condition found tbRes List
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


TumCG, Tumor cell growth: Click to Expand ⟱
Source:
Type:
Normal cells grow and divide in a regulated manner through the cell cycle, which consists of phases (G1, S, G2, and M).
Cancer cells often bypass these regulatory mechanisms, leading to uncontrolled proliferation. This can result from mutations in genes that control the cell cycle, such as oncogenes (which promote cell division) and tumor suppressor genes (which inhibit cell division).
Scientific Papers found: Click to Expand⟱
3033- RosA,    Rosemary (Rosmarinus officinalis) Extract Modulates CHOP/GADD153 to Promote Androgen Receptor Degradation and Decreases Xenograft Tumor Growth
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, LNCaP - vitro+vivo, NA, NA
ER Stress↑, A significant modulation of endoplasmic reticulum stress proteins was observed in cancer cells while normal prostate epithelial cells did not undergo endoplasmic reticulum stress.
selectivity↑,
AR↓, rosemary extract to decrease androgen receptor expression that appears to be regulated by the expression of CHOP/GADD153
TumCG↓, Rosemary extract modulates cell growth and induces cell cycle arrest in prostate cancer cell lines.
TumCCA↑,
CHOP↑, We observed an increase in overall protein expression of CHOP
PERK↓, decrease in PERK expression in prostate epithelial cells was observed following treatment with rosemary extract.
GRP78/BiP↑, rosemary extract induced BiP expression is essential for apoptosis.
PSA↓, AR and PSA is decreased and that of CHOP is increased in rosemary extract treated tissue lysates compared to lysates from control group animals.

3037- RosA,    Unraveling rosmarinic acid anticancer mechanisms in oral cancer malignant transformation
- in-vitro, Oral, SCC9 - in-vitro, Oral, HSC3
survivin↓, Rosmarinic acid significantly downregulates BIRC5, the encoded gene for Survivin, in highly invasive oral cancer cells.
AntiCan↑, Rosmarinic acid (RA) has been recognized for its anticancer properties
Vim↓, downregulation of VIM, CADM2, SNAIL1, and SOX9 highlighted the modulation of epithelial-mesenchymal transition
Snail↓,
SOX9↓,
EMT↓,
MMP2↓, remodeling of the extracellular matrix by the downregulation of MMP-2 and MMP-9
MMP9↓,
P-gp↓, RA interacts with P-glycoprotein with the highest docking score of −6.4 kcal/mol.
TumCG↓, RA also shrank the growth and the metabolic activity of multicellular tumor spheroids
ROS↑, RA evokes cell death through the increase of intracellular reactive oxygen species production and the modulation of mitochondrial membrane potential in OSCC cells
MMP↓, significant decrease in the MMP was observed in both cell lines
GSH↓, significant decrease in the glutathione levels in treated HSC-3 cells.
P-gp↓, RA can bind to nine sites of the P-gp ATP model, with a strong binding affinity of −6.3 kcal/mol to −5.4 kcal/mol.
ATP↓,

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↓, anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes,
*antiOx↑,
*neuroP↑,
*IL6↓, diabetic rat model treated with RA, there is an anti-inflammatory activity reported. This activity is achieved through the inhibition of the expression of various proinflammatory factors, including in IL-6, (IL-1β), tumour
*IL1β↓,
*NF-kB↓, inhibiting NF-κB activity and reducing the production of prostaglandin E2 (PGE2), nitric oxide (NO), and cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
*PGE2↓,
*COX2↓,
*MMP↑, RA inhibits cytotoxicity in tumour patients by maintaining the mitochondrial membrane potential
*memory↑, amyloid β(25–35)-induced AD in rats was treated with RA, which mitigated the impairment of learning and memory disturbance by reducing oxidative stress
*ROS↓,
*Aβ↓, daily consumption of RA diminished the effect of neurotoxicity of Aβ25–35 in mice
*HMGB1↓, SH-SY5Y in vitro and ischaemic diabetic stroke in vivo, and the studies revealed that a 50 mg/kg dose of RA decreased HMGB1 expression
TumCG↓, Rosemary and its extracts have been shown to exhibit potential in inhibiting the growth of cancer cells and the development of tumours in various cancer types, including colon, breast, liver, and stomach cancer
MARK4↓, Another study reported the inhibition of Microtubule affinity regulating kinase 4 (MARK4) by RA
Zeb1↓, Fig 4 BC:
MDM2↓,
BNIP3↑,
ASC↑, Skin Cancer
NLRP3↓,
PI3K↓,
Akt↓,
Casp1↓,
E-cadherin↑, Colon Cancer
STAT3↓,
TLR4↓,
MMP↓,
ICAM-1↓,
AMPK↓,
IL6↑, PC and GC
MMP2↓,
Warburg↓,
Bcl-xL↓, CRC: Apoptosis induction caspases ↑, Bcl-XL ↓, BCL-2 ↓, Induces cell cycle arrest, Inhibition of EMT and invasion, Reduced metastasis
Bcl-2↓,
TumCCA↑,
EMT↓,
TumMeta↓,
mTOR↓, Inhibits mTOR/S6K1 pathway to induce apoptosis in cervical cancer
HSP27↓, Glioma ↓ expression of HSP27 ↑ caspase-3
Casp3↑,
GlucoseCon↓, GC: Inhibited the signs of the Warburg effect, such as high glucose consumption/anaerobic glycolysis, lactate production/cell acidosis, by inhibiting the IL-6/STAT3 pathway
lactateProd↓,
VEGF↓, ↓ angiogenic factors (VEGF) and phosphorylation of p65
p‑p65↓,
GIT1↓, PC: Increased degradation of Gli1
Foxm1↓, inhibiting FOXM1
cycD1↓, RA treatment in CRC cells inhibited proliferation-induced cell cycle arrest of the G0/G1 phase by reducing the cyclin D1 and CDK4 levels,
CDK4↓,
MMP9↓, CRC cells, and it led to a decrease in the expressions of matrix metalloproteinase (MMP)-2 and MMP-9.
HDAC2↓, PCa cells through the inhibition of HDAC2

3002- RosA,    Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols
- Review, Var, NA
TumCG↓, SW480 colon cancer cells and found RE to significantly decrease cell growth at a concentration of 31.25 µg/mL (48 h),
TumCP↓, Cell proliferation was dramatically decreased and cell cycle arrest was induced in HT-29 and SW480 c
TumCCA↑,
ChemoSen↑, RE enhanced the inhibitory effects of the chemotherapeutic drug 5-fluorouracil (5-FU) on proliferation and sensitized 5-FU resistant cells
NRF2↑, HCT116 ↑ Nrf2, ↑ PERK, ↑ sestrin-2, ↑ HO-1, ↑ cleaved-casp 3
PERK↑,
SESN2↑,
HO-1↑,
cl‑Casp3↑,
ROS↑, HT-29 ↑ ROS accumulation, ↑ UPR, ↑ ER-stress
UPR↑,
ER Stress↑,
CHOP↑, HT-29: ↑ ROS levels, ↑ HO-1 and CHOP
HER2/EBBR2↓, SK-BR-3: ↑ FOS levels, ↑ PARP cleavage, ↓ HER2, ↓ ERBB2, ↓ ERα receptor.
ER-α36↓,
PSA↓, LNCaP : ↑ CHOP, ↓ PSA production, ↑ Bax, ↑ cleaved-casp 3, ↓ androgen receptor expression
BAX↑,
AR↓,
P-gp↓, A2780: ↓ P-glyco protein, ↑ cytochrome c gene, ↑ hsp70 gene
Cyt‑c↑,
HSP70/HSPA5↑,
eff↑, This study noted that the rosemary essential oil was more potent than its individual components (α-pinene, β-pinene, 1,8-cineole) when tested alone at the same concentrations.
p‑Akt↓, A549: ↓ p-Akt, ↓ p-mTOR, ↓ p-P70S6K, ↑ PARP cleavage
p‑mTOR↓,
p‑P70S6K↓,
cl‑PARP↑,
eff↑, RE containing 10 µM equivalent of CA, or 10 µM CA alone (96 h) potentiated the ability of vitamin D derivatives to inhibit cell viability and proliferation, induce apoptosis and cell cycle arrest and increase differentiation of WEHI-3BD murine leukem

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↓, Rosmarinic acid (RA) reduced the glioma growth and motility in 2D- and 3D-cultures
EMT↓, RA suppressed epithelial-mesenchymal transition and stem-cell property in spheroids.
SIRT1↓, RA downregulated SIRT1/FOXO1/NF-κB axis independently of p53 or PTEN function.
FOXO1↓,
NF-kB↓,
angioG↓, RA dose-dependently reduced angiogenesis and intracellular ROS levels, suppressed glioma growth,
ROS↓,
PTEN↓, RA also inhibited the PTEN/PI3K/AKT pathway in U-87MG cells.
PI3K↓,
Akt↓,
*Inflam↓, anti-inflammatory, antimicrobial, cardioprotective, hepatoprotective, neuroprotective, antidiabetic, and especially anticancer effects (
*cardioP↑,
*hepatoP↑,
*neuroP↑,
Warburg↓, suppresses Warburg effect

3010- RosA,    Exploring the mechanism of rosmarinic acid in the treatment of lung adenocarcinoma based on bioinformatics methods and experimental validation
- in-vitro, Lung, A549 - in-vivo, NA, NA
TumCG↓, RosA could inhibit the growth of transplanted tumors in nude mice bearing tumors of lung cancer cells, reduce the positive expression of Ki67 in lung tumor tissue, and hinder the proliferation of lung tumor cells.
Ki-67↓,
FABP4↑, Upregulated expression of PPARG and FABP4 by activating the PPAR signaling pathway increases the level of ROS in lung tumor tissues and promotes apoptosis of lung tumor cells.
PPARα↑,
ROS↑, RosA increases ROS levels in lung tumor tissues and induces apoptosis
Apoptosis↑,
MMP9↓, In addition, RosA can also reduce the expression of MMP-9 and IGFBP3, inhibit the migration and invasion of lung tumor tissue cells.
IGFBP3↓,
MMP2↓, In addition, RosA down-regulated the expression of MMP-9 and MMP2, regulated epithelial-mesenchymal transition to inhibit cell invasion, and slow down tumor development.
EMT↓,
TumCI↓,
PI3K↓, his study also confirmed that RosA down-regulated the expression of the PI3K/AKT/mTOR pathway-related proteins
Akt↓,
mTOR↓,
Gli1↓, Xiang Zhou et al. [28] reported that RosA inhibited the growth of PDAC tumors by inhibiting Gli1.
PPARγ↑, Upregulated expression of PPARG
Cyt‑c↑, figure 7


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
Akt↓,3,   p‑Akt↓,1,   AMPK↓,1,   angioG↓,1,   AntiCan↑,1,   Apoptosis↑,1,   AR↓,2,   ASC↑,1,   ATP↓,1,   BAX↑,1,   Bcl-2↓,1,   Bcl-xL↓,1,   BNIP3↑,1,   Casp1↓,1,   Casp3↑,1,   cl‑Casp3↑,1,   CDK4↓,1,   ChemoSen↑,1,   CHOP↑,2,   cycD1↓,1,   Cyt‑c↑,2,   E-cadherin↑,1,   eff↑,2,   EMT↓,4,   ER Stress↑,2,   ER-α36↓,1,   FABP4↑,1,   Foxm1↓,1,   FOXO1↓,1,   GIT1↓,1,   Gli1↓,1,   GlucoseCon↓,1,   GRP78/BiP↑,1,   GSH↓,1,   HDAC2↓,1,   HER2/EBBR2↓,1,   HO-1↑,1,   HSP27↓,1,   HSP70/HSPA5↑,1,   ICAM-1↓,1,   IGFBP3↓,1,   IL6↑,1,   Ki-67↓,1,   lactateProd↓,1,   MARK4↓,1,   MDM2↓,1,   MMP↓,2,   MMP2↓,3,   MMP9↓,3,   mTOR↓,2,   p‑mTOR↓,1,   NF-kB↓,1,   NLRP3↓,1,   NRF2↑,1,   P-gp↓,3,   p‑p65↓,1,   p‑P70S6K↓,1,   cl‑PARP↑,1,   PERK↓,1,   PERK↑,1,   PI3K↓,3,   PPARα↑,1,   PPARγ↑,1,   PSA↓,2,   PTEN↓,1,   ROS↓,1,   ROS↑,3,   selectivity↑,1,   SESN2↑,1,   SIRT1↓,1,   Snail↓,1,   SOX9↓,1,   STAT3↓,1,   survivin↓,1,   TLR4↓,1,   TumCCA↑,3,   TumCG↓,6,   TumCI↓,1,   TumCP↓,1,   TumMeta↓,1,   UPR↑,1,   VEGF↓,1,   Vim↓,1,   Warburg↓,2,   Zeb1↓,1,  
Total Targets: 85

Results for Effect on Normal Cells:
antiOx↑,1,   Aβ↓,1,   cardioP↑,1,   COX2↓,1,   hepatoP↑,1,   HMGB1↓,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,2,   memory↑,1,   MMP↑,1,   neuroP↑,2,   NF-kB↓,1,   PGE2↓,1,   ROS↓,1,  
Total Targets: 15

Scientific Paper Hit Count for: TumCG, Tumor cell growth
6 Rosmarinic acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:142  Target#:323  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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