Rosmarinic acid / NF-kB Cancer Research Results

RosA, Rosmarinic acid: Click to Expand ⟱
Features: polyphenol
Polyphenol of many herbs - rosemary, perilla, sage mint and basil. Rosmarinic acid (RA) is predominantly found in a variety of medicinal and culinary herbs, especially those belonging to the Lamiaceae family, including rosemary (Rosmarinus officinalis), basil (Ocimum basilicum), sage (Salvia officinalis), thyme (Thymus vulgaris), and mints (Mentha spp.). In addition to the Lamiaceae family, RA is also present in plants from other families, such as Boraginaceae and Apiaceae.
-Rosmarinic acid is one of the hydroxycinnamic acids, and was initially isolated and purified from the extract of rosemary, a member of mint family (Lamiaceae)
-Its chemical structure allows it to act as a free radical scavenger by donating hydrogen atoms to stabilize ROS and free radicals.
RA’s dual nature as both a phenolic acid and a flavonoid-related compound enables it to chelate metal ions and prevent the formation of free radicals, thus interrupting oxidative chain reactions. It can modulate the activity of enzymes involved in OS, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), underscoring its potential role in preventing oxidative damage at the cellular level.
-divided as rosemary extract, carnosic acid, rosmarinic acid?

Summary:
-Capacity to chelate transition metal ions, particularly ironChelator (Fe2+) and copper (Cu2+)
-RA plus Cu(II)-induced oxidative DNA damage, which causes ROS
-rosmarinic acid (RA) as a potential inhibitor of MARK4↓ (inhibiting to tumor growth, invasion, and metastasis) activity (IC50 = 6.204 µM)

-Note half-life 1.5–2 hours.
BioAv water-soluble, rapid absorbtion
Pathways:
- varying results of ROS up or down in cancer cells. Plus a report of lowering ROS and no effect on Tumor cell viability.
However always seems to lower ROS↓ in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- No indication of Lowering AntiOxidant defense in Cancer Cells:
- Raises AntiOxidant defense in Normal Cells:(and perhaps even in cancer cells) ROS↓, NRF2↑***, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓">NF-kB, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, ROCK1↓, RhoA↓, NF-κB↓, ERK↓, MARK4↓
- reactivate genes thereby inhibiting cancer cell growth(weak) : HDAC2↓, DNMTs↓weak, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓??, LDHA↓, PFKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells (few references) : CSC↓, Hh↓, GLi1↓,
- Others: PI3K↓, AKT↓, STAT↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↓ ROS (dominant antioxidant effect) ↓ ROS Driver Antioxidant / redox buffering Rosmarinic acid is a strong phenolic antioxidant; cancer effects are largely redox-modulatory rather than cytotoxic
2 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of inflammatory survival signaling NF-κB inhibition explains anti-inflammatory, anti-proliferative, and chemopreventive effects
3 MAPK signaling (ERK / JNK / p38) ↓ ERK; ↑ JNK/p38 (context-dependent) ↔ minimal Secondary Stress-modulated signaling MAPK modulation reflects redox-sensitive signaling rather than direct kinase inhibition
4 Cell cycle regulation ↑ G0/G1 arrest (mild) ↔ spared Phenotypic Cytostatic growth control Growth inhibition is modest and non-cytotoxic in most models
5 Apoptosis ↑ apoptosis (weak / context-dependent) ↓ apoptosis Phenotypic Threshold-dependent cell death Apoptosis is not a dominant mechanism and usually requires high doses or co-stress
6 NRF2 antioxidant response ↑ NRF2 (adaptive) ↑ NRF2 (protective) Adaptive Antioxidant gene induction NRF2 activation reflects reinforcement of antioxidant capacity


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.


Scientific Papers found: Click to Expand⟱
3615- RosA,    Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer's Disease, Parkinson's Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome
- Review, AD, NA - Review, Park, NA
*NLRP3↓, *Inflam↓, *neuroP↑, *NRF2↑, *TNF-α↓, *NF-kB↓, *HO-1↑, *ROS↓,
3006- RosA,    Rosmarinic acid attenuates glioblastoma cells and spheroids’ growth and EMT/stem-like state by PTEN/PI3K/AKT downregulation and ERK-induced apoptosis
- in-vitro, GBM, U87MG - in-vitro, GBM, LN229
TumCG↓, EMT↓, SIRT1↓, FOXO1↓, NF-kB↓, angioG↓, ROS↓, PTEN↓, PI3K↓, Akt↓, *Inflam↓, *cardioP↑, *hepatoP↑, *neuroP↑, Warburg↓,
1745- RosA,    Rosmarinic acid and its derivatives: Current insights on anticancer potential and other biomedical applications
- Review, Var, NA - Review, AD, NA
ChemoSideEff↓, ChemoSen↑, antiOx↑, MMP2↓, MMP9↓, p‑AMPK↑, DNMTs↓, tumCV↓, COX2↓, E-cadherin↑, Vim↓, N-cadherin↓, EMT↓, Casp3↑, Casp9↓, ROS↓, GSH↑, ERK↓, Akt↓, ROS↓, NF-kB↓, p‑IκB↓, p50↓, p65↓, neuroP↑, Dose↝,
1746- RosA,    Rosmarinic acid sensitizes cell death through suppression of TNF-α-induced NF-κB activation and ROS generation in human leukemia U937 cells
- in-vitro, AML, U937
TNF-α↓, ROS↓, Casp↑, NF-kB↓, IκB↓, p50↓, p65↓, IAP1↓, IAP2↓, XIAP↓, Apoptosis↑,
3003- RosA,    Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases
- Review, Var, NA - Review, AD, NA - Review, Park, NA
*Inflam↓, *antiOx↑, *neuroP↑, *IL6↓, *IL1β↓, *NF-kB↓, *PGE2↓, *COX2↓, *MMP↑, *memory↑, *ROS↓, *Aβ↓, *HMGB1↓, TumCG↓, MARK4↓, Zeb1↓, MDM2↓, BNIP3↑, ASC↑, NLRP3↓, PI3K↓, Akt↓, Casp1↓, E-cadherin↑, STAT3↓, TLR4↓, MMP↓, ICAM-1↓, AMPK↓, IL6↑, MMP2↓, Warburg↓, Bcl-xL↓, Bcl-2↓, TumCCA↑, EMT↓, TumMeta↓, mTOR↓, HSP27↓, Casp3↑, GlucoseCon↓, lactateProd↓, VEGF↓, p‑p65↓, GIT1↓, FOXM1↓, cycD1/CCND1↓, CDK4↓, MMP9↓, HDAC2↓,
3007- RosA,    Hepatoprotective effects of rosmarinic acid: Insight into its mechanisms of action
- Review, NA, NA
*ROS↓, *lipid-P↓, *Inflam↓, *neuroP↑, *angioG↓, *eff↑, *AST↓, *ALAT↓, *GSSG↓, *eNOS↓, *iNOS↓, *NO↓, *NF-kB↓, *MMP2↓, *MDA↓, *TNF-α↓, *GSH↑, *SOD↑, *IL6↓, *PGE2↓, *COX2↓, *mTOR↑,
3017- RosA,  Per,    Molecular Mechanism of Antioxidant and Anti-Inflammatory Effects of Omega-3 Fatty Acids in Perilla Seed Oil and Rosmarinic Acid Rich Fraction Extracted from Perilla Seed Meal on TNF-α Induced A549 Lung Adenocarcinoma Cells
- in-vitro, Lung, A549
TumCD∅, ROS↓, IL1β↓, IL6↓, IL8↓, TNF-α↓, COX2↓, SOD2↓, FOXO1↓, NF-kB↓, JNK↓, antiOx↑, tumCV∅,
3018- RosA,    Rosemary (Rosmarinus officinalis L.) polyphenols and inflammatory bowel diseases: Major phytochemicals, functional properties, and health effects
- Review, IBD, NA
*Inflam↓, *GutMicro↑, *antiOx↑, *NF-kB↓, *NLRP3↓, *STAT3↓, *NRF2↑,
3015- RosA,  Rad,    Rosmarinic Acid Prevents Radiation-Induced Pulmonary Fibrosis Through Attenuation of ROS/MYPT1/TGFβ1 Signaling Via miR-19b-3p
- in-vivo, Nor, IMR90
*radioP↑, *Inflam↓, *ROS↓, *NF-kB↓, *Rho↓, *ROCK1↓, *other↓,
3012- RosA,  Rad,    Rosmarinic Acid Prevents Radiation-Induced Pulmonary Fibrosis Through Attenuation of ROSMYPT1TGFβ1 Signaling Via miR-19b-3p
- in-vitro, Nor, IMR90
*Inflam↓, *ROS↓, *p‑NF-kB↓, *Rho↓, *ROCK1↓, *radioP↑, *MCP1↓, *RANTES↓, *ICAM-1↓, *PGC1A↑, *NOX4↓, *Dose↝,
3009- RosA,    Rosmarinic acid sensitizes cell death through suppression of TNF-alpha-induced NF-kappaB activation and ROS generation in human leukemia U937 cells
- in-vitro, AML, U937
TNF-α↓, NF-kB↓, ROS↓, IAP1↓, IAP2↓, XIAP↓,

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

antiOx↑, 2,   GSH↑, 1,   ROS↓, 6,   SOD2↓, 1,  

Mitochondria & Bioenergetics

MMP↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis

AMPK↓, 1,   p‑AMPK↑, 1,   GlucoseCon↓, 1,   lactateProd↓, 1,   SIRT1↓, 1,   Warburg↓, 2,  

Cell Death

Akt↓, 3,   Apoptosis↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp↑, 1,   Casp1↓, 1,   Casp3↑, 2,   Casp9↓, 1,   IAP1↓, 2,   IAP2↓, 2,   JNK↓, 1,   MDM2↓, 1,   TumCD∅, 1,  

Transcription & Epigenetics

tumCV↓, 1,   tumCV∅, 1,  

Protein Folding & ER Stress

HSP27↓, 1,  

Autophagy & Lysosomes

BNIP3↑, 1,  

DNA Damage & Repair

DNMTs↓, 1,  

Cell Cycle & Senescence

CDK4↓, 1,   cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

EMT↓, 3,   ERK↓, 1,   FOXM1↓, 1,   FOXO1↓, 2,   HDAC2↓, 1,   mTOR↓, 1,   PI3K↓, 2,   PTEN↓, 1,   STAT3↓, 1,   TumCG↓, 2,  

Migration

E-cadherin↑, 2,   GIT1↓, 1,   MARK4↓, 1,   MMP2↓, 2,   MMP9↓, 2,   N-cadherin↓, 1,   TumMeta↓, 1,   Vim↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature

angioG↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling

ASC↑, 1,   COX2↓, 2,   ICAM-1↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL6↑, 1,   IL8↓, 1,   IκB↓, 1,   p‑IκB↓, 1,   NF-kB↓, 5,   p50↓, 2,   p65↓, 2,   p‑p65↓, 1,   TLR4↓, 1,   TNF-α↓, 3,  

Protein Aggregation

NLRP3↓, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 1,   Dose↝, 1,  

Clinical Biomarkers

FOXM1↓, 1,   IL6↓, 1,   IL6↑, 1,  

Functional Outcomes

ChemoSideEff↓, 1,   neuroP↑, 1,  
Total Targets: 77

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 2,   GSH↑, 1,   GSSG↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NOX4↓, 1,   NRF2↑, 2,   ROS↓, 5,   SOD↑, 1,  

Mitochondria & Bioenergetics

MMP↑, 1,  

Core Metabolism/Glycolysis

ALAT↓, 1,   PGC1A↑, 1,  

Cell Death

iNOS↓, 1,  

Transcription & Epigenetics

other↓, 1,  

Proliferation, Differentiation & Cell State

mTOR↑, 1,   STAT3↓, 1,  

Migration

MMP2↓, 1,   Rho↓, 2,   ROCK1↓, 2,  

Angiogenesis & Vasculature

angioG↓, 1,   eNOS↓, 1,   NO↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 2,   HMGB1↓, 1,   ICAM-1↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 7,   MCP1↓, 1,   NF-kB↓, 5,   p‑NF-kB↓, 1,   PGE2↓, 2,   RANTES↓, 1,   TNF-α↓, 2,  

Protein Aggregation

Aβ↓, 1,   NLRP3↓, 2,  

Drug Metabolism & Resistance

Dose↝, 1,   eff↑, 1,  

Clinical Biomarkers

ALAT↓, 1,   AST↓, 1,   GutMicro↑, 1,   IL6↓, 2,  

Functional Outcomes

cardioP↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 4,   radioP↑, 2,  
Total Targets: 48

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
11 Rosmarinic acid
2 Radiotherapy/Radiation
1 Perilla
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#:142  Target#:214  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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