Half-Life Cancer Research Results
Half-Life, Half-Life: Click to Expand ⟱
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For many drugs, the half-life is the time it takes for half of the drug’s active substance to be eliminated from the bloodstream.
In medicine, knowing a drug’s half-life helps in designing treatment regimens that reduce adverse effects.
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Scientific Papers found: Click to Expand⟱
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*Inflam↓, long history of use in traditional medicine and exhibits an array of biological properties, including anti-inflammatory, antioxidant, antimicrobial, bronchodilatory, analgesic, and pro-apoptotic effects.
*antiOx↑,
*neuroP↑, recent studies have highlighted the neuroprotective, analgesic, and pro-apoptotic properties of 1,8-cineole, underscoring its potential beneficial role in a broad spectrum of conditions such as Alzheimer’s disease, neuropathic pain, and cancer
*BioAv↑, Marked by a logP value of 2.74, 1,8-cineole strikes an optimal equilibrium between solubility and permeability, hinting at its favorable potential for oral bioavailability
*Half-Life↝, In rabbits, oral administration of 200 mg/kg has led to rapid attainment of peak plasma concentration within 1 h, indicating efficient absorption
*toxicity↓, compound’s toxicity profile, the oral acute LD50 value in rats is documented at 2480 mg/kg body weight
*PGE2↓, 1,8-cineole decreased the release of prostaglandin E2 and leukotriene B4 (LTB4) from peripheral blood mononuclear cells in asthmatic patients, and reduced TNF-α, IL-1β, LTB4, and thromboxane B2 in lipopolysaccharide (LPS)-stimulated peripheral blood
*TNF-α↓,
*IL1β↓,
*NO↓, 1,8-cineole hindered LPS-induced nitric oxide (NO) production in mouse macrophage cell lines
*NF-kB↓, inhibition of nuclear translocation of NF-κB p65 and PPARγ, leading to the suppression of immune response genes.
*PPARγ↓,
COX2↓, ,8-cineole has been found to impede UVB-induced COX-2 protein and mRNA production in HaCaT cells
*ROS↓, 1,8-cineole’s antioxidant properties play a crucial role in its therapeutic potential, as it is effective in neutralizing reactive oxygen species (ROS)
*SOD↑, 1,8-cineole treatment enhanced antioxidant enzymes activities, such as superoxide dismutase (SOD) and catalase (CAT), increased total antioxidant capacity, and decreased ROS and malondialdehyde (MDA)
*Catalase↑,
*TAC↑,
*MDA↓,
*lipid-P↓, 1,8-cineole has demonstrated the ability to inhibit LP
*NRF2↑, The antioxidant activity of 1,8-cineole is mediated, in part, by activating the Nrf2/Keap1 system
*HO-1↑, increased expression of phase II detoxifying enzymes and antioxidant proteins, such as heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 (NOQ1)
*NADPH↑,
*GPx↑, 1,8-cineole treatment has been shown to enhance the activities of antioxidant enzymes, such as SOD, GPx, and CAT,
*AntiBio↑, Antibacterial properties: activity, synergy with antibiotics, and impact on biofilm formation and cell morphology
*eff↑, Although 1,8-cineole exhibited weaker bactericidal activity than commonly used antibiotics such as gentamicin and amoxicillin (AMX)/clavulanic acid, it significantly reduced the minimum inhibitory concentration of antibiotics when used in combination
*AntiFungal↑, Antifungal properties: inhibition of fungal growth and disruption of biofilm formation
*AntiViral↑, Antiviral properties: inhibition of viral replication and enhancement of antiviral responses
*TRPA1↑, 1,8-cineole could activate TRPA1 channels in the dorsal root ganglia (DRG),
eff↑, when combined with simvastatin, increased G0/G1 cell cycle arrest and sensitized cells to apoptosis
TumCCA↑, 1,8-cineole induced G0/G1 arrest and senescence in HepG2 cells through oxidative stress and various signaling pathways such as MAPK, AMPK, and Akt/mTOR
ROS↑,
MAPK↝,
mTOR↝,
Apoptosis↑, HCT116 and RKO human colon cancer cell lines, 1,8-cineole selectively promoted apoptosis rather than necrosis
survivin↓, This process was linked to survivin and Akt inactivation, along with p38 activation.
Akt↓,
p38↑,
cl‑PARP↑, triggered subsequent cleavage of PARP and caspase-3, resulting in apoptosis.
cl‑Casp3⇅,
P53↑, increasing p53 expression, as well as the expression of apoptotic proteins (Bax/Bcl-2, Cyt-c, caspase-9, and caspase-3)
BAX↑,
Cyt‑c↑,
Casp9↑,
Dose↝, efficacious concentrations of 1,8-cineole reported for inhibiting in vitro cancer cell proliferation range from micromolar [135], [136] to millimolar (mM)
*Aβ↓, 1,8-cineole in rat PC12 cells (pheochromocytoma cells) demonstrated effective mitigation of the Aβ induced cytotoxicity and oxidative stress
*tau↓, 1,8-cineole has shown the ability to modulate tau phosphorylation by suppressing GSK-3β activity and to reduce Aβ production by inhibiting beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), both in vitro and in vivo
*GSK‐3β↓,
*BACE↓,
*cardioP↑, 1,8-cineole enhanced cell viability, inhibited cardiac hypertrophy, attenuated cardiac remodeling, improved cardiac function, and decreased the concentrations of atrial natriuretic peptide and brain natriuretic peptide in rat hearts
MFN2↑, 1,8-cineole was also found to inhibit the activation of dynamin-related protein 1 and promote mitochondrial fusion by increasing MFN2.
*BioAv↑, 1,8-cineol is well absorbed from breathing air, with a peak plasma concentration after ∼18 min.
*Half-Life↝, The elimination of this fragrance compound from the blood is biphasic, with a mean distribution half-life of 6.7 min and an elimination half-life of 104.6 min.
*Half-Life↝, biological half-life of 5-HTP ranged from 2.2 to 7.4 hours, and the plasma clearnce ranged from 0.10 to 0.23 1/kg/hour.
*BioAv↑, The bioavailability of 5-HTP after oral administration in combination with carbidopa was calculated as 48% ± 15 (mean ± SD). T
*Dose?, Subjects received orally 6 mg (p.o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days.
*Half-Life↝, The mean gold maximum concentration in plasma (Cmax) at day 7 was 0.312 μg/ml and the half-life (t1/2) 35 days, so steady-state blood levels would not be reached in short-term therapy.
*Dose↑, The highest concentration of gold, 13 μM (auranofin equivalent), or more than 25× the 50% inhibitory concentration (IC50) for E. histolytica and 4× that for Giardia, was in feces at 7 days.
*toxicity↝, Long-term (months to years) auranofin therapy was linked to side effects, including diarrhea (40% of subjects), skin rashes (2% to 5%), hematologic abnormalities (rare), and proteinuria (5%)
*Bacteria↓, Higher doses of auranofin will clearly be required for some infections.
*Dose↑, The FDA has approved clinical trials using auranofin at up to 21 mg/day for treatment of relapsed chronic lymphocytic leukemia after daily doses of 9 and 12 mg for at least 28 days were well tolerated
Dose↝, 6mg dose(equivalent to 1.74mg of gold) radioactive
Half-Life↝, plasma terminal half-life was 17days
*Dose↝, the mean maximum plasma concentration (Cmax) values of AGS-IV were 2.12, 3.59, 3.71 and 5.17 μg ml−1 after single doses of 200, 300, 400 and 500 ml of AI, respectively.
Half-Life↝, mean values of elimination half-life (t1/2) were 2.14, 2.59, 2.62 and 2.69 h, respectively.
*toxicity↓, AI was safe and well tolerated, and the adverse events, such as raised total bilirubin and rash, were mild and resolved spontaneously. AI was safe and well tolerated in this study,
*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
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*Inflam↓, It showed neuroprotective effects, exhibited anti-inflammatory properties, demonstrated anticancer activity, acted as an antioxidant, provided cardioprotection, exerted antidiabetic effects, and offered hepatoprotection.
AntiCan↑,
*antiOx↑,
*cardioP↑, This vasodilatory effect helps protect against cardiovascular diseases by reducing the risk of hypertension and atherosclerosis.
*hepatoP↑,
*BBB↑, This allows allicin to easily traverse phospholipid bilayers and the blood-brain barrier
*Half-Life↝, biological half-life of allicin is estimated to be approximately one year at 4°C. However, it should be noted that its half-life may differ when it is dissolved in different solvents, such as vegetable oil
*H2S↑, allicin undergoes metabolism in the body, leading to the release of hydrogen sulfide (H2S)
*BP↓, H2S acts as a vasodilator, meaning it relaxes and widens blood vessels, promoting blood flow and reducing blood pressure.
*neuroP↑, It acts as a neuromodulator, regulating synaptic transmission and neuronal excitability.
*cognitive↑, Studies have suggested that H2S may enhance cognitive function and protect against neurodegenerative diseases like Alzheimer's and Parkinson's by promoting neuronal survival and reducing oxidative stress.
*neuroP↑, various research studies suggest that the neuroprotective mechanisms of allicin can be attributed to its antioxidant and anti-inflammatory properties
*ROS↓,
*GutMicro↑, may contribute to the overall health of the gut microbiota.
*LDH↓, Liu et al. found that allicin treatment led to a significant decrease in the release of lactate dehydrogenase (LDH),
*ROS↓, allicin's capacity to lower the production of reactive oxygen species (ROS), decrease lipid peroxidation, and maintain the activities of antioxidant enzymes
*lipid-P↓,
*antiOx↑,
*other↑, allicin was found to enhance the expression of sphingosine kinases 2 (Sphk2), which is considered a neuroprotective mechanism in ischemic stroke
*PI3K↓, allicin downregulated the PI3K/Akt/nuclear factor-kappa B (NF-κB) pathway, inhibiting the overproduction of NO, iNOS, prostaglandin E2, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha induced by interleukin-1 (IL-1)
*Akt↓,
*NF-kB↓,
*NO↓,
*iNOS↓,
*PGE2↓,
*COX2↓,
*IL6↓,
*TNF-α↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
*MPO↓, Furthermore, allicin significantly decreased tumor necrosis factor-alpha (TNF-α) levels and myeloperoxidase (MPO) activity, indicating its neuroprotective effect against brain ischemia via an anti-inflammatory pathway
*eff↑, Allicin, in combination with melatonin, demonstrated a marked reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and NF-κB genes in rats with brain damage induced by acryl
*NRF2↑, Allicin treatment decreased oxidative stress by upregulating Nrf2 protein and downregulating Keap-1 expression.
*Keap1↓,
*TBARS↓, It significantly reduced myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) levels,
*creat↓, and decreased blood urea nitrogen (BUN), creatinine, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels.
*LDH↓,
*AST↓,
*ALAT↓,
*MDA↓,
*SOD↑, Allicin also increased the activity of superoxide dismutase (SOD) as well as the levels of glutathione S-transferase (GST) and glutathione (GSH) in the liver, kidneys, and brain
*GSH↑,
*GSTs↑,
*memory↑, Allicin has demonstrated its ability to improve learning and memory deficits caused by lead acetate injury by promoting hippocampal astrocyte differentiation.
chemoP↑, Allicin safeguards mitochondria from damage, prevents the release of cytochrome c, and decreases the expression of pro-apoptotic factors (Bax, cleaved caspase-9, cleaved caspase-3, and p53) typically activated by cisplatin
IL8↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
Cyt‑c↑, In addition, allicin was reported to induce cytochrome c, increase expression of caspase 3 [86], caspase 8, 9 [82,87], caspase 12 [80] along with enhanced p38 protein expression levels [81], Fas expression levels [82].
Casp3↑,
Casp8↑,
Casp9↑,
Casp12↑,
p38↑,
Fas↑,
P53↑, Also, significantly increased p53, p21, and CHK1 expression levels decreased cyclin B after allicin treatment.
P21↑,
CHK1↓,
CycB/CCNB1↓,
GSH↓, Depletion of GSH and alterations in intracellular redox status have been found to trigger activation of the mitochondrial apoptotic pathway was the antiproliferative function of allicin
ROS↑, Hepatocellular carcinoma (HCC) cells were sensitised by allicin to the mitochondrial ROS-mediated apoptosis induced by 5-fluorouracil
TumCCA↑, According to research findings, allicin has been shown to decrease the percentage of cells in the G0/G1 and S phases [87], while causing cell cycle arrest at the G2/M phase
Hif1a↓, Allicin treatment was found to effectively reduce HIF-1α protein levels, leading to decreased expression of Bcl-2 and VEGF, and suppressing the colony formation capacity and cell migration rate of cancer cells
Bcl-2↓,
VEGF↓,
TumCMig↓,
STAT3↓, antitumor properties of allicin have been attributed to various mechanisms, including promotion of apoptosis, inhibition of STAT3 signaling
VEGFR2↓, suppression of VEGFR2 and FAK phosphorylation
p‑FAK↓,
*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
*Half-Life↝, The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3+/-15.0 and 3.4+/-0.46 h, respectively.
*Half-Life↝, Artemisinin was found to induce its own metabolism with a mean induction time of 1.9 h, whereas the enzyme elimination half-life was estimated to 37.9 h.
BioAv↝, Artemisinin produces a rapid onset of enzyme induction, resulting in a decrease in its own bioavailability over time.
*Half-Life↓, Plasma artemisinin concentrations reach a peak within 2–3 h after oral intake and decline with a short half-life of 1.5–2 h
BioAv↑, Artemisinin is believed to pass through the gut membrane relatively easily [3, 4], although high oral clearance values are indicative of high first-pass metabolism of the compound, resulting in low bioavailability
*Dose↝, either a daily single dose of 500 mg oral artemisinin for 5 days, or single oral doses of 100/100/250/250/500 mg on each of the first 5 days.
Half-Life↝, The pharmacokinetic study demonstrates that a dose of
4 mg/kg in mice results in 2 μM concentration in plasma (with
a half-life of 1.3 h, in the breast cancer model of mice),
Inflam↓, WA has many biological activities: anti-inflammatory (Dubey et al. 2018), immunomodulatory (Davis and Girija 2000), antistress (Singh et al. 2016), antioxidant (Sumathi et al. 2007) and anti-angiogenesis
antiOx↓,
angioG↓,
ROS↑, WA induces oxidative stress (ROS) determining mitochondrial dysfunction as well as apoptosis in leukaemia cells
BAX↑, withaferin mediates apoptosis by ROS generation and activation of Bax/Bak.
Bak↑,
E6↓, The results of the study show that withaferin treatment downregulates the HPV E6 and E7 oncoprotein and induces accumulation of p53 result in the activation of various apoptotic markers (e.g. Bcl2, Bax, caspase-3 and cleaved PARP).
E7↓,
P53↑,
Casp3↑,
cl‑PARP↑,
STAT3↓, WA treatment also decreases the level of STAT3
eff↑, This study concludes that combination of DOX with WA can reduce the doses and side effects of the treatment which gives valuable possibilities for future research.
HSP90↓, by inhibiting the HSP90
TGF-β↓, WA inhibited TGFβ1 and TNFα- induced EMT;
TNF-α↓,
EMT↑,
mTOR↓, by downregulation of mTOR/STAT3 signalling.
NOTCH1↓, WA showed inhibition of pro-survival signalling markers (Notch1, pAKT and NFκB)
p‑Akt↓,
NF-kB↓,
Dose↝, WA dose escalation sets consisted of 72, 108, 144 and 216 mg, fractioned in 2-4 doses/day.
*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
*AMPK↑,
*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
*chemoPv↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
OXPHOS↓,
PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
AMPK↑,
TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
Akt↓,
Bcl-2↓,
Casp3↑,
Apoptosis↑,
eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
PI3K↓, WA inhibited PI3K/AKT pathway.
FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
N-cadherin↓,
EMT↓,
FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
ACLY↓,
ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
NRF2↑,
HO-1↑,
NQO1↑,
JNK↑,
mTOR↓, suppressing the mTOR/STAT3 pathway
neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
*IL1β↓,
*IL6↓,
*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
*IL18↓,
RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117
*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.
Half-Life↝, 10 - 14 hours (AsIII), 32 hours for MMAV and 70 hours for DMA
*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]
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*neuroP↑, Recent studies have shown its good protective effect on neurons and brain tissues [14].
*antiOx↑, strong anti-inflammatory and antioxidant properties.
*Inflam↓,
*BioAv↝, When taken orally, baicalin is converted to baicalein via β-glucuronidase (GUS), which is produced by the intestinal flora.
*BioAv↑, Pharmacokinetics indicate that baicalein has a higher absorption rate than baicalein [19], but once it is absorbed, baicalein is quickly degraded in the bloodstream, yielding baicalein
*Half-Life↝, The distribution half-life and elimination half-life of baicalin in the CSF of normal rats are 0.8868 and 26.0968 min, respectively.
*TLR4↓, Inhibition of the TLR4/MyD88/NF-κB signal
*NF-kB↓,
*iNOS↓, decreasing the synthesis of iNOS, COX2, and TNF-α
*COX2↓,
*TNF-α↓,
*12LOX↓, downregulation of 12/15-LOX after cerebral ischemia
*NLRP3↓, Inhibition of the expression of NLRP3, HT-22 cells
*ROS↓, Decrease in the ROS levels in the ICH, thus inhibiting high NLRP3
*IL1β↓, Reduced the amounts of IL-1β and IL-6 and inhibited the activation of the NLRP3 inflammasome
*IL6↓,
*GSK‐3β↓, Inhibiting the activation of the GSK3β/NF-κB/NLRP3 signaling pathway
*NRF2↑, Fang et al. reported that the activation of the Akt pathway resulted in increased Nrf2 nuclear translocation and immunoreactivity in a group treated with baicalin
*BBB↑, baicalein effectively crosses the blood‒brain barrier (BBB) and stimulates the Nrf2/HO-1 pathway via specialized brain-targeted exosomes
*SOD↑, increased serum levels of SOD and GSH-Px.
*GPx↑,
*MDA↓, baicalin inhibited the ROS production and reduced MDA levels in brain tissues from a rat model of cerebral I/R injury induced by middle cerebral artery occlusion (MCAO).
*toxicity↓, Baicalein tablet was generally safe and well‐tolerated.
*BioAv↑, Oral baicalein tablets were rapidly absorbed with peak plasma levels being reached within 2 h after multiple administration.
*Half-Life↝, highest urinary excretion of baicalein and its metabolites peaked in 2 h, followed by 12 h, with a double peak trend.
*Dose↝, steady‐state concentration of baicalein was achieved after 6 days of multiple dosing, and the mean Cavg and AUC0–τ,ss of baicalein were 633.64 (290.36) ng/ml and 5069.16 (2322.87) h ng/ml for 600 mg.
*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
*Akt↑, Akt1 mRNA expression levels were significantly decreased in AD mice and significantly increased after BBR treatment (p < 0.05).
*neuroP↑, BBR may exert a neuroprotective effect by modulating the ERK and AKT signaling pathways.
*p‑ERK↑, Besides, AKT and ERK phosphorylation decreased in the model group, and BBR significantly increased their phosphorylation levels.
*Aβ↓, BBR has therapeutic potential in the treatment of AD by targeting amyloid beta plaques, neurofibrillary tangles, neuroinflammation, and oxidative stress
*Inflam↓,
*ROS↓,
*BioAv↑, oral bioavailability (OB) = 36.86%, drug-likeness (DL) = 0.78,
*BBB↑, blood brain barrier (BBB) = 0.57,
*Half-Life↝, half-life (HL) = 6.57. BBR half-life (t1/2) is in the mid-elimination group.
*memory↑, BBR improves the performance of memory and recognition tasks in AD mice
*cognitive↑,
*HSP90↑, Among the core targets, Akt1 (t = −5.01, p = 0.002), Hsp90aa1 (t = −3.66, p = 0.011), Hras (t = −2.99, p = 0.024) and Igf1 (t = 3.75, p = 0.019) mRNA levels were significantly increased after BBR treatment
*APP↓, BBR reduces Aβ levels by modulating APP processing and ameliorates Aβ pathology by inhibiting the mTOR/p70S6K signaling pathway
*mTOR↓,
*P70S6K↓,
*CD31↑, it promotes the formation of brain microvessels by enhancing CD31, VEGF, N-cadherin, Ang-1 and inhibits neuronal apoptosis (Ye et al., 2021).
*VEGF↑,
*N-cadherin↑,
*Apoptosis↓,
AntiCan↑, BA has a range of well-documented pharmacological and biological effects, including antibacterial, immunomodulatory, diuretic, antiviral, antiparasitic, antidiabetic, and anticancer activities
TumCD↑, anticancer properties of BA are mediated by the activation of cell death and cell cycle arrest, production of reactive oxygen species, increased mitochondrial permeability, modulation of nuclear factor-κB and Bcl-2 family signaling
TumCCA↑,
ROS↑,
NF-kB↓,
Bcl-2↓,
Half-Life↝, The half-life eliminations were 11.8 and 11.5 h after 500 and 250 mg/kg of intraperitoneal (i.p.) BA administration
GLUT1↓, the expression of HIF target genes, such as GLUT1, VEGF, and PDK1 was also suppressed by BA
VEGF↓,
PDK1↓,
Half-Life↝, The estimated plasma half-life was 6-9 h.
Dose↝, After oral multidosing (3 g/day), plasma concentration reached as much as 5,000 pg/ml by 48 h.
Dose↝, 10.8 micrograms of bromelain was present in plasma in the 3- to 51-h period.
*BioAv↑, After per oral application, natural borneol was absorbed rapidly into the brain and could be determined 5 min after dosing.
*Half-Life↝, The maximal brain concentration (86.52 μg/g) was reached after 1 h post-dosing.
other↝, L: -glutamic acid increased significantly at 0.333 h and decreased from 1.5 to 5 h, gamma-amino-N-butyric acid increased significantly from 0.167 to 5 h,
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*eff↑, L-borneol has better potential in cerebrovascular diseases.
*eff↑, D-borneol exhibits better antitumour sensitizing effects than L-borneol.
*toxicity↝, Synthetic borneol is less safe. Synthetic borneol is widely used because of its advantages of low cost and easy availability.
*Inflam↓, It has anti-inflammatory, analgesic, antipyretic, antibacterial, neuroprotective, and permeation-promoting effects.
*Bacteria↓,
*neuroP↑,
*Half-Life↝, oral administration. It reaches its highest concentration in 30 min, and its half-life is 18 h
*BBB↑, and can easily pass through the BBB and blood–ocular barrier (BOB).
*BioEnh↑, Borneol can promote the absorption and affect the distribution of other drugs, which is beneficial for reducing the dosage, prolonging the action time, and improving the curative effects of these drugs
*P-gp↓, inhibitory activity against P-gp is as follows: L-borneol > D-borneol ≈ synthetic borneol.
*CYP3A4↓, inhibition of intestinal CYP3A4 would improve the bioavailability of drugs.
*ROS↓, and reduce the rate of cerebral oedema and the volume of infarcts by inhibiting oxidative stress
*neuroP↑, neuroprotective effects of the three kinds of borneol are as follows: L-borneol > synthetic borneol > D-borneol
*Half-Life↝, the half-life for elimination was essentially the same (approx 21 h) by either route of exposure.
*Inflam↓, anti-inflammatory, antimicrobial, antioxidant, and pro-proliferative effects.
*antiOx↑,
*ROS↓, The antioxidant properties of boron help protect cells from oxidative stress, a common feature of chronic wounds that can impair healing
*angioG↑, Boron compounds exhibit diverse therapeutic actions in wound healing, including antimicrobial effects, inflammation modulation, oxidative stress reduction, angiogenesis induction, and anti-fibrotic properties.
*COL1↑, Boron has been shown to increase the expression of proteins involved in wound contraction and matrix remodeling, such as collagen, alpha-smooth muscle actin, and transforming growth factor-beta1.
*α-SMA↑,
*TGF-β↑,
*BMD↑, Animals treated with boron showed favorable changes in bone density, wound healing, embryonic development, and liver metabolism
*hepatoP↑,
*TNF-α↑, BA elevates TNF-α and heat-shock proteins 70 that are related to wound healing.
*HSP70/HSPA5↑,
*SOD↑, antioxidant properties of BA showed that boron protects renal tissue from I/R injury via increasing SOD, CAT, and GSH and decreasing MDA and total oxidant status (TOS)
*Catalase↑,
*GSH↑,
*MDA↓,
*TOS↓,
*IL6↓, Boron supports gastric tissue by alleviating ROS, MDA, IL-6, TNF-α, and JAK2/STAT3 action, as well as improving AMPK activity
*JAK2↓,
*STAT3↓,
*AMPK↑,
*lipid-P↓, boron may improve wound healing by hindering lipid peroxidation and increasing the level of VEGF
*VEGF↑,
*Half-Life↝, Boron is a trace element, usually found at a concentration of 0–0.2 mg/dL in plasma with a half-life of 5–10 h, and 1–2 mg of it is needed in the daily diet
TumCP↓, Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α).
eIF2α↑, Phosphorylation of eIF2α occurs following BA treatment of DU-145 and LNCaP prostate cells
ATF4↑, post-treatment increases in eIF2α protein at 30 min and ATF4 and ATF6 proteins at 1 h and 30 min, respectively
ATF6↑,
GADD34↑, The increase in ATF4 was accompanied by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp),
CHOP↓, but a decrease in GADD153/CCAAT/enhancer-binding protein homologous protein (CHOP), a pro-apoptotic gene.
GRP78/BiP↑, The increase in ATF6 was accompanied by an increase in expression of its downstream genes GRP78/BiP, calreticulin, Grp94, and EDEM.
GRP94↑,
Risk↓, Low boron status has been associated with increased cancer risk, low bone mineralization, and retinal degeneration
*BMD↑,
Ca+2↓, LNCaP and DU-145: BA binds to cADPR and inhibits cADPR-activated Ca2+ release from the endoplasmic reticulum (ER) in a dose-dependent manner [15, 16] and lowers ER luminal Ca2+ concentrations
*Half-Life↝, lood levels of BA are dynamic, rising rapidly after a meal with an elimination half-life from 4 to 27.8 h depending on dose
IRE1∅, BA does not activate IRE1
chemoP↑, Dietary boron has been connected to three seemingly unconnected observations, increased bone mass and strength [10, 74, 75], chemoprevention
*Half-Life↝, (Boron) is excreted with a half-life of 21 hours, and is mostly eliminated with only a low level of accumulation in bone.
*eff↑, 13 subjects predetermined to be vitamin D deficient found that during a 60-day supplementation period with 6 mg boron/day, serum 25-hydroxyvitamin D levels rose by an average of 20%
PSA↓, one study using nude mice implanted with human prostate adenocarcinoma (LNCaP) cells found that boron supplementation reduced serum prostate-specific antigen (PSA) levels, and reduced tumor size and expression of IGF-1,
TumVol↓,
IGF-1↓,
*memory↓, Boron deprivation : results in significantly poorer performance on tasks involving eye-hand coordination, attention, and short-term memory (Penland 1994 and 1998).
*motorD↓,
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*AntiCan↑, Emerging studies show that it displays potent anti-tumor activity in several human cancers.
*TRPV1↑, The “heat-sensation” of capsaicin arises due to the binding of capsaicin to transient receptor potential vanilloid (TRPV) ion-channel receptors
*cardioP↑, some of the biological activities of capsaicin, like its anti-neoplastic, cardioprotective effects, have been found to be independent of the TRPV1 receptor.
AntiCan↓, Exposure to high doses of capsaicin (above 100 mg capsaicin per kg body weight) for a prolonged time causes peptic ulcers, accelerates the development of prostate, stomach, duodenal, and liver cancers and enhances breast cancer metastasis [5, 6].
Apoptosis↑, Capsaicin induces robust apoptosis in multiple types of human cancer cells both in vitro and in mice models.
ChemoSen↑, Capsaicin potentiates the apoptotic activity of cisplatin in human stomach cancer and attenuates cisplatin-induced renal toxicity in rodent models
*Inflam↓, oral or local administration of capsaicin reduces inflammation and pain from rheumatoid arthritis, fibromyalgia and chemical hyperalgesia
*Pain↓,
*AntiAg↑, The anti-platelet and anti-coagulant activity of capsaicin was independent of TRPV1
*Weight↓, capsaicinoids show anti-obesity activity by enhancing energy expenditure of the body
*BioAv↑, Capsaicin is robustly absorbed from the skin upon topical administration [4]
BioAv↑, capsaicin is rapidly absorbed from the stomach and the intestine following oral administration.
Half-Life↝, The liver and kidney displayed maximal amounts of capsaicin in 3 hours and 6 hours, respectively.
Half-Life↓, An interesting fact to note is that the bioavailability and half-life of capsaicin is quite low in the plasma, irrespective of the route of administration.
*Dose↝, Those products include intramammary, topical and intravaginal preparations, each dosed at two levels.
Half-Life↝, For topical and intramammary products, levels were measurable in the plasma, liver, kidney and fat up to 72 h after the last dose.
Half-Life↝, The plasma half-lives were short for thymol (approximately 1.6 h) and carvacrol (approximately 1.5 h)
Half-Life↝, whereas the estimated half-lives for these substances in tissues ranged from 13.9 to 31.5 h for thymol and from 16.9 to 25 h for carvacrol.
*eff?, CBC products are commercially available over-the-counter and are being widely utilized with little or no evidence of their safety or efficacy.
*Half-Life↝, relatively significant half-life in both plasma (98 minutes) and brain (193 minutes),
*Inflam↓, The anti-inflammatory properties of CBC are the most characterized and have been documented in both in vitro and in vivo animal models.
*cognitive↑, Centella asiatica is reputed in Eastern medicine to improve cognitive function in humans.
*NRF2↑, aqueous extracts of C. asiatica improve cognition in mouse models of aging and Alzheimer’s disease (AD) through the modulation of mitochondrial biogenesis and nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant response genes.
*Dose↝, Single administration of 2 g or 4 g of CAP was safe and well-tolerated.
*memory↑, Preclinical studies have shown that aqueous extracts of C. asiatica (CAW) have important biological effects on aging, mood, learning, memory, and, potentially, AD development
*ROS↓, CAW was found to mediate the impact of oxidative stress, which is implicated in cognitive decline and AD, thereby preventing cognitive deficits
*mitResp↑, increase mitochondrial respiration in neuroblastoma cells
*neuroP↑, Such evidence strongly supports the hypothesis that CQAs have strong neuroprotective properties, contribute to the biological activity of C. asiatica,
*Half-Life↝, The maximum plasma concentrations (Cmax) of asiatic acid (133–259 ng/mL) and madecassic acid (36–68 ng/mL) occurred at 2 h (Tmax)
*Half-Life↝, Isoferulic acid had the earliest Cmax (0.9–2 ng/mL) at 0.75 h (Table 3). The maximum plasma concentrations (Cmax) of dihydrocaffeic acid (1–2 ng/mL) and dihydroferulic acid (11–20 ng/mL) occurred at 4 h (Tmax),
*Half-Life↝, while the Cmax of caffeic acid (0.3–0.5 ng/mL), ferulic acid (1–1.4 ng/mL), and 3-(3-hydroxyphenyl)propionic acid (32–42 ng/mL) occurred later, at 6 h
*toxicity↓, CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg.
Half-Life↝, A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t1/2 of 0.95–1.27 h on day 1 and 1.19–1.39 h on day 30
BBB↑, CGA has been found to penetrate the blood-brain barrier
*Dose↝, ingested a black coffee drink (CGAs 299 mg in 184 mL) after fasting for 14 h.
*BioAv↑, The results indicated that CQAs and FQAs are absorbed in their intact forms into the plasma after ingestion of the coffee.
*Half-Life↝, The concentrations of CQAs and FQAs in the plasma reached a maximum (C max) at 0.5 and 2 h after ingestion, respectively, and then almost completely disappeared from the plasma at 6h.
*BioAv↓, absolute oral bioavailability of cucurbitacin B was approximately 10%.
*Half-Life↝, maximum concentration in plasma after normalization by dose ranged from 4.85–7.81 μg/L and the time to reach maximum value was approximately within 30 min after oral dosing.
*AST∅, The results demonstrated that after treatment, neither AST nor ALT changed significantly compared to prior treatment.
*ALAT∅,
*RenoP↝, Kidney function was determined by using creatinine as a biomarker and the results demonstrated that there was no difference between pre- and post-dosing.
*Half-Life↝, The elimination half-life was calculated from intravenous data and the value was approximately 5.08 ± 2.87 h.
TumCG↓, inhibition of tumor cell growth via induction of apoptosis, cell-cycle arrest, anti-metastasis and anti-angiogenesis are major promising chemo-preventive actions of cucurbitacins.
Apoptosis↑,
TumCCA↑,
TumMeta↓,
angioG↓,
chemoPv↑,
BioAv↓, CuB has been studied to be ~10% with plasma concentration ranging from 4.85 to 7.81 μg/L after 30 mins of oral dosing.
Half-Life↝, Studies have shown that they reach highest plasma concentration within 1.75 h and an elimination half-life of ~2.5 h.
cycD1/CCND1↓, decreased Cyclin D1 and Cyclin E1 levels.
cycE/CCNE↓,
Casp3↑, CRC cell lines underwent in vitro cell death when exposed to CuB, which was accompanied by caspase-3 and cleaved PARP
cl‑PARP↑,
JNK↑, (TNBC), cucurbitacin E strongly boosted JNK activation while considerably decreasing AKT and ERK activation in MDA-MB-468 cells.
Akt↓,
ERK↓,
survivin↓, also significantly decreased expression of Cyclin D1, Survivin, XIAP, Bcl2 and Mcl-1
XIAP↓,
Bcl-2↓,
Mcl-1↓,
ROS↑, In the pancreatic cancer cell line Capan-1, CuD induced cell-cycle arrest and death via the ROS/p38 pathway [43
NRF2↓, Recent studies have shown that CuIIb and cucurbitacin B induced apoptosis in cervical cancer cell lines by Nrf2 inhibition,
FAK↓, It successfully inhibited angiogenesis by targeting the FAK/MMP-9 signaling axis
MMP9↓,
VEGF↓, suppressed angiogenesis by downregulating the expression of HIF-1 targets, VEGF, VEGFR2 phosphorylation and erythropoietin
VEGFR2↓,
*NF-kB↓, Dietary cucurbitacin E has been shown to reduce inflammation and immunosuppression by downregulating the NF-κB signaling pathway
TLR4↝, Cucurbitacin B was observed to directly bind to toll-like receptor 4 (TLR4) and activate NLRP3 inflammasome, which further ultimately executed pyroptosis in A549 cells.
NLRP3↑,
Pyro↑,
GSH↓, It was observed that treatment with CuI and doxorubicin decreased glutathione (GSH) levels, enhancing cytotoxicity in tumors.
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*Inflam↓, results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities
*antiOx↑,
*hepatoP↑,
*neuroP↑,
*AntiCan↑,
*toxicity↝, Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability.
*BioAv↓,
*HO-1↑, CuB can exert its anti-inflammatory effect via the induction of heme oxygenase-1 (HO-1) by the activation Nrf2 [25].
*NRF2↑,
*NLRP3↑, CuB could act as an anti-inflammatory agent to inhibit gouty arthritis in mice [28]. The mechanism of action was mainly attributed to inhibition of the formation and activation of the NOD-like receptor thermal protein domain associated protein 3 (NLR
*SOD↑, Its antioxidant activity may be indirectly realized by increasing the activities of the antioxidant enzymes total SOD and SOD-1, and thereby eliminating excessive ROS and other free radicals in cells
*SOD1↑,
*ROS↓,
*AntiAge↑, this study also confirmed that CuB could exert anti-aging effects by regulating autophagy, ROS, and aging-related genes, which suggested that CuB might be a promising anti-aging drug
*ARE↑, activating the Nrf2/ARE signaling pathway and inhibiting the STAT/NF-κB signaling pathway, and thereby exerting a protective effect on cortical neurons
*STAT↓,
*NF-kB↓,
*neuroG↑, CuB (0.1 mg/kg) could also promote neurogenesis in APP/PS1 mice and alleviate memory deficits associated with enhanced neurogenesis in mice.
*memory↑,
ROS↑, Figure 2
NLRP3↑,
CIP2A↓,
Akt↓,
STAT3↑,
VEGFR2↓,
DNMTs↓, tudies have shown that in H1299 human lung cancer cells CuB (6, 60, 600, and 860 nM) can inhibit DNA methyltransferases (DNMTs)
MAPK↓,
YAP/TEAD↓,
PI3K↓,
Wnt↓,
NOTCH↓,
TumCCA↑,
TumCG↓, Inhibit cell growth and proliferation
TumCP↓,
FAK↑, CuB inhibited the migration, invasion, and adhesion of KKU-452 CCA cells in a dose-dependent manner by suppressing the activation of FAK and down-regulating MMP-9,
MMP9↓,
TumAuto↑, CuB ccould induce autophagy in BEL-7402 hepatocellular carcinoma cells by affecting autophagy-related proteins, such as up-regulating the expression of light chain 3 (LC3)-II
toxicity↝, Most experiments have demonstrated that CuB is moderately cytotoxic, both to human cancer cells and to normal cells
BioAv↓, When Wistar rats were given CuB orally at a dose of 8 mg/kg, the absorption degree was low and the absorption speed was slowest, which was specifically reflected in the fact that the time to peak concentration was longest (180 min, Tmax = 3 h). T
Half-Life↝, When CuB was administered intravenously at 0.1 mg/kg and orally at 1 mg/kg, the clearance rates of CuB in Wistar rats were similar, with a half-life (t1/2) of 5.08 ± 2.87 h and 5.09 ± 2.20 h, respectively [139].
BioAv↑, CuB-loaded mixed micelles with collagen peptides as a carrier, which improved the solubility of CuB and enhanced the absorption of orally administered CuB, and its relative bioavailability increased by a factor of 3.43
selectivity∅, Although CuB displays potent activity against tumor cells, its non-selective toxicity has limited its clinical applications.
BioAv↑, co-administration of curcumin with an extract obtained from the black pepper has been shown to increase the absorption (AUC) of curcumin by 1.5-fold.
BioAv↑, Whereas, a complex of curcumin with phospholipids increased absorption by 3.4-fold
BioAv↑, and a formulation of curcumin with a micellar surfactant (polysorbate) has been shown to increase the absorption of curcumin in mice 9.0-fold
BioAv↑, A micro emulsion system of curcumin, which consists of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol P aqueous solution (co-surfactant) has been shown to increase the relative absorption in rats by 22.6-fold
BioAv↑, Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol (PEG) (PLGA-PEG) blend nanoparticles increased curcumin absorption by 15.6- and 55.4-fold, respectively, compared to an aqueous suspension of curcumin in rats
BioAv↓, curcumin are limited by its poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination.
Half-Life↝, Our data indicated that the curcumin half-life was estimated to be 6-7 hours
*antiOx↑, Curcumin as an antioxidant, anti-inflammatory and lipophilic action improves the cognitive functions in patients with AD
*Inflam↓,
*lipid-P↓,
*cognitive↑,
*memory↑, overall memory in patients with AD has improved.
*Aβ↓, curcumin may help the macrophages to clear the amyloid plaques found in Alzheimer's disease.
*COX2↓, Curcumin is found to inhibit cyclooxygenase (COX-2),
*ROS↓, The reduction of the release of ROS by stimulated neutrophils, inhibition of AP-1 and NF-Kappa B inhibit the activation of the pro-inflammatory cytokines TNF (tumor necrosis factor)-alpha and IL (interleukin)-1 beta
*AP-1↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*SOD↑, It also increased the activity of superoxide dismutase, sodium-potassium ATPase that normally decreased with aging.
*GSH↑, followed by a significant elevation in oxidized glutathione content.
*HO-1↑, curcumin induces hemoxygenase activity.
*IronCh↑, curcumin effectively binds to copper, zinc and iron.
*BioAv↓, Curcumin has poor bioavailability. Because curcumin readily conjugated in the intestine and liver to form curcumin glucuronides.
*Half-Life↝, , serum curcumin concentrations peaked one to two hours after an oral dose
*Dose↝, Peak serum concentrations were 0.5, 0.6 and 1.8 micromoles/L at doses of 4, 6 and 8 g/day respectively.
*BBB↑, Curcumin crosses the blood brain barrier and is detected in CSF
*BioAv↑, Absorption appears to be better with food.
*toxicity∅, A phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for three months found no toxicity from curcumin.
*eff↑, Co-supplementation with 20 mg of piperine (extracted from black pepper) significantly increase the bioavailablity of curcumin by 2000%
Src↓, Dasatinib is an oral, potent adenosine triphosphate-competitive inhibitor of multiple tyrosine kinases including BCR-ABL, c-KIT, platelet-derived growth factor receptor, and Src family kinases (SFKs).
PDGF↓,
ABL1↓, One striking feature of dasatinib is its promiscuous nature as a
kinase inhibitor.
BioAv↝, Maximum plasma concentrations (Cmax ) of dasatinib are observed 0.5 – 6 h after oral administration.
Half-Life↝, The overall mean terminal half-life of dasatinib is 3 – 5 h.
Dose↝, 67 patients were treated; the MTDs were 120 mg twice daily for the 5D2 and 70 mg twice daily for the CDD group.
eff↑, The recommended Phase II dose is capecitabine 1000 mg/m 2 plus dasatinib 100 mg daily.
PDK1↓, Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK).
Half-Life↝, The initial half‐life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant.
eff↑, Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (−1002A, rs7160195) for GSTZ1.
NP/CIPN↑, This patient displayed the strongest response, but also the strongest neuropathy.
Dose↝, single oral dose of 25 mg/kg taken at approximately 9 am.
Half-Life↝, DCA was then cleared with a mean half‐life of 93 min (Table 2), with 90% of the drug being cleared by 6 hours, and DCA being undetectable at 24 hours
COX2↓, DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism.
PGE2↓,
angioG↓,
ChemoSen↑,
RadioS↑,
Dose↝, Typical doses for rheumatic disease and musculoskeletal disorders are in the range 75–150 mg in 2–3 divided doses, orally or rectally. Post-operative pain may be treated with diclofenac injections, either deep intramuscularly or intravenously, at a d
toxicity↝, Rare but serious adverse events include GI bleeding, anaemia, liver failure, pancreatitis and pneumonia.
toxicity↝, As with all NSAIDs, long-term use DCF is also associated with a small increase in the risk of cardiovascular events, particularly myocardial infarction and stroke.
BioAv↑, Oral DCF is rapidly absorbed and almost completely distributed to plasma and tissues with little evidence of drug accumulation after repeated dosing within the normal therapeutic range
Half-Life↝, Terminal half-life is 1.8 hours after oral dosing.
lactateProd↓, Lactate production by cells was significantly reduced at a concentration of 100 μM.
eff↑, DCF is a component of the anti-angiogenic combinational drug combination TL-118, the other components being cimetidine, low dose cyclophosphamide and sulfasalazine.
*AntiAg↑, DCF at 50 mg three times a day for six days ex vivo COX-1 level (expressed as thromboxane B2 generation in clotting whole blood) was reduced by 53% compared to base-line, and platelet aggregation was also significantly reduced
Apoptosis↑, highlighting its ability to induce apoptosis, inhibitpro-inflammatory pathways like TLR4/NF-κB, and modulate gut microbiota.
*Inflam↓,
TLR4↓,
NF-kB↓,
*GutMicro↑, DRE modulates the gut microbiota composition,increasing the abundance of short-chain fatty acid-producing bacteria such as Lactobacillus and Bifidobacterium, which are known to suppress tumorigenesis
mtDam↑, Key constituents such as taraxasterol, chlorogenic acid, inulin, and various flavonoids exhibit synergistic effects that promote mitochondrial-mediated cell death, reduce oxidative stress, and preserve normal colonocyte function.
*ROS↓,
Casp1↑, DRE induces the upregulationof pro-apoptotic genes such as CASP1, TNF, TNFRSF1A, andSNCA, while downregulating anti-apoptotic regulators includingBCL2, BCL2A1, and PARP
(PDF) Therapeutic Potential of Dandelion (Taraxacum officinale) Root Extract in
TNF-α↑,
Bcl-2↓,
PARP↓,
MMP↓, mitochondrial membrane depolarization, cytochrome c release, and caspase-3 activation have been confirmed following DRE treatment in CRC cells
Cyt‑c↓,
Casp3↑,
TumVol↓, DRE led to over 90% reduction in tumour volume without significant weight loss or systemic toxicity
COX2↓, taraxasterol has been shown to inhibit NF-κB nuclear translocation and block downstream activation of COX-2 and iNOS, contributing to an anti-inflammatory tumour microenvironment
iNOS↓,
ROS↑, revealed early mitochondrial membrane depolarization, followed by elevated ROS generation and activation of intrinsic apoptotic enzymes such as caspase 3 and caspase 8 in cancer cells effects not seen in NCM460 controls
selectivity↑,
TumCMig↓, RE significantly inhibits CRC cell migration and invasion, while normal epithelial cell motility remains intact.
TumCI↓,
ER Stress↑, One notable pathway involves the induction of EndoplasmicReticulum (ER) stress via activation of the PERK/eIF2α/ATF4/CHOP axis.
PERK↑,
eIF2α↑,
ATF4↑,
CHOP↑,
TumCCA↑, Treated TNBC cells displayed G2/M phase arrest associated with decreased levels of cyclin D1 and p21 and increased p53
cycD1/CCND1↓,
P21↓,
P53↑,
BioAv↝, Taraxasterol, alipophilic pentacyclic triterpenoid, shows poor oral bioavailability due to limited solubility and hepatic metabolism via CYP3A4enzymes.
Half-Life↝, Its analogs have half-lives ranging from 4-6 hr, with high plasma protein binding, suggesting a need for solubility-enhancing delivery systems such as liposomes or cyclodextrin complexes to improve bioavailability
*BioAv↑, Alkamides were rapidly absorbed and were measurable in plasma 20 min after tablet ingestion and remained detectable for up to 12 h.
*Half-Life↝, The maximal concentrations for the sum of alkamides in human plasma were reached within 2.3 h post ingestion and averaged 336+/-131 ng eq/mL plasma.
*Dose↝, one dose three times daily regimen already recommended for echinacea.
Dose?, Volunteers received echinacea orally (4 tablets, each containing extract equivalent to 675 mg of E. purpurea root plus 600 mg of E. angustifolia root prepared from the dried ethanolic extracts of the two Echinacea species) at approximately 0800 h.
BioAv↓, The rather poor bioavailability of EGCG needs to be considered when we extrapolate results obtained in vitro to situations in vivo.
Half-Life↝, The peak plasma concentrations of EGCG are reached in 1–2 h in healthy subjects with one oral dose in the morning after an overnight fasting period. These levels diminish gradually to undetectable levels in 24 h.
Half-Life↝, The elimination half-life of EGCG takes place at 3.4 ± 0.3 h
BioAv↝, Factors Influencing EGCG Bioavailability: Figure2
*BioAv↑, fasting, albumin, vitc, fish oil, piperine
*BioAv↓, oxidation, Ca+, Mg2+, metals
*BioAv↑, overnight fasting period together with 200 mg ascorbic acid and 1000 mg omega-3 fatty acids from salmon
*BioAv↑, Ascorbic acid alone may improve EGCG bioavailability [6,18] by preventing oxidation
*Dose↝, A daily dose of 800 mg caffeine free EGCG for 4 weeks was shown to be safe and well tolerated in healthy human subjects
*toxicity↝, EGCG and other phenolic compounds may be hepatotoxic at higher doses
*Dose↝, administration of a single oral dose of green tea or decaffeinated green tea (20 mg tea solids/kg) or EGCG (2 mg/kg) to eight subjects.
BioAv↝, EGCG, EGC, and EC in the three repeated experiments with green tea were 77.9 +/- 22.2, 223.4 +/- 35.2, and 124.03 +/- 7.86 ng/ml, respectively,
Half-Life↝, The time needed to reach the peak concentrations was in the range of 1.3-1.6 h. The elimination half-lives were 3.4 +/- 0.3, 1.7 +/- 0.4, and 2.0 +/- 0.4 h, respectively.
AntiCan↑, Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has shown the potential to combat various types of cancer cells through its ability to modulate multiple signaling pathways.
BioAv↓, However, its low bioavailability and rapid degradation hinder its clinical application.
BioAv↑, Nanoparticles improve the physicochemical stability and pharmacokinetics of EGCG, leading to enhanced therapeutic outcomes in cancer treatment.
EPR↑, Nanoencapsulation allows for targeted drug delivery, controlled release, enhanced cellular uptake, and reduced premature degradation of EGCG.
TumCG↓, EGCG-loaded nanoparticles significantly inhibited tumor growth in various models, demonstrating enhanced penetration and efficacy through active targeting mechanisms.
*Half-Life↝, The half-life of EGCG in the body ranges from 1.9 to 4.6 h, indicating that its levels in the blood gradually decrease to undetectable levels within 24 h
BioAv↑, EGCG-NLC employs a nanostructured lipid carrier functionalised with folic acid to enhance the oral bioavailability of EGCG.
eff↑, Gly-NPs and EGCG showed a superior antitumor effect compared to free EGCG, with a significant inhibition of tumor growth in vivo
eff↑, EGCG-Loaded PLGA-NPs enhance the therapeutic efficacy against lung cancer by offering improved bioavailability and stability, higher encapsulation efficiency, and superior inhibition of NF-κB
eff↑, EGCG-gold nanoparticles (E-GNPs). are more effectively internalized by cancer cells, enabling sustained EGCG release, inhibiting NF-κB activity
NF-kB↓,
ROS↑, selenium nanoparticles (SeNPs), named SM-EGCG-SeNPs, through Se-O bonding and polysaccharide-polyphenol interactions. These nanoparticles induced apoptosis in cancer cells by activating multiple caspases and generating excess ROS.
ChemoSen↑, nanoparticles to combine EGCG with chemotherapy, PTT, and PDT in combined therapies, which have shown the potential to enhance therapeutic effects by making cancer cells more sensitive to conventional therapies and reducing resistance
*toxicity↝, There is still limited preclinical toxicity data on EGCG nanoparticles.
*AntiCan↑, EGCG’s therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes
*cardioP↑,
*neuroP↑,
*BioAv↝, Factors such as fasting, storage conditions, albumin levels, vitamin C, fish oil, and piperine have been shown to affect plasma concentrations and the overall bioavailability of EGCG
*BioAv↓, Conversely, bioavailability is reduced by processes such as air oxidation, sulfation, glucuronidation, gastrointestinal degradation, and interactions with Ca2+, Mg2+, and trace metals,
*BioAv↓, EGCG’s oral bioavailability is generally low, with marked differences observed across species, for example, bioavailability rates of 26.5% in CF-1 mice and just 1.6% in Sprague Dawley rats
*Dose↝, plasma concentrations exceeded 1 μM only when doses of 1 g or higher were administered.
*Half-Life↝, Specifically, a dose of 1600 mg yielded a Cmax of 3392 ng/mL (range: 130–3392 ng/mL), with peak levels observed between 1.3 and 2.2 h, AUC (0–∞) values ranging from 442 to 10,368 ng·h/mL, and a half-life (t1/2z) of 1.9 to 4.6 h.
*BioAv↑, Studies on the distribution of EGCG have revealed that, despite its limited absorption, it is rapidly disseminated throughout the body or quickly converted into metabolites
*BBB↑, Additionally, EGCG can cross the blood–brain barrier, allowing it to reach the brain
*hepatoP↓, Several studies have documented liver damage linked to green tea consumption [48,49,50,51,52,53].
*other↓, EGCG has also been shown to inhibit the intestinal absorption of non-heme iron in a dose-dependent manner in a controlled clinical trial
*Inflam↓, EGCG has been widely recognized for its anti-inflammatory effects
*NF-kB↓, EGCG has been shown to suppress NF-κB activation, inhibit its nuclear translocation, and block AP-1 activity
*AP-1↓,
*iNOS↓, downregulation of pro-inflammatory enzymes like iNOS and COX-2 and scavenging of ROS/RNS, including nitric oxide and peroxynitrite
*COX2↓,
*ROS↓,
*RNS↓,
*IL8↓, EGCG has been shown to suppress airway inflammation by reducing IL-8 release, a cytokine involved in neutrophil aggregation and ROS production.
*JAK↓, EGCG blocks the JAK1/2 signaling pathway
*PDGFR-BB↓, downregulate PDGFR and IGF-1R gene expression
*IGF-1R↓,
*MMP2↓, reduce MMP-2 mRNA expression
*P53↓, downregulation of the p53-p21 signaling pathway and the enhanced expression of Nrf2
*NRF2↑,
*TNF-α↓, 25 to 100 μM reduced the levels of TNF-α, IL-6, and ROS while enhancing the expression of E2F2 and superoxide dismutases (SOD1 and SOD2), enzymes vital for cellular antioxidant defense.
*IL6↓,
*E2Fs↑,
*SOD1↑,
*SOD2↑,
Casp3↑, EGCG has been shown to activate key apoptotic pathways, such as caspase-3 activation, cytochrome c release, and PARP cleavage, in various cell models, including PC12 cells exposed to oxidative stress
Cyt‑c↑,
PARP↑,
DNMTs↓, (1) the inhibition of DNA hypermethylation by blocking DNA methyltransferase (DNMT)
Telomerase↓, (2) the repression of telomerase activity;
Hif1a↓, (3) the suppression of angiogenesis via the inhibition of HIF-1α and NF-κB;
MMPs↓, (4) the prevention of cellular metastasis by inhibiting matrix metalloproteinases (MMPs);
BAX↑, (5) the promotion of apoptosis through the activation of pro-apoptotic proteins like BAX and BAK
Bak↑,
Bcl-2↓, while downregulating anti-apoptotic proteins like BCL-2 and BCL-XL;
Bcl-xL↓,
P53↑, (6) the upregulation of tumor suppressor genes such as p53 and PTEN;
PTEN↑,
TumCP↓, (7) the inhibition of inflammation and proliferation via NF-κB suppression;
MAPK↓, (8) anti-proliferative activity through the modulation of MAPK and IGF1R pathways
HGF/c-Met↓, EGCG inhibits hepatocyte growth factor (HGF), which is involved in tumor migration and invasion
TIMP1↑, EGCG has also been shown to influence the expression of tissue inhibitors of metalloproteinases (TIMPs) and MMPs, which are involved in tumorigenesis
HDAC↓, nhibition of UVB-induced DNA hypomethylation and modulation of DNMT and histone deacetylase (HDAC) activities
MMP9↓, inhibiting MMPs such as MMP-2 and MMP-9
uPA↓, EGCG may block urokinase-like plasminogen activator (uPA), a protease involved in cancer progression
GlutMet↓, EGCG can exert antitumor effects by inhibiting glycolytic enzymes, reducing glucose metabolism, and further suppressing cancer-cell growth
ChemoSen↑, EGCG’s combination with standard chemotherapy drugs may enhance their efficacy through additive or synergistic effects, while also mitigating chemotherapy-related side effects
chemoP↑,
AntiAg↑, EGCG significantly reduced ADP- and COL-induced platelet aggregation in dose-dependent manner
eff↑, no further increase of bleeding risk by EGCG in the participants who were already taking other anti-platelet agents.
Half-Life↝, half-life of EGCG is approximately 3 hours
other∅, EGCG significantly inhibited the human platelet aggregation without any changes on P-selectin and PAC-1 expressions.
*antiOx↑, antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy.
*Inflam↓,
*neuroP↑, neuroprotective strategy against AD due to its promising antioxidant and anti-inflammatory properties.
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B), a key mediator of proinflammatory cytokine signaling pathway, which promotes the synthesis of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), leading to neuroinflammation
*NLRP3↓, also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1),
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK↓, Ferulic acid was also able to affect the mitogen activated protein kinases (MAPKs) pathway, by inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK)
*p38↓,
*JNK↓,
*IL6↓, reduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) mRNA expression
*IL8↓,
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen
*RenoP↑, renal protective effects by enhancing the CAT activity and PPAR γ gene expression
*Catalase↑,
*PPARγ↑,
*ROS↓, it was able to scavenge free radicals, inhibit the generation of reactive oxygen species (ROS)
*Fenton↓, inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu)
*IronCh↑,
*SOD↑, increasing the activity of the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes
*MDA↓, lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker,
*lipid-P↓,
*NRF2↑, ferulic acid has been found associated to the modulation of several signaling pathways, and to an increased expression of the nuclear translocation of the transcription factor NF-E2-related factor (Nrf2)
*HO-1↑, Particularly, Nrf2 binds the antioxidant responsive element (ARE) in the promoter region of the heme oxygenase-1 (HO-1) gene,
*ARE↑,
*Bil↑, production of bilirubin, which acts as an efficient ROS scavenger, in human umbilical vein endothelial cells (HUVEC) under radiation-induced oxidative stress
*radioP↑,
*GCLC↑, HO-1 upregulation, an increased expression of other antioxidant genes, such as glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic
*GCLM↑,
*NQO1↑,
*Half-Life↝, highest plasma concentration varies greatly depending on the investigated species: it is reached at 24 min and 2 min after ingestion in humans and rats, respectively
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*Aβ↓, ferulic acid was able to inhibit the aggregation of Aβ25–35, Aβ1–40, and Aβ1–42 and to destabilize pre-aggregated Aβ.
*BDNF↑, up-regulation of brain-derived neurotrophic factor (BDNF) gene were observed after treatment with ferulic acid
*Ca+2↓, prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*lipid-P↓,
*PGE2↓,
*cognitive↑, highlighted that ferulic administration (0.002–0.005% in drinking water) for 28 days improved the trimethyltin-induced cognitive deficit: an increase in the choline acetyltransferase activity was hypothesized as a possible mechanism of action.
*ChAT↑,
*memory↑, Another study showed that ferulic acid, administered intragastrically (30 mg/kg) for 3 months, improved memory in the transgenic APP/PS1 mice, and reduced Aβ deposits,
*Dose↝, 4-week prospective, open-label trial, in which patients (n = 20) assumed daily Feru-guard® (3.0 g/day), was designed.
*toxicity↓, Salau et al. [130] did not find signs of toxicity of ferulic acid in hippocampal neuronal cell lines HT22 cells, thus concluding that the substance seems to be safe in healthy brain cells
Showing Research Papers: 1 to 50 of 93
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 93
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↓, 1, GSH↓, 2, HO-1↑, 1, MFN2↑, 1, NQO1↑, 1, NRF2↓, 1, NRF2↑, 1, OXPHOS↓, 1, ROS↓, 1, ROS↑, 9,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ABL1↓, 1, MMP↓, 1, mtDam↑, 1, XIAP↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ACLY↓, 1, AMPK↑, 1, FASN↓, 1, GlutMet↓, 1, HMG-CoA↓, 1, lactateProd↓, 1, LDH↓, 1, PDK1↓, 2,
Cell Death(tgid=5) ⓘ
Akt↓, 4, p‑Akt↓, 1, Apoptosis↑, 5, Bak↑, 2, BAX↑, 3, Bcl-2↓, 6, Bcl-xL↓, 1, Casp1↑, 1, Casp12↑, 1, Casp3↑, 6, cl‑Casp3⇅, 1, Casp8↑, 1, Casp9↑, 2, Cyt‑c↓, 1, Cyt‑c↑, 3, Fas↑, 1, GADD34↑, 1, HGF/c-Met↓, 1, iNOS↓, 1, JNK↑, 2, MAPK↓, 2, MAPK↝, 1, Mcl-1↓, 1, p38↑, 2, Pyro↑, 1, survivin↓, 2, Telomerase↓, 1, TumCD↑, 1, YAP/TEAD↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
other↝, 1, other∅, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
ATF6↑, 1, CHOP↓, 1, CHOP↑, 1, eIF2α↑, 2, ER Stress↑, 1, GRP78/BiP↑, 1, GRP94↑, 1, HSP90↓, 2, IRE1∅, 1, PERK↑, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
TumAuto↑, 1,
DNA Damage & Repair(tgid=10) ⓘ
CHK1↓, 1, DNMTs↓, 2, P53↑, 5, PARP↓, 1, PARP↑, 1, cl‑PARP↑, 3, PCNA↓, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
CycB/CCNB1↓, 1, cycD1/CCND1↓, 2, cycE/CCNE↓, 1, P21↓, 1, P21↑, 1, TumCCA↑, 7,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
CIP2A↓, 1, CSCs↓, 1, EMT↓, 1, EMT↑, 1, ERK↓, 1, FOXO3↑, 1, HDAC↓, 1, IGF-1↓, 1, mTOR↓, 2, mTOR↝, 1, NOTCH↓, 1, NOTCH1↓, 1, NOTCH3↓, 1, PI3K↓, 2, PTEN↑, 1, Src↓, 1, STAT3↓, 3, STAT3↑, 1, TumCG↓, 3, Wnt↓, 1,
Migration(tgid=13) ⓘ
AntiAg↑, 1, Ca+2↓, 1, FAK↓, 1, FAK↑, 1, p‑FAK↓, 1, MMP9↓, 3, MMPs↓, 1, N-cadherin↓, 1, PDGF↓, 1, TGF-β↓, 1, TIMP1↑, 1, TumCI↓, 1, TumCMig↓, 2, TumCP↓, 3, TumMeta↓, 1, uPA↓, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 3, ATF4↑, 2, EPR↑, 1, Hif1a↓, 2, VEGF↓, 3, VEGFR2↓, 3,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 1, GLUT1↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2↓, 3, IL6↓, 1, IL8↓, 1, Inflam↓, 1, NF-kB↓, 5, PGE2↓, 1, PSA↓, 1, TLR4↓, 1, TLR4↝, 1, TNF-α↓, 1, TNF-α↑, 1,
Protein Aggregation(tgid=19) ⓘ
NLRP3↑, 2,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 6, BioAv↑, 11, BioAv↝, 5, ChemoSen↑, 4, Dose?, 1, Dose↝, 9, eff↑, 11, Half-Life↓, 1, Half-Life↝, 24, RadioS↑, 2, selectivity↑, 1, selectivity∅, 1,
Clinical Biomarkers(tgid=22) ⓘ
E6↓, 1, E7↓, 1, IL6↓, 1, LDH↓, 1, PSA↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↓, 1, AntiCan↑, 3, chemoP↑, 3, chemoPv↑, 1, neuroP↑, 1, NP/CIPN↑, 1, Risk↓, 1, toxicity↝, 3, TumVol↓, 2,
Total Targets: 160
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
AntiBio↑, 1, TRPA1↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 9, ARE↑, 2, Bil↑, 1, Catalase↑, 3, Fenton↓, 1, GCLC↑, 1, GCLM↑, 1, GPx↑, 2, GSH↑, 3, GSTs↑, 1, HO-1↑, 4, Keap1↓, 1, lipid-P↓, 7, MDA↓, 5, MPO↓, 1, NQO1↑, 1, NRF2↑, 7, RNS↓, 1, ROS↓, 14, SOD↑, 7, SOD1↑, 2, SOD2↑, 1, TAC↑, 1, TBARS↓, 1, TOS↓, 1,
Metal & Cofactor Biology(tgid=2) ⓘ
IronCh↑, 2,
Mitochondria & Bioenergetics(tgid=3) ⓘ
mitResp↑, 1, OCR↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
12LOX↓, 1, ALAT↓, 1, ALAT∅, 1, AMPK↑, 3, CYP3A4↓, 1, H2S↑, 1, LDH↓, 2, LDL↓, 1, NADPH↑, 1, PPARγ↓, 1, PPARγ↑, 1, p‑PPARγ↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 1, Akt↑, 1, Apoptosis↓, 1, iNOS↓, 4, JNK↓, 1, p‑MAPK↓, 1, p38↓, 1, TRPV1↑, 1,
Transcription & Epigenetics(tgid=7) ⓘ
other↓, 1, other↑, 1, other↝, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
HSP70/HSPA5↑, 1, HSP90↑, 1,
DNA Damage & Repair(tgid=10) ⓘ
DNArepair↑, 1, P53↓, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
E2Fs↑, 1,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
p‑ERK↑, 1, GSK‐3β↓, 2, IGF-1R↓, 1, mTOR↓, 1, neuroG↑, 1, P70S6K↓, 1, PI3K↓, 1, STAT↓, 1, STAT3↓, 1,
Migration(tgid=13) ⓘ
AntiAg↑, 2, AP-1↓, 2, APP↓, 1, Ca+2↓, 1, CD31↑, 1, COL1↑, 1, MMP2↓, 1, N-cadherin↑, 1, TGF-β↑, 1, VCAM-1↓, 1, α-SMA↑, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↑, 1, NO↓, 2, PDGFR-BB↓, 1, VEGF↑, 2,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 6, P-gp↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2↓, 5, ICAM-1↓, 1, IL18↓, 1, IL1β↓, 5, IL6↓, 6, IL8↓, 3, Inflam↓, 13, JAK↓, 1, JAK2↓, 1, NF-kB↓, 8, PGE2↓, 3, TLR4↓, 1, TNF-α↓, 7, TNF-α↑, 1,
Synaptic & Neurotransmission(tgid=18) ⓘ
BDNF↑, 1, ChAT↑, 1, tau↓, 1,
Protein Aggregation(tgid=19) ⓘ
Aβ↓, 4, BACE↓, 1, NLRP3↓, 2, NLRP3↑, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 10, BioAv↑, 17, BioAv↝, 3, BioEnh↑, 1, ChemoSen↑, 1, Dose?, 1, Dose↑, 4, Dose↝, 12, eff?, 1, eff↑, 6, eff↝, 1, Half-Life↓, 1, Half-Life↝, 34,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 1, ALAT∅, 1, AST↓, 1, AST∅, 1, Bil↑, 1, BMD↑, 2, BP↓, 1, creat↓, 1, GutMicro↑, 3, IL6↓, 6, LDH↓, 2,
Functional Outcomes(tgid=23) ⓘ
AntiAge↑, 1, AntiCan↑, 3, cardioP↑, 7, chemoPv↑, 1, cognitive↑, 6, hepatoP↓, 1, hepatoP↑, 5, memory↓, 1, memory↑, 6, motorD↓, 1, neuroP↑, 12, Pain↓, 1, radioP↑, 1, RenoP↑, 2, RenoP↝, 1, toxicity↓, 6, toxicity↝, 5, toxicity∅, 1, Weight↓, 1,
Infection & Microbiome(tgid=24) ⓘ
AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 2,
Total Targets: 151
Scientific Paper Hit Count for: Half-Life, Half-Life
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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