BioAv Cancer Research Results
BioAv, bioavailability: Click to Expand ⟱
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Bioavailability (usually in %) absorbed by the body.
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Scientific Papers found: Click to Expand⟱
TumCG↓, In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal
toxicity↓, In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA.
BioAv↝, It is possible that in the microencapsulated formulation, 3-BrPA, is more bioavailable for uptake into tumor cells and less available to the normal cells that apparently mediate its toxicity
GAPDH↓, 3-Bromopyruvate (3-BrPA), a highly potent small-molecular inhibitor of the enzyme GAPDH, represents the only available antiglycolytic drug candidate that is able to enter cancer cells selectively through the monocarboxylate transporter 1 (MCT1; refs.
toxicity↑, However, due to its alkylating properties, 3-BrPA is associated with significant toxicity when delivered systemically in therapeutic doses, which has impeded the clinical development and use of this drug in patients with cancer
Dose↝, Encapsulation of 3-BrPA in β-CD was achieved by portionwise addition of 3-BrPA (166 mg, 1 mmol/L) to a stirring solution of β-CD (1,836 mg in 30 mL DI water). The resulting solution was sonicated for 1 hour at room temperature and then shaken overnig
ATP↓, ability of microencapsulated 3-BrPA (β-CD-3-BrPA) to achieve dose-dependent ATP depletion and cell death, two human pancreatic cancer cell lines were employed.
eff↑, both PDAC cell lines were more sensitive to the drugs when hypoxic (Fig. 2)
TumCI↓, MiaPaCa-2 and Suit-2 cells showed a reduction in invasion at drug concentrations as low as 12.5 µmol/L.
MMP9↓, marked reduction in the secretion of MMP-9 was detected in both cell lines.
toxicity↓, No organ toxicities or tissue damage was observed in animals treated with β-CD–3-BrPA
*BioAv↝, intramuscularly administered gold is greater than 95% bioavailable, whereas only 20 to 30% of an orally administered dose of auranofin is absorbed.
*Dose↝, 50mg intramuscular injection of GST, serum gold concentrations rise sharply, peaking between 4 and 8 mg/L in approximately 2 hours and declining to an average of 3 mg/L by 7 days.
*Half-Life↑, Both compounds are retained within the body for prolonged periods.
*BioAv↝, In human subjects, parenterally administered gold is widely distributed among bodily tissues, showing a predilection for tissues of the reticuloendothelial system as well as the kidney and adrenal cortex.
*other↝, auranofin but animal studies have shown comparatively less affinity for the liver, kidney and spleen.
*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↝, absorption rangesfrom 0.4% to 10% depending at the species, such as 10% and 6% for dogs and monkeys, respectively [31
OS↑, remission
Dose↓, Electron microscopy of AgNP solution revealed bimodal nanoparticle size
distribution: 3 and 12 nm.
BioAv↝, basal **silver ion** concentrations of 32 ng/g, rising to 46 ng/g 1 hour after ingesting 60 mL of AgNP solution.
toxicity↓, no toxicities were observed and he had complete radiographic resolution of his cancer
Remission↑,
other↝, patient serum was analyzed and intact nanoparticles were not identified. Thus, we could not isolate the circulating AgNP form
other↝, Analysis of urine showed no AgNP or detectable nanoparticle fragments
other↝, AgNP solution was also exposed to simulated gastric fluid, in which they aggregated into larger nanoparticles according to UV-Vis absorption.
Dose↝, GDH: based on repeat setup, estimated PPM is 20PPM assuming 67% effecient. 1.2mg/60mL (he took 160mL/day
BioAv↝, GDH: chatAI computed the estimated bioavailability at 7%
*AntiAg↑, Garlic and its components are known to possess antiplatelet activity
BioAv↝, Though garlic components leave the body quickly, a slow build-up of the active ingredients may take place.
Dose↝, Each capsule contained oil equivalent to I g of raw garlic. oil extract of garlic was encapsulated. 2 capsules of
garlic three times a day (i.e. 6 capsules/day) for a period of 1 month.
*AntiCan↑, Allicin has shown anticancer, antimicrobial, antioxidant properties and also serves as an efficient therapeutic agent against cardiovascular diseases
*antiOx↑,
*cardioP↑,
*neuroP↑, present review describes allicin as an antioxidant, and neuroprotective molecule
cognitive↑, that can ameliorate the cognitive abilities in case of neurodegenerative and neuropsychological disorders.
*ROS↓, As an antioxidant, allicin fights the reactive oxygen species (ROS) by downregulation of NOX (NADPH oxidizing) enzymes, it can directly interact to reduce the cellular levels of different types of ROS produced by a variety of peroxidases.
*NOX↓,
*TLR4↓, inhibition of TLR4/MyD88/NF-κB, P38 and JNK pathways.
*NF-kB↓,
*JNK↓,
*AntiAg↑, A low concentration of allicin (0.4 mM) can inhibit the platelet aggregation up to 90%, the impact is significantly higher than of similar concentration of aspirin.
*H2S↑, Allicin decomposes rapidly and undergoes a series of reactions with glutathione resulting in the production of hydrogen sulphide (H2S).
*BP↓, H2S is a gaseous signalling molecule involved in the regulation of blood pressure.
Telomerase↓, Allicin inhibits the activity of telomerase in a dose dependent manner subsequently inhibiting the proliferation in the cancer cells
*Insulin↑, Studies have shown a significant increase in the blood insulin levels after treatment with allicin
BioAv↝, optimum temperature for the activity of alliinase is 33 °C, it operates best at pH 6.5, the enzyme is sensitive to acids [42,43] (Figure 3), enteric-coated formulations of garlic supplements are therefore recommended
*GSH↑, It helps to lower the hyperglycaemic conditions and improves the glutathione and catalase biosynthesis [37,38]
*Catalase↑,
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BioAv↝, After processing, such as cutting, crushing, chewing, or dehydration, alliinase rapidly breaks down alliin to form allicin. Allicin is immediately decomposed to other organosulfur compounds such as diallyl sulphide (DAS), diallyl disulfide(DADS), and
TumCCA↑, The results show DATS can reduce tumor growth by inhibits cell cycle progression and promotes p53-mediated tumor suppression pathways
P53↑,
HDAC↓, The findings demonstrate that DATS can inhibit U87MG cell growth in vivo by inhibiting HDAC [10].
CSCs↓, Inhibition of cancer stem cells(CSC)
ROS↑, DATS can induce apoptosis by ROS through regulation of Bcl-2 and have anticancer effect on human glioblastoma (U87MG) and neuroblastoma (SH-SY5Y) cells
ChemoSen↑, The most interesting thing is allicin can enhance the sensitivity of TMZ-resistant cells to TMZ by inhibiting MGMT expression.
MGMT↓,
*BioAv↝, For enteric tablets, ABB varied from 36–104%
*eff↓, but it was reduced to 22–57% when consumed with a high-protein meal, due to slower gastric emptying.
*BioAv↝, garlic powder capsules gave 26–109%
*BioAv↝, Kwai garlic powder tablets, which have been used in a large number of clinical trials, gave 80% ABB, validating it as representing raw garlic in those trials
*eff↑, Hence, many brands of garlic supplements have been enteric-coated to prevent disintegration in the stomach
*Half-Life∅, Hence, many brands of garlic supplements have been enteric-coated to prevent disintegration in the stomach
*eff↑, all brands of normal tablets gave high allicin bioavailability
*eff↑, Hence, both low-protein and high-protein meals would provide a gastric pH ≥ 4.0 for an ample amount of time for the alliinase in disintegrated normal tablets and capsules to convert most of the alliin to allicin in the stomach.
*Dose∅, Three tablets has been the most common dose used in these trials. The N1 tablets in these trials have been consistently standardized to contain 3.9 mg alliin/tablet and to yield 1.8 mg allicin/tablet
*eff↑, The bioavailability of allicin from garlic powder supplements containing alliin and active alliinase can be as high as that from an equivalent amount of crushed raw garlic containing maximum allicin, when consumed with a meal.
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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 (
*cognitive↑, ALA improves cognitive function in ageing mice.
*Apoptosis↓, ALA downregulates apoptosis, and neuroinflammatory associated proteins in ageing mice.
*Inflam↓,
*antiOx↑, Alpha lipoic acid (ALA), a powerful antioxidant, has the potential to relieve age-related cognitive impairment and neurodegenerative disease.
*BioAv↝, Alpha lipoic acid (ALA) is a sulfur-containing and both water-soluble and lipid-soluble coenzyme involved in the energy metabolism of carbohydrates, proteins and lipids
*neuroP↑, neuroprotective action of alpha lipoic acid has been demonstrated in a number of cellular or animal models of Parkinson's disease (PD), AD and amyotrophic lateral sclerosis (ALS) due to its antioxidative and anti-inflammatory properties
*ROS↓, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age.
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑,
*antiOx↑, LA has long been touted as an antioxidant
*NRF2↑, activate Phase II detoxification via the transcription factor Nrf2
*MMP9↓, lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*VCAM-1↓,
*NF-kB↓,
*cognitive↑, it has been used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits, and has been implicated as a modulator of various inflammatory signaling pathways
*Inflam↓,
*BioAv↝, LA bioavailability may be dependent on multiple carrier proteins.
*BioAv↝, observed that approximately 20-40% was absorbed [
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies
*H2O2∅, Neither species is active against hydrogen peroxide
*neuroP↑, chelation of iron and copper in the brain had a positive effect in the pathobiology of Alzheimer’s Disease by lowering free radical damage
*PKCδ↑, In addition to PKCδ, LA activates Erk1/2 [92, 93], p38 MAPK [94], PI3 kinase [94], and Akt [94-97].
*ERK↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, In skeletal muscle, LA is proposed to recruit GLUT4 from its storage site in the Golgi to the sarcolemma, so that glucose uptake is stimulated by the local increase in transporter abundance.
*GlucoseCon↑,
*BP↝, Feeding LA to hypertensive rats normalized systolic blood pressure and cytosolic free Ca2+
*eff↑, Clinically, LA administration (in combination with acetyl-L-carnitine) showed some promise as an antihypertensive therapy by decreasing systolic pressure in high blood pressure patients and subjects with the metabolic syndrome
*ICAM-1↓, decreased demyelination and spinal cord expression of adhesion molecules (ICAM-1 and VCAM-1)
*VCAM-1↓,
*Dose↝, Considering the transient cellular accumulation of LA following an oral dose, which does not exceed low micromolar levels, it is entirely possible that some of the cellular effects of LA when given at supraphysiological concentrations may be not be c
*Inflam↓, LA and ALA attenuate neuroinflammation by modulating inflammatory signaling.
*other↝, ratio of LA to ALA in typical Western diets is reportedly 8–10:1 or higher, which is rather higher than the ideal ratio of LA to ALA (1–2:1) required to reach the maximal conversion of ALA to its longer chain PUFAs
*other↝, LA and ALA are essential PUFAs that must be obtained from dietary intake because they cannot be synthesized de novo
*neuroP↑, several studies have also suggested that lower dietary intake of LA influences AA metabolism in brain and subsequently causes progressive neurodegenerative disorders
*BioAv↝, LA cannot be synthesized in the human body
*adiP↑, study suggested that LA-rich oil consumption leads to the high levels of adiponectin in the blood [114], which could stimulate mitochondrial function in the liver and skeletal muscles for energy thermogenesis
*BBB↑, Although LA can penetrate the BBB, most of the LA that enters the brain cannot be changed into AA [48,49], and 59 % of the LA that enters the brain is broken down by fatty acid β-oxidation
*Casp6↓, In neurons, LA and ALA attenuate the activation of cleaved caspase-3/-9, p-NF-Kb and the production of TNF-a, IL-6, IL-1b, and ROS by binding GPR40 and GPR120.
*Casp9↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*ROS↓,
*NO↓, LA reduces NO production and inducible nitric oxide synthases (iNOS) protein expression in BV-2 microglia
*iNOS↓,
*COX2↓, ALA increases antioxidant enzyme activities in the brain [182] and inhibits the activation of COX-2 in AD models
*JNK↓, ALA has also been shown to suppress the activation of c-Jun N-terminal kinases (JNKs) and p-NF-kB p65 (Ser536), which is involved in inflammatory signaling
*p‑NF-kB↓,
*Aβ↓, and to inhibit Aβ aggregation and neuronal cell necrosis
*BP↓, LA also improves blood pressure, blood triglyceride and cholesterol levels, and vascular inflammation
*memory↑, One study suggested that long-term intake of ALA enhances memory function by increasing hippocampal neuronal function through activation of cAMP response element-binding protein (CREB) [192], extracellular signal-regulated kinase (ERK), and Akt signa
*cAMP↑,
*ERK↑,
*Akt↑,
cognitive?, Furthermore, ALA administration inhibits Aβ induced neuroinflammation in the cortex and hippocampus and enhances cognitive function
*neuroP↑, potential therapeutic effects for the prevention or treatment of neurodegenerative disease
*Inflam↓, ALA is able to regulate inflammatory cell infiltration into the central nervous system and to down-regulate VCAM-1 and human monocyte adhesion to epithelial cells
*VCAM-1↓, down-regulate vascular cell adhesion molecule-1 (VCAM-1) and the human monocyte adhesion to epithelial cells
*5HT↑, ALA is able to improve the function of the dopamine, serotonin and norepinephrine neurotransmitters
*memory↑, scientific evidence shows that ALA possesses the ability to improve memory capacity in a number of experimental neurodegenerative disease models and in age-related cognitive decline in rodents
*BioAv↝, Between 27 and 34% of the oral intake is available for tissue absorption; the liver is one of the main clearance organs on account of its high absorption and storage capacity
*Half-Life↓, The plasma half-life of ALA is approximately 30 minutes. Peak urinary excretion occurs 3-6 hours after intake.
*NF-kB↓, As an inhibitor of NF-κβ, ALA has been studied in cytokine-mediated inflammation
*antiOx↑, In addition to the direct antioxidant properties of ALA, some studies have shown that both ALA and DHLA and a great capacity to chelate redox-active metals, such as copper, free iron,
zinc and magnesium, albeit in different ways (
*IronCh↑, ALA is able to chelate transition metal ions and, therefore, modulate the iron- and copper-mediated oxidative stress in Alzheimer’s plaques
*ROS↓, iron and copper chelation with DHLA may explain the low level of free radical damage in the brain and the improvement in the pathobiology of Alzheimer’s Disease
*ATP↑, ALA may increase the mitochondrial synthesis of ATP in the brain of elderly rats, thereby increasing the activity of the mitochondrial enzymes
*ChAT↑, ALA may also play a role in the activation of the choline acetyltransferase enzyme (ChAT), which is essential in the anabolism of acetylcholine
*Ach↑,
*cognitive↑, One experimental study has shown that in rats that had been administered ALA there was an inversion in the cognitive dysfunction with an increase in ChAT activity in the hippocampus
*lipid-P↓, administration of ALA reduces lipid peroxidation in different areas of the brain and increases the activity of antioxidants such as ascorbate (vitamin C), α-tocopherol (vitamin E), glutathione,
*VitC↑,
*VitE↑,
*GSH↑,
*SOD↑, and also the activity of superoxide dismutase, catalase, glutathione-peroxidase, glutathione-reductase, glucose-6-P-dehydrogenase
*Catalase↑,
*GPx↑,
*Aβ↓, Both ALA and DHLA have been seen to inhibit the formation of Aβ fibrils
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neuroblastoma, |
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PDH↑, ALA is capable of activating pyruvate dehydrogenase in tumor cells.
TumCG↓, ALA also significantly inhibited tumor growth in mouse xenograft model using BCPAP and FTC-133 cells
ROS↑, ALA is able to generate ROS, which promote ALA-dependent cell death in lung cancer [75], breast cancer [76] and colon cancer
AMPK↑,
EGR4↓,
Half-Life↓, Data suggests that ALA has a short half-life and bioavailability (about 30%)
BioAv↝,
*GSH↑, Moreover, it is able to increase the glutathione levels inside the cells, that chelate and excrete a wide variety of toxins, especially toxic metals from the body
*IronCh↑, The existence of thiol groups in ALA is responsible for its metal chelating abilities [14,35].
*ROS↓, ALA exerts a direct impact in oxidative stress reduction
*antiOx↑, ALA is being referred as the universal antioxidant
*neuroP↑, ALA has neuroprotective effects on Aβ-mediated cytotoxicity
*Ach↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*lipid-P↓, ALA has multiple and complex effects in this way, namely scavenging ROS, transition metal ions, increasing the levels of reduced glutathione [59,63], scavenging of lipid peroxidation products
*IL1β↓, ALA downregulated the levels of the inflammatory cytokines IL-1B and IL-6 in SK-N-BE human neuroblastoma cells
*IL6↓,
TumCP↓, ALA inhibited cell proliferation, [18F]-FDG uptake and lactate formation and increased apoptosis in neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and in the breast cancer cell line SkBr3.
FDG↓,
Apoptosis↑,
AMPK↑, ALA suppressed thyroid cancer cell proliferation and growth through activation of AMPK and subsequent down-regulation of mTOR-S6 signaling pathway in BCPAP, HTH-83, CAL-62 and FTC-133 cells lines.
mTOR↓,
EGFR↓, ALA inhibited cell proliferation through Grb2-mediated EGFR down-regulation
TumCI↓, ALA inhibited metastatic breast cancer cells migration and invasion, partly through ERK1/2 and AKT signaling
TumCMig↓,
*memory↑, Alzheimer’s Disease: ALA led to a marked improvement in learning and memory retention
*BioAv↑, Since ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
*BioAv↝, ALA were found to be considerably higher in adults with mean age greater than 75 years as compared to young adults between the ages of 18 and 45 years.
*other↓, ALA treatment has been recently studied by some clinical trials to explain its efficacy in preventing miscarriage
*other↝, 1800 mg of ALA or placebo were administrated orally every day, except during the period 2 days before to 4 days after administration of each dose of platinum to avoid potential interference with platinum’s antitumor effects
*Half-Life↓, Data shows a short half-life and bioavailability of about 30% of ALA due to mechanisms involving hepatic degradation, reduced ALA solubility as well as instability in the stomach.
*BioAv↑, ALA bioavailability is greatly reduced after food intake and it has been recommended that ALA should be admitted at least 2 h after eating or if taken before; meal should be taken at least 30 min after ALA administration
*ChAT↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*GlucoseCon↑,
AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value
*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.
*COX1↓, Aspirin is the acetate ester of salicylic acid and acts by binding irreversibly to cyclooxygenase-1 and cyclooxygenases-2
*COX2↓,
*cardioP↑, Aspirin is consumed most often at low-doses for cardio-protection and at higher doses as an analgesic, antipyretic, and anti-inflammatory agents.
*BioAv↑, Orally ingested aspirin is absorbed rapidly and the peak concentration is reached in about 1 hour.
*BioAv↝, a rise in pH also increases the solubility of aspirin and thus the dissolution of the tablets and the presence of food delays absorption of aspirin.
*Half-Life↓, The elimination half-life of aspirin in plasma is about 20 min
Risk↓, Patients who received 100 mg daily of aspirin had reduced risks of colorectal cancer and gastric cancer and an increased risk of gastrointestinal bleeding [6].
*other↑, Low-dose of aspirin treatment significantly improves ovarian responsiveness, uterine and ovarian blood flow velocity, and pregnancy-rates in women undergoing in-vitro fertilization [19].
*AntiAg↑, antiplatelet effect of aspirin [13],
*BioAv↝, The oral bioavailability was determined to be 32.4 ± 4.8% based on intravenous (5 mg/kg) and oral (10 mg/kg) administrations of WA in male rats.
*other↝, he in vitro results showed that WA could be easily transported across Caco-2 cells and WA did not show as a substrate for P-glycoprotein.
*Half-Life↓, and in liver microsomes (rapid depletion, with a half-life of 5.6 min). WA was further verified by rat intestine-liver in situ perfusion, revealing that WA rapidly decreased and 27.1% remained within 1 h,
MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 ± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2ârelated factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44
and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 )
through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway
*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
Dose↑, However, most in vitro and in vivo studies have used ASX at concentrations that are not achievable by humans.
*BioAv↝, consuming a single dose of 40 mg ASX, the plasma ASX concentration of 32 male subjects (average body weight: 81.5 kg) increased to ∼190 μg/L
*BioAv↝, 100 mg ASX supplementation in male volunteers (90–100 kg BW) resulted in circulating concentrations of ASX reaching a maximum of 120 μg/L (21). This is equivalent to 0.4 μΜ ASX treatment in the cells with 2 mL media
*antiOx↑, Because the potent antioxidative efficacy of ASX has attracted growing interest and attention in recent years, much evidence has accumulated with regard to ASX treatment in alleviating lung diseases.
*NRF2↑, ASX exerts its antioxidative effects by activating the Nrf2 –antioxidant response element (ARE) signaling pathway
*ERK↓, In mice, ASX showed substantial efficacy in inhibiting ERK1/2 activation in the chronic lung inflammation model (100 mg/kg BW ASX), as well as the ALI model (5 mg/kg BW ASX)
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.
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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).
*BioAv↝, Baicalin and wogonoside in Scutellariae-Paeoniae couple extract had shown better absorption than which in pure baicalin and Radix Scutellariae extract
*other↝, The present result suggested that baicalin might convert to wogonoside in the rat body.
*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↓,
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toxicity↝, We have found that baicalin and baicalein demonstrated cytotoxicity towards both cell lines, with more potent effects observed in baicalein.
ChemoSen↑, Both flavonoids, baicalin (167 µmol/L) and baicalein (95 µmol/L), synergistically enhanced the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel in breast cancer cells.
selectivity↑, Surprisingly, low concentrations of baicalin and baicalein had a greater effect on MCF-7 viability. A
Apoptosis↑, Induction of Apoptosis and Necrosis by Baicalin and Baicalein Used alone and in Combination with Anticancer Drugs
necrosis↑,
MMP↓, After treatment with baicalin and baicalein at high concentrations (IC50), the ΔΨm of cancer cells was diminished to 30% of the control value
DNAdam↑, DNA Damage Induced by Baicalin and Baicalein Used Alone and in Combination with Anticancer Drugs
cl‑PARP↑, PARP Cleavage Induced by Baicalin and Baicalein Used Alone and in Combination with Anticancer Drugs
MRP1↓, Moreover, baicalin and baicalein reduced cisplatin resistance by inhibiting the expression of genes involved in drug resistance, such as MRP1 [30] and Bcl-2, and via the Akt/mTOR and Nrf2/Keap 1 pathway [26].
Bcl-2↓,
hepatoP↑, baicalin and baicalein can also help decrease the side effects of cisplatin treatment by protecting the liver from damage [31]
cardioP↑, Similar to baicalein, baicalin also significantly protects against doxorubicin’s cardiotoxicity.
BioAv↝, This is because baicalein has a smaller size and high lipophilicity, contributing to fast absorption and an improved ability to penetrate cells [60].
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cardioP↑, cardioprotective activities.
Inflam↓, Decreasing the accumulation of inflammatory mediators and improving cognitive function
cognitive↑,
*hepatoP↑, Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms
*ROS?, Reducing oxidative stress and protecting the mitochondria to inhibit apoptosis are proposed as hepatoprotective mechanisms of baicalin in NAFLD
*SOD↑, Baicalin could reduce the levels of ROS and fatty acid-induced MDA, and increase superoxide dismutase (SOD) and glutathione amounts compared to the control.
*GSH↑,
*MMP↑, Moreover, baicalin could partially restore mitochondrial morphology and increase ATP5A expression and mitochondrial membrane potential (Gao et al., 2022).
*GutMicro↑, After baicalein treatment, a remodelling in the overall structure of the gut microbiota was observed
ChemoSen↑, Besides, a combination of baicalin and doxorubicin could elevate the chemosensitivity of MCF-7 and MDA-MB-231 breast cancer cells
*TNF-α↓, Baicalin can protect cardiomyocytes from hypoxia/reoxygenation injury by elevating the SOD activity and anti-inflammatory responses through reducing TNF-α, enhancing IL-10 levels, decreasing IL-6, and inhibiting the translocation of NF-κB to the nucl
*IL10↑,
*IL6↓,
*eff↑, Studies show that baicalin and baicalein may be effective against IBD by suppressing oxidative stress and inflammation, and regulating the immune system.
*ROS↓,
*COX2↓, baicalein can improve the symptoms of ulcerative colitis by lowering the expression of pregnane X receptor (PXR), (iNOS), (COX-2), and caudal-type homeobox 2 (Cdx2), as well as the NF-κβ and STAT3
*NF-kB↓,
*STAT3↓,
*PGE2↓, Administration of baicalin (30-90 mg/kg) could decrease the levels of prostaglandin E2 (PEG2), myeloperoxidase (MPO), IL-1β, TNF-α, and the apoptosis-related genes including Bcl-2 and caspase-9
*MPO↓,
*IL1β↓,
*MMP2↓, Rheumatoid arthritis RA mouse model by supressing relevant proinflammatory cytokines such as IL-1b, IL-6, MMP-2, MMP-9, TNF-α, iNOS, and COX-2)
*MMP9↓,
*β-Amyloid↓, Alzheimer’s disease (AD) : reduce β-amyloid and trigger non-amyloidogenic amyloid precursor proteins.
*neuroP↑, For instance, administration of baicalin orally for 14 days (100 mg/kg body weight) exhibited neuroprotective effects on pathological changes and behavioral deficits of Aβ 1–42 protein-induced AD in vivo.
*Dose↝, administration of baicalin (500 mg/day, orally for 12 weeks) could improve the levels of total cholesterol, TGs, LDLC and apolipoproteins (APOs), and high-sensitivity C-reactive protein (hs-CRP) in patients with rheumatoid arthritis and coronary arte
*BioAv↝, the total absorption of baicalin depends on the activity of intestinal bacteria to convert baicalin to baicalein as the first step.
*BioAv↝, Kidneys, liver, and lungs are the main organs in which baicalin accumulates the most.
*BBB↑, Baicalin and baicalein can pass through the blood brain barrier (BBB)
*BDNF↑, mechanism of action for baicalein is illustrated in Figure 3. Activation of the BDNF/TrkB/CREB pathway, inhibition of NLRP3/Caspase-1/GSDMD pathway,
*BioAv↝, The relative absorption for baicalin was 65% when compared with baicalein.
*BioAv↝, indicating baicalin was absorbed more slowly and to a lesser extent than baicalein.
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↑,
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TumCD↑, Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells.
*toxicity↓, In contrast, YAMC(normal) cells were not sensitive to berberine-induced cell death. less cytotoxic effects on normal colon epithelial cells.
selectivity↑, see figure 2
ROS↑, berberine-stimulated ROS production
*ROS∅, ROS production in a concentration-dependent manner only in IMCE cells, but not in YAMC cells. In YAMC cells, berberine did not induce ROS production
MMP↓, berberine induced mitochondrial depolarization in a concentration-dependent manner in IMCE cells, but not in YAMC cells
*MMP∅, but not in YAMC cells
PARP↑, Berberine Activation of PARP
BioAv↝, absorption of berberine by YAMC is lower than that by IMCE cells
*BioAv↝, The chemical compound salt form of Ber includes hydrochloride, sulfate, and phosphate with various water solubilities. For example, hydrochloride salt is less soluble in water, whereas sulfate and phosphate salts are relatively water-soluble.
*BioAv↝, Meanwhile, chloride or sulfate of Ber is commonly used as an over-the-counter (OTC), orally administered drug for clinical purposes
*BioAv↝, After oral administration, Ber is transformed into different phase I metabolites, including berberrubine, thalifendine, demethyleneberberine, and jatrorrhizine, in the liver by cytochrome P450 enzymes (CYPs)
*Half-Life↓, A rapid elimination half-life about 0.22h has been observed in plasma, whereas a slow elimination half-life about 12h in the hippocampus was observed after intravenous administration in rats.
*APP↓, BBR were decreased in the mRNA and protein expression of APP and presenilin 1 while PPARG was increased with a reduction in the NF-κB pathway.
*PPARγ↑, upregulated PPARG with decreasing its downstream NF-ΚB pathway
*NF-kB↓,
*Aβ↓, BBR played a protective role in the AD mice model via blocking APP processing and amyloid plaque formation.
*cognitive↑, berberine significantly reduced amyloid accumulation and improved cognitive impairment in APP/PS1 mice
*antiOx↑, via anti-oxidative stress, anti-neuroinflammation, inhibition of neuronal cell apoptosis, etc
*Inflam↓,
*Apoptosis↓,
*BioAv↑, BBR was found to be metabolized to dihydro-berberine by intestinal bacteria, whose bioavailability was five times higher than that of BBR
*BioAv↝, oral bioavailability (OB, >30%),
*BBB↑, blood-brain barrier (BBB, >0.3)
*motorD↑, BBR treated 5×FAD mice ameliorated their behavior activity including in locomotor activity and cognitive function compared to control.
*NRF2↑, BBR enhanced cellular antioxidant capacity, regulated antioxidant-related pathways such as Nrf2 and HO-1, and thereby reduced oxidative stress damage
*HO-1↑,
*ROS↓,
*p‑Akt↑, BBR significantly increased the phosphorylation levels of AKT and ERK
*p‑ERK↑,
*BioAv↝, The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%.
BioAv↓, The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability.
BioAv↑, Nasal administration of borneol was quickly absorbed into the blood and brain, was easy to use and had a greater safety than infection
*eff↑, Plasma levels of both acetyl-alpha-boswellic acid (AalphaBA) and alphaBA became only detectable when administered with treatment B, i.e., the high-fat meal.
BioAv↝, BAs after oral dosing of an extract and demonstrate a profound effect of food intake on the pharmacokinetic profile of the BAs
Dose↝, tributyrin at doses from 150 to 200 mg/kg three times daily.
BioAv↝, median butyrate concentration of 52 microM was obtained but there was considerable interpatient variability
toxicity↓, Tributyrin is well tolerated and levels associated with in vitro activity are achieved with three times daily dosing
OS↝, There were four patients with prolonged disease stabilization ranging from 3 to 23 months; median progression-free survival was 55 days.
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*BBB↓, crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition.
*GutMicro↑, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. often favoring the growth of beneficial taxa such as Ruminococcaceae, Lac
Obesity↓, These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects
*Inflam↓,
*AntiCan↑,
*TRPV1↑, Capsaicin is a potent agonist perceived by TRPV1, a transmembrane cation channel that functions with Ca2+.
*Ca+2↑, causes an increase in Ca2+ flux,
*antiOx↑, Capsaicin is a bioactive compound of chili peppers responsible for their spicy flavor, which also shows antioxidant, anti-obesity, analgesic, anti-inflammatory, anticarcinogenic, and cardioprotective effects
*cardioP↑,
*BioAv↓, capsaicin exhibits low systemic bioavailability due to its rapid metabolism in the liver and other tissues, resulting in a short plasma half-life of approximately 25 min in humans
*Half-Life↓,
*BioAv↝, Capsaicin’s bioavailability is determined by multiple interrelated factors, including its physicochemical properties, metabolic transformations, route of administration, and the biological context of the host, including gut microbiota composition.
*BioAv↑, For instance, polymeric micelles, liposomes, and hydroxypropyl-β-cyclodextrin complexes have demonstrated the capacity to enhance capsaicin’s oral bioavailability, prolong its plasma half-life, and improve therapeutic consistency
*neuroP↑, capsaicin exposure alters glutamate, GABA, and serotonin levels in distinct brain regions, with potential implications for neuroprotection, mood regulation, and energy metabolism.
Apoptosis↑, apoptosis is the main mechanism by which capsaicin induces cell death in cancer cells.
p38↑, capsaicin triggers a calcium flux within the cell via TRPV1, activating the p38 pathway.
ROS↑, As a result, reactive oxygen species (ROS) are produced, along with depolarization of the mitochondrial membrane potential and opening of the mitochondrial permeability transition pore.
MMP↓,
MPT↑,
Cyt‑c↑, Consequently, cytochrome c is released, the apoptosome is assembled, and caspases are activated, ultimately leading to cell death
Casp↑,
TRIB3↑, capsaicin enhances TRIB3 gene expression, which allowed an increase in the antiproliferative and proapoptotic effects of TRIB3 in cancer cells
NADH↓, Capsaicin has also been seen to downregulate and inhibit tumor-associated NADH oxidase (tNOX) and Sirtuin1 (SIRT1) in multiple cancer cell lines such as bladder cancer, which led to reduced cell growth and migration
SIRT1↓,
TumCG↓,
TumCMig↓,
TOP1↓, pointing out that capsaicin had an inhibitory effect on topoisomerases I and II, causing a reduction in metabolic activity and proliferation of a human colon cancer cell line
TOP2↓,
β-catenin/ZEB1↓, with capsaicin, the β-catenin transcription gets downregulated
*ROS↓, Capsaicin has also been proven to alleviate redox imbalance or oxidative stress, thanks to its antioxidative activity.
*Aβ↓, Alsheimer’s disease, attenuating neurodegeneration in mice by reducing amyloid-beta levels via the promotion of non-amyloidogenic processing of amyloid precursor protein
*Bacteria↓, Carvacrol, either alone or in combination with other compounds, has a strong antimicrobial effect on many different strains of bacteria and fungi that are dangerous to humans
*Inflam↓, Carvacrol also exerts strong anti-inflammatory properties by preventing the peroxidation of polyunsaturated fatty acids by inducing SOD, GPx, GR, and CAT, as well as reducing the level of pro-inflammatory cytokines in the body.
*SOD↑,
*GPx↑,
*GSR↑,
*Catalase↑,
*toxicity↓, Carvacrol is considered a safe compound despite the limited amount of data on its metabolism in humans.
*Pain↓, carvacrol has been used as a substitute for cretol and carbolic acid in the treatment of toothache, sensitive dentine, and alveolar abscess, and as an antiseptic in the pulp canals of the teeth
*other↑, because it has much greater activity as a mosquito repellent than the commercial preparation, N,N-diethyl-m-methylbenzamide
*cardioP↑, other biological activities, including cardio-, reno-, and neuroprotective [20]; immune response-modulating [21]; antioxidant; anti-inflammatory [22];
*RenoP↑,
*neuroP↑,
*antiOx↑,
*AntiDiabetic↑, antidiabetic; hepatoprotective [28]; and anti-obesity properties
*hepatoP↑,
*Obesity↓,
*AntiAg↑, figure 1
*BioAv↓, challenges surrounding the wider use of carvacrol in food or feed are its unpleasant and pungent taste at higher doses; low bioavailability;
BioAv↝, sensitivity to the surrounding environment, such as in processing conditions (e.g., heat or other ingredients); and the acidic environment in the digestive tract.
*OS↑, pneumonia. Administration of carvacrol to mice (10, 25, 50 mg/kg) was associated with increased survival and significantly reduced bacterial load
MMP↓, carvacrol was found to cause greater membrane depolarization and increased oxidative stress in E. coli cells;
ROS↑,
*MDA↓, In studies conducted in guinea pigs, carvacrol concentrations of 120 and 240 μg/mL have been shown to reduce malondialdehyde levels compared to the control group
*lipid-P↓, Carvacrol prevents lipid peroxidation by inducing SOD, GPx, GR, and CAT [85,86].
*COX2↓, A decrease in COX-2 gene expression was found at carvacrol concentrations of 0.008% and 0.016%
*Dose↝, Phase I clinical trial, carvacrol was administered to healthy subjects at 1 and 2 mg/kg/day for 1 month, and no critical adverse reactions
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eff↑, The thymol/carvacrol mixture demonstrated superior cytotoxicity (IC50 = 0.92–1.70 µg/mL) and increased selectivity compared to cisplatin,
selectivity↑, with high selectivity indices (144.88–267.71).
BioAv↝, The bioavailability score for both thymol and carvacrol is 0.55, indicating moderate bioavailability
BBB↑, The blood–brain barrier (BBB) permeability values are 1.82 for thymol and 1.99 for carvacrol, indicating that both compounds have moderate permeability across the BBB.
*toxicity↝, carvacrol may be slightly less toxic than thymol. Both compounds have a predicted toxicity class of 4, indicating moderate toxicity.
*antiOx↑, This remarkable synergy in antioxidant activity
COX2↓, carvacrol and thymol showed considerable outcomes, their mixture proved more effective in suppressing COX-2.
5LO↓, synergistic effect observed with the thymol/carvacrol mixture, particularly pronounced for 5-LOX and COX-2 inhibition
*Inflam↓, Monoterpenes like thymol and carvacrol are recognized for their anti‐inflammatory and anticancer properties,
AntiCan↑,
PI3K↓, Thymol derivatives, such as 1,2,3‐triazoles and carvacrol, effectively target breast cancer (BC) through PI3K/AKT/mTOR and NOTCH pathways and inhibit PIK3CA expression.
Akt↓,
mTOR↓,
NOTCH↓,
PIK3CA↓,
EGFR↓, thymol exhibits anti‐EGFR activity, while carvacrol modulates the HIF‐1α/VEGF pathway, making them potential candidates for colorectal cancer (CRC) management.
Hif1a↓,
VEGF↓,
ChemoSen↑, Their synergistic potential with chemotherapy, radiotherapy, and other bioactive compounds strengthens their therapeutic promise.
RadioS↑,
eff↝, challenges such as stability, bioavailability, and the need for clinical trials hinder their clinical application.
*cardioP↑, cardioprotective (Joshi et al. 2023), neuroprotective (Forqani et al. 2023) and hepato‐nephroprotective
*neuroP↑,
*hepatoP↑,
Apoptosis↑, Induction of Apoptosis
MMP↓, The apoptosis was due to ROS production, variations in the mitochondrial membrane, caspase‐3 activation, and DNA damage
Casp3↑,
ROS↑,
DNAdam↑,
eff↑, Thymol derivative, known as compound 10 (IC50 6.17 μM) exhibited 3.2‐fold more inhibition than 5‐fluorouracil (IC50 20.09 μM) against MCF‐7
BAX↑, Carvacrol (25, 50, 75, and 90 μM) enhanced the expression of Bax, Bad, Fas‐L, and cytochrome c, activated caspase‐9/3 and caspase‐8, induced cell cycle at G0/G1
BAD↑,
FasL↑,
Cyt‑c↑,
Casp9↑,
Casp8↑,
TumCCA↑,
P21↑, improved the expression of proteins (p21, cyclin D1, CDK4), and downregulated the SMO and GLI1 proteins expression in CC
Smo↓,
Gli1↓,
JNK↑, Moreover, thymol activated JNK and p38 MAPK while impeding the ERK pathway
ERK↓,
MAPK↓, Besides thymol, carvacrol has also been reported to inhibit MAPK or ERK pathways in previous studies.
TRPM7↓, inhibited TRPM7 expression in liver fibrotic C57BL/6J mice
Wnt/(β-catenin)↓, hymol inhibited HCT116 and LoVo cell line invasion via downregulating the Wnt/β‐catenin pathway and reducing c‐Myc and Cyclin D1 expression
BioAv↝, thymol and carvacrol are volatile, and their stability is influenced by these factors (temperature, light, oxygen, and pH)
BioAv↑, Ultrasonication is an effective technique to enhance the stability of thymol and other bioactive compounds. 400 watts of power elevated the performance of NC‐CH formulations, and NC‐CH‐400 displayed increased solubility.
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*memory↑, Carvacrol enhances memory and cognition by modulating the effects of oxidative stress, inflammation, and Aβ25-35-induced neurotoxicity in AD
*cognitive↑,
*ROS↓, reduces the production of reactive oxygen species and proinflammatory cytokine levels in PD
*Inflam↓,
*motorD↑, improves motor functions
*toxicity↓, in general, it is potentially safe for consumption
*TRPV3↑, Carvacrol is a potent agonist of transient receptor potential vanilloid 3 (TRPV3)
*other↓, mitigating oxidative stress (OS)/ADP-ribose (ADPR)-induced TRPM2 and GSK1016790A (GSK)-mediated TRPV4 activations
*antiOx↑, Essential oils, high in carvacrol, have powerful antioxidant properties [85-88] similar to vitamin E, ascorbic acid, and butyl hydroxyl toluene
*LDL↓, Low-density lipoprotein (LDL) is inhibited by carvacrol in vitro and mediates LDL oxidation within an incubation period of 12 h
*COX2↓, suppressing the expression level of cyclooxygenase-2 (COX-2),
*PPARα↑, triggering the peroxisome proliferator-activated receptors (PPAR) α and γ
*NO↓, inhibiting NO production
*AChE↓, Carvacrol's acetylcholinesterase inhibitory action is 10 times higher than thymol's, even though the two compounds have a relatively similar structure
*eff↑, carvacrol nanoemulsion treatment has shown more notable effects compared to carvacrol oil.
*SOD↑, increases superoxide dismutase (SOD) and catalase (CAT) activity
*Catalase↑,
*neuroP↑, neuroprotective effects of carvacrol against cognitive impairments and its potential in AD are shown in Fig. (2)
*BioAv↝, In rabbits, 1.5 g of orally administered carvacrol is progressively absorbed from the intestines, with approximately 30% of the whole dose remaining in the gastrointestinal system and 25% eliminated via urine after 22 h of administratio
*BBB↑, carvacrol in the brain tissues as it easily crosses the blood-brain barrier owing to its low molecular weight (150.2 g/mol) and higher lipophilicity
*BioAv↑, liposomal encapsulation [136], and solid lipid nanoparticles [137], were developed and found bioavailable on oral administration. These formulations exhibit improved solubility, stability, and bioavailability and enhance drug accumulation in the tiss
*BioAv↝, The inconsistency between catechins’ superior in vitro biological activity and low absorption in in vivo studies can also be attributed to its low stability,
*BioAv↓, Even if administered intravenously, catechins were partially degraded before reaching the target tissues
*ROS⇅, Tea polyphenols are antioxidants, but they can also generate reactive oxygen species (ROS).
*NRF2↑, may also activates nuclear factor erythroid 2-related factor 2 (Nrf2) to activate antioxidant and detoxifying enzymes
*BioAv↑, Many studies showed promising EGCG-loaded nano-carriers with sustained release and improved bioavailability even at much lower doses than conventional preparations.
*Half-Life↓, Although the half-life period of EGCG (5.0–5.5 h) is about two times longer than that of EGC or EC (2.5–3.4 h), it is still too short to exert clinical effect.
*BioAv↑, Catechins + Ascorbic acid (and sucrose or xylitol): Improving catechins bioavailability by enhancing bioaccessibility and intestinal uptake.
*BioAv↑, Piperine Increasing EGCG bioavailability by inhibiting glucuronidation and gastrointestinal transit.
BioAv↑, Caffeine Enhancing the absorption of EGCG in humans.
Dose↝, UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily
*DNArepair↑, Uncaria tomentosa (Ut, Cat's claw) has antioxidant properties [10] and can stimulate DNA repair [11] and myelopoiesis
toxicity↝, Treatment with Ut did not alter liver function, defined as elevation of liver enzymes (alanine aminotransferase-ALT, aspartate aminotransferase-AST, γ glutamyl transpeptidase-GGT), and bilirubin levels, and kidney function
BioAv↝, consider the fact that all CRC patients in the present study underwent colectomy, which could interfere with the absorption of Ut.
eff∅, Ut at dose 300 mg dry extract daily is not effective in reducing the most prevalent adverse events due to treatment with 5FU/Leucovorin and oxaliplatin in patients with advanced CRC.
*BioAv↝, These microbial metabolites accounted for 57.4% (mol/mol) of the chlorogenic acid intake. Such a high abundance of microbial metabolites shows that the bioavailability of chlorogenic acid depends largely on its metabolism by the gut microflora.
*BioAv↝, CGAs were not well absorbed in their intact form, regardless of the dose.
*other↝, CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose.
BioAv↓, Fig 4: <2% plasma bioavailability of coffee chlorogenic and phenolic acids expressed as sum of areas under the curve, by coffee doses (low dose, black; medium dose, dark gray; and high dose, light gray; geometric mean.
*BioAv↝, As a dietary component, CGA exhibits moderate oral bioavailability [9], and its molecular structure remains largely intact during oral digestion
*BioAv↝, The composition of gut microbiota plays a critical role in CGA’s metabolism and absorption, producing 11 key metabolites, with the most primary products dihydrocaffeic acid, dihydroferulic acid, and 3-(3-hydroxyphenyl) propionic acid [
*BP↓, eported that CGA lowers blood pressure by relaxing vascular smooth muscle and improving endothelial function
*ROS↓, inhibiting the sources of reactive oxygen species (ROS), such as NADPH oxidase,
*NADPH↓,
*AntiAg↑, he downregulation of thromboxane A2 plays a crucial role in CGA-mediated inhibition of platelet aggregation
*TXA2↓,
*antiOx↑, cCGA exhibited the strongest antioxidant effect, which may be related to improved mitochondrial function [
*cardioP↑, CGA exerts significant cardioprotective effects by modulating multiple signaling pathways.
*Inflam↓, reduce infarct size in MI induced by left anterior descending artery (LAD) ligation in rats. It achieves this by suppressing inflammation and enhancing the activity of antioxidant enzymes, such as SOD and CAT, thereby improving cardiac function
*SOD↑,
*Catalase↑,
*Ferroptosis↓, CGA’s ability to alleviate ferroptosis
*NF-kB↓, inhibiting the NF-κB and JNK signaling pathways, highlighting its cardioprotective potential in a TAC mouse model
*JNK↓,
*NRF2↑, CGA reduces oxidative stress and ROS-induced damage by upregulating the Nrf2/HO-1 pathway, thereby mitigating doxorubicin-induced cardiotoxicity and improving cardiac tissue integrity
*HO-1↑,
*toxicity↓, which are widely used in traditional Chinese medicine [60,61], it is generally considered safe.
*BioAv↓, CGA struggles to cross lipophilic membranes, resulting in poor absorption and bioavailability [69]. Simply increasing the oral dose is not an advisable solution, as it carries significant risks.
*BioAv↑, in vitro study reported that the covalent bonding between CGA and soluble oat β-glucan significantly improved CGA’s structural stability and maximized its pharmacological potential
*BioAv↑, Studies have reported that CGA-loaded liposomes, prepared from cholesterol and phosphatidylcholine, showed a relative oral bioavailability of 129.38% compared to free CGA.
eff↑, bovine serum albumin (BSA)-decorated chlorogenic acid silver nanoparticles (AgNPs-CGA-BSA) exhibited significant antioxidant and anticancer effects both in vitro and in vivo.
antiOx↑, They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit.
TumCCA↑, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK
Apoptosis↑,
Wnt↝,
PI3K↝,
MAPK↝,
ROS↓, CGAs have demonstrated significant reactive oxygen species (ROS) scavenging potential through two direct mechanisms: hydrogen atom transfer (HAT) and radical adduct formation (RAF)
BioAv↝, bioavailability of CGAs in humans involves a complex process of digestion, absorption, and metabolism (Figure 7), primarily occurring within the stomach, small and large intestines, governed by the interplay between host enzymes and gut microbiota
P53↑, ↑ p53, ↑ p21, ↑ p18, ↑ CDKI, ↓ cyclin-D1, ↑ G1 cell population
P21↑,
CDK1↑,
Ki-67↓, ↓ Ki-67
Ca+2↑, ↑ Ca2+ levels Caco-2—cell culture
p‑Akt↓, ↓ p-AKT, ↓ mTOR
mTOR↓,
GSH↑, ↑ GSH, ↑ Nrf-2, ↑ HO-1 Caco-2—cell culture
NRF2↑,
HO-1↑,
COX2↓, ↓ COX-2, ↓ TNF-α, ↓ IL-1β, ↓ IL-6 LPS-induced SW480—cell culture
TNF-α↓,
IL1β↓,
IL6↓,
*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,
*BioAv↓, CGA’s oral bioavailability remains limited, prompting research into optimized extraction methods, novel formulations, and structural modifications.
*antiOx↑, antioxidant, anti-inflammatory, anticancer, antibacterial, hepatoprotective, cardioprotective and neuroprotective effects, and modulation of lipid and glucose metabolism
*Inflam↓,
*Bacteria↓,
*hepatoP↑,
*cardioP↑,
*neuroP↑,
*ROS↓, CGA action include inhibition of oxidative stress, regulation of inflammatory responses through modulation of the NF-κB pathway and activation of the Nrf2 pathway
*NF-kB↓, inhibition of NF-κB
*NRF2↑,
*Obesity↓, Research demonstrates that CGA may influence body weight regulation through multiple pathways, including modulation of gut microbiota, reduction of inflammation, regulation of adipogenesis, and stimulation of thermogenesis.
*GutMicro↑, increasing the abundance of probiotic bacteria such as Bifidobacterium and Lactobacillus, while reducing the abundance of bacterial strains found in obese patients and animals, such as Desulfovibrionaceae, Ruminococcaceae, Lachnospiraceae, and Erysip
*AntiAg↑, antiplatelet effects of CGA are supported by both in vitro and in vivo studies
*cardioP↑, CGA was recognized as a compound with high cardioprotective potential, considering its antioxidant, anti-inflammatory, and antihypertensive activities
*AntiDiabetic↑, CGA alleviates the effects of type 2 diabetes mellitus (DM) and helps prevent its development
*NLRP3↓, CGA also inhibits the NLRP3 inflammasome via Nrf2 activation, significantly decreasing proteinuria, creatinine, and urea levels in diabetic rats
*OCLN↓, figure 3
*VEGF↓,
BioAv↝, CGA is water-soluble but highly unstable when exposed to elevated temperature, light, oxygen, or alkaline pH
*ROS↓, The in vitro biological evaluation revealed that CGA could clear the ROS induced by Aβ40 aggregates,
*Aβ↓, Interestingly, CGA@SeNPs show an enhanced inhibition effect on Aβ40 aggregation and, more importantly, protect PC12 cells from Aβ aggregation-induced cell death.
*BioAv↝, use of CGA is limited by its low bioavailability and stability, and only one third of CGA absorbed from the gastrointestinal tract reaches blood circulation
*BioAv↑, we have explored the binding of CGA to SeNPs (CGA@SeNPs) to improve CGA potential therapeutic efficacy.
*Dose↝, We found that the best concentration ratio of Na2SeO3 to CGA was 1:6. CGA@SeNPs have a spherical structure with a diameter about 100 nm
*ROS↓, CGA@SeNPs have strong scavenging activities against radicals in a concentration-dependent manner. The point to be noted is that the modification of CGA on SeNPs exerts a synergistic effect on antioxidant activity.
*H2O2↓, As shown in Fig. 2, CGA@SeNPs and CGA decreased H2O2 in a dose-dependent manner.
*toxicity↓, Furthermore, the CGA@SeNPs were non-toxic to PC12 cells
Showing Research Papers: 1 to 50 of 109
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 109
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 1, Ferroptosis↑, 2, GPx4↓, 2, GSH↓, 1, GSH↑, 1, HO-1↑, 3, Iron↑, 1, NADH↓, 1, NQO1↑, 1, NRF2↑, 2, OXPHOS↓, 1, ROS↓, 3, ROS↑, 10,
Metal & Cofactor Biology ⓘ
Ferritin↓, 1,
Mitochondria & Bioenergetics ⓘ
ATP↓, 1, MMP↓, 5, MPT↑, 1,
Core Metabolism/Glycolysis ⓘ
ACLY↓, 1, AMPK↑, 4, CYP3A2↓, 1, FASN↓, 1, FDG↓, 1, GAPDH↓, 1, Glycolysis↓, 3, lactateProd↓, 1, LDH↓, 1, NADPH↓, 1, PDH↑, 2, PIK3CA↓, 1, SIRT1↓, 1, SIRT1↑, 1, TCA↓, 2,
Cell Death ⓘ
Akt↓, 5, p‑Akt↓, 1, Apoptosis↑, 7, BAD↑, 1, BAX↑, 4, Bcl-2↓, 3, BIM↑, 1, Casp↑, 1, Casp3↑, 2, cl‑Casp3↑, 1, Casp8↑, 1, Casp9↑, 1, Cyt‑c↑, 3, DR5↑, 1, FasL↑, 1, Ferroptosis↑, 2, JNK↑, 3, MAPK↓, 1, MAPK↑, 2, MAPK↝, 1, necrosis↑, 1, p27↑, 1, p38↑, 2, Telomerase↓, 1, TumCD↑, 1,
Kinase & Signal Transduction ⓘ
RET↓, 1,
Transcription & Epigenetics ⓘ
other↝, 4,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, eIF2α↓, 1, HSP90↓, 2,
Autophagy & Lysosomes ⓘ
LC3II↑, 1, p62↓, 1, TumAuto↑, 1,
DNA Damage & Repair ⓘ
DNAdam↑, 2, MGMT↓, 1, p16↑, 1, P53↑, 3, PARP↑, 1, cl‑PARP↑, 1, PCNA↓, 1,
Cell Cycle & Senescence ⓘ
CDK1↓, 1, CDK1↑, 1, CDK4↓, 1, cycD1/CCND1↓, 1, P21↑, 3, TumCCA↑, 7,
Proliferation, Differentiation & Cell State ⓘ
CD44↓, 2, cMET↓, 1, CSCs↓, 5, EMT↓, 3, ERK↓, 1, FOXO3↑, 1, Gli1↓, 1, HDAC↓, 1, HDAC1↓, 1, HDAC8↓, 1, mTOR↓, 5, Nanog↓, 2, NOTCH↓, 1, NOTCH1↓, 1, NOTCH3↓, 1, OCT4↓, 1, PI3K↓, 4, PI3K↝, 1, Smo↓, 1, SOX2↓, 2, STAT3↓, 2, TOP1↓, 1, TOP2↓, 1, TRPM7↓, 1, TumCG↓, 3, Wnt↓, 3, Wnt↝, 1, Wnt/(β-catenin)↓, 1,
Migration ⓘ
5LO↓, 1, AP-1↓, 1, Ca+2↑, 1, E-cadherin↑, 1, Ki-67↓, 1, MMP2↓, 2, MMP9↓, 3, N-cadherin↓, 1, TRIB3↑, 1, TumCI↓, 3, TumCMig↓, 3, TumCP↓, 2, uPA↓, 2, β-catenin/ZEB1↓, 4,
Angiogenesis & Vasculature ⓘ
angioG↓, 1, EGFR↓, 3, EGR4↓, 1, Hif1a↓, 1, LOX1↓, 1, VEGF↓, 2, VEGF↑, 1,
Barriers & Transport ⓘ
BBB↑, 1, P-gp↓, 1,
Immune & Inflammatory Signaling ⓘ
COX2↓, 4, Dectin1↝, 1, IL1β↓, 1, IL6↓, 2, IL8↓, 1, Imm↑, 1, Inflam↓, 1, NF-kB↓, 4, PD-L1↓, 1, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 5, BioAv↑, 4, BioAv⇅, 1, BioAv↝, 23, ChemoSen↑, 5, Dose↓, 1, Dose↑, 1, Dose↝, 6, eff↑, 7, eff↝, 2, eff∅, 1, Half-Life↓, 2, MRP1↓, 1, RadioS↑, 2, selectivity↑, 3,
Clinical Biomarkers ⓘ
E6↓, 1, E7↓, 1, EGFR↓, 3, Ferritin↓, 1, IL6↓, 2, Ki-67↓, 1, LDH↓, 1, PD-L1↓, 1, TRIB3↑, 1,
Functional Outcomes ⓘ
AntiCan↑, 6, AntiTum↑, 1, cardioP↑, 2, cognitive?, 1, cognitive↑, 2, hepatoP↑, 1, neuroP↑, 1, Obesity↓, 1, OS↑, 1, OS↝, 1, Remission↑, 1, Risk↓, 1, toxicity↓, 4, toxicity↑, 2, toxicity↝, 2,
Infection & Microbiome ⓘ
Dectin1↝, 1, Sepsis↓, 1,
Total Targets: 180
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 17, Catalase↑, 6, Ferroptosis↓, 1, GPx↑, 4, GSH↑, 7, GSR↑, 1, H2O2↓, 1, H2O2∅, 2, HDL↑, 1, HO-1↓, 1, HO-1↑, 2, Keap1↓, 1, lipid-P↓, 3, MDA↓, 3, MPO↓, 1, NQO1∅, 1, NRF2↑, 10, ROS?, 1, ROS↓, 17, ROS⇅, 1, ROS∅, 1, SOD↑, 7, SOD1↑, 1, VitC↑, 1, VitE↑, 1,
Metal & Cofactor Biology ⓘ
IronCh↑, 4,
Mitochondria & Bioenergetics ⓘ
ATP↑, 1, Insulin↑, 1, MMP↑, 1, MMP∅, 1,
Core Metabolism/Glycolysis ⓘ
12LOX↓, 1, adiP↑, 1, AMPK↑, 2, cAMP↑, 1, glucose↝, 1, GlucoseCon↑, 2, GLUT2↑, 1, H2S↑, 1, HMG-CoA↓, 1, LDL↓, 1, NADPH↓, 1, PPARα↑, 1, PPARγ↑, 1, p‑PPARγ↓, 1,
Cell Death ⓘ
Akt↑, 2, p‑Akt↑, 1, Apoptosis↓, 2, Casp3↓, 1, Casp6↓, 1, Casp9↓, 2, Fas↓, 1, Ferroptosis↓, 1, HGF/c-Met↑, 1, iNOS↓, 3, JNK↓, 3, MAPK↓, 1, MAPK↑, 1, TRPV1↑, 1,
Kinase & Signal Transduction ⓘ
TRPV3↑, 1,
Transcription & Epigenetics ⓘ
Ach↑, 2, other↓, 2, other↑, 2, other↝, 7,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, GRP78/BiP↑, 1, GRP94↑, 1,
DNA Damage & Repair ⓘ
DNArepair↑, 1,
Proliferation, Differentiation & Cell State ⓘ
ERK↓, 1, ERK↑, 2, p‑ERK↑, 2, GSK‐3β↓, 1, PI3K↑, 1, PTEN↓, 1, STAT3↓, 1,
Migration ⓘ
AntiAg↑, 6, APP↓, 1, Ca+2↑, 1, MMP2↓, 1, MMP9↓, 2, PKCδ↑, 1, VCAM-1↓, 3,
Angiogenesis & Vasculature ⓘ
NO↓, 2, TXA2↓, 1, VEGF↓, 1,
Barriers & Transport ⓘ
BBB↓, 1, BBB↑, 6, GLUT4↑, 1, OCLN↓, 1,
Immune & Inflammatory Signaling ⓘ
COX1↓, 1, COX2↓, 7, ICAM-1↓, 1, IL10↑, 1, IL18↓, 1, IL1α∅, 1, IL1β↓, 6, IL1β∅, 1, IL6↓, 5, IL8↓, 1, IL8∅, 1, Inflam↓, 16, MCP1∅, 1, NF-kB↓, 10, p‑NF-kB↓, 1, PGE2↓, 1, TLR2↓, 1, TLR4↓, 4, TNF-α↓, 5,
Cellular Microenvironment ⓘ
NOX↓, 1,
Synaptic & Neurotransmission ⓘ
5HT↑, 1, AChE↓, 1, BDNF↑, 1, ChAT↑, 2,
Protein Aggregation ⓘ
AGEs↓, 1, Aβ↓, 5, NLRP3↓, 2, β-Amyloid↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 7, BioAv↑, 14, BioAv↝, 40, Dose↑, 1, Dose↝, 8, Dose∅, 1, eff↓, 1, eff↑, 9, Half-Life↓, 9, Half-Life↑, 1, Half-Life↝, 4, Half-Life∅, 1,
Clinical Biomarkers ⓘ
BP↓, 3, BP↝, 1, GutMicro↑, 4, IL6↓, 5,
Functional Outcomes ⓘ
AntiAge↑, 1, AntiCan↑, 2, AntiDiabetic↑, 2, cardioP↓, 1, cardioP↑, 9, chemoPv↑, 1, cognitive↑, 6, hepatoP↑, 6, memory↑, 5, motorD↑, 3, neuroP↑, 15, Obesity↓, 2, OS↑, 1, Pain↓, 1, RenoP↑, 2, toxicity↓, 6, toxicity↝, 1, toxicity∅, 1,
Infection & Microbiome ⓘ
Bacteria↓, 2,
Total Targets: 151
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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