LDL Cancer Research Results
LDL, LDL-cholesterol: Click to Expand ⟱
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The relationship between LDL (low-density lipoprotein) cholesterol and cancer is a complex and evolving area of research. LDL cholesterol is often referred to as "bad" cholesterol because high levels are associated with an increased risk of cardiovascular diseases.
Protumorigenic: High levels of LDL cholesterol can promote tumor growth by providing lipids that are essential for cell membrane synthesis and energy production. Additionally, LDL can influence inflammation and angiogenesis, further supporting tumor development.
Antitumorigenic: Some studies suggest that lowering LDL cholesterol through lifestyle changes or medications (like statins) may have a protective effect against certain cancers, although the evidence is not uniform across all cancer types.
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Scientific Papers found: Click to Expand⟱
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*cardioP↑, Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection.
*neuroP↑,
*Inflam↓, Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function
*antiOx↓,
*GutMicro↑, Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health
*Half-Life↑, However, >50% of the 13C still remained in the body after 48 h
*LDL↓, controlled study of 58 diabetic patients, blueberry intake led to a decline in LDL cholesterol, triglycerides, and adiponectin and an increase in HDL cholesterol
*adiP↓,
*HDL↑,
*CRP↓, reduction was documented in inflammatory markers, including serum high-sensitivity C-reactive protein, soluble vascular adhesion molecule-1, and plasma IL-1β
*IL1β↓,
*Risk↓, lower Parkinson disease risk was associated with the highest quintile of anthocyanin (RR: 0.76) and berry (RR: 0.77) intake
*Risk↓, Nurse's Health Study, greater intake of blueberries and strawberries was associated with slower rates of cognitive decline in older adults, with an estimated delay in decline of about 2.5 y
*cognitive↑, Cognitive performance in elderly adults improved after 12 wk of daily intake of blueberry (94) or Concord grape (95) juice.
*memory↑, Better task switching and reduced interference in memory was found in healthy older adults after 90 d of blueberry supplementation
*other↑, After 12 wk of blueberry consumption, greater brain activity was detected using magnetic resonance imaging in healthy older adults during a cognitive challenge.
*BOLD↑, Similarly, during a memory test, regional blood oxygen level-dependent activity detected by MRI (99) was enhanced in the subjects taking blueberry, but not in those taking placebo.
*NO↓, 50–200 mg/d bilberry showed a dose-dependent decrease in neurotoxic NO and malondialdehyde, combined with an increase in neuroprotective antioxidant capacity due to glutathione, vitamin C, superoxide dismutase, and glutathione peroxidase
*MDA↓,
*GSH↑,
*VitC↑,
*SOD↑,
*GPx↑,
*eff↓, The percentage loss of blueberry anthocyanins during −18°C storage was 12% after 10 mo of storage
*eff↓, Freeze-dried blueberry powder loses anthocyanins in a temperature-dependent manner with a half-life of 139, 39, and 12 d when stored at 25, 42, and 60°C, respectively
*eff↓, Blueberries are low in ascorbic acid and high in anthocyanins (187), and notably anthocyanins are readily degraded by ascorbic acid
*eff↝, Shelf-stable blueberry products like jam (196), juice (197), and extracts (198) can lose polyphenolic compounds when stored at ambient temperature whereas refrigeration mitigates losses.
*Risk↓, It can be safely stated that daily moderate intake (50 mg anthocyanins, one-third cup of blueberries) can mitigate the risk of diseases and conditions of major socioeconomic importance in the Western world.
*LDL↓, Indeed, clinical studies on healthy subjects have evidenced that standardized garlic treatment (900 mg/day) significantly reduces total cholesterol (TC) and low-density lipoprotein cholesterol (c-LDL).
*antiOx↑, Multiple studies have focused on allicin therapeutic potential as an antioxidant (inducing antioxidant product production),
AntiCan↑, anticancer (triggering cancer cells apoptosis and inhibiting tumor growth),
*cardioP↑, cardioprotective (decreasing angiogenesis and inducing vasorelaxation)
*BP↓, Conversely, aged garlic extract supplementation was shown to be more effective than the placebo in lowering systolic blood pressure
*Weight↓, Garlic powder supplementation (800 mg/daily) resulted in a significant decrease in body weight and body fat mass (
NK cell↑, Actually, aged garlic administration in patients with advanced cancer of the digestive system led to an improvement of natural killer (NK) cell activity but did not cause improvement in QoL
*AntiDiabetic↑, Actually, daily garlic allicin supplementation (0.05–1.5 g) displayed a positive and sustained role in blood glucose, total cholesterol (TC), and high/low density lipoprotein (HDL-c/LDL-c) regulation in type 2 diabetes mellitus (T2DM) management
*GSH↑, 2-month application of coated garlic powder tablets (900 mg with alliin and allicin contents of 1.3% and 0.6%, respectively), the glutathione (GSH) concentration significantly increased in circulating human erythrocytes
*Inflam↓, It has anti-inflammatory, rheumatological, ulcer inhibiting, anticholinergic, analgesic, antimicrobial, antistress, antidiabetes, anticancer, liver protection, anthelmintics, antioxidants, antifungal, and wound healing propertie
*AntiBio↑,
*AntiDiabetic↑,
*hepatoP↑,
*antiOx↑,
*AntiFungal↑,
*Wound Healing↑,
*other↑, Garlic has a higher concentration of sulfur compounds (allicin, diallyl disulfide, S-allylcysteine, and diallyl trisulfide), which are responsible for its therapeutic properties.
*BP↓, Garlic consumption lowers blood pressure, inhibits atherosclerosis, decreases serum cholesterol and triglycerides, suppresses platelet aggregation, and increases fibrinolytic activity, among other things
*LDL↓,
*AntiAg↑,
*cognitive↑, Garlic can also aid in preventing cognitive decline by shielding neurons from neurotoxicity and apoptosis, which helps to prevent ischemia, obsessive-compulsive disorder (OCD), and neuronal death while also boosting learning and memory retention
*memory↑,
Risk↑, People who consumed more garlic had a 54% decreased risk of pancreatic cancer than those who consumed fewer amounts of garlic
*COX1↓, Garlic supplements have been demonstrated to reduce cyclooxygenase activity and thromboxane A2 production, resulting in antiplatelet action
*TXA2↓,
GSH↓, allicin reacts with GSH
Bacteria↓, Antimicrobial
LDL↓, reduction without altering HDL
ROS↑, antioxidant at low doses
NRF2↑,
cognitive↑, by activating the Nrf2-system
memory↑, by activating the Nrf2-system
BP↓, via H2S generation
RNS↓,
*Dose↝, Eligible healthy adult subjects (n = 15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study
*other↑, The amla intake showed significant improvements in the primary efficacy parameter of blood fluidity.
*LDL↓, significant improvement in HDL-cholesterol and lowering the LDL-cholesterol levels.
*HDL↑,
*toxicity↑, No substantial changes were observed in liver hepatotoxicity, urinalysis, and hematology after consumption of amla compared to baseline or placebo.
*ROS↓, In conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced oxidative stress.
*CRP↓, Following Amla supplementation, pooled results showed a significant reduction in CRP (p = 0.002), fasting blood glucose (FBG) (p < 0.001), low-density lipoprotein cholesterol (LDL-c) (p < 0.001),
*glucose↓,
*LDL↓,
Dose↑, More over, the supplement was more effective in doses of 1 g/d
*Inflam↓, amla has been proven to have anti-hyperglycemic, hypoglycemic, anti-inflammatory, anti-hyperlipidemic, and antioxidant activities
*antiOx↑,
*GSH↑, a study using the extract from amla leaves (200–400 mg/kg BW) indicated a similar protective effect in diabetic mice by reducing inducing the activity of GSH, GPx, SOD, and CAT activity and also reducing lipid peroxidation
*GPx↑,
*SOD↑,
*Catalase↑,
*lipid-P↓, significant reduction in the peroxidation level and increased antioxidant status were observed in subjects that consumed 250 mg (twice a day) for 60 days
*ROS↓, polyphenols (especially tannins and flavonoids) present in this fruit extract significantly reduced oxidative stress by scavenging NOx.
*cardioP↑, Fruit Gallic acid Cardioprotective activity
*AntiDiabetic↑, Fruit Ellagic acid Antidiabetic activity
*neuroP↑, Fruit Emblicanin A and B Neuroprotective activity
*GastroP↑, Fruit Tannins and gallic acid Gastrointestinal protective activity
*COX2/PTGS2↓, inhibited the enhanced mitochondrial COX-2, MDA, and Bax expressions in the liver
*MDA↓,
*BAX↓,
*TG/TAG↓, Figure 2
*HDL↑,
*LDL↓,
*HMG-CoA↓,
*Dose↝, At the human level, a 500 mg dose of P. emblica L. extract (twice a day) for three months reduced the high sensitive C-reactive protein (CRP), total cholesterol, and LDL levels in Class I obese subjects
*CRP↓,
DNAdam↑, Particularly for amla extracts, DNA fragmentation, increased activity of caspase-3, 7, and 8, and up-regulation of Fas protein were observed in the HeLa cell line,
Casp3↑,
Casp7↑,
Casp8↑,
Fas↑,
TumCI↓, This study also indicated that P. emblica L. decreased the invasiveness of MDA-MB-231 cells (in vitro Matrigel invasion study), and no cytotoxicity was seen in normal lung fibroblasts (MRC5)
selectivity↑,
*HDL↑, a significant improvement in HDL-cholesterol and lowering the LDL-cholesterol levels.
*LDL↓,
*ROS↓, In conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced oxidative stress.
*AntiAg↑, Inhibition of platelet aggregation by oral supplementation of amla is attributable primarily to the abundance of low molecular weight (<1000 Da) hydrolysable ellagitannins
*TBARS↓, The oral administration of amla reduced TBARS levels in plasma, suggesting amla consumption could also
ameliorate oxidative stress due to aging-related mitochondrion dysfunction.
*Dose↝, These results indicate the tolerance and safety of a daily 500 mg dose of amla in healthy humans
Apoptosis↑, Despite statins’ ability to induce apoptosis or autophagy, arrest cell cycle, or modulate favorable epigenetic reprogramming, their efficacy is highly context-dependent
TumAuto↑,
TumCCA↑,
BioAv↓, Challenges such as statin resistance, low bioavailability and pharmacokinetic variability further complicate their application in oncology.
eff↑, including nanoparticle-based drug delivery systems and combination therapies with chemotherapy, radiotherapy or immunotherapy, appear to help overcome these limitations.
HMGCR↓, statins reduce cholesterol levels by targeting HMGCR
LDL↓,
cardioP↑, statins have become a cornerstone in the management of hypercholesterolemia and the prevention of cardiovascular diseases [23], [24], [25], [26].
AntiTum↑, Notably, while research suggests that statins possess anti-tumor effects, evidence remains conflicting and highly context-dependent
ChemoSen↑, suggest that statins can sensitize cancer cells to chemotherapy and radiotherapy, potentially improving treatment outcomes,
RadioS↑,
toxicity↓, Statins are widely regarded as safe and well-tolerated. However, like any medication, they are not without potential side effects, though these are generally mild [232].
*cardioP↑, atorvastatin is FDA-approved for the prevention of cardiovascular events in patients with cardiac risk factors and abnormal lipid profiles.[1]
*LDL↓, patients should be prescribed high-intensity statin therapy to achieve a ≥50% reduction in low-density lipoprotein cholesterol (LDL-C) and reduce the risk of major adverse cardiovascular events (MACE).
HMG-CoA↓, Atorvastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.[12]
Half-Life↝, Atorvastatin is rapidly absorbed after oral administration with a peak plasma concentration at 1 to 2 hours. The half-life of atorvastatin is about 14 hours, while its active metabolites have a half-life of about 20 to 30 hours.
BioAv↓, The bioavailability is low at 14% due to extensive first-pass metabolism.
Dose↝, Atorvastatin is available as atorvastatin calcium tablets in strengths of 10, 20, 40, and 80 mg. It is also available as an oral suspension in a strength of 20 mg/5 mL.[20]
lipid-P↓, Statins exhibit “pleiotropic” properties that are independent of their lipid-lowering effects.
TumCG↓, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types.
Apoptosis↑,
ChemoSen↑, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling.
RAS↓,
HMG-CoA↓, Statins are potent, competitive inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR).
HMGCR↓,
LDL↓, Statins reduce blood plasma cholesterol levels by decreasing de novo cholesterol biosynthesis and by inducing changes in low density lipoprotein (LDL) receptor expression [2].
toxicity↓, Due to the well-established safety profile of statins, such studies are less expensive than the development of novel drugs.
Risk↓, statin use in cancer patients was associated with reduced cancer-related mortality. The risk of cancer death was significantly lower in postmenopausal women
P21↑, Other proposed mechanisms leading to an increase of p21 levels include the release of promoter-associated histone deacetylase and inhibition of histone deacetylase
HDAC↓,
Bcl-2↓, Statins trigger the intrinsic apoptosis pathway and decrease Bcl-2 protein expression [[154], [155], [156]], increase Bax and BIM protein expression [[156], [157], [158], [159]], and activate several caspases
BAX↑,
BIM↑,
Casp↑,
cl‑PARP↑, thereby increasing cleaved PARP-1 levels.
MMP↓, different tumor cell lines (breast, brain, and lung) showed that simvastatin-induced apoptosis is dependent on decreasing mitochondrial membrane potential and increasing reactive oxygen species (ROS) production
ROS↑,
angioG↓, Statins inhibit angiogenesis and metastasis
TumMeta↓,
PTEN↑, n breast cancer xenografts, simvastatin prevented tumor growth by reducing Akt phosphorylation and BclXL transcription, while simultaneously increasing the transcription of pro-apoptotic/anti-proliferative PTEN
eff↑, In mice, the administration of a combination of celecoxib and atorvastatin was more effective than each individual treatment, and effectively prevented prostate cancer progression from androgen dependent to androgen independent
OS↑, Long-term statin use may improve survival in GBM patients treated with temozolomide chemotherapy
Remission↑, statin use during or after chemotherapy is not associated with improved disease-free-, recurrence-free-, or overall survival in stage II colon cancer patients
*AChE↓, Berberine (9) has gained considerable attention due to its wide pharmacological potentials and several biological properties, such as acetylcholinesterase and butyrylcholinesterase inhibitory, antioxidant, monoamine oxidase oxidase,
*Aβ↓, amyloid-b peptide level-reducing, cholesterol- lowering and renoprotective activities
*LDL↓,
*RenoP↑,
*BChE↓,
*eff↑, Above all, the berberine-pyrocatechol hybrid (14) showed a strong AChE inhibitor activity (IC50 of 123 ± 3 nM)
[34]
*BACE/β-secretase↓, Curcumin: inhibite the rBACE1 activity [42]. In addition, it has made good inhibitory effect on acetylcholinesterase activity
*AChE↓, EGCG promoted brain health, prevented AD progression, and inhibited the AChE activity [52,53].
*eff↑, EGCG could enhance the effect of huperzine A on inhibiting AChE.
*antiOx↑, multiple activities of berberine, including antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitory,
*AChE↓, inhibit AChE with an IC50 of 0.44 μM
*BChE↓, BChE inhibitor and the corresponding IC50 was estimated to be 3.44 μM
*MAOA↓, inhibitory activity on MAO-A with an IC50 value of 126 μM
*Aβ↓, monoamine oxidase inhibitory, amyloid-b peptide level-reducing and cholesterol-lowering activities.
*LDL↓, effectively reduce serum cholesterol and LDL-cholesterol levels in hyperlipidemic hamsters and human hypercholesterolemic patients
*ROS↓, First, it was reported that berberine can scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS)
*RNS↓,
*lipid-P↓, Secondly, berberine can inhibit lipid peroxidation
*Dose↝, berberine can inhibit AChE with an IC50 of 0.44 μM
*MAOB↓, inhibition of berberine against MAO-B: IC50 was estimated to be 98.4 μM
*memory↑, beneficial effect of berberine in ameliorating memory dysfunction in a rat model of streptozotocin-induced diabetes
*toxicity↓, Berberine is generally considered to be non-toxic at doses used in clinical situations and lacks genotoxic, cytotoxic or mutagenic activity
*BBB↑, Berberine can be administered orally [67] and pass through the blood-brain barrier
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eff↑, Inhibition of ACLY using bempedoic acid used in combination with palbociclib reduced cell viability in a panel of breast and pancreatic cancer cell lines.
Apoptosis↑, Mechanistically, palbociclib inhibited cell proliferation, whereas bempedoic acid stimulated apoptosis.
TumCI↓, ACLY inhibition blocked cell invasion, when used alone or in combination with palbociclib.
ACLY↓, In 2019, an inhibitor of ACLY, bempedoic acid (BA), was FDA-approved to reduce levels of low-density lipoprotein cholesterol in patients (21).
LDL↓,
eff↑, The present study aimed to determine the combined effect of ACLY inhibition using BA and CDK4/6 inhibition using Palb on the proliferation and EMT/invasion of cancer cells.
TumCP↓, Palb inhibits proliferation, while BA induces apoptosis
LDL↓, Bempedoic acid (ETC-1002) is a small molecule intended to lower LDL-C in hypercholesterolemic patients,
AMPK↑, demonstrated that ETC-1002 treatment increased AMP-activated protein kinase (AMPK)26,
ACLY↓, ETC-1002 inhibits ACL and increases AMPK activity,
ACLY↓, Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells
PD-L1↑,
mtDam↑, Mechanistically, ACLY inhibition causes polyunsaturated fatty acid (PUFA) peroxidation and mitochondrial damage, which triggers mitochondrial DNA leakage to activate the cGAS-STING innate immune pathway.
cGAS–STING↑, ACLY inhibition leads to cGAS-STING activation
LDL↓, bempedoic acid (BemA; also named ETC-1002) has been recently approved by U.S. Food and Drug Administration (FDA) for lowering low-density lipoprotein cholesterol
eff↑, dietary PUFA supplementation is sufficient to mimic the enhanced efficacy of PD-L1 blockade by ACLY inhibition, providing promising combinational strategies for immunotherapy-resistant tumors therapy.
*ACLY↓, Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events
*LDL↓, mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter
*MusCon↓,
Dose↝, receive oral bempedoic acid, 180 mg daily, or placebo
cardioP↑, Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization)
*Imm↑, traditional uses that include improving immune response and cardiovascular function.
*cardioP↑,
*LDL↓, Multiple clinical trials have provided evidence that different forms of orally administered bergamot can reduce total cholesterol and low-density lipoprotein cholesterol.
toxicity↓, The use of bergamot in multiple clinical trials has consistently shown that it is well tolerated in studies ranging from 30 days to 12 weeks.
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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/PTGS2↓, 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
*LDL↓, chitosan group significantly reduced total and LDL cholesterol (F=4.21, P=0.02, and F=3.46, P=0.04, respectively) compared with placebo.
*Weight↝, As a dietary supplement, chitosan has been claimed to control obesity and to lower serum cholesterol.
*LDL↓, In man, dietary chitosan has been reported to reduce serum total cholesterol levels by 5.8-42.6% and low-density lipoprotein levels by 15.1-35.1%.
*antiOx↑, Antioxidant effects of cocoa may directly influence insulin resistance and, in turn, reduce risk for diabetes.
*AntiDiabetic↑,
*cognitive↑, beneficial effects on satiety, cognitive function, and mood.
*AntiAg↑, Bordeaux and colleagues found that, among healthy participants in a platelet function study, those who had consumed chocolate before testing (n=141) had reduced platelet activity compared to nonconsumers.
*AntiAg↑, dark chocolate consumption decreased platelet adhesion 2 h after consumption in 22 heart transplant patients
*LDL↓, ll three significantly improved LDL and HDL levels from baseline in subjects with high LDL at the start of the study.
*HDL↑, in another trial, HDL increased by 11.4% and 13.7% when subjects consumed dark chocolate and polyphenol-enriched dark chocolate
*BP↓, A relationship between cocoa consumption and reduced BP was first observed in the Zutphen Elderly Study. A 2010 study found that a daily dose of 1052 mg cocoa flavanols was required to reduce 24-h ambulatory BP
*eff↓, Rimbach et al. noted that beneficial effects on BP, FMD, and platelet aggregation have not been found in all human trials (67, 73). Further, improvements are often small when they are observed
*ROS↓, Cocoa intake increases serum antioxidant capacity, protecting the endothelium from oxidative stress and endogenous ROS
*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2/PTGS2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2/PTGS2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,
*Dose↝, beneficial effects of Chy (at the dose of 1 and 2% w/w of diet) administered daily for 15 successive days in mice with memory deficits.
*memory↑, The administration of Chy for 15 consecutive days significantly protected the animals from developing memory impairment.
*TBARS↓, there was a significant decrease in brain TBARS and increase in GSH levels after administration of Chy (2% w/w), thereby indicating decreased free radical generation and increased scavenging of free radical, respectively
*GSH↑,
*ROS↓,
*cognitive↑, Thus, Chy may prove to be a useful remedy for the management of Alzheimer's disease owing to its antioxidant effect, pro-cholinergic action and/or antiamnesic potential.
*AntiAge↑, Chy had been one of the most respected anti-ageing ayurvedic tonic, long before the clinical importance of vitamins, minerals and antioxidants was appreciated
*hepatoP↑, It is not only hepatoprotective but it also streamlines the metabolism of fats and proteins
*antiOx↑, It possesses promising antioxidant, cardiotonic, cholesterol lowering and anti-inflammatory properties
*LDL↓,
*Inflam↓,
*other↝, Chy is made in anwala base (Indian gooseberry, Emblica officinalis) [16], which is one of the richest sources of vitamin C (ascorbic acid)
*AChE∅, No statistically significant differences were observed in brain AChE activity of Chy-treated mice and control group mice.
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*neuroP↑, This versatile spice has shown potential as a natural remedy fora wide range of chronic diseases, such as neurodegenerative disorders, type 2 diabetes,cardiovascular problems, and metabolic sy
*AntiDiabetic↑,
*tau↓, Key compounds in cinnamon, particularly cinnamaldehyde, are believed to protect the brain by inhibiting the aggregation of tau and amyloid-beta (Aβ) proteins, both of which are hallmark features of Alzheimer’s disease.
*Aβ↓,
*antiOx↑, cinnamon’s antioxidant and anti-inflammatory properties help mitigate oxidative stress and inflammation in the brain
*Inflam↓,
*ROS↓, Neurochemicalanalysis showed reduced oxidative stress, evidenced by lower levels of malondialdehyde and nitrites, as well as increased reduced glutathione.
*MDA↓,
*GSH↓,
*cardioP↑, es, has long beenutilized in herbal medicine to support cardiovascular health and treat cardiovascular diseases(CVDs
*LDL↓, Specifically, cinnamon can lower levels of LDL (bad) cholesterol andtriglycerides, while increasing HDL (good) cholester
*HDL↑,
*other↝, particularly beneficial for treatinginflammatory bowel diseases (IBD) such as colitis.
*TNF-α↓, lowering levels of inflammatory markers such as TNF-α, IL-6, and MPO, andby downregulating the expression of TLR-4.
*IL6↓,
*MPO↓,
*TLR4↓,
*GutMicro↑, cinnamon can also support a balanced gut microbiota, which is essential for overall digestive health. By inhibiting the growth of harmful bacteria and fungi, while promoting the growth of beneficial microorganisms
*lipid-P↓, can improve ulcerative colitis (UC) in rats by reducinginflammation, lipid peroxidation, and histological damage
*Wound Healing↑, Combining cinnamon oil(CO) with aloe vera (AV) (COVA) has been shown to effectively inhibit bacterial growth and promote wound healing.
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*antiOx↑, Cinnamon is known to have antioxidant, antibacterial, anti-inflammatory, and other therapeutic properties.
*Inflam↓,
*cardioP↑, natural remedy to treat serious diseases such as type 2 diabetes, chronic digestion problems, cardiovascular diseases, and even cancer and Alzheimer’s disease.
angioG↓, cinnamon extract (CE) displays anticancer activity5 and inhibits angiogenesis by blocking vascular endothelial growth factor (VEGF) 2 signaling
VEGF↓,
*LDL↓, , and low-density lipoprotein cholesterol (7–27%) for patients who consumed 1 g, 3 g, or 5 g of cinnamon for 40 days.
COX2/PTGS2↓, treatment of melanoma cell lines with CE also induced a decrease in Cox-2 and HIF-1α expression in the tumor tissues that mediate the potent antitumor activity of cinnamon
Hif1a↓,
*Aβ↓, A study found that Cinnamon (肉桂 ròu guì) extract (CEppt) inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells.
*tau↓, he extract of the whole cinnamon effectively inhibited the aggregation of human tau in vitro, and this could be attributed to both proanthocyanidin timer and cinnamaldehyde in CE
*toxicity↓, In one study, the intake of up to 6 g/d of C. cassia for > 40 days did not show any adverse effects.
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*AntiAge↑, supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics.
*cardioP↑, Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ10
*Inflam↓, Administration of CoQ10 in doses ranging from 60 to 500 mg/day for a 1-week to 4-month intervention period significantly decreased production of inflammatory cytokines
*antiOx↑,
*lipid-P↓, The concentrations of CoQ10 in the plasma of elderly people are positively correlated with levels of physical activity and cholesterol concentrations (Del Pozo-Cruz et al., 2014a,b), as well as with lower lipid oxidative damage.
*QoL↑, Older individuals given a combination of selenium and CoQ10 over a 4-year period reported an improvement in vitality, physical performance, and quality of life
*neuroP↑, health benefits in elderly people by preventing chronic oxidative stress associated with cardiovascular and neurodegenerative diseases
*Dose↝, the highest dose for CoQ10 supplementation is 1200 mg daily according to well-designed randomized, controlled human trials, although doses as high as 3000 mg/day have been used in shorter clinical trials
*BP↓, These authors interpreted the results to indicate a significant reduction in systolic blood pressure without improvements in other CVD risk factors, such as diastolic blood pressure, total cholesterol, LDL- and high-density lipoprotein (HDL)-choleste
*IGF-1↑, elderly healthy participants who received selenium and CoQ10 supplementation for over 4 years, an increase in insulin-like growth factor 1 (IGF-1) and postprandial insulin-like growth factor-binding protein 1 (IGFBP-1) levels
*IGFBP1↑,
*eff↑, A combination of CoQ10 with red yeast rice, berberina, policosanol, astaxanthin, and folic acid significantly decreased total cholesterol, LDL-cholesterol, triglycerides, and glucose in the blood while increasing HDL-cholesterol levels
*LDL↓,
*HDL↑,
*eff↑, 60 patients suffering from statin-associated myopathy were enrolled in a 3-month study to test for efficacy of CoQ10 and selenium treatment. A consistent reduction in their symptoms, including muscle pain, weakness, cramps, and fatigue was observed
*other↑, Because of its capacity to reduce the side-effects of statins, CoQ10 has been proposed to prevent and/or slow the progression of frailty and sarcopenia in the elderly chronically treated with statins.
*RenoP↑, experiments performed on rats showed a promising protective effect of ubiquinol in the kidneys
*ROS↓, 65 patients undergoing hemodialysis, supplementation with high amounts of CoQ10 (1200 mg/day) lowered F2-isoprostane plasma levels indicative of a reduction in oxidative stress
*TNF-α↓, low grade inflammation, respond well to CoQ10 supplementation with significant decrease in TNF-α plasma levels without having an effect on C-reactive protein and IL-6 production
*IL6↓, Another study reported that CoQ10 therapy in doses ranging from 60 to 300 mg/day caused no significant decrease in C-reactive protein while eliciting a significant reduction in IL-6 levels
*other↝, Preclinical studies demonstrated that CoQ can preserve mitochondrial function and reduce the loss of dopaminergic neurons in the case of Parkinson's disease
*other∅, There was no improvement observed in oxidative stress or neurodegeneration markers in a randomized clinical trial in Alzheimer's Disease patients with CoQ10 supplementation at a dose of 400 mg/day for 16 weeks
*hepatoP↑, Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent.
*Dose↝, 100 subjects with ultrasound-diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2-month period.
*toxicity↓, with no side effects reported.
*BloodF↑, Doppler sonography showed increased hepatic vein flow (p < .001), reduced portal vein diameter (p < .001) and liver size (p < .001), reduction in serum ALT (p < .001) and AST (p < .001) levels, improvement in AST/ALT ratio
*ALAT↓,
*AST↓,
*Bil↓, and reduction in total bilirubin
*LDL↓, ALE supplementation reduced total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations
*HDL↓,
*TG/TAG↓,
*LDL↓, A significantly decreased difference was also found for the mean change in total cholesterol (p = 0.033), low-density lipoprotein (LDL)-cholesterol
*HDL↑, favouring in particular the increase in HDL-C, besides decreasing total cholesterol and LDL-cholesterol.
Dose↝, two daily oral assumptions (before lunch and dinner) of film-coated tablets of 250 mg of standardized ALE
(>20% caffeoylquinic acids, >5% flavonoids and >5% cynaropicrin,
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*Inflam↓, C. scolymus exhibits anti-inflammatory, antioxidant, liver-protective, bile-expelling, antimicrobial, and lipid-lowering neuroprotective properties.
*antiOx↑, Of particular interest is the abundance of chlorogenic acid, a type of caffeoylquinic acid known also by its antioxidant activity.
*hepatoP↑,
*lipid-P↓,
*TNF-α↓, Pectins from artichoke reduced the expression of inflammatory markers such as TNF-α, ICAM-I, IL-1β, and IL-6 in mice. This has resulted in a decrease in iNOS and TLR4 expression in favor of reducing inflammation.
*ICAM-1↓,
*IL1β↓,
*IL6↓,
*MUC1↑, artichoke pectin increased the intestinal barrier genes expression, MUC-1 and Occludin.
*OCLN↑,
*IBI↑, artichoke pectin has the potential to improve IBD by inhibiting inflammation and promoting the expression of genes involved in intestinal barrier function
*ROS↓, The beneficial components derived from artichoke have shown important scavenging activity against reactive oxygen species (ROS) and free radicals.
*cardioP↑, Moreover, artichoke leaf extracts supplementation has also decreased the cardiac markers and increased the antioxidant enzyme SOD, GPx, and GSH activities [80].
*SOD↑,
*GPx↑,
*GSH↑,
*TG/TAG↓, resulting in lower triglyceride (TG) levels
*LDL↓, 8 weeks with artichoke leaf extracts (administered as two daily doses of 250 mg). This treatment significantly reduced total cholesterol (TC), LDL cholesterol (LDL-c),
*neuroP↑, Growing evidence highlights the neuroprotective role of polyphenols
*5HT↑, Polyphenols have been shown to improve mood by increasing serotonin levels in the brain, stimulating the production of brain-derived neurotrophic factor (BDNF), and reducing inflammation
*BDNF↑,
*LDL↓, Meta-analysis of data from 9 trials including 702 subjects suggested a significant decrease in plasma concentrations of total cholesterol , Low Density Lipoprotein-Cholesterol and triglycerides
*TG/TAG↓,
*HDL∅, No significant alteration in plasma High Density Lipoprotein-Cholesterol (HDL-C) concentrations was observed
*antiOx↑, Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties
*Inflam↓,
*AntiAge↑, Its potential anti-aging properties are due to its power to alter the levels of proteins associated with senescence, such as adenosine 5′-monophosphate-activated protein kinase (AMPK) and sirtuins
*AMPK↑,
*SIRT1↑,
*NF-kB↓, preventing pro-aging proteins, such as nuclear factor-kappa-B (NF-κB) and mammalian target of rapamycin (mTOR)
*mTOR↓,
*NLRP3↓, Moreover, curcumin, by inhibiting the NF-κB pathway, can directly restrain the assembly or even inhibit the activation of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome
*NADPH↓, by inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and elevating the activity of antioxidant enzymes and consequently lowering reactive oxygen species (ROS)
*ROS↓,
*COX2/PTGS2↓, (COX-2), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) can be decreased by curcumin
*MCP1/CCL2↓,
*IL1β↓, by decreasing IL-1β, IL-17, IL-23, TNF-α, and myeloperoxidase, enhancing levels of IL-10, and downregulating activation of NF-κB
*IL17↓,
*IL23↓,
*TNF-α↓,
*MPO↓,
*IL10↑,
*lipid-P↓, curcumin showed a significant decline in lipid peroxidation and increased superoxide dismutase levels, in addition to a reduction in Aβ aggregation and tau hyperphosphorylation through the regulation of GSK3β, Cdk5, p35, and p25
*SOD↑,
*Aβ↓,
*p‑tau↓,
*GSK‐3β↓,
*CDK5↓,
*TXNIP↓, Curcumin also has an inhibitory role on the thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway
*NRF2↑, well as upregulation of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO1), HO-1, and γ-glutamyl cysteine synthetase (γ-GCS) in brain cells.
*NQO1↑,
*HO-1↑,
*OS↑, significant improvement in OS, and a positive evolution in memory and spatial learning
*memory↑,
*BDNF↑, Besides that, it promoted neurogenesis through increasing brain-derived neurotrophic factor (BDNF) levels
*neuroP↑, Curcumin can promote neuroprotection
*BACE/β-secretase↓, Figure 7
*AChE↓, figure 7
*LDL↓, and reduced total cholesterol and LDL levels.
*Inflam↓, known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions.
*antiOx↑,
*memory↑,
*Aβ↓, curcumin prevents Aβ aggregation and crosses the blood-brain barrier,
*BBB↑,
*cognitive↑, curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD
*tau↓, curcumin's effect on inhibition of A and tau,copper binding ability, cholesterol lowering ability, anti-inflammatory and modulation of microglia, acetylcholinesterase (AChE) inhibition, antioxidant properties,
*LDL↓,
*AChE↓,
*IL1β↓, Curcumin reduced the levels of oxidized proteins and IL1B in the brains of APP mice
*IronCh↑, Curcumin binds to redox-active metals, iron and copper
*neuroP↑, Curcumin, a neuroprotective agent, has poor brain
bioavailability.
*BioAv↝,
*PI3K↑, They found that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1, and ferritin expression
*Akt↑,
*NRF2↑,
*HO-1↑,
*Ferritin↑,
*HO-2↓, and that it significantly downregulates heme oxygenase 2, ROS, and A40/42 expression.
*ROS↓,
*Ach↑, significant increase in brain ACh, glutathione, paraoxenase, and BCL2 levels with respect to untreated group associated with significant decrease in brain AChE activity,
*GSH↑,
*Bcl-2↑,
*ChAT↑, nvestigation revealed that the selected treatments
caused marked increase in ChAT positive cells.
*Imm↑, Fermented foods containing probiotic bacteria and fungi can enhance the immune system, improve gastrointestinal health, and lower the risk of developing various inflammatory diseases.
*GastroP↑,
*Inflam↓,
AntiCan↑, Kombucha tea possesses anticancer, antimicrobial, and hepatoprotective properties
*AntiBio↑,
*hepatoP↑,
*CD4+↑, Kombucha consumption also reduced inflammation by increasing polarization of CD4+ T cells (by induction of IL-4 and TGF-β) and by inhibiting IFN-γ and IL-17
*IFN-γ↓,
*IL17↓,
*GutMicro↑, Kombucha intake also promoted the growth of butyrate-producing bacteria in the gut that exert anti-inflammatory effects
*antiOx↑, fermented turmeric demonstrated stronger antioxidative activity than raw turmeric.
*AST↓, After 5 days of fermentation with Bacillus natto, fermented turmeric dramatically decreased the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in contrast to unfermented turmeric.
*ALAT↓,
*HDL↑, After fermentation, there was a considerable rise in HDL cholesterol and a significant decrease in LDL cholesterol [45].
*LDL↓,
*ROS↓, Kimchi has also demonstrated potent radical scavenging and antioxidant activity in vitro, enhancing LLC-PK1 cell viability by protection against lipid peroxidation.
*lipid-P↓,
*Inflam↓, The anti-inflammatory properties of sauerkraut LAB were emphasized in a randomized, double-blinded pilot study on 34 Norwegian inflammatory bowel syndrome (IBS) patients.
*Aβ↓, Mice fed with doenjang-infused high-fat feed had reduced β-amyloid peptide (Aβ) and neuroinflammatory gene levels, further reinforcing the protective effect of fermented soy on the aging brain
*GutMicro↑, Improving the gut microbiome and reducing inflammation through dietary inputs like fermented foods may therefore be a path to improving human health status
*Inflam↓,
*BP↓, figure 2
*LDL↓,
*HDL↑,
*CRP↓,
*IL6↓,
*TNF-α↓,
*Obesity↓,
*AntiDiabetic↑,
*cardioP↑, fermented dairy consumption was associated with a decreased risk of general CVD compared with controls
*GutMicro↑, yogurt consumption also coincided with transient increases in Streptococcus thermophilus and Bifidobacterium animalis subsp. lactis in feces, microbes commonly found in yogurt cultures, suggesting a role for the gut microbiome in mediating effects [
*neuroP↑, Evidence also suggests a potential protective role of fermented foods against age-related neurologic diseases such as dementia and Alzheimer’s disease.
*cognitive↑, 30 participants with Alzheimer’s disease found that daily consumption of 200 mL milk fermented with L. acidophilus, Lacticaseibacillus casei, B. bifidum, and Limosilactobacillus fermentum (2 × 109 CFU/g each) for 12 wk improved mini-mental state exam
Risk↓, IF has shown potential for reducing cancer risk and enhancing therapeutic efficacy by sensitizing tumor cells to chemotherapy and radiotherapy.
ChemoSen↑, intermittent fasting (IF) may enhance the effectiveness of chemotherapy and targeted therapies by activating autophagy. IF enhances the effectiveness of chemotherapy, including drugs such as cisplatin, cyclophosphamide, and doxorubicin
RadioS↑, disease stabilization, improved response to radiotherapy patients with glioma
*Dose↝, 16:8—16 h of fasting with an 8 h eating window;
*Dose↝, 5:2—consuming a standard number of calories for 5 days and reducing intake to 25% of daily requirements for 2 days;
*Dose↝, Eat–Stop–Eat—complete fasting for 24–48 h.
*LDL↓, IF during Ramadan (approximately 18 h of fasting for 29–30 days) reduces LDL cholesterol levels and increases HDL cholesterol in women, as well as reducing inflammatory markers such as CRP and TNF-α
*CRP↓,
*TNF-α↓,
TumAuto↓, Intermittent fasting activates autophagy as an adaptive mechanism to nutrient deprivation, which may modulate tumor development and treatment
GLUT1↓, fasting reduces the expression of glucose transporters GLUT1/2, which slow down cancer metabolism and increase the susceptibility of cancer cells to oxidative stress
GLUT2↓,
glucose↓, studies on cell and animal models have shown that intermittent fasting reduces glucose and insulin-like growth factor (IGF-1) levels [103], as well as insulin [104,105], resulting in the inhibition of the mTOR kinase pathway (PI3K/Akt/mTOR), suppress
IGF-1↓,
Insulin↓,
mTOR↓,
mTORC1↓, suppression of mTORC1 [22], and activation of AMPK through increased ADP/ATP ratio in cells, which supports autophagy and induces apoptosis
AMPK↑,
Warburg↓, Moreover, IF counteracts the Warburg effect by promoting oxidative phosphorylation, leading to an increase in the production of reactive oxygen species (ROS) and enhanced oxidative stress in cancer cells [106,108], causing DNA damage and the activati
OXPHOS↑,
ROS↑,
DNAdam↑,
JAK1↓, fasting reduces the production of adenosine by cancer cells, inhibiting the activation of the JAK1/STAT pathway, thereby reducing cancer cell proliferation
STAT↓,
TumCP↓,
QoL↑, reduction in IGF-1 levels, improved quality of life patients with multiple cancer types
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Risk↓, Intermittent fasting (IF) has emerged as a potential adjunctive strategy in cancer prevention, mitigation, and treatment.
TumCMig↓,
IGF-1↓, IF may reduce cancer risk, including its effects on insulin-like growth factor 1 suppression, autophagy induction, and chronic inflammation reduction.
TumAuto↑,
Inflam↓, IF has been shown to reduce chronic inflammation,13,40 a risk factor for various cancers
ChemoSen↑, we discuss IF’s potential to enhance the efficacy of conventional cancer therapies by sensitizing cancer cells, promoting apoptosis, and reducing treatment-related side effects.
Apoptosis↑,
chemoP↑, IF has shown potential in protecting healthy tissues during chemotherapy.
*glucose↓, Fasting has been shown to enhance metabolic health by improving insulin sensitivity, lowering blood sugar levels, and reducing the risk of type 2 diabetes.
*AntiDiabetic↑,
*cardioP↑, Recent studies support the cardioprotective effect of IF by reducing cholesterol levels, lowering blood pressure, and improving cardiovascular health
*LDL↓,
*BP↓,
*neuroP↑, IF may reduce the risk of neurodegenerative diseases, enhance cognitive function, and improve memory
*cognitive↑,
*memory↑,
*OS↑, some studies have suggested that IF may extend lifespan and improve overall health
*QoL↑,
Imm↑, In the context of cancer prevention, IF may directly affect the function of immune cells, reducing their production of inflammatory cytokines and promoting a more anti-inflammatory environment.5
TumCG↓, Evidence suggests that FMDs can effectively slow tumor growth by altering cancer cell metabolism, enhance the efficacy of traditional cancer therapies by reducing side effects, and potentially bolster antitumor immune surveillance
ChemoSideEff↓, IF may also help alleviate common side effects such as fatigue, nausea, and weight loss associated with cancer treatments
QoL↑, Results showed that chemotherapy-induced QoL decline was significantly less pronounced during fasting periods compared to non-fasting periods
*LDL↓, ellagic acid treatment improved the levels of blood lipid metabolism with a 4.7% decline in total cholesterol, 7.3% decline in triglycerides, 26.5% increase in high-density lipoprotein, and 6.5% decline in low-density lipoprotein.
*HDL↑,
*BDNF↑, ellagic acid increased plasma BDNF by 21.2% in the overweight group and showed no effects on normal-weight participants
*cognitive↑, ellagic acid has a potential to restore cognitive performance related to mild age-related declines
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Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP/DDIT3↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,
*antiOx↑, bioactivities of EGCG, including its antioxidant, anti-inflammatory, anticancer, cardiovascular protective, metabolic regulatory, neuroprotective, gut microbiota-modulating, and antimicrobial properties.
*Inflam↓,
*AntiCan↑,
*cardioP↑,
*neuroP↑,
*GutMicro↑,
*AntiBio↑,
*ROS↓, Figure 1, anti inflammatory
*TNF-α↓,
*IL6↓,
TumCP↓,
*LDL↓, cardioprotective
*NO↓,
*Obesity↓, Metabolic syndrome
*p‑tau↓, nervous system
*Aβ↓,
*NRF2↑, , EGCG has been shown to activate the Keap1/P62/Nrf2 signaling pathway,
*SOD↑, upregulation of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, indirectly diminishing the levels of intracellular oxygen free radicals
*Catalase↑,
*GPx↑,
*NLRP3↓, EGCG also restores autophagy levels, suppresses the activation of the NLRP3 inflammasome by inhibiting the mammalian target of rapamycin signaling pathway
*mTOR↓,
TumCCA↑, Cancer: induce cell cycle arrest and inhibit tumor cell proliferation
NRF2↓, EGCG inhibits CCL5-stimulated lung cancer cell proliferation by down-regulating Nrf2 expression
Apoptosis↑, Inducing Apoptosis in Cancer Cells
SIRT1↓, EGCG activates the mitochondrial apoptotic pathway by downregulating SIRT1 expression to modulate the SIRT1-p53 axis
miR-25-5p↓, In breast cancer, EGCG induces apoptosis by inhibiting miR-25 expression and elevating PARP, pre-caspase-3 and pre-caspase-9 protein levels
PARP↑,
Casp3↑,
Casp9↑,
ER Stress↑, in multiple myeloma, EGCG promotes apoptosis by activating the endoplasmic reticulum stress pathway
TumAuto↑, EGCG induces autophagic cell death in breast cancer cells by retaining YAP1 in the cytoplasm and promoting the assembly of the CHMP2B-VPS4B complex
EMT↓, EGCG has been demonstrated to inhibit EMT, invasion, and migration by blocking the TGFβ/Smad signaling pathway
TumCI↓,
TumCMig↓,
TGF-β↓,
Smad1↓,
STAT3↓, EGCG can directly bind to STAT3, reducing nuclear localization and inhibiting the transcription of PLXNC1.
VEGF↓, widely believed that EGCG can block this process by reducing the expression of vascular endothelial growth factor, a key factor in angiogenesis,
angioG↓, The inhibition of angiogenic mimicry by EGCG through the Twist/VE-calmodulin/AKT pathway has also been demonstrated in prostate cancer cells
Imm↑, Acting as an Immunomodulator
EGFR↓, EGCG possesses the ability to interact with EGFR and inhibit activity, strengthening the anticancer evidence for EGCG
*GutMicro↑, EGCG can regulate the balance of gut flora. For example, EGCG can inhibit the growth of harmful bacteria such as Escherichia coli and Salmonella, while promoting the proliferation of probiotics like Bifidobacterium and Lactobacillus
*Bacteria↓, Antibacterial and Antiviral Properties of EGCG
*AntiViral↑,
*BioAv↓, EGCG, its low bioavailability in the human body limits clinical efficacy.
*BioAv↑, Nanotechnology strategy of EGCG.
*eff↑, Co-encapsulation assay of EGCG with quercetin shows that the two synergistically enhanced the antioxidant capacity of EGCG
*BioAv↑, Combining EGCG with resveratrol increases its solubility and significantly improves its absorption in the small intestine.
eff↑, combination of EGCG and curcumin inhibits the activity of metabolic enzymes, reduces the rate of metabolism in the liver and enhances its antitumor efficacy
ChemoSen↑, synergistic effects of EGCG combined with chemotherapeutic agents such as 5-fluorouracil, celecoxib, cisplatin, and tamoxifen have also been reported
*toxicity↝, The European Food Safety Authority notes in scientific opinion that daily oral doses of 800 mg or higher of EGCG represent a common starting point for observed cases of liver injury
*OS↑, Dietary intake of epicatechin promoted survival in the diabetic mice (50% mortality in diabetic control group vs. 8.4% in epicatechin group after 15 wk of treatment),
*Inflam↓, reduced systematic inflammation markers and serum LDL cholesterol,
*LDL↓,
*AntiAge↑, epicatechin may be a novel food-derived, antiaging compound.
*GSH↑, In addition, the GSH concentration and total SOD activity in the livers of the db+EC group were significantly greater,
*SOD↑,
*AMPKα↑, Epicatechin improves AMPKα activity in the liver and skeletal muscle of diabetic mice.
*Weight∅, whereas blood pressure, blood glucose, food intake, and body weight gain were not significantly altered.
Dose↝, 30 mg synthetic genistein daily. Genistein at a dose that can be easily obtained from a diet rich in soy reduced the level of serum PSA in patients with localized CaP, without any effects on hormones. It was well tolerated and had a beneficial effect
PSA↓, Serum prostate specific antigen (PSA) decreased by 7.8% in the genistein arm and increased by 4.4% in the placebo arm
*LDL↓, Total cholesterol was significantly lower in the genistein arm (P = 0.013).
*Inflam↓, gingerol and shogaol classes of compounds, might exert several beneficial effects including anti-inflammatory, antioxidant, and cholesterol lowering properties
*antiOx↑,
*LDL↓,
*AntiAg↑, previous clinical trials report few side-effects, mostly minor in nature (e.g. mild nausea, heartburn).[1] Of these reported side effects, potentially the most significant is an antiplatelet effect.
*AntiAg∅, In contrast, two studies reported that 2–3.6g of ginger had no effect on measures of platelet aggregation in health adults.
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Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.
*Inflam↓, H2 demonstrates numerous biologically therapeutic properties, including anti-inflammatory, antioxidant, anti-cancer, anti-stress, anti-apoptotic, anti-allergic effects, signaling molecule functions, regulation of redox balance
*antiOx↓,
*Stress↓,
*Dose↝, The administration methods of hydrogen include inhalation, hydrogen-rich water, hydrogen-rich saline, hydrogen-rich eye drops, and hydrogen-rich bathing.
*cardioP↑, graphical abstract and figure 4
*GastroP↑,
*BBB↑, H2 is its ability to easily cross the blood-brain barrier and penetrate biomembranes, diffusing throughout the different tissues and organs.
*eff↑, The above-cited properties led some researchers to refer to it as a "miracle" molecule
*toxicity↓, Regarding the biosafety of hydrogen, numerous reports, including those from the US government and the EU, have indicated that hydrogen is safe for biological systems, showing no acute or chronic toxicity under normal pressure
*Dose↝, human large intestine often produces approximately 70–140 mL of hydrogen daily through the action of coliform bacteria such as Escherichia coli under typical environmental conditions.
*hepatoP↑, including cardioprotective properties, improved liver function, reduced oxidative stress, and prevention of Parkinson's disease
*ROS↓,
*SOD↑, 1.5–2.0 L/day drinking HRW orally 0.55–0.65 mM 1.65–2.6 mg H2/day 8 weeks SOD: ↑ TRABS: ↓ HDL: ↑
*TBARS↓,
*HDL↑,
*LDL↓, figure 4
*Obesity↓, figure 5 obesity
*GSH↑, HRW treatment partially alleviated colitis symptoms, improved histopathological changes, significantly increased glutathione (GSH) concentration, and reduced the level of TNF-α.
*TNF-α↓,
*GutMicro↑, HRW was found to exhibit partial relief of inflammation, oxidative stress, and dysbiosis in the intestinal flora of mice with chronic ulcerative colitis (UC) induced by dextran sulfate sodium (DSS)
*DNAdam↓, HRW-treated mice exhibited decreased levels of markers associated with oxidative DNA damage, such as phosphorylated histone H2AX and 8-hydroxy-2′-deoxyguanosine, as well as markers indicative of aging
*γH2AX↓,
*p‑p38↓, Treatment with HRS also inhibited the activation of p-p38 and NF-κB while suppressing the production of several pro-inflammatory mediators,
*NF-kB↓,
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*antiOx↑, antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level
*NRF2↑, activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes.
*HO-1↑,
*Inflam↓, hydrogen may prevent inflammation
*neuroP↑, prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer.
*cardioP↑,
*other↓, It also prevented ischemia-reperfusion (I/R) injury and stroke in a rat model
*ROS↓, H2 has been shown to exert its beneficial effects in various pathological conditions that involve free radicals and oxidative stress
*NADPH↓, figure 2, H2 Inhibits NADPH Oxidase Activity
*Catalase↑,
*GPx1↑,
*NO↓, H2 Indirectly Reduces Nitric Oxide (NO) Production
*mt-ROS↓, H2 Decreases Mitochondrial ROS
*SIRT3↑, In the kidneys, H2 suppressed the downregulated Sirt3 expression, which is the most abundant member of the sirtuin family, by reducing oxidative stress reactions
*SIRT1↑, In the liver, H2 elevated HO-1 to induce Sirt1 expression
*TLR4↓, H2 inhibits TLR4, which involves hyperglycemia in type 2 diabetes mellitus
*mTOR↓, For example, H2 inhibits mTOR, activates autophagy, and alleviates cognitive impairment resulting from sepsis
*cognitive↑,
*Sepsis↓,
*PTEN↓, It inhibits the activation of the PTEN/AKT/mTOR pathway and alleviates peritoneal fibrosis
*Akt↓,
*NLRP3↓, It also facilitates autophagy-mediated NLRP3 inflammasome inactivation and alleviates mitochondrial dysfunction and organ damage
*AntiAg↑, antiageing mechanism of H2 and the influence on ageing hallmarks are summarized in Figure 3.
*IL6↓, significantly suppressed inflammatory cytokines (IL-6, TNF-α, and IL-1β), MDA, and 8-OHdG, and improved memory dysfunction
*TNF-α↓,
*IL1β↓,
*MDA↓,
*memory↑,
*FOXO3↑, HRW can also upregulate Sirt1-Forkhead box protein O3a (FOXO3a
TumCG↓, H2 inhibits lung cancer progression
*LDL↓, Decreases oxidized LDL; improves HDL function
chemoPv↑, In this review, we discuss the chemopreventive properties and possible mechanisms of various H. sabdariffa extracts.
*ROS↓, PCA and HAs protected against oxidative damage induced by tert-butyl droperoxide (t-BHP) in rat primary hepatocytes
*other↝, HSE could be pursued as atherosclerosis chemopreventive agents as they inhibit LDL oxidation, foam cell formation, as well as smooth muscle cell migration and proliferation.
*hepatoP↑, extracts also offer hepatoprotection by influencing the levels of lipid peroxidation products and liver marker enzymes in experimental hyperammonemia.
*lipid-P↓,
Apoptosis↑, HAs and HPE were demonstrated to cause cancer cell apoptosis, especially in leukemia and gastric cancer.
*LDL↓, The anti-cholesterol action of 0.5% or 1% H. sabdariffa aqueous extracts (HSE) was confirmed in rabbits
RAS↓, PCA down-regulated the oncogenic Ras/Akt/NF-kB tumor progression pathway by targeting activation of the tumor suppressor RhoB, which in turn led to a reduction of matrix metalloproteinase
Akt↓,
NF-kB↓,
Rho↝,
MMPs↓,
*AntiDiabetic↑, H. SABDARIFFA EXTRACTS AND ANTIDIABETES
*Catalase↑, HSE or HPE significantly increased the activity of catalase and glutathione and reduced lipid peroxidation
*GSH↑,
*Bacteria↓, Extracts showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others.
*hepatoP↑,
*diuretic↑,
*LDL↓,
*antiOx↑, This might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, inhibition of angiotensin-converting enzymes (ACE), and direct vaso-relaxant effect or calcium channel modulation.
*ACE/ACE1↓,
*Ca+2↝,
*toxicity↓, Hs has an excellent safety and tolerability record.
*ROS↓, The antioxidant activity of the extract is due to its strong scavenging effect on reactive oxygen and free radicals
*RenoP↑, Two studies were reported on the nephroprotective activity of Hs extracts on diabetic nephropathy in streptozotocin-induced type 1 diabetic rats
AntiCan↑, Hibiscus sabdariffa (HS) plant, including anthocyanin, flavonoids, saponins, tannins, polyphenols, organic acids, caffeic acids, citric acids, protocatechuic acid, and others, extracts of this plant have been reported to have anti-cancer effects.
TumCP↓, These compounds have been shown to reduce cancer cell proliferation, induce apoptosis, and cause cell cycle arrest.
Apoptosis↑,
TumCCA↑,
P53↑, They also increase the expression levels of the cell cycle inhibitors (p53, p21, and p27) and the pro-apoptotic proteins (BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9).
P21↑,
p27/CDKN1B↑,
BAD↑,
BAX↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
*AntiBio↑, Anti-microbial effect
*Inflam↓, Anti-inflammatory effect
*antiOx↑, In calyces of HS, compounds such as anthocyanins have antioxidant properties
*BP↓, The tea made from the HS leaves effectively lowers the blood pressure level in patients because of the presence of phytochemicals that induce systemic vasodilation along
*AntiDiabetic↑, calyces extract of HS can reduce the blood sugar level in diabetic patients
HDAC1↓, HS extract mediated inhibitory responses which were attributed to their inhibition of histone deacetylases (HDACs), specifically HDAC1 and HDAC3.
HDAC3↓,
tumCV↓, PCA dependently decreased cell viability, increased lactate dehydrogenase (LDH) leakage, enhanced DNA fragmentation, reduced mitochondrial membrane potential
LDL↓,
DNAdam↑,
MMP↓,
*Catalase↑, Ethanolic extract of the HS substantially increases the levels of the antioxidants CAT, SOD, GPx and reduced glutathione (GSH) in brain tissue, thus possessing significant antioxidant activity.
*SOD↑,
*GPx↑,
*GSH↑,
*antiOx↑,
*ROS↓, Anthocyanin in the extract of HS acts on the anti-oxidant system, and scavenges free radicals thus reducing damage to genomes of regular cells and the mutations, thus stopping tumor formation
TumCMig↓, PCA found in extract of HS inhibited cell migration and invasion to non-cytotoxic cells via down-regulation of the Ras/Akt/NF-κβ pathway and MMP-2 production [92].
TumCI↓,
selectivity↑,
RAS↓,
Akt↓,
NF-kB↓,
MMP2↓,
PI3K↓, decreasing PI3K, P-Akt protein, MMP expression, anti-apoptotic Bcl-2, Bcl-xL proteins, and PCNA, cyclin A, D1, B1, and E.
Bcl-2↓,
Bcl-xL↓,
PCNA↓,
cycA1/CCNA1↓,
cycD1/CCND1↓,
cycE/CCNE↓,
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*IRes↓, number of synthetic and natural insulin sensitizers, including inositol, have been recognized to exert both anti-diabetic as well as anti-cancer properties.
*AntiDiabetic↑,
*glucose↝, beneficial effect of inositol in fostering glucose homeostasis as well as in antagonizing cancer growth.
AntiCan↑,
PI3K↓, NOSITOL INHIBITS THE PI3K/AKT PATHWAY IN CANCER CELLS
Akt↓,
Glycolysis↓, On the contrary, in cancer cells, IPGs and myo-Ins inhibits Akt reducing both glycolysis and glucose entry in the cell, while re-establishing the oxidative degradation of carbohydrates along the TCA.
STK11/LKB1↑, As inositol enhances specifically the LKB1 activity, it is worth noting that the AMPK-related anticancer activities are tightly dependent of that pathway
*FASN↓, Inositol inhibits fatty acids biosynthesis and reduces plasma LDL-cholesterol and non-esterified fatty acids (NEFA) levels [74-76].
*LDL↓,
*FFA/NEFA↓,
*ROS↓, Myo-Ins counteracts oxidative damage in fish exposed to environmental oxidative stress
ROS↑, anti-oxidant effects seem to be contextdependent, given that in cancer cells inositol actually increases free radical production
IGF-1↓, Furthermore, myoIns may likely inhibit IGF-1 release downstream of the induced inhibition
Showing Research Papers: 1 to 50 of 75
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 75
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
CD47↓, 1, miR-124-3p↓, 1, PFS↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
GSH↓, 1, HO-1↓, 1, lipid-P↓, 1, lipid-P↑, 1, NRF2↓, 2, NRF2↑, 1, OXPHOS↑, 1, RNS↓, 1, ROS↑, 6,
Mitochondria & Bioenergetics(tgid=3) ⓘ
Insulin↓, 1, MMP↓, 2, MMP↑, 2, mtDam↑, 1, PGC-1α↑, 1, XIAP↓, 2,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ACLY↓, 3, ALAT↓, 1, AMPK↑, 2, glucose↓, 1, GLUT2↓, 1, Glycolysis↓, 1, HK2↓, 1, HMG-CoA↓, 2, lactateProd↓, 1, LDH↓, 1, LDL↓, 8, PDK1↓, 1, PPARα↓, 1, SCD1↓, 1, SIRT1↓, 1, STK11/LKB1↑, 1, Warburg↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 6, p‑Akt↓, 1, Apoptosis↑, 9, BAD↑, 2, Bak↑, 1, BAX↑, 2, Bcl-2↓, 2, Bcl-xL↓, 2, BIM↑, 1, Casp↑, 1, Casp3↑, 5, Casp7↑, 2, Casp8↓, 1, Casp8↑, 3, Casp9↑, 2, Cyt‑c↑, 1, Fas↑, 2, hTERT/TERT↓, 1, IAP2/BIRC3↓, 1, iNOS↓, 1, Mcl-1↓, 1, Myc↓, 1, p27/CDKN1B↑, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
miR-25-5p↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
EZH2↓, 1, tumCV↓, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↑, 1, p‑eIF2α↑, 1, ER Stress↑, 3, GRP78/BiP↑, 2, UPR↑, 2, XBP-1↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
ATG5↑, 1, Beclin-1↑, 1, LC3B↑, 1, LC3II↑, 1, TumAuto↓, 1, TumAuto↑, 3,
DNA Damage & Repair(tgid=10) ⓘ
DNAdam↑, 4, P53↑, 1, PARP↑, 3, cl‑PARP↑, 1, PCNA↓, 1, TP53↓, 1,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK4↓, 1, cycA1/CCNA1↓, 1, cycD1/CCND1↓, 2, cycE/CCNE↓, 1, P21↑, 2, TumCCA↑, 3,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
EMT↓, 2, ERK↓, 1, HDAC↓, 2, HDAC1↓, 1, HDAC3↓, 1, HMGCR↓, 2, IGF-1↓, 3, IGF-1R↑, 1, mTOR↓, 2, mTORC1↓, 1, NOTCH1↑, 1, NOTCH3↓, 1, PI3K↓, 3, PTEN↑, 1, RAS↓, 3, STAT↓, 1, STAT3↓, 2, TOP1↓, 1, TumCG↓, 3, Wnt↑, 1,
Migration(tgid=13) ⓘ
Ca+2↑, 1, CLDN1↓, 1, E-cadherin↑, 1, Fibronectin↓, 1, MALAT1↓, 1, MMP-10↓, 1, MMP2↓, 2, MMP9↓, 1, MMPs↓, 1, Rho↝, 1, Slug↓, 1, Smad1↓, 1, Snail↓, 1, TET1↑, 1, TGF-β↓, 1, TumCI↓, 5, TumCMig↓, 4, TumCP↓, 5, TumMeta↓, 1, Twist↓, 1, Vim↓, 1, Zeb1↑, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 4, ATF4↑, 1, EGFR↓, 2, Hif1a↓, 3, VEGF↓, 4,
Barriers & Transport(tgid=15) ⓘ
GLUT1↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX2/PTGS2↓, 1, COX2/PTGS2↑, 1, IL10↓, 1, IL1β↓, 1, IL6↓, 1, Imm↑, 2, Inflam↓, 1, JAK1↓, 1, NF-kB↓, 2, NK cell↑, 2, PD-L1↑, 1, PGE2↓, 1, PSA↓, 1, TLR4↓, 1, TNF-α↓, 1,
Cellular Microenvironment(tgid=17) ⓘ
cGAS–STING↑, 1,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
CDK6↑, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 2, BioAv↑, 1, ChemoSen↑, 6, Dose↑, 1, Dose↝, 6, eff↑, 11, Half-Life↝, 1, RadioS↑, 2, selectivity↑, 3,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 1, ALP↓, 1, BP↓, 1, EGFR↓, 2, EZH2↓, 1, hTERT/TERT↓, 1, IL6↓, 1, LDH↓, 1, Myc↓, 1, PD-L1↑, 1, PSA↓, 1, TP53↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 4, AntiTum↑, 1, cardioP↑, 3, chemoP↑, 2, chemoPv↑, 1, ChemoSideEff↓, 1, cognitive↑, 1, memory↑, 1, neuroP↑, 1, NP/CIPN↓, 1, OS↑, 1, QoL↑, 3, radioP↑, 1, Remission↑, 1, RenoP↑, 1, Risk↓, 3, Risk↑, 1, toxicity↓, 3, TumVol↓, 1,
Infection & Microbiome(tgid=24) ⓘ
Bacteria↓, 1, CD8+↑, 2,
Total Targets: 192
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
ACE/ACE1↓, 1, AntiBio↑, 4, compII↑, 1, diuretic↑, 1, FFA/NEFA↓, 1, IRes↓, 1, Stress↓, 1, Stroke↓, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↓, 2, antiOx↑, 22, Bil↓, 1, Catalase↑, 7, GPx↑, 6, GPx1↑, 1, GSH↓, 1, GSH↑, 10, HDL↓, 1, HDL↑, 12, HDL∅, 1, HO-1↑, 4, HO-2↓, 1, lipid-P↓, 8, MDA↓, 5, MPO↓, 4, NQO1↑, 1, NRF2↑, 5, RNS↓, 1, ROS↓, 22, mt-ROS↓, 1, SIRT3↑, 1, SOD↑, 10, TBARS↓, 3, VitC↑, 1,
Metal & Cofactor Biology(tgid=2) ⓘ
Ferritin↑, 1, IronCh↑, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↑, 1, compIII↑, 1, MMP↑, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
ACLY↓, 1, adiP↓, 1, ALAT↓, 3, AMPK↑, 1, FASN↓, 1, glucose↓, 3, glucose↝, 1, HMG-CoA↓, 1, LDL↓, 42, NADPH↓, 2, PPARα↑, 1, SIRT1↑, 2,
Cell Death(tgid=5) ⓘ
Akt↓, 1, Akt↑, 2, BAX↓, 2, Bcl-2↑, 1, Casp12↓, 1, Cyt‑c↓, 1, GranB/GZMB↓, 1, iNOS↓, 1, p‑JNK↓, 1, p38↓, 1, p‑p38↓, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
AMPKα↑, 1, TRPV3↑, 1,
Transcription & Epigenetics(tgid=7) ⓘ
Ach↑, 1, other↓, 2, other↑, 5, other↝, 4, other∅, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↓, 1, p‑eIF2α↓, 1, ER Stress↓, 1, GRP78/BiP↓, 1, XBP-1↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
LC3‑Ⅱ/LC3‑Ⅰ↑, 1,
DNA Damage & Repair(tgid=10) ⓘ
DNAdam↓, 1, γH2AX↓, 1,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
FOXO3↑, 1, GSK‐3β↓, 1, IGF-1↑, 1, IGFBP1↑, 1, mTOR↓, 4, PI3K↑, 2, PTEN↓, 1,
Migration(tgid=13) ⓘ
AntiAg↑, 6, AntiAg∅, 1, APP↓, 1, Ca+2?, 1, Ca+2↝, 1, CDK5↓, 1, MUC1↑, 1, TGF-β↑, 1, TXNIP↓, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
ATF4↓, 1, NO↓, 4, TXA2↓, 1,
Barriers & Transport(tgid=15) ⓘ
BBB↑, 4, GastroP↑, 3, IBI↑, 2, OCLN↑, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
CD4+↑, 2, COX1↓, 1, COX2/PTGS2↓, 4, CRP↓, 5, ICAM-1↓, 1, IFN-γ↓, 2, IL10↑, 2, IL17↓, 2, IL1β↓, 6, IL23↓, 1, IL4↓, 1, IL6↓, 7, Imm↑, 3, Inflam↓, 22, LPS↓, 1, MCP1/CCL2↓, 1, NF-kB↓, 4, TLR4↓, 2, TNF-α↓, 10,
Synaptic & Neurotransmission(tgid=18) ⓘ
5HT↑, 1, AChE↓, 6, AChE∅, 1, BChE↓, 2, BDNF↑, 3, ChAT↑, 1, MAOA↓, 1, tau↓, 3, p‑tau↓, 2,
Protein Aggregation(tgid=19) ⓘ
Aβ↓, 9, BACE/β-secretase↓, 3, MAOB↓, 1, NLRP3↓, 4,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 1, BioAv↑, 3, BioAv↝, 3, Dose↝, 14, eff↓, 4, eff↑, 8, eff↝, 1, Half-Life↑, 1,
Clinical Biomarkers(tgid=22) ⓘ
ALAT↓, 3, AST↓, 4, Bil↓, 1, BloodF↑, 1, BP↓, 7, creat↓, 1, CRP↓, 5, Ferritin↑, 1, GutMicro↑, 9, IL6↓, 7, TG/TAG↓, 4, Urea↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiAge↑, 4, AntiCan↑, 1, AntiDiabetic↑, 10, antiPs↑, 1, BOLD↑, 1, cardioP↑, 16, cognitive↑, 11, hepatoP↑, 10, memory↑, 10, motorD↑, 1, MusCon↓, 1, neuroP↑, 15, Obesity↓, 4, OS↑, 3, QoL↑, 2, RenoP↑, 4, Risk↓, 3, toxicity↓, 6, toxicity↑, 1, toxicity↝, 1, Weight↓, 1, Weight↝, 1, Weight∅, 1, Wound Healing↑, 2,
Infection & Microbiome(tgid=24) ⓘ
AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 2, Sepsis↓, 2,
Total Targets: 179
Scientific Paper Hit Count for: LDL, LDL-cholesterol
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
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:% Target#:71 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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