Database Query Results : Rosmarinic acid, ,

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">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


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↓, Previously we have reported curcumin to induce mortality in Cx. pipiens by inhibiting AChE.
*other↓, The next hit, gingerol, is also reported to be an AChE inhibitor [61].
*other↓, Capsaicin, a phytochemical is reported to be AChE inhibitor [62].
*other↓, Rosmarinic acid is a polyphenol found in multiple aromatic plants and is reported to inhibit glutathione S-transferase, lactoperoxidase, AChE, BChE and carbonic anhydrase isoenzymes
*other↓, The next hit, piperine is known to inhibit ChEs, moreover curcumin and piperine are reported to synergically inhibit AChE and BChE in humans
*other↓, Sesamin is a phytochemical found in Cortex Acanthopanacis radicis, is reported to inhibit AChE, and known to improve memory impairment in mouse [65]
*other↓, Lastly as represented earlier, ursolic and oleanolic acid from the leaves of C. talcana are reported to inhibit AChE [14]

3759- NarG,  RT,  CGA,  RosA,    Polyphenols as acetylcholinesterase inhibitors: Structural specificity and impact on human disease
- Review, AD, NA
AChE↓, With regards to the AChE inhibition, the flavanone naringenin, a major flavonoid present in citrus has been shown to exert AChE inhibitory activity in vitro and anti-amnesic activity in vivo
*other↓, Indeed, Hernandez et al. [85] postulated that the active AChE inhibitors in Hypericum were phenolics such as chlorogenic acid, rutin,
*other↓, These results indicate that rosmarinic acid may permeate the blood brain barrier and act as an acetylcholinesterase inhibitor in the brain.

3028- RosA,    Network pharmacology mechanism of Rosmarinus officinalis L.(Rosemary) to improve cell viability and reduces apoptosis in treating Alzheimer’s disease
- in-vitro, AD, HT22 - in-vivo, NA, NA
*Aβ↓, It was found that rosemary could reversed Aβ25–35 induced damage to mouse hippocampal neuron HT22 cells,
*Apoptosis↓, significantly improved the viability of damaged cells, and reduced apoptosis
*antiOx↑, main antioxidant compound in rosemary, carnosic acid, also has neuroprotective effects.
*neuroP↑,
*eff↑, main active carnosic acid, carnosol, rosmarinol, rosmadial, genkwanin, cirsimaritin, rosmarinic acid and caffeic acid in Rosmarinus officinalis L,
*IGF-1↑, rosemary could elevated expression of IGF1, MMP9 and decreased mRNA levels of SRC, MAPK14, compared with the control group.
*MMP9↑,
*Src↓,
*MAPK↓,
*MMP↑, Rosemary reduced Aβ-induced HT22 cell damage in AD models to enhance the mitochondrial membrane potential levels

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↓,

3036- RosA,    Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells
- in-vitro, CRC, HCT8 - in-vitro, CRC, HCT116 - in-vitro, CRC, LS174T
GlucoseCon↓, RA suppressed glucose consumption and lactate generation in colorectal carcinoma cells;
lactateProd↓,
Hif1a↓, RA inhibited the expression of transcription factor hypoxia-inducible factor-1α (HIF-1α) that affects the glycolytic pathway.
Inflam↓, RA could not only repress proinflammatory cytokines using enzyme-linked immunosorbent assay but it could also suppress microRNAs related to inflammation by real-time PCR
miR-155↓, MiR-155 induces the Warburg effect and is reversed by RA
STAT3↓, RA could inhibit the expression of transcription factor STAT3, and it suppressed the phosphorylation of STAT3
Glycolysis↓, Meanwhile, RA inhibited the expression of transcription factor HIF-1α that affected the glycolytic pathway
IL6↓, RA could significantly regulate miR-155 and in turn alter the IL-6/STAT3 signaling, resulting in the inhibition of inflammation in the tumor micro environment and the eventual anti-Warburg effect
Warburg↓,

3035- RosA,    Rosmarinic Acid Decreases the Malignancy of Pancreatic Cancer Through Inhibiting Gli1 Signaling
- in-vitro, PC, NA - in-vivo, NA, NA
Gli1↓, RA dramatically down-regulated Gli1 and its downstream targets
TumCCA↑, RA induced G1/S cell cycle arrest and apoptosis in the PDAC cells through regulating the expression of P21, P27, CDK2, Cyclin E, Bax, and Bcl-2, it inhibited the PDAC cell migration and invasion via E-cadherin and MMP-9.
TumCMig↓,
TumCI↓,
CDK2↓,
cycE↓,
P21↑,
p27↑,

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

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.

3031- RosA,    Effects of rosmarinic acid against aflatoxin B1 and ochratoxin-A-induced cell damage in a human hepatoma cell line (Hep G2)
- in-vitro, Liver, HepG2
ROS↓, Ros A dose dependently attenuated ROS production and DNA and protein synthesis inhibition induced by both of the toxins.

3030- RosA,    Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials
- Review, Var, NA
ROS⇅, could defend against their oxidative damage of DNA, proteins, and lipids [15], although, as subsequently observed, the derivatives of rosemary are, in some conditions, capable of inducing a cytotoxic effect precisely through the release of ROS
*NRF2↑, scavenging action, RE has also been stated to control intracellular antioxidant systems, by stimulating the activation of nuclear transcription factor (Nrf)2 target genes
*GSH↑, augmenting the glutathione level, with an increase in its reduced form (GSH) compared with that of its oxidized form (GSSG)
HDAC2↓, Similar to the effects of SAHA, RA reduced cell growth and blocked cancer spheroid formation, caused the apoptosis of tumor cells, and blocked the expression of HDAC2

3029- RosA,    Rosmarinic Acid, a Component of Rosemary Tea, Induced the Cell Cycle Arrest and Apoptosis through Modulation of HDAC2 Expression in Prostate Cancer Cell Lines
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
TumCP↓, RA decreased the cell proliferation in cell viability assay, and inhibited the colony formation and tumor spheroid formation.
tumCV↓,
Apoptosis↑, RA induced early- and late-stage apoptosis of PC-3 and DU145 cells
HDAC2↓, RA inhibited the expression of HDAC2, as SAHA did
PCNA↓, (PCNA), cyclin D1 and cyclin E1 were downregulated by RA, whereas p21 was upregulated. In addition,
cycD1↓,
cycE↓,
P21↑,
DNAdam↑, apoptotic cells observed by DNA fragmentation were significantly increased
Casp3↑, expression of Caspase-3 was upregulated by SAHA and RA in both cell lines

3039- RosA,    Rosmarinic acid liposomes suppress ferroptosis in ischemic brain via inhibition of TfR1 in BMECs
- in-vivo, Nor, NA - in-vivo, Stroke, NA
*Ferroptosis↓, RosA-LIP inhibited ferroptosis by ameliorating mitochondrial abnormalities, increasing GPX4 levels, and decreasing ACSL4/LPCAT3/Lox-dependent lipid peroxidation.
*GPx4↑,
*ACSL4↓,
*BBB↑, RosA-LIP effectively improved blood‒brain barrier (BBB) permeability, increased tight junctions (TJs) protein expression
*IronCh↑, reduced iron levels in ischemic tissue and brain microvascular endothelial cells (BMECs) by modulating FPN1 and TfR1 levels.
*TfR1/CD71↓, Furthermore, RosA-LIP suppressed TfR1 to attenuate ACSL4/LPCAT3/Lox-mediated ferroptosis in TfR1EC cKO mice subjected to dMCAO.
*neuroP↑, proposed neuroprotection of RosA-LIP during ischemic stroke.

3027- RosA,    Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway
- in-vitro, HCC, SMMC-7721 cell
TumCP↓, RosA significantly inhibited the proliferation of SMMC-7721 cells and induced G1 arrest and apoptosis in a dose-dependent manner
TumCCA↑,
Apoptosis↑,
EMT↓, RosA might inhibit cell invasion by regulating epithelial-mesenchymal transition
TumCI↓,
PI3K↓, IGF-1 could reverse the inhibition of PI3K/AKT/mTOR signal pathway by RosA
Akt↓,
mTOR↓,
TumCMig↓, inhibition effect of migration and invasion by regulation MMPs, Vimentin and EMT.
MMPs↓,
Vim↓,

3026- RosA,    Modulatory Effect of Rosmarinic Acid on H2O2-Induced Adaptive Glycolytic Response in Dermal Fibroblasts
- in-vitro, Nor, NA
*ROS↓, H2O2 caused a significant ROS increase in the cells, and pre-treatment with rosmarinic acid (5–50 µM) decreased ROS significantly in the presence of glutathione
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*HK2↓, (HK-2), phosphofructokinase-2 (PFK-2), and lactate dehydrogenase A (LDHA), were downregulated in cells treated with rosmarinic acid
*PFK2↓,
*LDHA↓,
*GSR↑, GSR), glutathione peroxidase-1 (GPx-1), and peroxiredoxin-1 (Prx-1) and redox protein thioredoxin-1 (Trx-1) were upregulated in treated cells compared to control cells.
*GPx↑,
*Prx↑,
*Trx↑,
*antiOx↑, To sum up, the rosmarinic acid could be used as an antioxidant against H2O2-induced adaptive responses in fibroblasts by modulating glucose metabolism, glycolytic genes, and GSH production.
*GSH↑, The pre-treatment of rosmarinic acid could raise intracellular GSH to protect cells from ROS
*ROS↓, rosmarinic acid pre-treatment reduced the amount of ROS in the fibroblasts upon the addition of H2O2
*GlucoseCon↓, both compounds also decreased glucose consumption and lactate production
*lactateProd↓,
*Glycolysis↝, The results indicated that rosmarinic acid is able to shape cellular glucose utilization, glycolysis, and GSH.
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*PPP↓,

3025- RosA,    Rosmarinic acid alleviates intestinal inflammatory damage and inhibits endoplasmic reticulum stress and smooth muscle contraction abnormalities in intestinal tissues by regulating gut microbiota
- in-vivo, IBD, NA
*GutMicro↑, RA upregulated the abundance of Lactobacillus johnsonii and Candidatus Arthromitus sp SFB-mouse-NL and downregulated the abundance of Bifidobacterium pseudolongum, Escherichia coli, and Romboutsia ilealis.
*ROCK1↓, RA downregulated the expressions of ROCK, RhoA, CaM, MLC, MLCK, ZEB1, ZO-1, ZO-2, occludin, E-cadherin, IL-1β, IL-6, TNF-α, GRP78, PERK, IRE1, ATF6, CHOP, Caspase12, Caspase9, Caspase3, Bax, Cytc, RIPK1, RIPK3, MLKL
*Rho↓,
*CaMKII ↓,
*Zeb1↓,
*ZO-1↓,
*E-cadherin↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*GRP78/BiP↓,
*PERK↓,
*IRE1↓,
*ATF6↓,
*CHOP↓,
*Casp12↓,
*Casp9↓,
*BAX↓,
*Casp3↓,
*Cyt‑c↓,
*RIP1↓,
*MLKL↓,
*IL10↑, upregulated the expression of IL-10 and Bcl-2.
*Bcl-2↑,
*ER Stress↓, RA inhibited the inflammation, which is caused by tight junction damage, by repairing intestinal flora dysbiosis, relieved endoplasmic reticulum stress, inhibited cell death

3024- RosA,    rmMANF prevents sepsis-associated lung injury via inhibiting endoplasmic reticulum stress-induced ferroptosis in mice
- in-vivo, Sepsis, NA
*Ferroptosis↓, rmMANF pretreatment inhibits ferroptosis by suppressing GRP78/PERK/ATF4 axis.
*GRP78/BiP↓,
*PERK↓,
*ATF4↓,
*Sepsis↓,
*GSH↑, LPS administration mice exhibited elevated MDA immunoactivity, total iron level, and declined GSH level, and SOD, CAT activities, while these effects of LPS were effectively against by rmMANF pretreatment
*SOD↑,
*Catalase↑,

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↑, RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement,
*Inflam↓, decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice.
*ER Stress↓,
*Ferroptosis↓, the anti-ferroptosis effect of RA in LPS-induced septic
*Sepsis↓,
*GRP78/BiP↓, Previously, we reported that RA markedly ameliorated septic-associated mortality and lung injury via inhibiting GRP78/IRE1α/JNK pathway-mediated ERS
*IRE1↓,
JNK↓,

3038- RosA,    Prooxidant action of rosmarinic acid: transition metal-dependent generation of reactive oxygen species
- in-vitro, Nor, NA
IronCh↑, rosmarinic acid may be related to the prooxidant action resulting from metal-reducing activity
ROS↑, Rosmarinic acid and caVeic acid could act as prooxidants by generating reactive oxygen species, which was demonstrated by the inactivation of aconitase, the most sensitive to reactive oxygen species

1048- RosA,  Ger,    Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis
- in-vivo, Colon, MC38
TumCMig↓,
TumCI↓,
PD-1↓, RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1
COX2↓,
PD-L1↓,

3615- RosA,    Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer's Disease, Parkinson's Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome
- Review, AD, NA - Review, Park, NA
*NLRP3↓, potential applications of CA and CS for Alzheimer’s disease (AD), Parkinson’s disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome
*Inflam↓, CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation.
*neuroP↑,
*NRF2↑,
*TNF-α↓, CA can suppress the TNF-α signaling pathway by inhibiting the inhibitor of nuclear factor κ-B (NF-κB) as well as via upregulation of HO-1 expression
*NF-kB↓,
*HO-1↑,
*ROS↓, NRF2 activators would be expected to downregulate ROS and hence limit NLRP3 inflammasome activation

3616- RosA,    Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders
- Review, AD, NA
*Inflam↓, worthy source for curing inflammation, analgesic, anti-anxiety, and memory boosting.
*memory↑,
*toxicity↓, Rosmarinic acid was observed to have very scarce toxicity with an LD50 of 561 mg/kg in mice
*ROS↓, Figure 1
*Catalase↑,
*SOD↑,
*NRF2↑,
*Aβ↓,
*AChE↓, decreased hippocampal AChE activity in bulbectomized mice.
*Ca+2↓,
*NO↓,
*IL2↓,
*COX2↓,
*PGE2↓,
*MMPs↓,
*TNF-α↓,
*iNOS↓,
*TLR4↓,
*cognitive↑, These cognitive-enhancing effects of rosmarinic acid might be beneficial to populations of advanced age
*cortisol↓, aroma of rosemary oil improved performance in exam students by enhancing free radical scavenging activity and decreasing cortisol levels
*lipid-P↓, Anti-oxidant components of rosemary extract (250, 500 and 750 mg/kg) reduced lipid peroxidation

3617- RosA,  Aroma,    Effect of aromatherapy on patients with Alzheimer's disease
- in-vivo, AD, NA
*other↝, Aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening
*cognitive↑, All patients showed significant improvement in personal orientation related to cognitive function on both the GBSS-J and TDAS after therapy.
*motorD↑, In addition, some improvement in movement was noted

3618- RosA,    Antioxidant and Antimicrobial Properties of Rosemary (Rosmarinus officinalis, L.): A Review
- Review, AD, NA
*hepatoP↑, rosemary extracts show biological bioactivities such as hepatoprotective, antifungal, insecticide, antioxidant and antibacterial.
*antiOx↑,
*angioG↓, Rosemary extracts have been used in the treatment of diseases, due to its hepatoprotective potential [6], therapeutic potential for Alzheimer’s disease [7] and its antiangiogenic effect [
*other↓, used in food preservation, because they prevent oxidation
*Inflam↓, properties such as anti-inflammatory [32], antidiabetic [33], hepatoprotective [34] and antimicrobial activity
*ROS↓, antioxidant properties of rosemary are attributed to its richness in isoprenoid quinones, which act as chain terminators of free radicals, and as chelators of reactive oxygen species (ROS)
*IronCh↑, Fang and Wada [39] pointed out that these compounds could act as metal ion chelators (Fe+2 fundamentally)
*lipid-P↓, main constituents with antioxidant properties are carnosic acid and carnosol that are responsible for 90% of the properties. Both are inhibitors of lipid peroxidation
*antiOx↑, In addition, rosemary has been added as an antioxidant in oils:

3619- RosA,    Rosmarinic acid suppresses Alzheimer’s disease development by reducing amyloid β aggregation by increasing monoamine secretion
- Review, AD, NA
*BioAv↓, confirmed that the intestinal permeability of RA is <1% of its intake volume
*BBB↝, migrates to the brain with difficulty due to the presence of the BBB
*monoA↑, RA administration increases monoamines in the brain
*TGF-β↓, Several studies have reported that RA suppresses the expression of Tgf-β1 in vivo and in vitro2
*Aβ↓, Suppression of Aβ aggregation by DA and other monoamines

3620- RosA,    Rosmarinus officinalis and Methylphenidate Exposure Improves Cognition and Depression and Regulates Anxiety-Like Behavior in AlCl3-Induced Mouse Model of Alzheimer's Disease
- in-vivo, AD, NA
*antiOx↑, potentially known to have antioxidant and anti-inflammatory properties
*Inflam↓,
*memory↑, R. officinalis improved cognitive abilities, it did not reduce the amyloid plaque burden
*Aβ∅,
*GutMicro↑, rebalanced gut  microbiota

3621- RosA,    Short-Term Study on the Effects of Rosemary on Cognitive Function in an Elderly Population
- Trial, AD, NA
*cognitive↑, the lowest dose (750 mg) of rosemary had a statistically significant beneficial
*Dose↝, whereas the highest dose (6,000 mg) had a significant impairing effect
*BioAv↑, ursolic acid, rosmarinic acid, and carnosic acid found in rosemary are bioavailable and have characterized physiological effects that may influence cognitive functioning.

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↓, RA (10 mg/kg) significantly reduced the level of lipid peroxidation in hippocampus
*AChE↓, AChE in hippocampus (58%), cortex (46%) and striatum (30%) in comparison with the control. On the other hand, the treatment with RA reversed this effect to the level of control after 3 weeks

3623- RosA,    Rosmarinic acid inhibits some metabolic enzymes including glutathione S-transferase, lactoperoxidase, acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase isoenzymes
- in-vitro, AD, NA
*AChE↓, best inhibitory effect of rosmarinic acid was observed against both AChE and BChE.

3632- RosA,  CA,  QC,    Evolving Role of Natural Products from Traditional Medicinal Herbs in the Treatment of Alzheimer's Disease
- Review, AD, NA
*AChE↓, rosmarinic acid, carnosic acid, quercetin, and isorosmanol were isolated from Saliva species, and these constituents also showed the reduction in AChE activity

3755- RosA,  CUR,    Development of Acetylcholinesterase (AChE) Inhibitor
- Study, AD, NA
*AChE↓, rosmarinic acid and curcumin possess antioxidant and anti-inflammatory properties yet able to bind uniquely and inhibit the activity of AChE
*antiOx↑,
*Inflam↓,

3757- RosA,  Sage,  Croc,  NarG,  Caff  Food-derived Acetylcholinesterase Inhibitors as Potential Agents against Alzheimer’s Disease
- Review, AD, NA
AChE↓, Saffron components have also been demonstrated as strong AChE inhibitors with IC50 values of 21.09, 96.33 and 107.1 µM for safranal, crocetin and dimethylcrocetin, respectively

3792- RosA,    Molecular docking and dynamics simulations revealed the potential inhibitory activity of honey-iQfood ingredients against GSK-3β and CDK5 protein targets for brain health
- Analysis, AD, NA
*CDK5↓, Two potential compounds, andrographolide, and rosmarinic acid, produced the best binding affinities following the molecular docking of the active compounds against the GSK-3β and CDK5 targets.
*GSK‐3β↓,

3021- RosA,    Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway
- in-vivo, Sepsis, NA
*eff↑, RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury.
*SOD↑, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity.
*MDA↓,
*GRP78/BiP↓, LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment.
*IRE1↓,
*JNK↓,
*Sepsis↓,

106- RosA,    Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells
- in-vivo, BC, MCF-7

1742- RosA,    Rosmarinic acid, a natural polyphenol, has a potential pro-oxidant risk via NADH-mediated oxidative DNA damage
- Analysis, Var, NA
ROS↑, RA plus Cu(II), but not Fe(III), significantly increased 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) formation, an indicator of oxidative DNA damage, in calf thymus DNA
eff↑, RA plus Cu(II) caused DNA cleavage, which was enhanced by piperidine treatment, suggesting that RA causes not only DNA strand breakage but also base modification.
eff↑, metals such as copper and iron could be associated with the pro-oxidant risk of RA;
eff↑, Interestingly, the addition of NADH markedly enhanced 8-oxodG formation by RA plus Cu(II) (approximately 30-fold increase at 0.1–0.5 µM) (Fig. 1B). On the other hand, RA plus Fe(III) did not increase 8-oxodG formation even in the presence of NADH
eff↑, RA caused DNA cleavage in a concentration-dependent manner, and piperidine treatment enhanced DNA cleavage.
eff↓, Catalase, an H2O2 scavenger, and bathocuproine, a Cu(I)-specific chelator [26], inhibited DNA damage induced by RA plus Cu(II)
Dose↝, The maximum serum concentration of RA was reported to reach approximately 0.16 µM after the administration of plant extracts containing 500 mg of RA in humans
Dose↝, In this study, 0.1 µM RA induced oxidative DNA damage in the presence of physiologically relevant concentrations of Cu(II) (20 µM) [35] and NADH (100 µM)

1743- RosA,    New insights into the competition between antioxidant activities and pro-oxidant risks of rosmarinic acid
- Analysis, Var, NA
ROS↑, Finally, the pro-oxidant risk of RA− was also considered via the Fe(iii)-to-Fe(ii) complex reduction process, which may initiate Fenton-like reactions forming reactive HO˙ radicals.
Fenton↑,
eff↑, RA− does not enhance the reduction process when ascorbate anions are present as reducing agents, whereas the pro-oxidant risk becomes remarkable when superoxide anions are found
antiOx↑, The antioxidant activity of RA in this studied system is remarkably higher than that of trolox, ascorbic acid and taxifolin
Iron↓, it is noteworthy that RA− represents strong chelating ability towards both Fe(ii) and Fe(iii) ions compared to its neutral form RA
ROS↑, it is noteworthy that RA− represents strong chelating ability towards both Fe(ii) and Fe(iii) ions compared to its neutral form RA

1744- RosA,    Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity
- Review, Var, NA
chemoR↓, Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics
ChemoSideEff↓, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy
RadioS↑, RA decreased radiation-induced ROS with RA by 21% compared to control
ROS↓, mainly due to its scavenger capacity
ChemoSen↑, recent years, evidence has emerged demonstrating the ability of RA to act as a chemosensitizer
BioAv↑, bioavailability of RA have been studied in animal models, revealing rapid absorption in the stomach and intestine
Half-Life↝, Urine was the primary route of RA excretion, with 83% of the total metabolites excreted during the period from 8 to 18 h after RA administration
antiOx↑, RA, well known for its antioxidant properties,
ROS↑, has recently been identified as a potential pro-oxidant in the presence of superoxide anions.
Fenton↑, Studies indicate that RA can facilitate the reduction of Cu (II) to Cu (I) and Fe (III) to Fe (II) leading to Fenton-type reactions that generate reactive hydroxyl radicals (HO˙)
DNAdam↑, These radicals are implicated in DNA damage and induction of apoptosis in cancer cells
Apoptosis↑,
CSCs↓, RA has demonstrated potential in controlling breast cancer stem cells (CSCs)
HH↓, RA inhibits stem-like breast cancer cells by targeting the hedgehog signaling pathway and modulating the Bcl-2/Bax ratio at concentrations of 270 and 810 μM
Bax:Bcl2↑,
MDR1↓, It has been observed to downregulate P-glycoprotein (P-gp) expression and decrease MDR1 gene transcription, thereby reversing MDR.
P-gp↓,
eff↑, RA has been reported to modulate the ADAM17/EGFR/AKT/GSK3β signaling axis in A375 melanoma cells, potentially enhancing synergy with cisplatin
eff↑, RA has demonstrated effectiveness in enhancing chemosensitivity to 5-FU, a commonly used chemotherapy agent for gastrointestinal cancers.
FOXO4↑, By upregulating FOXO4 expression, RA restored the sensitivity of cells to 5-FU
*eff↑, RA has been shown to reduce DOX-induced apoptosis in H9c2 cardiac muscle cells, and reduce intracellular ROS generation through downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as to restore the
*ROS↓,
*JNK↓,
*ERK↓,
*GSH↑, RA has also shown an antioxidant role, which is evidenced by the ability and recovery of levels of glutathione (GSH), hydrogen peroxide (H2O2), and superoxide radicals (O2·), reducing the expression of malondialdehyde
*H2O2↑,
*MDA↓,
*SOD↑, regulating the expression of antioxidant enzymes such as superoxide dismutase (SOD), as well as upregulating catalase heme oxygenase-1, resulting in significantly improved viability
*HO-1↑,
*CardioT↓, The cardioprotective effect of RA
selectivity↑, RA blocked caspases 3 and 9 activation, cytochrome c release, and ROS generation induced by cisplatin in HEI-OC1(normal)cells

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

1746- RosA,    Rosmarinic acid sensitizes cell death through suppression of TNF-α-induced NF-κB activation and ROS generation in human leukemia U937 cells
- in-vitro, AML, U937
TNF-α↓, Rosmarinic acid (RA), a naturally occurring polyphenol flavonoid, has been reported to inhibit TNF-α-induced NF-κB activation in human dermal fibroblasts.
ROS↓, RA treatment significantly sensitizes TNF-α-induced apoptosis in human leukemia U937 cells through the suppression of nuclear transcription factor-kappaB (NF-κB) and reactive oxygen species (ROS).
Casp↑, Activation of caspases in response to TNF-α was markedly increased by RA treatment
NF-kB↓, RA also suppressed NF-κB activation through inhibition of phosphorylation and degradation of IκBα, and nuclear translocation of p50 and p65
IκB↓,
p50↓,
p65↓,
IAP1↓, This inhibition was correlated with suppression of NF-κB-dependent anti-apoptotic proteins (IAP-1, IAP-2, and XIAP)
IAP2↓,
XIAP↓,
Apoptosis↑, These results demonstrated that RA inhibits TNF-α-induced ROS generation and NF-κB activation, and enhances TNF-α-induced apoptosis.

1747- RosA,    Molecular Pathways of Rosmarinic Acid Anticancer Activity in Triple-Negative Breast Cancer Cells: A Literature Review
- Review, BC, MDA-MB-231 - Review, BC, MDA-MB-468
TumCCA↑, Rosmarinic Acid arrests the G0/G1 phase in MDA-MB-231 cells and the S-phase in MDA-MB-468 cells following apoptosis (interruption of the G2/M process).
TNF-α↑, Rosmarinic Acid enhanced the expression of TNF (tumor necrosis factor), GADD45A (growth arrest and DNA damage-inducible 45 alpha), and the proapoptotic BNIP3
GADD45A↑,
BNIP3↑,
survivin↓, IRC5 (Survivin) inhibition appears to be the most important effect of Rosmarinic Acid on MDA-MB-468 cells
Bcl-2↓, Bcl-2 gene is downregulated while the Bax gene expression is increased in the presence of Rosmarinic Acid
BAX↑,
HH↓, The experiments showed that Rosmarinic Acid inhibited Hh signaling genes’ expression in BCSCs.
eff↑, rosemary extract with Rosmarinic Acid and carnosic acid as primary ingredients inhibited cancer cell viability in the ER+, HER2+, and TNBC subtypes (MDA-MB-231 and MDA-MB-468 cells)
ChemoSen↑, The inhibition of NF-κB increases chemotherapy and radiation results
RadioS↑,
TumCP↓, In vitro experiments in MDA-MB-231 cancer cells treated with Rosmarinic Acid have shown that proliferation and migration were significantly attenuated, and eventually, cells were led to apoptosis
TumCMig↓,
Apoptosis↑,
RenoP↑, Rosmarinic Acid decreased the hepatic and renal toxicity induced by methotrexate, as well as the cardiotoxicity of doxorubicin
CardioT↓,

1748- RosA,    The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity
- Review, Var, NA
AntiCan↑, RA exhibits significant potential as a natural agent for cancer prevention and treatment
*BioAv↝, Various factors, including its lipophilic nature, stability in the gastrointestinal tract, and interactions with food, can significantly influence its absorption
*CardioT↓, RA attenuated these effects by reducing ROS levels, indicating its potential role as a cardioprotective agent during chemotherapy.
*Iron↓, Another significant mechanism antioxidant activity of RA is its capacity to chelate transition metal ions, particularly iron (Fe2+) and copper (Cu2+), which can catalyze the formation of highly reactive hydroxyl radicals through the Fenton reaction.
*ROS↓, forming stable complexes with Fe2+ and Cu2+, thus inhibiting their pro-oxidant activity.
*SOD↑, SOD, CAT, and GPx, play crucial roles in neutralizing ROS and maintaining cellular redox homeostasis. RA upregulates the expression and activity of these enzymes
*Catalase↑,
*GPx↑,
*NRF2↑, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a primary regulator of the antioxidant response
MARK4↓, Anwar’s study demonstrated that RA inhibited MARK4 activity in MDA-MB-231 breast cancer cells, resulting in dose-dependent apoptosis
MMP9↓, RA effectively inhibited cancer cell invasion and migration by reducing matrix metalloproteinase-9 (MMP-9) activity
TumCCA↑, caused cell cycle arrest
Bcl-2↓, RA downregulates Bcl-2 expression and upregulates Bax, thereby promoting apoptosis
BAX↑,
Apoptosis↑,
E-cadherin↑, promoting E-cadherin expression, while downregulating N-cadherin and vimentin
N-cadherin↓,
Vim↓,
Gli1↓, induced apoptosis by downregulating Gli1, a key component of the Hedgehog signaling pathway,
HDAC2↓, RA induced apoptosis by modulating histone deacetylase 2 (HDAC2) expression
Warburg↓, anti-Warburg effect of RA in colorectal carcinoma
Hif1a↓, RA inhibits hypoxia-inducible factor-1 alpha (HIF-1α) and downregulates miR-155
miR-155↓,
p‑PI3K↑, RA has been shown to upregulate p-PI3K, protecting cells through the PI3K/Akt pathway,
ROS↑, RA, induces significant ROS generation in A549 cells, which triggers both apoptosis and autophagy.
*IronCh↑, 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,

1749- RosA,    Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer
- Review, Var, NA
antiOx↑, Rosmarinic acid (RA) is known for its excellent antioxidant properties and is safe and effective in preventing and inhibiting tumors
eff↑, Research has shown that foliar spraying with NO and Si and under Cu stress in S. officinalis elevated total RA content by 2-fold above control leaves.
*toxicity↝, For toxicology, a dose of 169.6 ± 32.4 mg/kg in Kunming mice (6 weeks old) was shown to be lethal, indicating that RA was slightly toxic
*BioAv↑, RA–phospholipid complexes increased oral bioavailability through enhanced intestinal permeability
*ROS↓, RA had the function of scavenging free radicals, including ROS and H2O2, and enhanced antioxidant enzymes and non-enzymic antioxidants
SOD↑, RA enhanced SOD, CAT, and glutathione peroxidase (GPx) activities and reduced lipid peroxidation and cytochrome P450, significantly reducing DMH-induced intestinal polyps in vivo
Catalase↑,
GPx↑,
lipid-P↓,
P450↓,
chemoP↑, RA protected ovaries without attenuating the anti-tumor effect of cisplatin
hepatoP↑, RA improved the hepatorenal toxicity induced by methotrexate
ChemoSen↑, RA acts as a chemosensitizer in a ROS-independent manner to inhibit DNA damage repair, thereby negatively responding to DNA damage

3001- RosA,    Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review
- Review, Var, NA
TumCP↓, including in tumor cell proliferation, apoptosis, metastasis, and inflammation
Apoptosis↑,
TumMeta↓,
Inflam↓,
*antiOx↑, RA is therefore considered to be the strongest antioxidant of all hydroxycinnamic acid derivatives
*AntiAge↑, , it also exerts powerful antimicrobial, anti-inflammatory, antioxidant and even antidepressant, anti-aging effects
*ROS↓, RA and its metabolites can directly neutralize reactive oxygen species (ROS) [10] and thereby reduce the formation of oxidative damage products.
BioAv↑, RA is water-soluble, and according to literature data, the efficacy of secretion of this compound in infusions is about 90%
Dose↝, Accordingly, it is possible to consume approximately 110 mg RA daily, i.e., approximately 1.6 mg/kg for adult men weighing 70 kg.
NRF2↑, liver cancer cell line, HepG2, transfected with plasmid containing ARE-luciferin gene, RA predominantly enhances ARE-luciferin activity and promotes nuclear factor E2-related factor-2 (Nrf2) translocation from cytoplasm to the nucleus
P-gp↑, and also increases MRP2 and P-gp efflux activity along with intercellular ATP level
ATP↑,
MMPs↓, RA concurrently induced necrosis and apoptosis and stimulated MMP dysfunction activated PARP-cleavage and caspase-independent apoptosis.
cl‑PARP↓,
Hif1a↓, inhibits transcription factor hypoxia-inducible factor-1α (HIF-1α) expression
GlucoseCon↓, it also suppressed glucose consumption and lactate production in colorectal cells
lactateProd↓,
Warburg↓, may suppress the Warburg effects through an inflammatory pathway involving activator of transcription-3 (STAT3) and signal transducer of interleukin (IL)-6
TNF-α↓, RA supplementation also reduced tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and IL-6 levels, and modulated p65 expression [
COX2↓,
IL6↓,
HDAC2↓, RA induced the cell cycle arrest and apoptosis in prostate cancer cell lines (PCa, PC-3, and DU145) [31]. These effects were mediated through modulation of histone deacetylases expression (HDACs), specifically HDAC2;
GSH↑, RA can also inhibit adhesion, invasion, and migration of Ls 174-T human colon carcinoma cells through enhancing GSH levels and decreasing ROS levels
ROS↓,
ChemoSen↑, RA also enhances chemosensitivity of human resistant gastric carcinoma SGC7901 cells
*BG↓, RA significantly increased insulin index sensitivity and reduced blood glucose, advanced glycation end-products, HbA1c, IL-1β, TNFα, IL-6, p-JNK, P38 mitogen-activated protein kinase (MAPK), and NF-κB levels
*IL1β↓,
*TNF-α↓,
*IL6↓,
*p‑JNK↓,
*p38↓,
*Catalase↑, The reduced activities of CAT, SOD, glutathione S-transferases (GST), and glutathione peroxidase (GPx) and the reduced levels of vitamins C and E, ceruloplasmin, and GSH in plasma of diabetic rats were also significantly recovered by RA application
*SOD↑,
*GSTs↑,
*VitC↑,
*VitE↑,
*GSH↑,
*GutMicro↑, protective effects of RA (30 mg/kg) against hypoglycemia, hyperlipidemia, oxidative stress, and an imbalanced gut microbiota architecture was studied in diabetic rats.
*cardioP↑, Cardioprotective Activity: RA also reduced fasting serum levels of vascular cell adhesion molecule 1 (VCAM-1), inter-cellular adhesion molecule 1 (ICAM-1), plasminogen-activator-inhibitor-1 (PAI-1), and increased GPX and SOD levels
*ROS↓, Finally, in H9c2 cardiac muscle cells, RA inhibited apoptosis by decreasing intracellular ROS generation and recovering mitochondria membrane potential
*MMP↓,
*lipid-P↓, At once, RA suppresses lipid peroxidation (LPO) and ROS generation, whereas in HSC-T6 cells it increases cellular GSH.
*NRF2↑, Additionally, it significantly increases Nrf2 translocation
*hepatoP↑, Hepatoprotective Activity
*neuroP↑, Nephroprotective Activity
*P450↑, RA also reduced CP-produced oxidative stress and amplified cytochrome P450 2E1 (CYP2E1), HO-1, and renal-4-hydroxynonenal expression.
*HO-1↑,
*AntiAge↑, Anti-Aging Activity
*motorD↓, A significantly delays motor neuron dysfunction in paw grip endurance tests,

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

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

3004- RosA,    Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system
- in-vitro, Nor, HSC-T6
*GSH↑, increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity
*MMP2↓,
*ROS↓, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells.
*lipid-P↓,
*NRF2↑, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)

3005- RosA,    Nanoformulated rosemary extract impact on oral cancer: in vitro study
- in-vitro, Laryn, HEp2
TumCCA↑, They induced apoptotic changes as well as cell cycle arrest at G2/M phase. They enhanced ROS expression in cancer cells
ROS↑, The treatment of cancer cells with RE leads to a strong increase in intracellular ROS that results in cell death.
Bcl-2↓,
BAX↑,
Casp3↑,
P53↑,
necrosis↑, RE in a dose of 20–40 µg/ml resulted in an obvious increase in ROS intracellularly which guided cells toward necrosis and death.
eff↑, Chitosan was chosen as a nanodrug delivery in our research as per our aim, and we intended to offer a locally acting formula that may be applicable in managing oral cancerous lesions. Chitosan has a penetration capability as it is able to open tight
BioAv↑, chitosan nanoparticles, an increase in the surface-to-volume ratio occurs as well as the specific surface area. This enhances the dissolution of poorly water-soluble drugs so increases their bioavailability.

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

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↓, • RA decreases viability and inhibits migration of human metastatic melanoma cells.
TumCMig↓,
ROS↓, RA decreases extracellular and intracellular ROS, and improvements in NPSH and PSH levels.
Casp3↑, RA modulates expression of apoptosis-related genes and increases the enzymatic activity of caspase 3 protein.
selectivity↑, On the other hand, it has no cytotoxic effect on non-tumoral cells.
Casp8↑, RA strongly upregulates the gene expression of the caspase 8 and caspase 3, and downregulates NLRP3 inflammasome expression.
NLRP3↓,

3022- RosA,    Rosmarinic acid against cognitive impairment via RACK1/HIF-1α regulated microglial polarization in sepsis-surviving mice
- in-vitro, Sepsis, NA
*cognitive↑, Rosmarinic acid alleviates cognitive impairment and glycolytic metabolism abnormality in sepsis mice model.
*neuroP↑, Rosmarinic acid attenuates neuronal injury and microglial activation.
*GlucoseCon↑, promoted whole-brain glucose uptake in mice.
*Hif1a↓, (rescued the decrease of RACK1 and increase of HIF-1α)

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↑, 20 and 40 mg/kg RA significantly improve endotoxin-induced cognitive dysfunction without dose differences
*PERK↓, 40 mg/kg RA treatment significantly decreased the hippocampal level of PERK protein
*GRP78/BiP↓, 120 μM RA pretreatment significantly inhibited LPS-conditioned culture-induced GRP78, PERK, and MANF upregulation in vitro.
*ER Stress↓, improving cognitive impairment and suppressing the endoplasmic reticulum stress mediated by the GRP78/IRE1α/JNK pathway.

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↝, Experiments in rats demonstrated that RA applied topically to skin was absorbed percutaneously and became distributed in skin, blood, bone and muscle while intravenously administered RA was distributed in various tissues such as lung, spleen, heart a
*Half-Life↝, RA compounds (free and conjugate forms) reached a maximum concentration of 4.63 Amol/l 0.5 h after RA administration.
*Half-Life↑, e maximum COA concentration of 0.75 Amol/l was reached gradually, peaking at 8 h post-intake
*Half-Life↝, About 83% of this excretion occurred within the period 8 to 18 h after RA administration
*BioAv↑, This result shows that orally administered RA was rapidly absorbed from the digestive tract.

3018- RosA,    Rosemary (Rosmarinus officinalis L.) polyphenols and inflammatory bowel diseases: Major phytochemicals, functional properties, and health effects
- Review, IBD, NA
*Inflam↓, rosemary polyphenols have the potential to decrease the severity of intestinal inflammation.
*GutMicro↑, including improved gut barrier (increased mucus secretion and tight junction), increased antioxidant enzymes,
*antiOx↑,
*NF-kB↓, inhibiting inflammatory pathways and cytokines (downregulation of NF-κB, NLRP3 inflammasomes, STAT3 and activation of Nrf2), and modulating gut microbiota community
*NLRP3↓,
*STAT3↓,
*NRF2↑,

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∅, We found that PSO and RA-RF were not toxic to TNF-α-induced A549 cells.
ROS↓, Both extracts significantly decreased the generation of reactive oxygen species (ROS) in this cell line.
IL1β↓, mRNA expression levels of IL-1β, IL-6, IL-8, TNF-α, and COX-2 were significantly decreased by the treatment of PSO and RA-RF.
IL6↓,
IL8↓,
TNF-α↓,
COX2↓,
SOD2↓, MnSOD, FOXO1, and NF-κB and phosphorylation of JNK were also significantly diminished by PSO and RA-RF treatment
FOXO1↓,
NF-kB↓,
JNK↓,
antiOx↑, PSO and RA-RF act as antioxidants
tumCV∅, PSO and RA-RF had no effect on A549 cell viability.

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↓, RA as an inhibitor of epidermal growth factor (EGF) st
tumCV↓, RA inhibited cell viability, migration and cellular production of ROS in HNSCC cell lines.
TumCMig↓,
ROS↓,
PI3K↓, down-regulation of the phosphatidylinositol 3-kinase Akt (PI3K/Akt) and mitogen-activated protein kinase ERK (MAPK/ERK) pathways.
Akt↓,
ERK↓,
antiOx↑, RA serves as a potent antioxidant in HNSCC
p‑EGFR↓, RA’s ability to attenuate EGFR phosphorylation

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↑, RA reduced X-ray-induced the expression of inflammatory related factors, and the level of reactive oxygen species.
*Inflam↓,
*ROS↓,
*NF-kB↓, RA down-regulated the phosphorylation of nuclear factor kappa-B (NF-κB)
*Rho↓, RA attenuated RhoA/Rock signaling through upregulating miR-19b-3p, leading to the inhibition of fibrosis.
*ROCK1↓,
*other↓, Rosmarinic Acid Inhibits MYPT1 Expression by Up-Regulating miR-19b-3p

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↑, Rats in Group 4 (cadmium-exposed and Rosmarinic acid-accessed) exhibited increased levels of total proteins, a significant increase in the levels of antioxidant markers including total thiols, glutathione, total antioxidant capacity (TAC),
*Thiols↑,
*GSH↑,
*TAC↑, decreased levels of total thiols, GSH, catalase, and TAC
*SOD↑, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase, and a significant decrease in the levels of blood cadmium, ALP, ALT, AST, creatinine, blood urea nitrogen (BUN), urea, bilirubin, and oxidation markers (H2O2, and MDA
*GPx↑,
*Catalase↑,
*ALP↓,
*ALAT↓,
*AST↓,
*creat↓,
*BUN↓,
*H2O2↓,
*MDA↓,
*ROS↓, significantly help attenuate the oxidative stress induced by cadmium
cardioP↑, benefits of RA are attributed to its anti-cancer, anti-depressive, antiallergic, anti-inflammatory, anti-angiogenic, cardioprotective, hepatoprotective, nephroprotective, neuroprotective, antimicrobial, hypoglycemic, and hypolipidemic bioactivities
hepatoP↑,
neuroP↑,

3013- RosA,    Rosmarinic acid inhibits angiogenesis and its mechanism of action in vitro
- in-vitro, NA, NA
*BioAv↑, Rosmarinic acid (RA), a water-soluble polyphenolic compound with anti-oxidative and anti-inflammatory activities
*antiOx↑,
*Inflam↓,
*ROS↓, RA also reduced intracellular reactive oxygen species (ROS) level, H2O2-dependent VEGF expression and IL-8 release of endothelial cells.
*VEGF↓,
*IL8↓,

3012- RosA,  Rad,    Rosmarinic Acid Prevents Radiation-Induced Pulmonary Fibrosis Through Attenuation of ROSMYPT1TGFβ1 Signaling Via miR-19b-3p
- in-vitro, Nor, IMR90
*Inflam↓, RA reduced X-ray-induced the expression of inflammatory related factors, and the level of reactive oxygen species.
*ROS↓,
*p‑NF-kB↓, RA down-regulated the phosphorylation of nuclear factor kappa-B (NF-κB).
*Rho↓, RA attenuated RhoA/Rock signaling through upregulating miR-19b-3p, leading to the inhibition of fibrosis
*ROCK1↓,
*radioP↑, RA attenuated radiation- induced damage by its capacity to relieve inflammation and regulate inflammatory factors.
*MCP1↓, RA treatment reduced RNA levels of NF-kB target gene, including MCP-1, RANTES, and ICAM-1
*RANTES↓,
*ICAM-1↓,
*PGC1A↑, Western blot analysis showed that RA promoted the expression of PGC-1a and reduced the expression of NOX-4, this evidence further suggested that RA inhibits the generation of ROS
*NOX4↓,
*Dose↝, RA exerted strongly protective effects in the X-ray-induced inflammation at doses of 60 mg/kg, and treat- ment with a higher dose (120 mg/kg) do not enhance its anti- inflammatory effect.

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↓, rosmarinic acid (RA) as a potential inhibitor of MARK4.
p‑tau↓, suggesting that RA treatment decreases phosphorylation of tau as compared to untreated cells
selectivity↑, RA did not affect the viability of HEK293 and MCF-10A cells
*toxicity∅, studied concentration range RA has no cytotoxic activity for non-cancer cells, on the other hand, they have significant cytotoxicity for cancer cells.

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

3009- RosA,    Rosmarinic acid sensitizes cell death through suppression of TNF-alpha-induced NF-kappaB activation and ROS generation in human leukemia U937 cells
- in-vitro, AML, U937
TNF-α↓, Rosmarinic acid (RA), a naturally occurring polyphenol flavonoid, has been reported to inhibit TNF-alpha-induced NF-kappaB activation in human dermal fibroblasts
NF-kB↓, RA treatment significantly sensitizes TNF-alpha-induced apoptosis in human leukemia U937 cells through the suppression of nuclear transcription factor-kappaB (NF-kappaB) and reactive oxygen species (ROS).
ROS↓,
IAP1↓, This inhibition was correlated with suppression of NF-kappaB-dependent anti-apoptotic proteins (IAP-1, IAP-2, and XIAP).
IAP2↓,
XIAP↓,

3007- RosA,    Hepatoprotective effects of rosmarinic acid: Insight into its mechanisms of action
- Review, NA, NA
*ROS↓, antioxidant properties as a ROS scavenger and lipid peroxidation inhibitor, anti-inflammatory, neuroprotective and antiangiogenic among others.
*lipid-P↓,
*Inflam↓,
*neuroP↑,
*angioG↓,
*eff↑, The hepatoprotective effects of RA alone and in combination with caffeic acid (CA) was reported in t-BHP-induced oxidative liver damage
*AST↓, significant reduction of indicators of hepatic toxicity, such as AST, ALT, GSSG, lipid peroxidation.
*ALAT↓,
*GSSG↓,
*eNOS↓, It also reduced the liver content of eNOS/iNOS and NO, attenuated NF-κB activation
*iNOS↓,
*NO↓,
*NF-kB↓,
*MMP2↓, It inhibited MMP-2 activity and suppressed ROS generation and lipid peroxidation.
*MDA↓, It also decreased malondialdehyde (MDA) and TNF-α levels while increasing GSH levels as well as SOD and GSH-Px activities in the livers and kidneys.
*TNF-α↓,
*GSH↑,
*SOD↑,
*IL6↓, RA decreased the hepatic level of IL-6, TNF-Alpha, and PGE2, as well as the activity of COX-2 It also decreased hepatic RAGE and sorbitol levels, and GLO-1 activity
*PGE2↓,
*COX2↓,
*mTOR↑, In the study, it was observed that RA stimulated hepatocyte proliferation. Specifically activated the mTOR signaling pathway during liver regeneration and rescued PH-impaired liver functions

3645- Sage,  RosA,    Acetylcholinesterase inhibitory, antioxidant and phytochemical properties of selected medicinal plants of the Lamiaceae family
- Study, AD, NA
*AChE↓, Rosmarinic acid was found to be the predominant constituent in most of the investigated medicinal plants (by RP-HPLC) and had a substantial influence on their AChE inhibitory and antioxidant properties, with the exception of Teucrium species.
*AChE↓, Lamiaceae species are a rich source of various natural AChE inhibitors and antioxidants that could be useful in the prevention and treatment of Alzheimer’s and other related diseases.

4217- Sage,  RosA,  Aroma,    Neuroprotective Potential of Aromatic Herbs: Rosemary, Sage, and Lavender
- Review, AD, NA - Review, Park, NA
*Inflam↓, Aromatic plants, sage (Salvia officinalis), lavender (Lavandula angustifolia), and rosemary (Salvia Rosmarinus) have already shown anxiolytics, anti-inflammatory, antioxidant, and neuroprotective effects.
*antiOx↑,
*neuroP↑,
*ERK↑, exert neuroprotective effects mainly through increasing neurotransmitters and antioxidants, activating ERK/CREB/BDNF pathway, and inhibition of β-amyloid, pro-inflammatory cytokines, and Acetylcholine esterase (AChE) activity.
*CREB↑,
*BDNF↑,
*Aβ↑,
*AChE↓,
*memory↑, Rosmarinus officinalis led to improvement in long-term memory and cognitive responses in rats, through the inhibition of acetylcholinesterase (AChE) activity
*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↑, UA and RA are potential neuroprotective compounds that reverses the histological hallmarks of AD and ameliorate impaired social memory and hippocampal neurogenesis.
*Aβ↓, RA and UA treatment reduces the accumulated amyloid beta burden
*p‑tau↓, RA describes its role in the inhibition of cognitive decline through the suppression of tau phosphorylation
*memory↑, Improvement of spatial memory and amelioration of Aβ25–35 accumulation by UA has also been demonstrated
*Inflam↓, It also exerts anti-apoptotic effect that results in the alleviation of inflammation and oxidative stress associated neurodegeneration as observed in a model for Parkinson’s disease
*ROS↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 66

Results for Effect on Cancer/Diseased Cells:
AChE↓,2,   Akt↓,6,   p‑Akt↓,1,   AMPK↓,1,   p‑AMPK↑,1,   angioG↓,1,   AntiCan↑,2,   antiOx↑,6,   Apoptosis↑,8,   AR↓,2,   ASC↑,1,   ATP↓,1,   ATP↑,1,   BAX↑,4,   Bax:Bcl2↑,1,   Bcl-2↓,4,   Bcl-xL↓,1,   BioAv↑,3,   BNIP3↑,2,   cardioP↑,1,   CardioT↓,1,   Casp↑,1,   Casp1↓,1,   Casp3↑,5,   cl‑Casp3↑,1,   Casp8↑,1,   Casp9↓,1,   Catalase↑,1,   CDK2↓,1,   CDK4↓,1,   chemoP↓,1,   chemoP↑,1,   chemoR↓,1,   ChemoSen↑,6,   ChemoSideEff↓,2,   CHOP↑,2,   COX2↓,4,   CSCs↓,1,   cycD1↓,2,   cycE↓,2,   Cyt‑c↑,2,   DNAdam↑,2,   DNMTs↓,2,   Dose↝,4,   E-cadherin↑,3,   eff↓,1,   eff↑,13,   eff↝,1,   EGF↓,1,   p‑EGFR↓,1,   EMT↓,6,   ER Stress↑,2,   ER-α36↓,1,   ERK↓,2,   FABP4↑,1,   Fenton↑,2,   Foxm1↓,1,   FOXO1↓,2,   FOXO4↑,1,   GADD45A↑,1,   GIT1↓,1,   Gli1↓,3,   GlucoseCon↓,3,   Glycolysis↓,1,   GPx↑,1,   GRP78/BiP↑,1,   GSH↓,1,   GSH↑,2,   Half-Life↝,1,   HDAC2↓,5,   hepatoP↑,2,   HER2/EBBR2↓,1,   HH↓,2,   Hif1a↓,3,   HO-1↑,1,   HSP27↓,1,   HSP70/HSPA5↑,1,   IAP1↓,2,   IAP2↓,2,   ICAM-1↓,1,   IGFBP3↓,1,   IL1β↓,1,   IL6↓,3,   IL6↑,1,   IL8↓,1,   Inflam↓,2,   Iron↓,1,   IronCh↑,1,   IκB↓,1,   p‑IκB↓,1,   JNK↓,2,   Ki-67↓,1,   lactateProd↓,3,   lipid-P↓,1,   MARK4↓,3,   MDM2↓,1,   MDR1↓,1,   miR-155↓,2,   MMP↓,2,   MMP2↓,4,   MMP9↓,5,   MMPs↓,2,   mTOR↓,3,   p‑mTOR↓,1,   N-cadherin↓,2,   necrosis↑,1,   neuroP↑,2,   NF-kB↓,5,   NLRP3↓,2,   NRF2↑,2,   P-gp↓,4,   P-gp↑,1,   P21↑,2,   p27↑,1,   P450↓,1,   p50↓,2,   P53↑,1,   p65↓,2,   p‑p65↓,1,   p‑P70S6K↓,1,   cl‑PARP↓,1,   cl‑PARP↑,1,   PCNA↓,1,   PD-1↓,1,   PD-L1↓,1,   PERK↓,1,   PERK↑,1,   PI3K↓,5,   p‑PI3K↑,1,   PPARα↑,1,   PPARγ↑,1,   PSA↓,2,   PTEN↓,1,   RadioS↑,2,   RenoP↑,1,   ROS↓,11,   ROS↑,10,   ROS⇅,1,   selectivity↑,4,   SESN2↑,1,   SIRT1↓,1,   Snail↓,1,   SOD↑,1,   SOD2↓,1,   SOX9↓,1,   STAT3↓,2,   survivin↓,2,   p‑tau↓,1,   TLR4↓,1,   TNF-α↓,4,   TNF-α↑,1,   TumCCA↑,8,   TumCD∅,1,   TumCG↓,6,   TumCI↓,4,   TumCMig↓,6,   TumCP↓,5,   tumCV↓,4,   tumCV∅,1,   TumMeta↓,2,   UPR↑,1,   VEGF↓,1,   Vim↓,4,   Warburg↓,5,   XIAP↓,2,   Zeb1↓,1,  
Total Targets: 166

Results for Effect on Normal Cells:
AChE↓,9,   ACSL4↓,1,   ALAT↓,2,   ALP↓,1,   angioG↓,2,   AntiAge↑,2,   antiOx↑,12,   Apoptosis↓,1,   AST↓,2,   ATF4↓,1,   ATF6↓,1,   ATP↑,2,   Aβ↓,5,   Aβ↑,1,   Aβ∅,1,   BAX↓,1,   BBB↑,1,   BBB↝,1,   Bcl-2↑,1,   BDNF↑,1,   BG↓,1,   BioAv↓,1,   BioAv↑,4,   BioAv↝,2,   BUN↓,1,   Ca+2↓,1,   CaMKII ↓,1,   cardioP↑,2,   CardioT↓,2,   Casp12↓,1,   Casp3↓,1,   Casp9↓,1,   Catalase↑,5,   CDK5↓,1,   CHOP↓,1,   cognitive↑,6,   cortisol↓,1,   COX2↓,3,   creat↓,1,   CREB↑,1,   Cyt‑c↓,1,   Dose↝,2,   E-cadherin↓,1,   eff↑,4,   eNOS↓,1,   ER Stress↓,3,   ERK↓,1,   ERK↑,1,   Ferroptosis↓,3,   GlucoseCon↓,1,   GlucoseCon↑,1,   Glycolysis↝,1,   GPx↑,3,   GPx4↑,2,   GRP78/BiP↓,5,   GSH↑,8,   GSK‐3β↓,1,   GSR↑,1,   GSSG↓,1,   GSTs↑,1,   GutMicro↑,4,   H2O2↓,1,   H2O2↑,1,   Half-Life↑,1,   Half-Life↝,2,   hepatoP↑,3,   Hif1a↓,1,   HK2↓,1,   HMGB1↓,1,   HO-1↑,3,   ICAM-1↓,1,   IGF-1↑,1,   IL10↑,1,   IL1β↓,3,   IL2↓,1,   IL6↓,4,   IL8↓,1,   Inflam↓,15,   iNOS↓,2,   IRE1↓,3,   Iron↓,1,   IronCh↑,3,   JNK↓,2,   p‑JNK↓,1,   lactateProd↓,1,   LDHA↓,1,   lipid-P↓,6,   MAPK↓,1,   MCP1↓,1,   MDA↓,4,   memory↑,5,   MLKL↓,1,   MMP↓,1,   MMP↑,2,   MMP2↓,2,   MMP9↑,1,   MMPs↓,1,   monoA↑,1,   motorD↓,1,   motorD↑,1,   mTOR↑,1,   NADPH↓,2,   neuroP↑,10,   NF-kB↓,5,   p‑NF-kB↓,1,   NLRP3↓,2,   NO↓,2,   NOX4↓,1,   NRF2↑,7,   other↓,10,   other↝,1,   p38↓,1,   P450↑,1,   PERK↓,3,   PFK2↓,1,   PGC1A↑,1,   PGE2↓,3,   PPP↓,1,   Prx↑,1,   radioP↑,2,   RANTES↓,1,   Rho↓,3,   RIP1↓,1,   ROCK1↓,3,   ROS↓,18,   Sepsis↓,3,   SOD↑,8,   Src↓,1,   STAT3↓,1,   TAC↑,1,   p‑tau↓,1,   TfR1/CD71↓,1,   TGF-β↓,1,   Thiols↑,1,   TLR4↓,1,   TNF-α↓,5,   toxicity↓,1,   toxicity↝,1,   toxicity∅,1,   Trx↑,1,   VEGF↓,1,   VitC↑,1,   VitE↑,1,   Zeb1↓,1,   ZO-1↓,1,  
Total Targets: 145

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:142  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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