Rosmarinic acid 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


Scientific Papers found: Click to Expand⟱
3011- RosA,    Rosmarinic Acid Exhibits Anticancer Effects via MARK4 Inhibition
- in-vitro, GBM, SH-SY5Y - in-vitro, Lung, A549 - in-vitro, Nor, HEK293 - in-vitro, Nor, MCF10
MARK4↓, p‑tau↓, selectivity↑, *toxicity∅,
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↝,
3013- RosA,    Rosmarinic acid inhibits angiogenesis and its mechanism of action in vitro
- in-vitro, NA, NA
*BioAv↑, *antiOx↑, *Inflam↓, *ROS↓, *VEGF↓, *IL8↓,
3014- RosA,    Rosmarinic Acid Supplementation Acts as an Effective Antioxidant for Restoring the Antioxidation/Oxidation Balance in Wistar Rats with Cadmium-Induced Toxicity
- in-vivo, Nor, NA
*antiOx↑, *Thiols↑, *GSH↑, *TAC↑, *SOD↑, *GPx↑, *Catalase↑, *ALP↓, *ALAT↓, *AST↓, *creat↓, *BUN↓, *H2O2↓, *MDA↓, *ROS↓, cardioP↑, hepatoP↑, neuroP↑,
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↓,
3016- RosA,    Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling
- in-vitro, HNSCC, UM-SCC-6 - in-vitro, HNSCC, UM-SCC-10B
chemoP↓, EGF↓, tumCV↓, TumCMig↓, ROS↓, PI3K↓, Akt↓, ERK↓, antiOx↑, p‑EGFR↓,
3008- RosA,    Rosmarinic acid decreases viability, inhibits migration and modulates expression of apoptosis-related CASP8/CASP3/NLRP3 genes in human metastatic melanoma cells
- in-vitro, Melanoma, SK-MEL-28
tumCV↓, TumCMig↓, ROS↓, Casp3↑, selectivity↑, Casp8↑, NLRP3↓,
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↑,
3019- RosA,    Orally administered rosmarinic acid is present as the conjugated and/or methylated forms in plasma, and is degraded and metabolized to conjugated forms of caffeic acid, ferulic acid and m-coumaric acid
- in-vivo, Nor, NA
*BioAv↝, *Half-Life↝, *Half-Life↑, *Half-Life↝, *BioAv↑,
3020- RosA,    Protective Effect of Rosmarinic Acid on Endotoxin-Induced Neuronal Damage Through Modulating GRP78/PERK/MANF Pathway
- in-vivo, Nor, NA - in-vitro, NA, SH-SY5Y
*cognitive↑, *PERK↓, *GRP78/BiP↓, *ER Stress↓,
3023- RosA,    Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis
- in-vivo, Sepsis, NA
*GPx4↑, *Inflam↓, *ER Stress↓, *Ferroptosis↓, *Sepsis↓, *GRP78/BiP↓, *IRE1↓, JNK↓,
3021- RosA,    Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway
- in-vivo, Sepsis, NA
*eff↑, *SOD↑, *MDA↓, *GRP78/BiP↓, *IRE1↓, *JNK↓, *Sepsis↓,
3645- Sage,  RosA,    Acetylcholinesterase inhibitory, antioxidant and phytochemical properties of selected medicinal plants of the Lamiaceae family
- Study, AD, NA
*AChE↓, *AChE↓,
4217- Sage,  RosA,  Aroma,    Neuroprotective Potential of Aromatic Herbs: Rosemary, Sage, and Lavender
- Review, AD, NA - Review, Park, NA
*Inflam↓, *antiOx↑, *neuroP↑, *ERK↑, *CREB↑, *BDNF↑, *Aβ↑, *AChE↓, *memory↑, *cognitive↑,
3788- UA,  RosA,    Ursolic acid and rosmarinic acid ameliorate alterations in hippocampal neurogenesis and social memory induced by amyloid beta in mouse model of Alzheimer’s disease
- in-vivo, AD, NA
*neuroP↑, *Aβ↓, *p‑tau↓, *memory↑, *Inflam↓, *ROS↓,
5023- UA,  CA,  RosA,    Therapeutic Effect of Rosemary and Its Active Constituent on Nervous System Disorders
- Review, Park, NA - Review, AD, NA
*memory↑, *cognitive↑, *ROS↓,

Showing Research Papers: 51 to 67 of 67
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 67

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   ROS↓, 3,   SOD2↓, 1,  

Mitochondria & Bioenergetics ⓘ

EGF↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Casp3↑, 1,   Casp8↑, 1,   JNK↓, 2,   TumCD∅, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,   tumCV∅, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   FOXO1↓, 1,   PI3K↓, 1,  

Migration ⓘ

MARK4↓, 1,   TumCMig↓, 2,  

Angiogenesis & Vasculature ⓘ

p‑EGFR↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL8↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

selectivity↑, 2,  

Clinical Biomarkers ⓘ

p‑EGFR↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoP↓, 1,   hepatoP↑, 1,   neuroP↑, 1,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 1,   Ferroptosis↓, 1,   GPx↑, 1,   GPx4↑, 1,   GSH↑, 1,   H2O2↓, 1,   MDA↓, 2,   NOX4↓, 1,   NRF2↑, 1,   ROS↓, 6,   SOD↑, 2,   TAC↑, 1,   Thiols↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   BUN↓, 1,   CREB↑, 1,   PGC1A↑, 1,  

Cell Death ⓘ

Ferroptosis↓, 1,   JNK↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 2,   GRP78/BiP↓, 3,   IRE1↓, 2,   PERK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   STAT3↓, 1,  

Migration ⓘ

Rho↓, 2,   ROCK1↓, 2,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

ICAM-1↓, 1,   IL8↓, 1,   Inflam↓, 7,   MCP1↓, 1,   NF-kB↓, 2,   p‑NF-kB↓, 1,   RANTES↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 3,   BDNF↑, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   Aβ↑, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 2,   BioAv↝, 1,   Dose↝, 1,   eff↑, 1,   Half-Life↑, 1,   Half-Life↝, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   creat↓, 1,   GutMicro↑, 1,  

Functional Outcomes ⓘ

cognitive↑, 3,   memory↑, 3,   neuroP↑, 2,   radioP↑, 2,   toxicity∅, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 2,  
Total Targets: 60

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

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