Database Query Results : Rosmarinic acid, , DNMTs

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↓, 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


DNMTs, DNA methyltransferase: Click to Expand ⟱
Source:
Type:
DNA methylation, an epigenetic modification, regulates gene transcription and maintains genome stability. DNA methyltransferase (DNMT) inhibitors can activate silenced genes at low doses and cause cytotoxicity at high doses.

High expression levels of DNMTs, particularly DNMT1 and DNMT3A, are often associated with poor prognosis in several cancers. This is due to their role in promoting tumor growth, metastasis, and resistance to therapies.
Scientific Papers found: Click to Expand⟱
3034- RosA,  RES,  Ba,    The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells
- in-vitro, BC, MCF-7
DNMTs↓, Figure 2B DNMT inhibition weak ~80% of control
eff↑, Note Resveratrol is stronger at 20% of control
eff↝, Baicalein also weak at 80% of control

1745- RosA,    Rosmarinic acid and its derivatives: Current insights on anticancer potential and other biomedical applications
- Review, Var, NA - Review, AD, NA
ChemoSideEff↓, updated review is to highlight the chemopreventive and chemotherapeutic effects of RA and its derivatives
ChemoSen↑,
antiOx↑, RA also showed antioxidant effects and suppressed the activity and expression of matrix metalloproteinase (MMP)− 2,9
MMP2↓,
MMP9↓,
p‑AMPK↑, show that RA prevents metastasis through AMPK phosphorylation and suppresses CRC cell growth
DNMTs↓, RA allegedly suppressed DNA methyltransferase activity in the human breast cancer MCF7 cell line
tumCV↓, A549 lung cancer cells were 50% suppressed by RA, which also prevented COX-2 activity in these cells.
COX2↓,
E-cadherin↑, upregulating E-cadherin expression while downregulating Vimentin and N-cadherin expression, indicating that RA could inhibit hepatocellular carcinoma cells' ability to invade by MMPs and EMT
Vim↓,
N-cadherin↓,
EMT↓,
Casp3↑, The activation of caspase-3 and caspase-9 by RA also prevented the migration and invasion of liver cancer cells
Casp9↓,
ROS↓, In addition to reducing ROS, RA also enhanced GSH synthesis, lowered the expression of MMP-2 and MMP-9
GSH↑,
ERK↓, By inhibiting ERK and Akt activation, RA may stop the progression of colon cancer
Akt↓,
ROS↓, In U937 cells, it has been demonstrated that treatment with RA in concentrations 60 µM suppresses ROS and NF-kB by blocking IκB-α from being phosphorylated and degraded and the nuclear translocation of p50 and p65
NF-kB↓,
p‑IκB↓,
p50↓,
p65↓,
neuroP↑, RA can prevent the pathophysiology of Alzheimer's disease by reducing Aβ aggregation
Dose↝, 60 µM suppresses ROS and NF-kB by blocking IκB-α from being phosphorylated and degraded and the nuclear translocation of p50 and p65


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GSH↑, 1,   ROS↓, 2,  

Core Metabolism/Glycolysis ⓘ

p‑AMPK↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Casp3↑, 1,   Casp9↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNMTs↓, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,  

Migration ⓘ

E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   Vim↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   p‑IκB↓, 1,   NF-kB↓, 1,   p50↓, 1,   p65↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 1,   eff↑, 1,   eff↝, 1,  

Functional Outcomes ⓘ

ChemoSideEff↓, 1,   neuroP↑, 1,  
Total Targets: 27

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: DNMTs, DNA methyltransferase
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#:469  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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