Rosmarinic acid / AChE 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


AChE, acetylcholinesterase: Click to Expand ⟱
Source:
Type:
AChE is an enzyme that rapidly hydrolyzes the neurotransmitter acetylcholine into choline and acetate, terminating cholinergic signals.
- In some cancers, studies have reported reduced AChE activity, which may contribute to an accumulation of acetylcholine.
- Lower levels or loss of AChE expression/activity have been associated with more aggressive tumor behavior and poor prognosis, possibly due to unchecked cholinergic signaling.

For AD (Alzheimer's), AChE inhibitors are used, to allow ACh, and ChAT to increase along with acetyl-CoA
-Natural AChE inhibitors: Ferulic Acid, Caffeic Acid, Rosmarinic Acid, Sage
-AChE inhibitors only temporarily relieve some of the disease’s cognitive symptoms and do not stop the patient’s cognitive loss
-adverse effects such as disorientation, falls, dizziness, and fatigue may occur with these medications and should be used only as recommended

- Natural AChE inhibitors paper
Scientific Papers found: Click to Expand⟱
3760- CUR,  GI,  CAP,  RosA,  PI  Extending the lore of curcumin as dipteran Butyrylcholine esterase (BChE) inhibitor: A holistic molecular interplay assessment
*AChE↓, *other↓, *other↓, *other↓, *other↓, *other↓, *other↓,
3759- NarG,  RT,  CGA,  RosA,    Polyphenols as acetylcholinesterase inhibitors: Structural specificity and impact on human disease
- Review, AD, NA
*AChE↓, *other↓, *other↓,
3616- RosA,    Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders
- Review, AD, NA
*Inflam↓, *memory↑, *toxicity↓, *ROS↓, *Catalase↑, *SOD↑, *NRF2↑, *Aβ↓, *AChE↓, *Ca+2↓, *NO↓, *IL2↓, *COX2↓, *PGE2↓, *MMPs↓, *TNF-α↓, *iNOS↓, *TLR4↓, *cognitive↑, *cortisol↓, *lipid-P↓,
3622- RosA,    Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin-induced diabetic rats
- in-vivo, Diabetic, NA
*lipid-P↓, *AChE↓,
3623- RosA,    Rosmarinic acid inhibits some metabolic enzymes including glutathione S-transferase, lactoperoxidase, acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase isoenzymes
- in-vitro, AD, NA
*AChE↓,
3632- RosA,  CA,  QC,    Evolving Role of Natural Products from Traditional Medicinal Herbs in the Treatment of Alzheimer's Disease
- Review, AD, NA
*AChE↓,
3755- RosA,  CUR,    Development of Acetylcholinesterase (AChE) Inhibitor
- Study, AD, NA
*AChE↓, *antiOx↑, *Inflam↓,
3757- RosA,  Sage,  Cro,  NarG,  Caff  Food-derived Acetylcholinesterase Inhibitors as Potential Agents against Alzheimer’s Disease
- Review, AD, NA
AChE↓,
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↑,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Synaptic & Neurotransmission ⓘ

AChE↓, 1,  
Total Targets: 1

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   lipid-P↓, 2,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

CREB↑, 1,  

Cell Death ⓘ

iNOS↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 8,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,  

Migration ⓘ

Ca+2↓, 1,   MMPs↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL2↓, 1,   Inflam↓, 3,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 10,   BDNF↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   Aβ↑, 1,  

Hormonal & Nuclear Receptors ⓘ

cortisol↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 2,   memory↑, 2,   neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 28

Scientific Paper Hit Count for: AChE, acetylcholinesterase
10 Rosmarinic acid
3 Salvia officinalis
2 Curcumin
2 Naringin
1 Ginger/6-Shogaol/Gingerol
1 Capsaicin
1 Piperine
1 Rutin
1 Chlorogenic acid
1 Carnosic acid
1 Quercetin
1 Crocetin
1 Caffeine
1 Aromatherapy
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#:1329  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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