tbResList Print — PI Piperine

Filters: qv=133, qv2=%, rfv=%

Product

PI Piperine
Description: <b>Compound</b> of black pepper that boosts bioavailability of curcumin<br>
<br>
piperine’s bioenhancing function, often more important than piperine’s direct anticancer activity
<pre>
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
</pre>


<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>

<tr>
<td>1</td>
<td>Wnt / β-catenin signaling</td>
<td>↓ Wnt/β-catenin (↓ β-catenin nuclear program)</td>
<td>Growth &amp; stemness suppression</td>
<td>Piperine suppresses canonical Wnt signaling and shows anti-cancer effects in colorectal cancer cells</td>
<td><a href="https://www.nature.com/articles/s41598-020-68574-2">(ref)</a></td>
</tr>

<tr>
<td>2</td>
<td>PI3K → AKT survival signaling</td>
<td>↓ PI3K/AKT signaling</td>
<td>Reduced survival / increased apoptosis</td>
<td>Gastric cancer study concludes piperine inhibits proliferation and induces apoptosis through inhibition of PI3K/Akt signaling</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7784594/">(ref)</a></td>
</tr>

<tr>
<td>3</td>
<td>AKT → mTOR axis</td>
<td>↓ Akt/mTOR</td>
<td>Anti-growth + anti-migration</td>
<td>Piperine downregulates Akt/mTOR signaling with associated inhibition of migration and MMP-9 expression</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5928620/">(ref)</a></td>
</tr>

<tr>
<td>4</td>
<td>NF-κB transcriptional program</td>
<td>↓ NF-κB activation</td>
<td>Reduced inflammatory / pro-survival gene expression</td>
<td>Piperine is reported as a potent inhibitor of NF-κB and related transcription factor activity in melanoma cells</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/15531295/">(ref)</a></td>
</tr>

<tr>
<td>5</td>
<td>STAT3 → Snail EMT axis</td>
<td>↓ STAT3 / ↓ Snail → ↓ EMT</td>
<td>Anti-migration / anti-invasion</td>
<td>Piperine inhibits colorectal cancer migration/invasion through a STAT3/Snail-mediated EMT mechanism</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/32500474/">(ref)</a></td>
</tr>

<tr>
<td>6</td>
<td>Multidrug resistance transporter ABCB1 (P-gp)</td>
<td>↓ P-gp-mediated efflux (chemosensitization)</td>
<td>Improved chemo response (MDR reversal)</td>
<td>Demonstrates piperine has chemosensitizing activity in P-gp–mediated MDR models (piperine characterized as P-gp substrate/modulator)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/29498663/">(ref)</a></td>
</tr>

<tr>
<td>7</td>
<td>ROS / oxidative stress</td>
<td>↑ ROS</td>
<td>Upstream stress trigger</td>
<td>Piperine induces oxidative stress in cancer cells (ROS increase shown) and links it to growth inhibition/apoptosis</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6558508/">(ref)</a></td>
</tr>

<tr>
<td>8</td>
<td>Intrinsic apoptosis (caspase activation)</td>
<td>↑ apoptosis</td>
<td>Programmed cell death</td>
<td>HeLa study: piperine induces apoptosis in a dose-dependent manner with apoptosis markers reported</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6558508/">(ref)</a></td>
</tr>

<tr>
<td>9</td>
<td>Autophagy-dependent cell death (ROS–Akt/mTOR coupling)</td>
<td>↑ autophagy-dependent death (with ↓ Akt/mTOR)</td>
<td>Stress-lethal program</td>
<td>Colon cancer study: piperine induces autophagy-dependent cell death by increasing ROS and inhibiting Akt/mTOR signaling</td>
<td><a href="https://www.sciencedirect.com/science/article/abs/pii/S0006291X24008763">(ref)</a></td>
</tr>

<tr>
<td>10</td>
<td>Cell-cycle progression</td>
<td>↑ cell-cycle arrest (context-dependent)</td>
<td>Proliferation blockade</td>
<td>Rectal cancer cell study: piperine impairs cell-cycle progression and produces cytostatic/cytotoxic effects</td>
<td><a href="https://www.sciencedirect.com/science/article/abs/pii/S0014480012001554">(ref)</a></td>
</tr>

<tr>
<td>11</td>
<td>Migration / invasion (MMP-9 axis)</td>
<td>↓ migration / ↓ MMP-9</td>
<td>Anti-metastatic phenotype</td>
<td>Piperine suppresses migration with MMP-9 downregulation and Akt/mTOR inhibition</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5928620/">(ref)</a></td>
</tr>

<tr>
<td>12</td>
<td>In vivo chemosensitization (doxorubicin)</td>
<td>↑ doxorubicin sensitivity</td>
<td>Enhanced therapeutic efficacy</td>
<td>Study evaluates piperine as an adjuvant to enhance doxorubicin sensitivity in triple-negative breast cancer models</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11303729/">(ref)</a></td>
</tr>

</table>

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↓, 4,   ERK↓, 1,   ERK↑, 1,   p‑ERK↓, 1,   IGF-1↓, 1,   mTOR↓, 3,   p‑mTOR↓, 1,   p‑PI3K↓, 1,   PI3K↓, 1,   PTEN↓, 1,   RAS↓, 1,   STAT3↓, 3,   STAT3⇅, 1,   TumCG↓, 4,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↑, 1,   E-cadherin↓, 2,   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↑, 3,   eff↓, 1,   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↑, 4,   antiOx↓, 2,   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,   p‑ERK↓, 1,   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

Research papers

Year Title Authors PMID Link Flag
2018Capsaicin and Piperine Can Overcome Multidrug Resistance in Cancer Cells to DoxorubicinHanmei LiPMC6017796https://pmc.ncbi.nlm.nih.gov/articles/PMC6017796/0
2022Extending the lore of curcumin as dipteran Butyrylcholine esterase (BChE) inhibitor: A holistic molecular interplay assessmentPriyashi Rao—https://journals.plos.org/plosone/article?id=10.1371/journal.pone.02690360
2022Therapeutic and Preventive Effects of Piperine and its Combination with Curcumin as a Bioenhancer Against Aluminum-Induced Damage in the Astrocyte CellsŞebnem Erfen36342584https://pubmed.ncbi.nlm.nih.gov/36342584/0
2019Synergistic 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 AssayAimi Syamima Abdul ManapPMC6718453https://pmc.ncbi.nlm.nih.gov/articles/PMC6718453/0
1998Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteersG Shoba9619120https://pubmed.ncbi.nlm.nih.gov/9619120/0
2024Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic TargetsWamidh H TalibPMC10976257https://pmc.ncbi.nlm.nih.gov/articles/PMC10976257/0
2004Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in miceJoshua D Lambert15284381https://pubmed.ncbi.nlm.nih.gov/15284381/0
2024Piperine enhances doxorubicin sensitivity in triple-negative breast cancer by targeting the PI3K/Akt/mTOR pathway and cancer stem cellsAndrew N HakeemPMC11303729https://pmc.ncbi.nlm.nih.gov/articles/PMC11303729/0
2024Piperine induces autophagy of colon cancer cells: Dual modulation of AKT/mTOR signaling pathway and ROS productionJianyu Xia—https://www.sciencedirect.com/science/article/abs/pii/S0006291X240087630
2024Potential of piperine for neuroprotection in sepsis-associated encephalopathyFlavia Monteiro Ferreira—https://www.sciencedirect.com/science/article/abs/pii/S00243205230098880
2022Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS–STAT3 pathwayDi ChenPMC9087272https://pmc.ncbi.nlm.nih.gov/articles/PMC9087272/0
2021Piperine: A review of its biological effectsIahtisham-Ul Haq32929825https://pubmed.ncbi.nlm.nih.gov/32929825/0
2021The Effect of Piperine on MMP-9, VEGF, and E-cadherin Expression in Breast Cancer MCF-7 Cell LineZahra Zare—https://www.researchgate.net/publication/349833024_The_Effect_of_Piperine_on_MMP-9_VEGF_and_E-cadherin_Expression_in_Breast_Cancer_MCF-7_Cell_Line0
2020Piperine inhibits colorectal cancer migration and invasion by regulating STAT3/Snail-mediated epithelial-mesenchymal transitionLingyu Song32500474https://pubmed.ncbi.nlm.nih.gov/32500474/0
2020Piperine Inhibits Cell Proliferation and Induces Apoptosis of Human Gastric Cancer Cells by Downregulating Phosphatidylinositol 3-Kinase (PI3K)/Akt PathwayHanyu ChenPMC7784594https://pmc.ncbi.nlm.nih.gov/articles/PMC7784594/0
2020Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma CellsLeonardo Marques da FonsecaPMC7235759https://pmc.ncbi.nlm.nih.gov/articles/PMC7235759/0
2020Piperine ameliorated memory impairment and myelin damage in lysolecethin induced hippocampal demyelinationHannaneh Roshanbakhsh—https://www.sciencedirect.com/science/article/abs/pii/S00243205203041970
2020Piperlongumine‑loaded nanoparticles inhibit the growth, migration and invasion and epithelial‑to‑mesenchymal transition of triple‑negative breast cancer cellsJavad Ghassemi Rad—https://www.researchgate.net/publication/346719612_Piperlongumine-loaded_nanoparticles_inhibit_the_growth_migration_and_invasion_and_epithelial-to-mesenchymal_transition_of_triple-negative_breast_cancer_cells0
2020Piperine suppresses the Wnt/β-catenin pathway and has anti-cancer effects on colorectal cancer cellsGracielle C de AlmeidaPMC7363889https://pmc.ncbi.nlm.nih.gov/articles/PMC7363889/0
2020Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal CancerJia-Rong HuangPMC7748110https://pmc.ncbi.nlm.nih.gov/articles/PMC7748110/0
2020Piperlongumine attenuates bile duct ligation-induced liver fibrosis in mice via inhibition of TGF-β1/Smad and EMT pathwaysShrilekha Chilvery32882664https://pubmed.ncbi.nlm.nih.gov/32882664/0
2019Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activationAsif JafriPMC6558508https://pmc.ncbi.nlm.nih.gov/articles/PMC6558508/0
2019Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer's diseaseChe Wang31207354https://pubmed.ncbi.nlm.nih.gov/31207354/0
2018Chronic diseases, inflammation, and spices: how are they linked?Ajaikumar B KunnumakkaraPMC5785894https://pmc.ncbi.nlm.nih.gov/articles/PMC5785894/0
2018Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP-9 signaling pathway in DU145 cellsYuan ZengPMC5928620https://pmc.ncbi.nlm.nih.gov/articles/PMC5928620/0
2017Piperine-like alkamides from Piper nigrum induce BDNF promoter and promote neurite outgrowth in Neuro-2a cellsYoung Sook Yun—https://link.springer.com/article/10.1007/s11418-017-1140-30
2016Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma modelsPetra BullovaPMC5130026https://pmc.ncbi.nlm.nih.gov/articles/PMC5130026/0
2016Antileukemic effects of piperlongumine and alpha lipoic acid combination on Jurkat, MEC1 and NB4 cells in vitroMerve Alpay27461609https://pubmed.ncbi.nlm.nih.gov/27461609/0
2015Piperine inhibits IL-1β-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cellsYong Xia25234193https://pubmed.ncbi.nlm.nih.gov/25234193/0
2015Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer's disease: optimization, biological efficacy, and potential toxicitySamar M.Etman—https://alzped.nia.nih.gov/intranasal-piperine-loaded0
2014Piperine 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 ResponseDong Ju SonPMC4145312https://pmc.ncbi.nlm.nih.gov/articles/PMC4145312/0
2013Black pepper and health claims: a comprehensive treatiseMasood Sadiq Butt23768180https://pubmed.ncbi.nlm.nih.gov/23768180/0
2013Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cellsPaul B. Yaffe—https://www.sciencedirect.com/science/article/abs/pii/S00144800120015540
2011Bioenhancers from mother nature and their applicability in modern medicineGurpreet Kaur RandhawaPMC3657948https://pmc.ncbi.nlm.nih.gov/articles/PMC3657948/0
2009Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's diseasePennapa Chonpathompikunlert20034530https://pubmed.ncbi.nlm.nih.gov/20034530/0
2009Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis modelsJun Soo BangPMC2688199https://pmc.ncbi.nlm.nih.gov/articles/PMC2688199/0
2009Inhibition of T cell activation by the phytochemical piperineCarolyn Doucette—https://www.researchgate.net/publication/366747108_Inhibition_of_T_cell_activation_by_the_phytochemical_piperine_50350
2004Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cellsC R Pradeep15531295https://pubmed.ncbi.nlm.nih.gov/15531295/0
2004Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stressR S Vijayakumar15231065https://pubmed.ncbi.nlm.nih.gov/15231065/0
2020Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR SignalingPeng Zhu33026807https://pubmed.ncbi.nlm.nih.gov/33026807/0
2014Combination Effects of Quercetin, Resveratrol and Curcumin on In Vitro Intestinal AbsorptionKaleb C. Lund, PhD—https://restorativemedicine.org/wp-content/uploads/2014/04/Combination-Effects-of-Quercetin-Resveratrol-and-Curcumin.pdf0