,
4221- PI,    Piperine-like alkamides from Piper nigrum induce BDNF promoter and promote neurite outgrowth in Neuro-2a cells
- in-vitro, NA, NA
*Mood↑, *BDNF↑,
4222- PI,    Potential of piperine for neuroprotection in sepsis-associated encephalopathy
- in-vivo, Sepsis, NA
*MMP9↓, *BDNF↑, *memory↑, *neuroP↑,
5208- PI,    Piperine Inhibits Cell Proliferation and Induces Apoptosis of Human Gastric Cancer Cells by Downregulating Phosphatidylinositol 3-Kinase (PI3K)/Akt Pathway
- in-vitro, GC, SNU16 - in-vitro, Nor, GES-1
TumCP↓, Apoptosis↑, BAX↑, BAD↑, Cyt‑c↑, cl‑PARP↑, cl‑Casp3↑, Bcl-2↓, Bcl-xL↓, p‑PI3K↓, p‑Akt↓, Ki-67↓, toxicity↓, RadioS↑,
5209- PI,    Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP-9 signaling pathway in DU145 cells
- in-vitro, Pca, DU145
TumCP↓, TumCMig↓, Apoptosis↑, p‑Akt↓, MMP9↓, p‑mTOR↓, TumMeta↓, *antiOx↓, *Inflam↓, *hepatoP↑, *Imm↑, *AntiCan↑,
5210- PI,    Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells
- in-vitro, Melanoma, B16-BL6
IL1β↓, TNF-α↓, MMPs↓, p65↓, p50↓, NF-kB↓, ATF2↓, cFos↓, CREB↓,
5211- PI,    Piperine inhibits colorectal cancer migration and invasion by regulating STAT3/Snail-mediated epithelial-mesenchymal transition
- in-vitro, CRC, NA
TumCMig↓, TumCI↓, EMT↓, Snail↓, STAT3↓,
5213- PI,    Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation
- in-vitro, Cerv, HeLa
Apoptosis↑, TumCG↓, ROS↑, MMP↓, DNAdam↑, Casp3↑, TumCCA↑, *Inflam↓, *antiOx↓, *hepatoP↑, ChemoSen↑, CSCs↓,
5214- PI,    Piperine induces autophagy of colon cancer cells: Dual modulation of AKT/mTOR signaling pathway and ROS production
- vitro+vivo, CRC, HCT116 - in-vitro, CRC, SW48 - in-vitro, CRC, SW-620
TumCP↓, TumAuto↑, Akt↓, mTOR↓, ROS↑,
5215- PI,    Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells
- in-vitro, CRC, NA
TumCCA↑, Apoptosis↑, ROS↑, eff↓, BioEnh↑,
3595- PI,    Black pepper and health claims: a comprehensive treatise
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *chemoP↑, TumCG↓, *cognitive↑, *MMPs↓, *PGE2↓, *AP-1↓, *5LO↓, *COX1↓, *other↑, *other↑, *other↑, *SOD↑, *Catalase↑, *GSTs↑, *GSR↑, *other↑, *Weight↓, *BioEnh↑, *BioAv↑, *eff↑, *CYP3A2↓, *neuroP↑, *BP↓, *other↑,
925- PI,    Bioenhancers from mother nature and their applicability in modern medicine
- Review, Nor, NA
*BioEnh↑,
1016- PI,    Piperine suppresses the Wnt/β-catenin pathway and has anti-cancer effects on colorectal cancer cells
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW480 - in-vitro, CRC, DLD1
β-catenin/ZEB1↓, Wnt↓, TumCP↓, TumCMig↓, *antiOx↑, *Inflam↓, *hepatoP↑, *neuroP↑, *Bacteria↓, *memory↑, AntiCan↑, NF-kB↓, cFos↓, ATF2↓, CREB↓,
1059- PI,    Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells
- in-vitro, Lung, A549 - in-vitro, BC, MDA-MB-231 - in-vitro, Liver, HepG2
EMT↓, p‑ERK↓, p‑SMAD2↓,
1131- PI,    Piperlongumine‑loaded nanoparticles inhibit the growth, migration and invasion and epithelial‑to‑mesenchymal transition of triple‑negative breast cancer cells
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, BT549
TumCG↓, tumCV↓, TumCMig↓, TumCI↓, MMP2↓, Slug↓, N-cadherin↓, β-catenin/ZEB1↓, SMAD3↓, E-cadherin↑, EMT↓,
1162- PI,    Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response
- in-vitro, NA, NA
*cPLA2↓, TXA2↓, COX2↓, PGE2↓, PGD2↓,
1163- PI,    The Effect of Piperine on MMP-9, VEGF, and E-cadherin Expression in Breast Cancer MCF-7 Cell Line
- in-vitro, BC, MC38
tumCV↓, VEGF↓, MMP9↓, E-cadherin↓,
1164- PI,    Inhibition of T cell activation by the phytochemical piperine
- in-vitro, Nor, NA
*other↓, *CD25+↓, *IFN-γ↓, *IL2↓, *IL4↓, *IL17↓, *CD69↓, *CTLA-4↓, *p‑ERK↓, *IKKα↓,
1165- PI,    Piperine inhibits IL-1β-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cells
- in-vitro, GC, TMK-1
p38↓, IL6↓, STAT3↓,
1254- PI,  VitC,    Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS–STAT3 pathway
- in-vivo, GC, NA
STAT3⇅, eff↑, ROS↑, Apoptosis↑,
1255- PI,  ALA,    Antileukemic effects of piperlongumine and alpha lipoic acid combination on Jurkat, MEC1 and NB4 cells in vitro
- in-vitro, CLL, NA
COX2↓, Casp3↑,
1256- PI,    Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models
- in-vitro, adrenal, PHEO - in-vivo, NA, NA
Apoptosis↑, ROS↑, TumCMig↓, TumCI↓, EMT↓, angioG↓, Necroptosis↑, MAPK↑, ERK↑,
1257- PI,    Piperlongumine attenuates bile duct ligation-induced liver fibrosis in mice via inhibition of TGF-β1/Smad and EMT pathways
- ex-vivo, LiverDam, NA
*Fibronectin↓, *α-SMA↓, *COL1↓, *COL3A1↓, *TGF-β↓, *EMT↓, *MMP2↓, *α-SMA↓, *Smad7↑, *E-cadherin↑, *Vim↓, *hepatoP↑, *antiOx↑, *GSH↑, *ROS↓,
1258- PI,    Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer
- in-vivo, CRC, NA
COX2↓, IL6↓, EMT↓, β-catenin/ZEB1↓, Snail↓, Symptoms∅,
3587- PI,    Piperine: A review of its biological effects
- Review, Park, NA - Review, AD, NA
*hepatoP↑, *Inflam↓, *neuroP↑, *antiOx↑, *angioG↑, *cardioP↑, *BioAv↑, *P450↓, *eff↑, *BioAv↑, E-cadherin↓, ER(estro)↓, MMP2↓, MMP9↓, VEGF↓, cMyc↓, BAX↑, P53↑, TumCG↓, OS↑, *cognitive↑, *GSK‐3β↓, *GSH↑, *Casp3↓, *Casp9↓, *Cyt‑c↓, *lipid-P↓, *motorD↑, *AChE↓, *memory↑, *cardioP↑, *ROS↓, *PPARγ↑, *ALAT↓, *AST↓, *ALP↓, *AMPK↑, *5HT↑, *SIRT1↑, *eff↑,
3589- PI,    Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models
- in-vivo, Arthritis, NA
*IL6↓, *MMP13↓, *PGE2↓, *AP-1↓, *Inflam↓, *5LO↓, *COX1↓, *COX2↓, *ERK↓, *BioEnh↑,
3596- PI,    Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress
- in-vivo, Nor, NA
*TBARS↑, *SOD↑, *Catalase↑, *GSTs↑, *GPx↑, *GSH↑, *ROS↓,
1946- PL,  PI,    Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling
- in-vitro, Liver, NA
eff↑, toxicity↓, TrxR↓, ROS↑, MMP↓, p38↑, Akt↓, mTOR↓,
873- QC,  RES,  CUR,  PI,    Combination Effects of Quercetin, Resveratrol and Curcumin on In Vitro Intestinal Absorption
- in-vitro, Nor, NA
*BioEnh↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 41

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

ROS↑, 6,   TrxR↓, 1,  

Mitochondria & Bioenergetics

MMP↓, 2,   Raf↓, 1,  

Core Metabolism/Glycolysis

cMyc↓, 2,   CREB↓, 2,   Glycolysis↓, 1,   HK2↓, 1,   Pyruv↓, 1,   Warburg↓, 1,  

Cell Death

Akt↓, 2,   p‑Akt↓, 3,   Apoptosis↑, 6,   ATF2↓, 2,   BAD↑, 1,   BAX↑, 2,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   Cyt‑c↑, 1,   MAPK↓, 1,   MAPK↑, 1,   Necroptosis↑, 1,   necrosis↑, 1,   p38↓, 1,   p38↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction

HER2/EBBR2↓, 1,  

Transcription & Epigenetics

other↑, 1,   p‑pRB↓, 1,   tumCV↓, 2,  

Autophagy & Lysosomes

TumAuto↑, 1,  

DNA Damage & Repair

DNAdam↑, 1,   P53↑, 2,   cl‑PARP↑, 2,  

Cell Cycle & Senescence

TumCCA↑, 3,  

Proliferation, Differentiation & Cell State

ALDH↓, 1,   cFos↓, 2,   CSCs↓, 1,   EMT↓, 5,   ERK↓, 1,   ERK↑, 1,   p‑ERK↓, 1,   IGF-1↓, 1,   mTOR↓, 3,   p‑mTOR↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,   PTEN↓, 1,   RAS↓, 1,   STAT3↓, 3,   STAT3⇅, 1,   TumCG↓, 4,   Wnt↓, 1,  

Migration

E-cadherin↓, 2,   E-cadherin↑, 1,   Ki-67↓, 1,   MMP2↓, 3,   MMP9↓, 4,   MMPs↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   p‑SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 2,   TumCI↓, 3,   TumCMig↓, 5,   TumCP↓, 4,   TumMeta↓, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature

angioG↓, 1,   EGFR↓, 1,   TXA2↓, 1,   VEGF↓, 3,  

Barriers & Transport

P-gp↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 3,   IL1β↓, 1,   IL6↓, 2,   NF-kB↓, 3,   p50↓, 1,   p65↓, 2,   PGD2↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors

ER(estro)↓, 1,  

Drug Metabolism & Resistance

BioEnh↑, 1,   ChemoSen↑, 3,   eff↓, 1,   eff↑, 3,   RadioS↑, 1,  

Clinical Biomarkers

EGFR↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 2,   Ki-67↓, 1,  

Functional Outcomes

AntiCan↑, 1,   cardioP↑, 1,   OS↑, 2,   Symptoms∅, 1,   toxicity↓, 2,   TumVol↓, 1,  
Total Targets: 101

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↓, 2,   antiOx↑, 4,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 2,   HO-1↑, 1,   lipid-P↓, 2,   NRF2↑, 1,   ROS↓, 5,   SOD↑, 2,   TAC↑, 1,   TBARS↑, 1,  

Core Metabolism/Glycolysis

ALAT↓, 1,   AMPK↑, 1,   cPLA2↓, 1,   CYP3A2↓, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death

Casp3↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,   iNOS↓, 1,   MAPK↓, 1,  

Transcription & Epigenetics

other↓, 7,   other↑, 5,  

Proliferation, Differentiation & Cell State

EMT↓, 1,   ERK↓, 1,   p‑ERK↓, 1,   GSK‐3β↓, 1,   STAT3↓, 1,  

Migration

5LO↓, 2,   AP-1↓, 3,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↑, 1,   Fibronectin↓, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   Smad7↑, 1,   TGF-β↓, 2,   Vim↓, 1,   α-SMA↓, 2,  

Angiogenesis & Vasculature

angioG↑, 1,  

Immune & Inflammatory Signaling

CD25+↓, 1,   CD69↓, 1,   COX1↓, 2,   COX2↓, 2,   CTLA-4↓, 1,   FOXP3↑, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↑, 2,   IL17↓, 1,   IL1β↓, 2,   IL2↓, 1,   IL4↓, 2,   IL5↓, 1,   IL6↓, 2,   Imm↑, 1,   Inflam↓, 6,   NF-kB↓, 2,   PGE2↓, 3,   TNF-α↓, 2,  

Synaptic & Neurotransmission

5HT↑, 1,   AChE↓, 4,   BDNF↑, 3,   tau↓, 1,  

Protein Aggregation

Aβ↓, 1,  

Drug Metabolism & Resistance

BioAv↑, 6,   BioEnh↑, 5,   eff↑, 4,   P450↓, 1,  

Clinical Biomarkers

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   BP↓, 1,   IL6↓, 2,   NOS2↓, 1,  

Functional Outcomes

AntiCan↑, 1,   cardioP↑, 2,   chemoP↑, 1,   cognitive↑, 3,   hepatoP↑, 5,   memory↑, 5,   Mood↑, 1,   motorD↑, 1,   neuroP↑, 7,   Weight↓, 1,  

Infection & Microbiome

Bacteria↓, 1,  
Total Targets: 93

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#:133  Target#:%  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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