Rosmarinic acid / PPP 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↓, 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

PPP, pentose phosphate pathway: Click to Expand ⟱

Source:

Type:

The pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentoses from glucose-6-phosphate. In cancer, the PPP is often upregulated to support the increased demand for NADPH, which is necessary for fatty acid synthesis, antioxidant defenses, and maintaining the balance of redox reactions.

High expression of PPP enzymes is often associated with poor prognosis in various cancers, including breast, lung, colorectal, prostate, pancreatic, and ovarian cancer.

Scientific Papers found: Click to Expand⟱

3026-

RosA,

Modulatory Effect of Rosmarinic Acid on H2O2-Induced Adaptive Glycolytic Response in Dermal Fibroblasts

in-vitro,

Nor,

0–100 μM

 dermal fibroblasts

*ROS↓, *ATP↑, *NADPH↓, *HK2↓, *PFK2↓, *LDHA↓, *GSR↑, *GPx↑, *Prx↑, *Trx↑, *antiOx↑, *GSH↑, *ROS↓, *GlucoseCon↓, *lactateProd↓, *Glycolysis↝, *ATP↑, *NADPH↓, *PPP↓,

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:

Total Targets: 0

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, GPx↑, 1, GSH↑, 1, GSR↑, 1, Prx↑, 1, ROS↓, 2, Trx↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 2,

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1, Glycolysis↝, 1, HK2↓, 1, lactateProd↓, 1, LDHA↓, 1, NADPH↓, 2, PFK2↓, 1, PPP↓, 1,
Total Targets: 16

Scientific Paper Hit Count for: PPP, pentose phosphate pathway

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