BioAv Cancer Research Results
BioAv, bioavailability: Click to Expand ⟱
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| Type: measurement |
Bioavailability (usually in %) absorbed by the body.
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Scientific Papers found: Click to Expand⟱
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in-vitro, |
GBM, |
U87MG |
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in-vitro, |
Nor, |
HEK293 |
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Glycolysis↓, We used the antiglycolytic 3-bromopyruvate (3BP) as a metabolic modifier to treat U118 glioblastoma cell
ROS↑, ROS generated in mitochondria were enhanced at 30 μM 3BP, possibly by unbalancing their generation and their disposal because of glutathione peroxidase inhibition.
GPx↓,
eff↓, Indeed, the scavenger of mitochondrial superoxide MitoTEMPO counteracted 3BP-induced cyt c release and weakened the potentiating effect of 3BP/
OXPHOS↓, (3BP) is a reactive non-specific drug that can act as a metabolic modifier by interfering with glycolysis and oxidative phosphorylation in cancer cells
HK2↓, The mitochondrial hexokinase-II is the main target since its activity is specifically blocked by the formation of a pyruvinyl adduct after reacting with 3BP at the surface of the outer mitochondrial membrane
ATP↓, In malignant tumour cell lines, 3BP inhibits ATPase activity, reduces ATP levels, and reverses chemoresistance by antagonizing drug efflux by acting on the ATP-binding cassette transporters (
ROS↑, Furthermore, 3BP increases the production of reactive oxygen species (ROS) (Ihrlund et al., 2008; Kim et al., 2008; Macchioni et al., 2011a), induces ER stress,
ER Stress↑,
BioAv↓, Unfortunately, prolonged treatment with the drug reduces ROS levels and confers resistance by inducing regulatory genes that act on antioxidant systems.
Cyt‑c↑, 3BP induces cytochrome c release without triggering an apoptotic cascade in U118 cells
eff↑, The ROS enhancers antimycin and menadione sensitize U118 cells to 3BP
TrxR↓, Gold derivatives are irreversible inhibitors of TrxR. Among them, auranofin (AF), a selective TrxR inhibitor, has proven its effectiveness as a drug for the treatment of rheumatoid arthritis
BioAv↓, further clinical application of AF could be challenging due to the low solubility and insufficient delivery to glioblastoma.
ROS↑, The inhibition of TrxR1, which leads to increased ROS levels, is currently recognized as the primary mechanism of AF cytotoxicity [106]. In vitro studies have also shown that AF inhibits other thioredoxin reductases, such as TrxR2 and TrxR3
eff↝, The literature indicates that not all cancer tumors exhibit the same level of TrxR expression, affecting their sensitivity to AF.
TET1?, AF was shown to inhibit TET1 in T-ALL models
BioAv↑, Encapsulating AF into nanoparticles or combining it with other pharmaceutical excipients can minimize its potential adverse effects, preserve its interaction with serum proteins, and result in greater stability.
AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms
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in-vitro, |
Colon, |
Caco-2 |
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BioAv↑, Both chitosan and sodium deoxycholate can increase the permeation efficiency of astragaloside IV.
BioAv↓, This study indicated that astragaloside IV having a low fraction dose absorbed in humans mainly due to its poor intestinal permeability, high molecular weight, low lipophilicity as well as its paracelluar transport may directly result in the low perm
*Half-Life↝, Fecal silver began to decline at 12 h for all the AgNPs and was at baseline levels by 48 h.
*toxicity↓, Acute ingestion of AgNP is well-tolerated at high doses, irrespective of size or coating
*Dose↑, The doses utilized in this study (0.1, 1 and 10 mg/kg bw/d) were equivalent to, respectively, 20×, 200× and 2000× the EPA oral reference dose (RfD, 0.005 mg/kg bw/d) for silver
*other↝, Previous estimates of colloidal silver doses associated with clinically evident argyria range between 40× and 700× the oral RfD, although these typically represent repeated exposures
*eff↝, Acute ingestion of AgNP is well-tolerated with concurrent antibiotic administration
*BioAv↓, Oral bioavailability was previously determined as low (4.2%) for a single 10 mg/kg bw dose of 7.9 nm AgNP-citrate in rats
*toxicity∅, concluding no detectable toxicity
*Dose↝, 10 ppm oral silver particle dosing [36 subjects] and 32 ppm oral silver particle dosing [24 subjects]). 100 μg/day for 10 ppm, and 480 μg/day for 32 ppm silver
*Dose↝, corresponding to ionic silver comprising some 84.3% of the total silver content in the product
administered orally to patients.
*BioAv↝, Peak serum silver concentration was detected in 42% of subjects in the 14-day 10 ppm dosing showing a mean of 1.6±0.4 mcg/L
*BioAv↝, The 32 ppm dose mean concentration was detected in 92% of subjects at 6.8±4.5 mcg/L
*H2O2∅, No statistically significant change in markers of hydrogen peroxide production or
peroxiredoxin protein expression were detected.
*IL8∅, Analysis of IL-8, IL-1α, IL-1β, MCP1 and NQO1 also showed no statistical difference between the active silver and placebo solutions.
*IL1α∅,
*IL1β∅,
*MCP1∅,
*NQO1∅,
*BioAv↓, miniscule (<1%) amounts of 10-nm gold nanoparticles permeate across the gut to enter systemic vascular circulation from the intestine in rodents.51 We assert that silver metallic particle absorption is similar
*BioAv↓, bioavailability of orally administered AgNPs was 1.2% in the group treated with 1 mg/kg AgNPs and 4.2% in the group treated with 10 mg/kg AgNPs.
*BioAv↑, another key property of allicin is its hydrophobicity, which allows it to be absorbed easily through the cell membrane without causing any physical or chemical damage to the phospholipid bilayer, thereby allowing its rapid metabolism to produce pharm
*cardioP↑, Allicin exhibits protective effects in multiple organ systems, including the brain, intestines, lungs, liver, kidneys, prostate, and heart.
*hepatoP↑,
*RenoP↑,
*Half-Life↝, half-life (t1/2)of allicin was 227 min–260 min. Because allicin is eliminated from the body by the respiratory tract, the concentration of allicin in lung tissue is significantly lower than that in the blood
*BioAv↓, We believe that the bioavailability of allicin is relatively low for the following reasons: At first, allicin is characterized by a distinctive garlic odor and chemical instability. It can be easily degraded under room temperature.
*neuroP↑, Neuroprotective activity
*cognitive↑, On the other hand, allicin improves cognitive deficits via Protein kinase R-like endoplasmic reticulum kinase (PERK)/Nuclear factor erythroid-2-related factor 2 (NRF2) signaling pathway and c-Jun N-terminal kinase (JNK) signaling pathways
*ROS↓, They found that allicin suppressed ROS generation and decreased lipid peroxidation in 6-hydroxydopamine (6-OHDA)-induced Pheochromocytoma 12 (PC12) cells
*lipid-P↓,
*DNArepair↑, Allicin not only directly protects DNA, but also indirectly protects DNA through antioxidant activity and regulation of oxidizing enzymes
*ChemoSen↑, Allicin combined with other chemotherapy drugs showed a better anti-cancer effect
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in-vitro, |
AML, |
Jurkat |
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in-vitro, |
Nor, |
L929 |
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necrosis↑, Allicin induces apoptosis or necrosis in a dose-dependent manner but biocompatible doses influence cellular metabolism and signalling cascades.
Thiols↓, Oxidation of protein thiols and depletion of the glutathione pool are thought to be responsible for allicin's physiological effects.
GSH↓,
ENO1↓, allicin caused inhibition of enolase activity, an enzyme considered a cancer therapy target.
Zn2+↑, Allicin leads to Zn2+ release in murine EL-4 cells
Glycolysis↓, suggests that allicin can inhibit glycolysis which provides electron donors for ATP generation required for cellular biosynthesis pathways and growth of the cells.
ATP↓,
BioAv↓, achieving therapeutically relevant concentrations of allicin via the oral route is therefore unlikely and more direct routes of application to the desired site of action need to be considered
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Review, |
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AD, |
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*antiOx↑, antioxidant potential and free radical scavenging activity.
*ROS↓,
*IronCh↑, Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
*cognitive↑, α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties.
*cardioP↓,
AntiCan↑,
*neuroP↑,
*Inflam↓, α-Lipoic acid can reduce inflammatory markers in patients with heart disease
*BioAv↓, bioavailability in its pure form is low (approximately 30%).
*AntiAge↑, As a dietary supplements α-lipoic acid has become a common ingredient in regular products like anti-aging supplements and multivitamin formulations
*Half-Life↓, it has a half-life (t1/2) of 30 min to 1 h.
*BioAv↝, It should be stored in a cool, dark, and dry environment, at 0 °C for short-term storage (few days to weeks) and at − 20 °C for long-term storage (few months to years).
other↝, Remarkably, neither α-lipoic acid nor dihydrolipoic acid can scavenge hydrogen peroxide, possibly the most abundant second messenger ROS, in the absence of enzymatic catalysis.
EGFR↓, α-Lipoic acid inhibits cell proliferation via the epidermal growth factor receptor (EGFR) and the protein kinase B (PKB), also known as the Akt signaling, and induces apoptosis in human breast cancer cells
Akt↓,
ROS↓, α-Lipoic acid tramps the ROS followed by arrest in the G1 phase of the cell cycle and activates p27 (kip1)-dependent cell cycle arrest via changing of the ratio of the apoptotic-related protein Bax/Bcl-2
TumCCA↑,
p27↑,
PDH↑, α-Lipoic acid drives pyruvate dehydrogenase by downregulating aerobic glycolysis and activation of apoptosis in breast cancer cells, lactate production
Glycolysis↓,
ROS↑, HT-29 human colon cancer cells; It was concluded that α-lipoic acid induces apoptosis by a pro-oxidant mechanism triggered by an escalated uptake of mitochondrial substrates in oxidizable form
*eff↑, Several studies have found that combining α-lipoic acid and omega-3 fatty acids has a synergistic effect in slowing functional and cognitive decline in Alzheimer’s disease
*memory↑, α-lipoic acid inhibits brain weight loss, downregulates oxidative tissue damage resulting in neuronal cell loss, repairs memory and motor function,
*motorD↑,
*GutMicro↑, modulates the gut microbiota without reducing the microbial diversity (
*antiOx↑, antioxidant and anti-inflammatory properties
*Inflam↓,
*PGE2↓, α-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-α, IL-1β, and IL-6
*COX2↓,
*iNOS↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*BioAv↓, α-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic
*Ach↑, α-LA increases the production of acetylcholine [30], inhibits the production of free radicals [31], and promotes the downregulation of inflammatory processes
*ROS↓,
*cognitive↑, Studies have shown that patients with mild AD who were treated with α-LA showed a slower progression of cognitive impairment
*neuroP↑, α-LA is classified as an ideal neuroprotective antioxidant because of its ability to cross the blood-brain barrier and its uniform uptake profile throughout the central and peripheral nervous systems
*BBB↑,
*Half-Life↓, α-LA presented a mean time to reach the maximum plasma concentration (tmax) of 15 minutes and a mean plasma half-life (t1/2) of 14 minutes
*BioAv↑, LA consumption is recommended 30 minutes before or 2 hours after food intake
*Casp3↓, α-LA had an effect on caspases-3 and -9, reducing the activity of these apoptosis-promoting molecules to basal levels
*Casp9↓,
*ChAT↑, α-LA increased the expression of M2 muscarinic receptors in the hippocampus and M1 and M2 in the amygdala, in addition to ChaT expression in both regions.
*cognitive↑, α-LA acts on these apoptotic signalling pathways, leading to improved cognitive function and attenuation of neurodegeneration.
*eff↑, Based on their results, the authors suggest that treatment with α-LA would be a successful neuroprotective option in AD, at least as an adjuvant to standard treatment with acetylcholinesterase inhibitors.
*cAMP↑, The increase of cAMP caused by α-LA inhibits the release of proinflammatory cytokines, such as IL-2, IFN-γ, and TNF-α.
*IL2↓,
*INF-γ↓,
*TNF-α↓,
*SIRT1↑, Protein expression encoded by SIRT1 showed higher levels after α-LA treatment, especially in liver cells.
*SOD↑, antioxidant enzymes (SOD and GSH-Px) and malondialdehyde (MDA) were analysed by ELISA after 24 h of MCAO, which showed that the enzymatic activities were recovered and MDA was reduced in the α-LA-treated groups i
*GPx↑,
*MDA↓,
*NRF2↑, The ratio of nucleus/cytoplasmic Nrf2 was higher in the α-LA group 40 mg/kg, indicating that the activation of this factor also occurred in a dose-dependent manner
ROS↑, direct anticancer effect of the antioxidant ALA is manifested as an increase in intracellular ROS levels in cancer cells
NRF2↑, enhance the activity of the anti-inflammatory protein nuclear factor erythroid 2–related factor 2 (Nrf2), thereby reducing tissue damage
Inflam↓,
frataxin↑,
*BioAv↓, Oral ALA has a bioavailability of approximately 30% due to issues such as poor stability in the stomach, low solubility, and hepatic degradation.
ChemoSen↑, ALA can enhance the functionality of various other anticancer drugs, including 5-fluorouracil in colon cancer cells and cisplatin in MCF-7 breast cancer cells
Hif1a↓, it is inferred that lipoic acid may inhibit the expression of HIF-1α
eff↑, act as a synergistic agent with natural polyphenolic substances such as apigenin and genistein
FAK↓, ALA inhibits FAK activation by downregulating β1-integrin expression and reduces the levels of MMP-9 and MMP-2
ITGB1↓,
MMP2↓,
MMP9↓,
EMT↓, ALA inhibits the expression of EMT markers, including Snail, vimentin, and Zeb1
Snail↓,
Vim↓,
Zeb1↓,
P53↑, ALA also stimulates the mutant p53 protein and depletes MGMT
MGMT↓, depletes MGMT by inhibiting NF-κB signalling, thereby inducing apoptosis
Mcl-1↓,
Bcl-xL↓,
Bcl-2↓,
survivin↓,
Casp3↑,
Casp9↑,
BAX↑,
p‑Akt↓, ALA inhibits the activation of tumour stem cells by reducing Akt phosphorylation.
GSK‐3β↓, phosphorylation and inactivation of GSK3β
*antiOx↑, indirect antioxidant protection through metal chelation (ALA primarily binds Cu2+ and Zn2+, while DHLA can bind Cu2+, Zn2+, Pb2+, Hg2+, and Fe3+) and the regeneration of certain endogenous antioxidants, such as vitamin E, vitamin C, and glutathione
*ROS↓, ALA can directly quench various reactive species, including ROS, reactive nitrogen species, hydroxyl radicals (HO•), hypochlorous acid (HclO), and singlet oxygen (1O2);
selectivity↑, In normal cells, ALA acts as an antioxidant by clearing ROS. However, in cancer cells, it can exert pro-oxidative effects, inducing pathways that restrict cancer progression.
angioG↓, Combining these two hypotheses, it can be hypothesized that ALA may regulate copper and HIF-2α to limit tumor angiogenesis.
MMPs↓, ALA was shown to inhibit invasion by decreasing the mRNA levels of key matrix metalloproteinases (MMPs), specifically MMP2 and MMP9, which are crucial for the metastatic process
NF-kB↓, ALA has been shown to enhance the efficacy of the chemotherapeutic drug paclitaxel in breast and lung cancer cells by inhibiting the NF-κB signalling pathway and the functions of integrin β1/β3 [138,139]
ITGB3↓,
NADPH↓, ALA has been shown to inhibit NADPH oxidase, a key enzyme closely associated with NP, including NOX4
*BioAv↓, We find that oral intake of dietary materials would require heroic ingestion amounts and is not feasible. However, use of supplements of semi-purified apigenin in capsule form could reach target blood levels using amounts that are within the range cu
Half-Life∅, elimination half-life (T1/2) averaging 2.52 ± 0.56h
*BioAv↓, bioavailability is in the region of 30%
Dose∅, Blood and urine samples were taken following a meal consisting of 2g parsley/kg body weight–which was equivalent to ∼17mg of apigenin -> 28–337nmol/L at 6–10h after consumption
eff↑, Apigenin and quercetin enhance their own and each other’s bioavailability by downregulating the activity of ABC transporters
CYP1A2↓, status of apigenin as an inhibitor of CYP1A2, CYP2C9 and CYP3A4
CYP2C9↓,
CYP3A4↓,
*BioAv↑, apigenin-7-O-glucoside, and acylated derivatives are more water soluble than apigenin [10] and their structures have a major impact on their absorption and bioavailability, with the best bioavailability occurring when apigenin is bound to β-glycoside
*BioAv↑, organic solvents like DMSO [34] and Tween 80 [31] are used to dissolve apigenin prior to their addition to an aqueous solution to increase solubility
*BioAv↑, dietary apigenin is available for metabolism by the gut microbiota
*BioAv↓, Human gut microbiota has been found to harbor enzymes that could degrade apigenin
*eff↑, This study strongly supports that the gut microbiota plays a major role in the metabolism of dietary apigenin.
*BioAv↓, Apigenin is not easily absorbed orally because of its low water solubility, which is only 2.16 g/mL
*Half-Life∅, Apigenin is slowly absorbed and eliminated from the body, as evidenced by its half‐life of 91.8 h in the blood
selectivity↑, selective anticancer effects and effective cell cytotoxic activity while exhibiting negligible toxicity to ordinary cells
*toxicity↓, intentional consumption in higher doses, as the toxicity hazard is low
Wnt/(β-catenin)↓, inhibiting the Wnt/β‐catenin
P53↑,
P21↑,
PI3K↓,
Akt↓,
mTOR↓,
TumCCA↑, G2/M
TumCI↓,
TumCMig↓,
STAT3↓, apigenin can activate p53, which improves catalase and inhibits STAT3,
PKM2↓,
EMT↓, reversing increases in epithelial–mesenchymal transition (EMT)
cl‑PARP↑, apigenin increases the cleavage of poly‐(ADP‐ribose) polymerase (PARP) and rapidly enhances caspase‐3 activity,
Casp3↑,
Bax:Bcl2↑,
VEGF↓, apigenin suppresses VEGF transcription
Hif1a↓, decrease in hypoxia‐inducible factor 1‐alpha (HIF‐1α
Dose∅, effectiveness of apigenin (200 and 300 mg/kg) in treating CC was evaluated by establishing xenografts on Balb/c nude mice.
GLUT1↓, Apigenin has been found to inhibit GLUT1 activity and glucose uptake in human pancreatic cancer cells
GlucoseCon↓,
TumCP↓,
TumCCA↑,
Apoptosis↑,
MMPs↓,
Akt↓,
*BioAv↑, delivery systems (nanosuspension, polymeric micelles, liposomes).
*BioAv↓, low solubility of apigenin in water (1.35 μg/mL) and its high permeability
Half-Life∅, (appearing in blood circulation after 3.9 h)
Hif1a↓, (HIF-1α) is targeted by apigenin in several cancers such as, ovarian cancer, prostate cancer, and lung cancer
GLUT1↓, GLUT-1 is blocked by apigenin (0–100 μM) under normoxic conditions
VEGF↓,
ChemoSen↑, apigenin can be applied as a chemosensitizer
ROS↑, accumulation of ROS produced were stimulated
Bcl-2↓, down-regulation of anti-apoptotic factors Bcl-2 and Bcl-xl as well as the up-regulation of apoptotic factors Bax and Bim.
Bcl-xL↓,
BAX↑,
BIM↑,
ChemoSen↑, Apigenin has also been studied for its potential as a sensitizer in cancer therapy, improving the efficacy of traditional chemotherapeutic drugs and radiotherapy
RadioS↑, Apigenin enhances radiotherapy effects by sensitizing cancer cells to radiation-induced cell death
eff↝, It works by suppressing the expression of involucrin (hINV), a hallmark of keratinocyte development. Apigenin inhibits the rise in hINV expression caused by differentiating agents
DR5↑, Apigenin also greatly upregulates the expression of death receptor 5 (DR5
selectivity↑, Surprisingly, apigenin-mediated increase of DR5 expression is missing in normal mononuclear cells from human peripheral blood and doesn't subject these cells to TRAIL-induced death.
angioG↓, Apigenin has been found to prevent angiogenesis by targeting critical signaling pathways involved in blood vessel creation.
selectivity↑, Importantly, apigenin has been demonstrated to selectively kill cancer cells while sparing normal ones
chemoP↑, This selective cytotoxicity is beneficial in cancer therapy because it reduces the negative effects frequently associated with traditional treatments like chemotherapy
MAPK↓, Apigenin's ability to suppress MAPK signaling adds to its anticancer properties.
PI3K↓, Apigenin suppresses the PI3K/Akt/mTOR pathway, which is typically dysregulated in cancer.
Akt↓,
mTOR↓,
Wnt↓, Apigenin inhibits Wnt signaling by increasing β-catenin degradation
β-catenin/ZEB1↓,
GLUT1↓, fig 3
radioP↑, while reducing radiation-induced damage to healthy tissues
BioAv↓, obstacles associated with apigenin's low bioavailability and stability
chemoPv↑, Especially as a chemopreventive agent for cancer
BioAv↓, Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug
lipid-P↑, promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo.
Ferroptosis↑,
Iron↑, Artemisinin and Its Derivatives Upregulate Fe2+ Levels in Cancer Cells
GPx4↓, GPX4-dependent defense system is significantly inhibited
GSH↓, , leading to a significant decrease in GSH, GPX4, and SLC7A11 protein expression
P53↑, ARTEs can upregulate p53 protein expression in multiple cancer cells
ER Stress↑, ARTEs can trigger ERS in cancer cells to activate the PERK-ATF4 pathway and upregulate GRP78 expression
PERK↑,
ATF4↑,
GRP78/BiP↑,
CHOP↑, which activates CHOP
ROS↑, promoting the accumulation of intracellular ROS, and leading to ferroptosis
NRF2↑, ARTEs can activate the nuclear factor erythroid-derived 2-like 2 (Nrf2) -γ-glutamyl-peptide pathway in cancer cells, resulting in cancer cell ferroptosis resistance
TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9
Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase
Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,
*BioAv↓, with High fat and high calorie meals
*BioAv↑, DHA dihydroartemisinin have improved bioavailability
Apoptosis↑,
EGFR↓,
CD31↓,
Ki-67↓,
P53↓,
TfR1/CD71↑,
P-gp↓, many artemisinin derivatives act as P-gp inhibitors
PD-1↝, Caution when used with mmunotherapy (PD1/PDL1 inhibitors)
*BioAv↓, Because the parent drug of artemisinin is poorly soluble in water or oil, the carbonyl group of artemisinin was reduced to obtain DHA
*Half-Life↓, artemisinins also have a very short elimination half-life (∼1 h)
*toxicity↓, Artemisinin and its derivatives are generally safe and well-tolerated.
*ROS↑, Artemisinins are considered prodrugs that are activated to generate carbon-centered free radicals or reactive oxygen species (ROS).
GSH↓, earlier studies suggest that artemisinins modulate parasite oxidative stress and reduce the levels of antioxidants and glutathione (GSH) in the parasite
selectivity↑, Many publications corroborate the essence of iron-dependent bioactivation
toxicity↝, generally well tolerated. Eleven adverse events of grade 1 or grade 2 severity were observed. No grade 3 or grade 4 adverse events were observed.
hepatoP↓, Elevation of liver enzymes (5/11) and skin rash (2/11) was the most common adverse events.
BioAv↓, However, WA appears to have low oral bioavailability.
Apoptosis↑, WA has been reported to induce apoptosis via intrinsic and extrinsic pathways in human prostate, breast and leukemic cancer cells among others
ROS↑, It has also shown the ability to induce apoptosis in osteosarcoma U2OS cell lines by generating ROS, also causing cell cycle arrest in osteosarcoma cell lines by inhibition of G2/M checkpoint proteins
TumCCA↑,
BioAv↑, The longer half-life and higher mean residence time of the higher strength extract WS-35, which contained 35% withanolide glycosides, demonstrated its enhanced oral bioavailability
BioAv↓, Singh et al. [20] tested the bioavailability of withaferin A (purity 99%) by oral (25 mg/kg) and withanoside IV (2 mg/kg) routes in Sprague Dawley rats and found its oral bioavailability to be poor (approximately 5%) despite rapid distribution after
TumCCA↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
TumCP↓,
CSCs↓,
TumMeta↓,
EMT↓,
angioG↓,
Vim↓,
HSP90↓,
annexin II↓, annexin II proteins directly bind to WA
m-FAM72A↓,
BCR-ABL↓,
Mortalin↓,
NRF2↓,
cMYB↓,
ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
TumCI↓,
Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability
| - |
in-vivo, |
Melanoma, |
B16-F10 |
|
|
|
Dose↝, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. 223 nm
TumCG↓, In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs
TumCP↓, AP has been found to inhibit the cell proliferation and DNA synthesis of various cancer cells, including breast, colon, glioblastoma, skin, and brain cancer cells (Naidu, 2003a).
BioAv↓, AP is limited due to its water insolubility, rapid degradation (accelerated by metal ions and/or light), and low bioavailability.
BioAv↑, Therefore, new technologies including nanoparticles that can enhance its delivery efficacy and reduce the dose of administration for Vc while not reducing its anti-cancer efficacy are highly desired.
other↑, These results conformed to the conclusion that only high doses of ascorbic acid have the ability to induce cancer cell death.
Apoptosis↑, Conclusively, the AP/PTX-SLNs exhibited a greater efficacy in inducing cell apoptosis by reducing the Bcl-2/Bax ratio accompanied by promoting tubulin polymerization
Bax:Bcl2↑,
EPR↑, such nanocarriers to permeate into tumor sites because of the enhanced permeation and retention (EPR) effect.
toxicity↝, AP/PTX synergistic combination-based SLN therapy did not induce toxicity and represents a promising strategy for paclitaxel/the vitamin C derivative in promoting anti-cancer effects.
*antiOx↑, Reports indicate that ASX’s antioxidant efficacy surpasses that of vitamin C, vitamin E, coenzyme Q10, and alpha-lipoic acid.
*neuroP↑, Astaxanthin is a powerful antioxidant compound that supports heart, skin, and eye health, helps manage diabetes, and offers brain-protective benefits.
AntiCan↑, Astaxanthin shows promise as an anticancer agent by limiting tumor growth, inducing cancer cell death, and reducing the spread of malignant cells.
TumCG↓,
TumCD↑,
TumCMig↓,
ChemoSen↑, Astaxanthin enhances the effects of chemotherapy, reduces its side effects, and helps overcome drug resistance.
chemoP↑,
*BioAv↓, Astaxanthin has limited absorption in the body, but using nanocarriers like nanoparticles and nano-emulsions can greatly enhance its bioavailability and therapeutic potential.
TumCP↓, ASX inhibits tumor formation, primarily by hindering cell proliferation, inducing cell cycle arrest, and promoting apoptosis.
TumCCA↑,
Apoptosis↑,
BioAv↑, Nanotechnology: a solution for improving astaxanthin bioavailability
*antiOx↑, Astaxanthin is a naturally occurring carotenoid with high anti-oxidant properties
*BioAv↓, but it is a very lipophilic compound with low oral bioavailability. The oral bioavailability of astaxanthin ranges around 10–50% of the given dose, as a result of its poor solubility in water and poor absorption by epithelial cells of the small intes
*Dose↝, compare the pharmacokinetic parameters of a novel astaxanthin preparation based on micellar solubilization technology, NovaSOL® 400-mg capsules (Test product), and those of astaxanthin 400-mg capsules (reference product),
*BioAv↑, The test micellar astaxanthin reached a Cmax of 7.21 µg/ml after 3.67 h compared to only 3.86 µg/ml after 8.5 h for the reference native astaxanthin.
*antiOx↑, Astaxanthin (ASTA) is a kind of food-derived active ingredient (FDAI) with antioxidant and antidiabetic functions.
*AntiDiabetic↑,
*toxicity∅, It is nontoxic but its poor solubility and low bioavailability hinder its application in the food industry.
*BioAv↓,
*BioAv↑, n this study, a novel carrier, polyethylene glycol-grafted chitosan (PEG-g-CS) was applied to enhance the bioavailability of astaxanthin.
*BioAv↓, Astaxanthin is a very strong antioxidant of the xanthophyll carotenoid group with
very lipophilic properties, so in oral administration, its bioavailability is very low
*antiOx↑,
*BioAv↑, The results showed that in the
astaxanthin nanoemulsion, there was an increasing in Cmax and AUC0-∞ which
affected increasing the bioavailability value.
*Half-Life↝, This is shown in pure astaxanthin, and the t1/2 elimination calculation is 22.53 hours longer than the astaxanthin nanoemulsion, which is a 14.50-hour t1/2 elimination.
Apoptosis↑, Despite statins’ ability to induce apoptosis or autophagy, arrest cell cycle, or modulate favorable epigenetic reprogramming, their efficacy is highly context-dependent
TumAuto↑,
TumCCA↑,
BioAv↓, Challenges such as statin resistance, low bioavailability and pharmacokinetic variability further complicate their application in oncology.
eff↑, including nanoparticle-based drug delivery systems and combination therapies with chemotherapy, radiotherapy or immunotherapy, appear to help overcome these limitations.
HMGCR↓, statins reduce cholesterol levels by targeting HMGCR
LDL↓,
cardioP↑, statins have become a cornerstone in the management of hypercholesterolemia and the prevention of cardiovascular diseases [23], [24], [25], [26].
AntiTum↑, Notably, while research suggests that statins possess anti-tumor effects, evidence remains conflicting and highly context-dependent
ChemoSen↑, suggest that statins can sensitize cancer cells to chemotherapy and radiotherapy, potentially improving treatment outcomes,
RadioS↑,
toxicity↓, Statins are widely regarded as safe and well-tolerated. However, like any medication, they are not without potential side effects, though these are generally mild [232].
*cardioP↑, atorvastatin is FDA-approved for the prevention of cardiovascular events in patients with cardiac risk factors and abnormal lipid profiles.[1]
*LDL↓, patients should be prescribed high-intensity statin therapy to achieve a ≥50% reduction in low-density lipoprotein cholesterol (LDL-C) and reduce the risk of major adverse cardiovascular events (MACE).
HMG-CoA↓, Atorvastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.[12]
Half-Life↝, Atorvastatin is rapidly absorbed after oral administration with a peak plasma concentration at 1 to 2 hours. The half-life of atorvastatin is about 14 hours, while its active metabolites have a half-life of about 20 to 30 hours.
BioAv↓, The bioavailability is low at 14% due to extensive first-pass metabolism.
Dose↝, Atorvastatin is available as atorvastatin calcium tablets in strengths of 10, 20, 40, and 80 mg. It is also available as an oral suspension in a strength of 20 mg/5 mL.[20]
Imm↑, β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models.
*Dose↝, Subjects were randomized to either the β -glucan (n = 10) or the control group (n = 5). Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days.
*BioAv↓, β-glucan was barely detectable in serum of volunteers at all time-points.
*toxicity↑, Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use.
Imm↑, β-glucan and its signaling pathway will undoubtedly open a new research area on its potential therapeutic applications, including as immunostimulants for antifungal and anti-cancer regimens.
BioAv↝, Despite their high molecular weight, β-glucans, when orally administered, are absorbed in the intestine and activate innate and adaptive immunities.
eff↑, It has been reported that a higher degree of structural complexity in β-glucans is associated with more potent immunomodulatory and anti-cancer effects. higher molecular weight (over than 450 kDa) glucan was more potent than lower molecular weight
AntiCan↑,
Dectin1↝, This review will depict in detail how the physicochemical nature of β-glucan contributes to its immunostimulating effect in hosts and the potential uses of β-glucan by elucidating the dectin-1 signal transduction pathway.
Dose↝, Orally administered, natural β-glucans, such as lentinan and schizophyllan, are known for showing their immunopotentiating effects, and have been used in tumor immunotherapy for more than 30 years.
BioAv↓, β-Glucans are too large to be absorbed in the small intestines.
Imm↑, The small β-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses.
*BioAv↓, Repeated measurements of β-glucans in serum, however, revealed no systemic absorption of the agent following the oral administration. Nonetheless, the immunoglobulin A concentration in saliva increased significantly for the 400 mg/day arm, suggesting
OS↑, In a randomized trial, SPG combined with conventional chemotherapy improved the long term survival rate of patients with ovarian cancer [72].
ChemoSen↑, Maitake D-Fraction extracted from Grifola frondosa (Maitake mushroom) was found to decrease the size of the lung, liver and breast tumors in >60% of patients when it was combined with chemotherapy in a 2 arms control study comparing with chemotherapy
*Inflam↓, pharmacological effects of baicalin and baicalein, such as anti-inflammation, anti-cancer, and anti-pruritic effects, have been reported in the literature [
AntiCan↑,
BioAv↝, Baicalin is metabolized to baicalein by β-glucuronidase in the intestine [12], and this metabolic process is a critical stage for absorption of baicalin [6,12].
BioAv⇅, literature indicated that the kinds and numbers of intestinal microbiota in individuals might affect the pre-systemic metabolism and absorption process of baicalin in the intestine
BioAv↓, significantly reduced bioavailability of baicalin was obtained in antibiotic-pretreated rats when compared with normal rats.
CYP3A2↓, CYP3A inhibition P-gp inhibition
P-gp↓,
*BioAv↓, Due to its poor water solubility (16.82 μg/ml), the therapeutic effectiveness and oral bioavailability of Baicalein are highly limited.
*BioAv↑, BE-TH cocrystals demonstrated 2.2-fold and 7.1-fold higher rate of dissolution than that of BE coarse powder in HCl (pH = 1.2) and phosphate buffer (PBS, pH = 6.8), respectively.
Apoptosis↑, Mechanistically, they modulate interconnected signaling cascades governing apoptosis, inflammation, and cell cycle control, and they enhance tumor sensitivity to chemotherapy and radiotherapy.
Inflam↓,
TumCCA↑,
ChemoSen↑,
RadioS↑,
TumCG↓, In-vivo models consistently demonstrate tumor growth inhibition, while clinical data suggest a favorable safety profile, even at relatively high oral doses.
toxicity↓,
BioAv↓, their clinical translation remains hampered by limited solubility, poor oral bioavailability, and rapid metabolism,
Half-Life↓, However, baicalein showed a partial bioavailability, poor solubility and pharmacokinetics, and a short half-life [6]
AntiTum↑, The anti-tumor functions of baicalein are mainly due to its capacities to inhibit complexes of cyclins to regulate the cell cycle, to scavenge oxidative radicals, to attenuate mitogen activated protein kinase (MAPK), protein kinase B (Akt) or mammali
TumCCA↓,
ROS↓,
MAPK↓,
Akt↓,
mTOR↓,
Casp3↑, , to induce apoptosis by activating caspase-9/-3 and to inhibit tumorinvasion and metastasis by reducing the expression of matrix metalloproteinase-2/-9 (MMP-2/-9).
Casp9↑,
TumCI↓,
TumMeta↓,
MMP2↓,
MMP9↓,
Securin↓, Baicalein also induced cell death by reducing the expression of securin, while also inhibiting cancer cell death by affecting the expression of p-AKT and γ-H2AX [26].
γH2AX↝,
N-cadherin↓, Baicalein also decreased the expression of metastasis-associated molecules, including N-cadherin, vimentin, ZEB1, and ZEB2.
Vim↓,
Zeb1↓,
ZEB2↓,
TumCMig↓, researchers demonstrated that baiclalein inhibited cellular adhesion, migration, invasion, and growth of HCC cells both in vitro and in vivo.
TumCG↑,
12LOX↓, Baicalein is an inhibitor of 12-LOX and induced apoptosis, morphological changes, and carbonic anhydrase expression in PaCa cells.
DR5↑, Baicalein lessened this resistance to TRAIL by upregulating DR5 expression and promoting the expression of ROS, thus causing TRAIL sensitization in PC3 cells [85]
ROS↑,
RadioS↑, baicalein increased the sensitivity of prostate cancer cells to radiation without affecting this sensitivity in normal cells
ChemoSen↑, Combination therapy of baicalein with paclitaxel, which were assembled by nanoparticles, was demonstrated to have synergistic anticancer effects in A549 lung cancer cells and in mice bearing A549/PTX drug-resistant lung cancer xenografts [97].
BioAv↓, It is worth noting that the bioavailability of baicalein in vivo remains low.
*tau↓, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action
*Dose↝, 85% at 500 μM of Baicalein and 75% at 100 μM Baicalein
*BioAv↓, the potency of Baicalein to be a therapeutic is hampered by its poor water solubility and low bioavailability.
| - |
in-vitro, |
Pca, |
DU145 |
|
|
|
- |
in-vitro, |
Pca, |
PC3 |
|
|
|
TumCG↓, baicalein potently suppressed the growth and induced the apoptosis of DU145 and PC-3
Apoptosis↑,
Cav1↓, baicalein can suppress caveolin-1 and the phosphorylation of AKT and mTOR in a time- and dose-dependent manner
p‑Akt↓,
p‑mTOR↓,
Bax:Bcl2↑, revealed that the Bax/Bcl-2 ratio was increased after baicalein treatment in a dose-dependent manner
survivin↓, survivin was decreased, whereas the level of cleaved PARP was elevated.
cl‑PARP↑,
BioAv↓, Although low water solubility, fast oxidative degradation, and fast metabolism limit its pharmaceutical use in some degree, various methods have been used to overcome these issues of flavonoids
chemoP↑, Compounds such as baicalein, offer promise in dietary chemoprevention, as chemotherapeutic adjuvants, or as targeted therapy.
ChemoSen↑,
12LOX?, LOX-12 specific inhibitor baicalein attenuates cancer cell growth
Bcl-2↓, baicalein, human pancreatic cancer cells expressed decreased anti-apoptotic proteins Bcl-2 and Mcl-1 and increased pro-apoptotic protein bax
BAX↑,
Mcl-1↓,
ERK↓, activation of the ERK pathway in melanoma
Prx6↑, up-regulation in the expression of PRDX6 in colorectal cancer
Dose↝, concentrations at which we and others have found baicalein to be anti-proliferative in vitro are between 10μM and 100μM.
BioAv↓, it is thought that only 10% of ingested dietary polyphenols or their conjugates are found in the urine or plasma.
eff↑, It is possible that the antitumor properties of baicalein in vivo are due to baicalin as opposed to baicalein, as these compounds are inter-converted in the intestine by naturally occurring microbes
AntiCan↑, Baicalin and baicalein exhibit anticancer activities against multiple cancers with extremely low toxicity to normal cells.
*toxicity↓,
BioAv↝, Baicalein permeates easily through the epithelium from the gut lumen to the blood underneath due to its low molecular mass and high lipophilicity, albeit a low presence of its transporters.
BioAv↓, In contrast, baicalin has limited permeability partly due to its larger molecular mass and higher hydrophilicity [24]. The overall low water solubility of baicalin and baicalein contributes to their poor bioavailability.
*ROS↓, baicalin protected macrophages against mycoplasma gallisepticum (MG)-induced ROS production and NLRP3 inflammasome activation by upregulating autophagy and TLR2-NFκB pathway
*TLR2↓,
*NF-kB↓,
*NRF2↑, Therefore, baicalin exerts strong antioxidant activity by activating NRF2 antioxidant program.
*antiOx↑,
*Inflam↓, These data suggest that by attenuating ROS and inflammation baicalein inhibits tumor formation and metastasis.
HDAC1↓, baicalein reduced CTCLs by inhibiting HDAC1 and HDAC8 and its effect on tumor inhibition was better than traditional HDAC inhibitors
HDAC8↓,
Wnt↓, Baicalein also reduced the proliferation of acute T-lymphoblastic leukemia (TLL) Jurkat cells by inhibiting the Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
PD-L1↓, baicalein and baicalin promoted antitumor immune response by suppressing PD-L1 expression of HCC cells, thus increasing tumor regression
Sepsis↓, Baicalein can also attenuate severe sepsis via ameliorating immune dysfunction of T lymphocytes.
NF-kB↓, downregulation of NFκB and CD74/CD44 signaling in EBV-transformed B cells
LOX1↓, baicalein is considered to be an inhibitor of lipoxygenases (LOXs)
COX2↓, inhibits the expression of NF-κB/p65 and COX-2
VEGF↑, Baicalin was shown to suppress the expression of VEGF, resulting in the inhibition of PI3K/AKT/mTOR pathway and reduction of proliferation and migration of human mesothelioma cells
PI3K↓,
Akt↓,
mTOR↓,
MMP2↓, baicalin suppressed expression of MMP-2 and MMP-9 via restriction of p38MAPK signaling, resulting in reduced breast cancer cell growth, invasion
MMP9↓,
SIRT1↑, The inhibition of MMP-2 and MMP-9 expression in NSCLC cells is mediated by activating the SIRT1/AMPK signaling pathway.
AMPK↑,
p‑mTOR↓, Baicalein treatment decreased the expression levels of p-mTOR, p-Akt, p-IκB and NF-κB proteins, and suppressed GC cells by inhibiting the PI3K/Akt
p‑Akt↓,
p‑IKKα↓,
NF-kB↓,
PI3K↓,
Akt↓,
ROCK1↓, Baicalin reduces HCC proliferation and metastasis by inhibiting the ROCK1/GSK-3β/β-catenin signaling pathway
GSK‐3β↓,
CycB/CCNB1↓, Baicalein induces S-phase arrest in gallbladder cancer cells by down-regulating Cyclin B1 and Cyclin D1 in gallbladder cancer BGC-SD and SGC996 cells while up-regulating Cyclin A
cycD1/CCND1↓,
cycA1/CCNA1↑,
CDK4↓, Following baicalein treatment, there is a down-regulation of Ezrin, CyclinD1, and CDK4, as well as an up-regulation of p53 and p21 protein levels, thereby leading to the induction of CRC HCT116 cell cycle arrest
P53↑,
P21↑,
TumCCA↑,
MMP2↓, baicalein was able to inhibit the metastasis of gallbladder cancer cells by down-regulating ZFX, MMP-2 and MMP-9.
MMP9↓,
EMT↓, Baicalein treatment effectively inhibits the snail-induced EMT process in CRC HT29 and DLD1 cells
Hif1a↓, Baicalein inhibits VEGF by downregulating HIF-1α, a crucial regulator of angiogenesis
Shh↓, baicalein inhibits the metastasis of PC by impeding the Shh pathway
PD-L1↓, Baicalin and baicalein down-regulate PD-L1 expression induced by IFN-γ by reducing STAT3 activity
STAT3↓,
IL1β↓, baicalein therapy significantly diminishes the levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), IL-2, IL-6, and GM-CSF
IL2↓,
IL6↓,
PKM2↓, Baicalein, by reducing the expression levels of HIF-1A and PKM2, can inhibit the glycolysis process in ESCC cells
HDAC10↓, Baicalein treatment increases the level of miR-3178 and decreases HDAC10 expression, resulting in the inactivation of the AKT signaling pathways.
P-gp↓, baicalein reverses P-glycoprotein (P-gp)-mediated resistance in multidrug-resistant HCC (Bel7402/5-FU) cells by reducing the levels of P-gp and Bcl-xl
Bcl-xL↓,
eff↓, Baicalein combined with gemcitabine/docetaxel promotes apoptosis of PC cells by activating the caspase-3/PARP signaling pathway
BioAv↓, baicalein suffers from low water solubility and susceptibility to degradation by the digestive system
BioAv↑, Encapsulation of baicalein into liposomal bilayers exhibits a therapeutic efficacy close to 90% for PDAC
| - |
in-vivo, |
Lung, |
B16-F10 |
|
|
|
- |
vitro+vivo, |
Lung, |
A549 |
|
|
|
- |
in-vitro, |
BC, |
MDA-MB-231 |
|
|
|
BioAv↓, major limitation of the compound includes poor bioavailability at the tumor site due to short plasma half-life.
Half-Life↓, Though BBM is a potent drug but its half-life in blood plasma is very short, owing to its quick renal clearance
eff↑, cellular experiments demonstrated enhanced therapeutic efficacy of BBM-NPs in inhibiting metastasis, cell proliferation and growth as compared to native BBM in highly metastatic cancer cell lines.
TumMeta↓,
TumCP↓,
TumCG↓,
Apoptosis↑, BBM shows its anticancer activity by induction of apoptosis, cell cycle arrest16 and reversing multidrug resistance17.
TumCCA↑,
MMP2↓, activation of MMP-2 &MMP-9 was suppressed effectively by BBM-NPs treated cells as compared to native BBM in both the cell lines
MMP9↓,
VEGF↓, the VEGF expression is lower in BBM-NPs treated case than that of native counterparts
Bcl-2↓, moderate down regulation of anti-apoptotic protein BCL-2 in BBM-NPs treated cells than that of native BBM treated case in both A549 and MDA-MB-231 cells
eff↑, BBM-NPs may be due to the enhanced accumulation of drug at the tumor site with sustained release phenomenon
EPR↑, The higher effectiveness of BBM-NPs may be attributed to the enhanced accretion of nanoparticulate drug at the tumor site with sustained release over a period of time, due to EPR effect
*antiOx?, Berberine has been noted as a potential therapeutic candidate for liver fibrosis due to its antioxidant and anti-inflammatory activities
*Inflam↓,
Apoptosis↑, Apoptosis induced by berberine in liver cancer cells caused cell cycle arrest at the M/G1 phase and increased the Bax expression
TumCCA↑,
BAX↑,
eff↑, mixture of curcumin and berberine effectively decreases growth in breast cancer cell lines
VEGF↓, berberine also prevented the expression of VEGF
PI3K↓, berberine plays an important role in cancer management through inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Telomerase↓, Berberine decreased the telomerase activity and level of the colorectal cancer cell line,
β-catenin/ZEB1↓, berberine and its derivatives have the ability to inhibit β-catenin/Wnt signaling in tumorigenesis
Wnt↓,
EGFR↓, berberine treatment decreased cell proliferation and epidermal growth factor receptor expression levels in the xenograft model.
AP-1↓, Berberine efficiently targets both the host and the viral factors accountable for cervical cancer development via inhibition of activating protein-1
NF-kB↓, berberine inhibited lung cancer cell growth by concurrently targeting NF-κB/COX-2, PI3K/AKT, and cytochrome-c/caspase signaling pathways
COX2↑,
NRF2↓, Berberine suppresses the Nrf2 signaling-related protein expression in HepG2 and Huh7 cells,
RadioS↑, suggesting that berberine supports radiosensitivity through suppressing the Nrf2 signaling pathway in hepatocellular carcinoma cells
STAT3↓, regulating the JAK–STAT3 signaling pathway
ERK↓, berberine prevented the metastatic potential of melanoma cells via a reduction in ERK activity, and the protein levels of cyclooxygenase-2 by a berberine-caused AMPK activation
AR↓, Berberine reduced the androgen receptor transcriptional activity
ROS↑, In a study on renal cancer, berberine raised the levels of autophagy and reactive oxygen species in human renal tubular epithelial cells derived from the normal kidney HK-2 cell line, in addition to human cell lines ACHN and 786-O cell line.
eff↑, berberine showed a greater apoptotic effect than gemcitabine in cancer cells
selectivity↑, After berberine treatment, it was noticed that berberine showed privileged selectivity towards cancer cells as compared to normal ones.
selectivity↑, expression of caspase-1 and its downstream target Interleukin-1β (IL-1β) was higher in osteosarcoma cells as compared to normal cells
BioAv↓, several studies have been undertaken to overcome the difficulties of low absorption and poor bioavailability through nanotechnology-based strategies.
DNMT1↓, In human multiple melanoma cell U266, berberine can inhibit the expression of DNMT1 and DNMT3B, which leads to hypomethylation of TP53 by altering the DNA methylation level and the p53-dependent signal pathway
cMyc↓, Moreover, berberine suppresses SLC1A5, Na+ dependent transporter expression through preventing c-Myc
*Inflam↓, BBR exerts remarkable anti-inflammatory (94–96), antiviral (97), antioxidant (98), antidiabetic (99), immunosuppressive (100), cardiovascular (101, 102), and neuroprotective (103) activities.
*antiOx↑,
*cardioP↑,
*neuroP↑,
TumCCA↑, BBR could induce G1 cycle arrest in A549 lung cancer cells by decreasing the levels of cyclin D1 and cyclin E1
cycD1/CCND1↓,
cycE/CCNE↓,
CDC2↓, BBR also induced G1 cycle arrest by inhibiting cyclin B1 expression and CDC2 kinase in some cancer cells
AMPK↝, BBR has been suggested to induce autophagy in glioblastoma by targeting the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/ULK1 pathway
mTOR↝,
Casp8↑, BBR has been revealed to stimulate apoptosis in leukemia by upregulation of caspase-8 and caspase-9
Casp9↑,
Cyt‑c↑, in skin squamous cell carcinoma A431 cells by increasing cytochrome C levels
TumCMig↓, BBR has been confirmed to inhibit cell migration and invasion by inhibiting the expression of epithelial–mesenchymal transition (EMT)
TumCI↓,
EMT↓,
MMPs↓, metastasis-related proteins, such as matrix metalloproteinases (MMPs) and E-cadherin,
E-cadherin↓,
Telomerase↓, BBR has shown antitumor effects by interacting with microRNAs (125) and inhibiting telomerase activity
*toxicity↓, Numerous studies have revealed that BBR is a safe and effective treatment for CRC
GRP78/BiP↓, Downregulates GRP78
EGFR↓, Downregulates EGFR
CDK4↓, downregulates CDK4, TERT, and TERC
COX2↓, Reduces levels of COX-2/PGE2, phosphorylation of JAK2 and STAT3, and expression of MMP-2/-9.
PGE2↓,
p‑JAK2↓,
p‑STAT3↓,
MMP2↓,
MMP9↓,
GutMicro↑, BBR can inhibit tumor growth through meditation of the intestinal flora and mucosal barrier, and generally and ultimately improve weight loss. BBR has been reported to modulate the composition of intestinal flora and significantly reduce flora divers
eff↝, BBR can regulate the activity of P-glycoprotein (P-gp), and potential drug-drug interactions (DDIs) are observed when BBR is coadministered with P-gp substrates
*BioAv↓, the efficiency of BBR is limited by its low bioavailability due to its poor absorption rate in the gut, low solubility in water, and fast metabolism. Studies have shown that the oral bioavailability of BBR is 0.68% in rats
BioAv↑, combining it with p-gp inhibitors (such as tariquidar and tetrandrine) (196, 198), and modification to berberine organic acid salts (BOAs)
*Inflam↓, According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity
*antiOx↑,
*Ca+2↓, Impaired cerebral arterial vasodilation can be alleviated by berberine in a diabetic rat model via down-regulation of the intracellular Ca2+ processing of VSMCs
*BioAv↓, poor oral absorption and low bioavailability
*BioAv↑, Conversion of biological small molecules into salt compounds may be a method to improve its bioavailability in vivo.
*BioAv↑, Long-chain alkylation (C5-C9) may enhance hydrophobicity, which has been shown to improve bioavailability; for example, 9-O-benzylation further enhances lipophilicity and imparts neuroprotective effect
*angioG↑, figure 2
*MAPK↓,
*AMPK↓, 100 mg/kg berberine daily for 14 days attenuated ischemia–reperfusion injury via hemodynamic improvements and inhibition of AMPK activity in both non-ischemic and ischemic areas of rat heart tissue
*NF-kB↓,
VEGF↓,
PI3K↓,
Akt↓,
MMP2↓,
Bcl-2↓,
ERK↓,
*BioAv↓, After oral administration of 20 mg/kg BBR, we were unable to detect BBR in the plasma
*Half-Life↝, In contrast, dhBBR at the same oral dose was rapidly detected in the plasma (Supplementary Fig. 2), displaying a half-life (t1/2) of 3.5 ± 1.3 h and a maximum concentration (Cmax) of 2.8 ± 0.5 ng/ml
*OCR↓, BBR produced a dose-dependent inhibition of oxygen consumption in isolated muscle mitochondria with complex I–linked substrate (pyruvate),
*AMPK↑, ability of BBR to activate AMPK
*BioAv↓, clinical use of berberine has been limited due to its poor intestinal absorption, low bioavailability and limited penetration.
*Half-Life↓, t1/2, Cmax and AUC observed in healthy human male volunteers after single dose administration of 300 mg orally and their values have been reported to be 0.87 ± 0.03 h, 394.7 ± 155.4 µg/L and 2799.0 ± 1128.5 µg/L respectively
*neuroP↑, neuroprotective action have been investigated determining enhanced blood brain barrier (BBB) penetrability
BBB↑,
toxicity↓, These also dole out in low cost, seldom side effects and easy availability.
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Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1↓,
PGE2↓,
COX2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB/CCNB1↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents
Showing Research Papers: 1 to 50 of 224
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 224
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
Ferroptosis↑, 3, frataxin↑, 1, GPx↓, 1, GPx4↓, 2, GSH↓, 4, Iron↑, 1, c-Iron↑, 1, lipid-P↑, 2, NRF2↓, 2, NRF2↑, 2, OXPHOS↓, 1, Prx6↑, 1, ROS↓, 2, ROS↑, 14, Thiols↓, 1, TrxR↓, 1,
Metal & Cofactor Biology ⓘ
TfR1/CD71↑, 1, Zn2+↑, 1,
Mitochondria & Bioenergetics ⓘ
ADP:ATP↑, 1, ATP↓, 2, BCR-ABL↓, 1, CDC2↓, 1, CDC25↓, 3, MMP↓, 2, Mortalin↓, 1, Raf↓, 1, XIAP↓, 1,
Core Metabolism/Glycolysis ⓘ
12LOX?, 1, 12LOX↓, 1, ACSL4↑, 1, AMPK↑, 2, AMPK↝, 1, Cav1↓, 1, cMyc↓, 2, CYP3A2↓, 1, CYP3A4↓, 1, ENO1↓, 1, GlucoseCon↓, 1, Glycolysis↓, 3, HK2↓, 1, HMG-CoA↓, 1, LDL↓, 1, NADPH↓, 1, PDH↑, 1, PKM2↓, 2, SIRT1↑, 1,
Cell Death ⓘ
Akt↓, 10, p‑Akt↓, 3, Apoptosis↑, 13, BAX↑, 7, Bax:Bcl2↑, 3, Bcl-2↓, 7, Bcl-xL↓, 4, BIM↑, 1, Casp↑, 1, Casp3↓, 2, Casp3↑, 3, Casp8↑, 3, Casp9↑, 5, Cyt‑c↑, 4, DR5↑, 2, Fas↑, 1, FasL↑, 1, Ferroptosis↑, 3, IAP1↓, 1, JNK↓, 1, MAPK↓, 3, Mcl-1↓, 2, MDM2↓, 2, necrosis↑, 1, p27↑, 2, survivin↓, 4, Telomerase↓, 2, TumCD↑, 1,
Kinase & Signal Transduction ⓘ
Sp1/3/4↓, 1,
Transcription & Epigenetics ⓘ
other↓, 1, other↑, 1, other↝, 1,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, ER Stress↓, 1, ER Stress↑, 2, GRP78/BiP↓, 1, GRP78/BiP↑, 2, HSP90↓, 1, PERK↑, 1,
Autophagy & Lysosomes ⓘ
LC3II↑, 1, TumAuto↑, 3,
DNA Damage & Repair ⓘ
ATM↑, 1, DNAdam↑, 2, DNMT1↓, 1, m-FAM72A↓, 1, MGMT↓, 1, P53↓, 1, P53↑, 5, cl‑PARP↑, 2, PCNA↓, 1, γH2AX↝, 1,
Cell Cycle & Senescence ⓘ
CDK2↓, 1, CDK4↓, 3, cycA1/CCNA1↑, 1, CycB/CCNB1↓, 3, cycD1/CCND1↓, 4, cycE/CCNE↓, 2, E2Fs↓, 1, P21↑, 3, RB1↑, 1, Securin↓, 1, TumCCA↓, 1, TumCCA↑, 15,
Proliferation, Differentiation & Cell State ⓘ
cMYB↓, 1, CSCs↓, 1, EMT↓, 6, EMT↑, 1, ERK↓, 5, GSK‐3β↓, 3, HDAC1↓, 1, HDAC10↓, 1, HDAC8↓, 1, HMGCR↓, 1, mTOR↓, 7, mTOR↝, 1, p‑mTOR↓, 2, NOTCH1↓, 1, PI3K↓, 7, RAS↓, 1, Shh↓, 1, STAT3↓, 3, p‑STAT3↓, 1, TOP2↓, 1, TumCG↓, 6, TumCG↑, 1, Wnt↓, 4, Wnt/(β-catenin)↓, 1, Zn2+↑, 1,
Migration ⓘ
annexin II↓, 1, AP-1↓, 2, CD31↓, 1, Cdc42↑, 1, E-cadherin↓, 1, E-cadherin↑, 1, FAK↓, 2, ITGB1↓, 1, ITGB3↓, 1, Ki-67↓, 1, MMP1↓, 1, MMP13↓, 1, MMP2↓, 9, MMP3↓, 1, MMP7↓, 1, MMP9↓, 8, MMPs↓, 3, N-cadherin↓, 1, PKCδ↓, 1, Rho↓, 1, ROCK1↓, 3, Snail↓, 1, TET1?, 1, TGF-β↓, 1, TIMP2↑, 1, TumCI↓, 5, TumCMig↓, 4, TumCP↓, 8, TumMeta↓, 5, uPA↓, 2, Vim↓, 4, Zeb1↓, 2, ZEB2↓, 1, β-catenin/ZEB1↓, 4,
Angiogenesis & Vasculature ⓘ
angioG↓, 5, ATF4↑, 1, EGFR↓, 5, EPR↑, 2, Hif1a↓, 5, LOX1↓, 1, VEGF↓, 7, VEGF↑, 1,
Barriers & Transport ⓘ
BBB↑, 1, GLUT1↓, 3, P-gp↓, 4,
Immune & Inflammatory Signaling ⓘ
CD4+↓, 1, COX2↓, 5, COX2↑, 1, CXCR4↓, 1, Dectin1↝, 1, p‑IKKα↓, 1, IL1↓, 1, IL12↑, 1, IL1β↓, 1, IL2↓, 1, IL2↑, 1, IL6↓, 2, IL8↓, 1, Imm↑, 4, Inflam↓, 3, p‑JAK2↓, 1, MCP1↓, 1, NF-kB↓, 7, PD-1↝, 1, PD-L1↓, 3, PGE2↓, 2, TNF-α↓, 1, TNF-α↑, 1,
Hormonal & Nuclear Receptors ⓘ
AR↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 25, BioAv↑, 8, BioAv⇅, 1, BioAv↝, 3, ChemoSen↑, 16, CYP1A2↓, 1, CYP2C9↓, 1, Dose↝, 4, Dose∅, 2, eff↓, 3, eff↑, 17, eff↝, 3, Half-Life↓, 3, Half-Life↝, 1, Half-Life∅, 2, MDR1↓, 1, RadioS↑, 5, selectivity↑, 8,
Clinical Biomarkers ⓘ
AR↓, 1, EGFR↓, 5, GutMicro↑, 1, IL6↓, 2, Ki-67↓, 1, PD-L1↓, 3,
Functional Outcomes ⓘ
AntiCan↑, 7, AntiTum↑, 3, cardioP↑, 1, chemoP↑, 4, chemoPv↑, 1, hepatoP↓, 1, OS↑, 1, QoL↑, 1, radioP↑, 1, RenoP↑, 1, toxicity↓, 3, toxicity↝, 2, TumVol↓, 1,
Infection & Microbiome ⓘ
Dectin1↝, 1, Sepsis↓, 1,
Total Targets: 242
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx?, 1, antiOx↑, 11, Catalase↑, 1, GPx↑, 2, H2O2∅, 1, lipid-P↓, 1, MDA↓, 1, NQO1∅, 1, NRF2↑, 2, ROS↓, 6, ROS↑, 1, SOD↑, 1,
Metal & Cofactor Biology ⓘ
IronCh↑, 1,
Mitochondria & Bioenergetics ⓘ
OCR↓, 1,
Core Metabolism/Glycolysis ⓘ
AMPK↓, 1, AMPK↑, 1, cAMP↑, 1, LDL↓, 1, SIRT1↑, 1,
Cell Death ⓘ
Casp3↓, 1, Casp9↓, 1, iNOS↓, 1, MAPK↓, 1,
Transcription & Epigenetics ⓘ
Ach↑, 1, other↝, 1,
DNA Damage & Repair ⓘ
DNArepair↑, 1,
Migration ⓘ
Ca+2↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↑, 1,
Barriers & Transport ⓘ
BBB↑, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 1, IL1α∅, 1, IL1β↓, 1, IL1β∅, 1, IL2↓, 1, IL6↓, 1, IL8∅, 1, INF-γ↓, 1, Inflam↓, 7, MCP1∅, 1, NF-kB↓, 2, PGE2↓, 1, TLR2↓, 1, TNF-α↓, 2,
Synaptic & Neurotransmission ⓘ
ChAT↑, 1, tau↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 27, BioAv↑, 13, BioAv↝, 3, ChemoSen↑, 1, Dose↑, 1, Dose↝, 5, eff↑, 3, eff↝, 1, Half-Life↓, 4, Half-Life↝, 4, Half-Life∅, 1,
Clinical Biomarkers ⓘ
GutMicro↑, 1, IL6↓, 1,
Functional Outcomes ⓘ
AntiAge↑, 1, AntiDiabetic↑, 1, cardioP↓, 1, cardioP↑, 3, cognitive↑, 4, hepatoP↑, 1, memory↑, 1, motorD↑, 1, neuroP↑, 6, RenoP↑, 1, toxicity↓, 5, toxicity↑, 1, toxicity∅, 2,
Total Targets: 71
Scientific Paper Hit Count for: BioAv, bioavailability
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include :
-low or high Dose
-format for product, such as nano of lipid formations
-different cell line effects
-synergies with other products
-if effect was for normal or cancerous cells
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