ER Stress Cancer Research Results

ER Stress, endoplasmic reticulum (ER) stress signaling pathway: Click to Expand ⟱
Source:
Type:
Protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress.
The endoplasmic reticulum (ER) stress signaling pathway plays a crucial role in maintaining cellular homeostasis and responding to various stressors, including those encountered in cancer. When cells experience stress, such as the accumulation of misfolded proteins, they activate a series of signaling pathways collectively known as the unfolded protein response (UPR). The UPR aims to restore normal function by enhancing the protein-folding capacity of the ER, degrading misfolded proteins, and, if the stress is unresolved, triggering apoptosis.
The activation of ER stress pathways can contribute to resistance against chemotherapy and targeted therapies. Cancer cells may utilize the UPR to survive treatment-induced stress, making it challenging to achieve effective therapeutic outcomes.

-ER stress-associated proteins include: phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12
Scientific Papers found: Click to Expand⟱
2657- AL,    Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases
- Review, CardioV, NA - Review, AD, NA
*Inflam↓, allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others).
*antiOx↑, improving the antioxidant system
*neuroP↑,
*cardioP↑,
*AntiTum↑,
*mtDam↑, Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes.
*HSP70/HSPA5↑, llicin improves mitochondrial function by enhancing the expression of HSP70 and decreasing RAAS activation
*NRF2↑,
*RAAS↓,
*cognitive↑, Allicin enhances the cognitive function of APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice by decreasing the expression levels of Aβ, oxidative stress, and improving mitochondrial function.
*SOD↑, positive effects on cognition in an AD mouse model by administrating a preventive dose of allicin. These effects might be mediated by an increase of SOD and reduction of ROS
*ROS↓,
*NRF2↑, Chronic treatment with allicin increased the expression of NRF2 and targeted downstream of NRF2, such as NADPH, quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (γ-GCS), in the hippocampus of aged mice
*ER Stress↓, protective effects of 16 weeks of allicin treatment in a rat model of endoplasmic reticulum stress-related cognitive deficits.
*neuroP↑, allicin was able to ameliorate depressive-like behaviors by decreasing neuroinflammation, oxidative stress iron aberrant accumulation,
*memory↑, allicin improved lead acetate-caused learning and memory deficits and decreased the ROS level
*TBARS↓, Oral administration of allicin was able to reduce thiobarbituric reactive substances (TBARS) and myeloperoxidase (MPO) levels, and concurrently increased (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in a rat model of
*MPO↓,
*SOD↑,
*GSH↑,
*iNOS↓, decreasing the expression of iNOS and increased the phosphorylation of endothelial NOS (eNOS)
*p‑eNOS↑,
*HO-1↑, OSCs upregulate the endogenous antioxidant NRF2 and heme oxygenase-1 (HO-1)

2637- Api,    Apigenin Alleviates Endoplasmic Reticulum Stress-Mediated Apoptosis in INS-1 β-Cells
- in-vitro, Diabetic, NA
*other↝, In the present study, the anti-diabetic effect of apigenin on pancreatic β-cell insulin secretion, apoptosis, and the mechanism underlying its anti-diabetic effects, were investigated in the INS-ID β-cell line
*Insulin↑, The results showed that apigenin concentration-dependently facilitated 11.1-mM glucose-induced insulin secretion, which peaked at 30 µM
ER Stress↓, Apigenin also concentration-dependently inhibited the expression of endoplasmic reticulum (ER) stress signaling proteins
*CHOP↓, CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) and cleaved caspase-3
*cl‑Casp3↓,
*ROS↓, In contrast, the cytoprotective effect of apigenin against oxidative stress, inflammation, apoptosis, and oxidative and ER stresses has been demonstrated in various cell types
*Inflam↓,
*TXNIP↓, expression of TXNIP, which was increased by the thapsigargin treatment, was downregulated in INS-1D cells in response to apigenin.

3391- ART/DHA,    Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug
- Review, Var, NA
TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

2675- BBR,    The therapeutic effects of berberine against different diseases: A review on the involvement of the endoplasmic reticulum stress
- Review, Var, NA
*Inflam↓, including anti-inflammatory, antioxidative, anti-apoptotic, antiproliferative, and antihypertensive.
*antiOx↑,
*ER Stress↓, BBR can decrease apoptosis and inflammation following different pathological conditions, which might be mediated by targeting ER stress pathways.
*cardioP↑, protective potential of BBR against several diseases, such as metabolic disorders, cancer, intestinal diseases, cardiovascular, liver, kidney, and central nervous system diseases, in both in vivo and in vitro studies.
*RenoP↑,
*hepatoP↑,

2676- BBR,    Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress
- in-vivo, Nor, NA - in-vivo, CardioV, NA
*cardioP↑, Pretreatment with BBR significantly reduced MI/R-induced myocardial infarct size, improved cardiac function, and suppressed myocardial apoptosis and oxidative damage.
*ROS↓,
*ER Stress↓, pretreatment with BBR suppressed MI/R-induced ER stress
*p‑PERK↓, evidenced by down-regulating the phosphorylation levels of myocardial PERK and eIF2α and the expression of ATF4 and CHOP in heart tissues.
*p‑eIF2α↓,
*ATF4↓,
CHOP↓,
*JAK2↑, Pretreatment with BBR also activated the JAK2/STAT3 signaling pathway in heart tissues
*STAT3↑,
*UPR↓, Therefore, reducing excessive UPR, also referred to as ER stress, is of great importance in ameliorating MI/R injury.

2677- BBR,    Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring
- in-vivo, Diabetic, NA
*hepatoP↑, berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM)
*LC3II↑, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats.
*Beclin-1↑,
*AMPK↑,
*mTOR↑,
*ER Stress↓, It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation.
*CHOP↓,
*JNK↓,
*ROS↓,
*Inflam↓,
*BG↓, Oral supplementation of diabetic rats either by Lip-BBR or Vild, 10 mg/kg of each, significantly (p < 0.001) lowered the blood glucose levels of tested diabetic rats compared to the diabetic group.
*SOD↑, when the diabetic rats received Lip-BBR, the decrements were less pronounced compared to the diabetic group by 1.16 fold, 2.52 fold, and 67.57% for SOD, GPX, and CAT, respectively.
*GPx↑,
*Catalase↑,
*IL10↑, Treatment of the diabetic rats with Lip-BBR significantly (p < 0.001) elevated serum IL-10 levels by 37.01% compared with diabetic rats.
*IL6↓, Oral supplementation of Lip-BBR could markedly (p < 0.0001) reduce the elevated serum levels of IL-6 and TNF-α when it is used as a single treatment by 55.83% and 49.54%,
*TNF-α↓,
*ALAT↓, ALT, AST, and ALP in the diabetic group were significantly higher (p < 0.0001) by 88.95%, 81.64%, and 1.8 fold, respectively, compared with those in the control group, but this was reversed by the treatment with Lip-BBR
*AST↓,
*ALP↓,

2679- BBR,    Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer’s Disease via Regulation of β-Amyloid Production and Endoplasmic Reticulum Stress
- in-vivo, AD, NA
*cognitive↑, berberine could improve cognitive deficits in the triple-transgenic mouse model of Alzheimer’s disease (3 × Tg AD) mice.
PERK↓, berberine treatment may inhibit PERK/eIF2α signaling-mediated BACE1 translation, thus reducing Aβ production and resultant neuronal apoptosis
*eIF2α↓,
*neuroP↑, berberine may have neuroprotective effects, via attenuation of ER stress and oxidative stress.
*ER Stress↓,
*ROS↓,

2683- BBR,    Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells
- in-vitro, Liver, HepG2
JNK↓, while the activation of JNK was blocked
p‑PERK↓, phosphorylation both on PERK and eIF2α were inhibited in cells pretreated with berberine.
p‑eIF2α↓,
*ER Stress↓, antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress

3681- BBR,    The efficacy and mechanism of berberine in improving aging-related cognitive dysfunction: A study based on network pharmacology
- in-vivo, AD, NA
*memory↑, treatment with berberine significantly improved spatial learning and memory in mice with cognitive decline induced by D-gal
*cognitive↑,
MAPK↑, core targets of berberine for improving cognitive function, include Mapk1, Src, Ctnnb1, Akt1, Pik3ca, Tp53, Jun, and Hsp90aa1.
*Akt↑,
*PI3K↑, PI3K-Akt signaling pathway and MAPK signaling pathway were significantly enriched.
*TP53↑, Tp53 and Jun expression showed a decreasing trend and were significantly lower in the BBR-H group
*Jun↓,
*HSP90↑, src, Ctnnb1, Akt1, Pik3ca, and Hsp90aa1 exhibited an increasing tendency in both the BBR-L and BBR-H groups
*neuroP↑, Akt1, Ctnnb1, Tp53, and Jun were involved in the neuroprotective actions of berberine.
*Inflam↓, pharmacological effects of BBR, including anti-inflammatory
*antiOx↑, BBR has antioxidant properties as well as protective effects against neurodegenerative diseases
*p16↓, BBR reduces the expression of P16 in brain tissue of cognitive dysfunctions mice
*ER Stress↓, inhibition of endoplasmic reticulum stress

3695- BM,    Bacopa monnieri (L.) wettst. Extract protects against glutamate toxicity and increases the longevity of Caenorhabditis elegans
- in-vitro, AD, HT22
*OS↑, B.monnieri could increase the median and maximal lifespan of wild type C.elegans, maintain a younger appearing phenotype in the aged C.elegans.
*mt-ROS↓, B.monnieri prevents mitochondrial, and oxidative stress in the cultured cells.
*ROS↓,
*neuroP↑, B.monnieri the potential for therapeutic and preventative use in neurodegenerative disease
*ER Stress↓, B.monnieri prevents ER stress, changing the expression s of ER Stress proteins CHOP and ERP57.

5952- Cela,    Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
- in-vivo, AD, NA
*memory↑, pre-treatment with celastrol could prevent learning and memory decline in AD mice by reducing inflammation and oxidative stress.
*Inflam↓,
*ROS↓,
*ER Stress↓, celastrol suppressed AD progression by targeting ER stress
*neuroP↑, celastrol treatment could be beneficial in addressing learning and memory deficits in AD, paving the way for potential neuroprotective treatments.
*Dose↝, administered celastrol intraperitoneally before the Aβ25-35 injection, while others received it after the injection. (1, 3, 6 mg/kg/day) for 2 days
*MDA↓, AD mouse group treated with celastrol showed lower levels of protein carbonyl and MDA and higher activity of CAT and SOD compared to the AD group
*SOD↑,
*Catalase↑,
*Aβ↓, Research has shown that celastrol can reduce cell death and Aβ production in cell experiments
BACE↓, celastrol treatment significantly restored the expression of BACE1, LRP1, NEP, and RAGE in the brain
LRP1↑, Activation of LRP1 by celastrol may lead to the attenuation of AD symptoms.
RAGE↓,

3890- Cin,    The Therapeutic Roles of Cinnamaldehyde against Cardiovascular Diseases
- Review, NA, NA
*cardioP↑, CA-related cardiovascular protective mechanisms could be attributed to the inhibition of inflammation and oxidative stress, improvement of lipid and glucose metabolism
*Inflam↓,
*ROS↓,
*lipid-P↓,
*AntiAg↑, suppression of cardiac fibrosis, and platelet aggregation and promotion of vasodilation and angiogenesis.
*angioG↑,
*GutMicro↑, CA is likely to inhibit CVD progression via affecting other possible processes including autophagy and ER stress regulation, gut microbiota and immune homeostasis, ion metabolism, ncRNA expression, and TRPA1 activation.
*ER Stress↓,

3997- CoQ10,    Coenzyme Q and Its Role in the Dietary Therapy against Aging
- Review, AD, NA
*AntiAge↑, anti-aging potential of CoQ and its possible use in dietary therapies to alleviate the effects of aging.
*Inflam↓, CoQ Exerts Anti-Inflammatory Effects through Its Antioxidant Activity
*antiOx↑,
*Apoptosis↓, protective role of CoQ10 against apoptosis by inducing the inhibition of cell death independently from its free radical scavenging properties or antioxidant effects
*BioAv↑, It has been reported that intestinal absorption is threefold faster if CoQ10 is administrated with food intake in rats
*other↝, Actually, it has been reported that NQO1 expression increases during the initial steps of Alzheimer’s disease, indicating a higher lipid peroxidation coupled to a higher necessity for CoQ-dependent antioxidant activity
*cognitive↑, In older mice with clear cognitive and psychomotor impairments, short-time (15 days) CoQ-supplementation improved spatial learning
*DNAdam↓, dietary CoQ has also been shown to improve DNA repair systems [213,214] and modulate inflammatory signaling cascade as well as to reduce endoplasmic reticulum stress [214].
*ER Stress↓,

3627- Cro,    The effects of Crocus sativus (saffron) and its constituents on nervous system: A review
- Review, AD, NA - Review, Stroke, NA
*other↑, anti-Alzheimer properties of saffron extract were shown in human and animal studies.
*monoA↑, increased glutamate and dopamine levels in the brain in a dose-dependent manner.
*Aβ↓, C. sativus stigmas has good antioxidant properties -higher than those of carrot and tomato- in a concentration and time-dependent manner which was accompanied by inhibition of Aβ fibrillogenesis.
*AChE↓, saffron extract had a moderate (up to 30 %) inhibitory activity on acetyl-cholinesterase (AChE)
*cognitive↑, results showed that the cognitive functions in saffron-treated group were significantly better than placebo
*neuroP↑, Neuroprotective effects of seven-day administration of crocetin
*lipid-P↓, crocin 10 μM inhibited the formation of peroxidized lipids in cultured PC12 cells, moderately restored superoxide dismutase (SOD) activity
*SOD↑,
*ROS↓, protective effects on different markers of oxidative damage in hippocampal tissue from ischemic rats
*GPx↑, crocin increased the activity of SOD and glutathione peroxidase (GPx) and remarkably reduced malondialdehyde (MDA) content in the ischemic cortex in rat model of ischemic stroke
*MDA↓,
*memory↑, Saffron extract and crocin can improve learning and memory
*antiOx↑, crocetin increases the antioxidant potential in brain and helps to fight against 6-OHDA-induced neurotoxicity
*Inflam↓, prevented diazinon (20 mg/kg)-induced increase of inflammation
*other↓, Administration of crocin (60 mg/kg), one hour before, or one hour after the induction of ischemia, reduced brain edema
*ER Stress↓, Administration of crocin on day 7 post-EAE induction, suppressed ER stress and inflammatory gene expression in the spinal cord

3832- Cro,    Traditional Chinese Medicine: Role in Reducing β-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, TCM known for its medicinal properties in neuropsychiatric disorders, such as depression, seizure, anxiety, and neurodegenerative disease.
*memory↑, Crocin can improve memory impairment and learning ability by reducing neuron apoptosis and Bax levels as well as increasing the expression of Bcl-2
*Apoptosis↓,
*cognitive↑, crocin alleviates malathion-induced neurological alterations and cognitive impairment by exerting its anti-apoptotic effects
*ER Stress↓, Regulate endoplasmic reticulum ,40 mg/kg

3206- EGCG,    Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration
- Review, AMD, NA
*Ca+2↓, EGCG restores [Ca2+]i homeostasis by decreasing ROS production through inhibition of prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis.
*ROS↓,
*Apoptosis↓,
*GRP78/BiP↓, EGCG downregulated GRP78, CHOP, PERK, ERO1α, IRE1α, cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of calnexinin MRPE cells
*CHOP↓,
*PERK↓,
*IRE1↓,
*p‑PARP↓,
*Casp3↓,
*Casp12↓,
*ER Stress↓,
*UPR↓, EGCG mitigates ER stress; maintain calcium homeostasis and inhibition of UPR to control the progression of AMD.

1323- EMD,    Anticancer action of naturally occurring emodin for the controlling of cervical cancer
- Review, Cerv, NA
TumCCA↑, cell cycle arrest in the G2/M phase
DNAdam↑,
mTOR↓,
Casp3↑,
Casp8↑,
Casp9↑,
TGF-β↑,
SMAD3↓,
p‑SMAD4↓,
ROS↑,
MMP↓,
CXCR4↓,
HER2/EBBR2↓,
ER Stress↓,
TumAuto↑, can increase the level of autophagy in A549 lung cancer cells, but did not affect autophagy in healthy non-cancerous Ha CaT cells
NOTCH1↓,

3716- FA,    Ferulic Acid as a Protective Antioxidant of Human Intestinal Epithelial Cells
- in-vitro, IBD, NA - in-vivo, NA, NA
*antiOx↑, Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties
*Inflam↓,
*ER Stress↓, FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells,
*other↑, FA has a protective effect on intestinal tight junctions
*angioG↑, A has been reported to induce hypoxia and enhance the angiogenesis of human umbilical vein endothelial cells (HUVEC) by increasing the expressions of HIF-1α and vascular endothelial growth factor (VEGF)
*Hif1a↑,
*VEGF↑,
*NO↓, suggesting FA attenuates NO production induced by inflammation.
*SIRT1↑, Another study suggested that FA activated SIRT1 to protect the heart from the adverse effects of ER stress via reduction of PERK/eIF2α/ATF4/CHOP pathway
*PERK↓,
*ATF4↓,
*CHOP↓,
*GutMicro↑, FA can mitigate intestinal inflammation, promote the growth of Bacteroides, and induce the production of SCFAs by modulating the gut microbiota in mouse and diabetic syndrome rat model

2514- H2,    Hydrogen: A Novel Option in Human Disease Treatment
- Review, NA, NA
*Inflam↓, Anti-Inflammatory Effect of H2
*IL1β↓, decrease the overexpression of early proinflammatory cytokines, such as interleukin- (IL-) 1β, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α
*IL6↓,
*IL8↓,
*IL10↓,
*TNF-α↓,
*ROS↓, . H2 can also downregulate ROS directly or as a regulator of a gas-mediated signal.
*HO-1↓, H2 can enhance the expression of the heme oxygenase-1 (HO-1) antioxidant by activating nuclear factor erythroid 2-related factor 2 (Nrf-2), an upstream regulating molecule of HO-1
*NRF2↑,
*ER Stress↓, hydrogen inhalation significantly reduced the ER stress-related protein and alleviated tissue damage in myocardial I/R injury a
H2O2↑, H2-induced ROS production can also be observed in cancer cells.

2507- H2,    Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis
- in-vivo, NA, NA
*RenoP↑, We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats.
*ROS↓,
*Apoptosis↓,
*ER Stress↓, endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated
*CHOP↓,
*Casp12↓,
*GRP78/BiP↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑, higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated.
*Beclin-1↑,
*p62↓,
*mTOR↓, Inhibition of mTOR may be involved in the upregulation of autophagy by H2

3769- H2S,    Research progress of hydrogen sulfide in Alzheimer's disease from laboratory to hospital: a narrative review
- Review, AD, NA
*APP↓, prevent the progress of the disease by affecting the amyloid precursor protein metabolism, anti-apoptosis, anti-inflammatory, and antioxidant pathways.
*Apoptosis↓,
*Inflam↓,
*antiOx↑,
*BP↓, H2S activates adenosine triphosphate-sensitive potassium channels, which in turn dilates blood vessels and lowers blood pressure, while improving myocardial ischemia-reperfusion injury
*NLRP3↓, activation of NLRP3 inflammatory bodies was inhibited
*ROS↓, catalase may be a key enzyme in the metabolism of H2S, which can convert H2S into sulfide, thereby achieving scavenging effect.
*Aβ↓, H2S can promote APP's non-amyloid metabolic pathway and reduce Aβ production.
*ER Stress↓, H2S may up-regulate brain-derived neurotrophic factor-TrkB pathway to suppress the stress of the endoplasmic reticulum,

2921- LT,    Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies
- Review, Nor, NA
*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
*AMPK↑, fig2
*SIRT1↑,
*ROS↓,
STAT3↓,
TNF-α↓,
NF-kB↓,
*IL2↓,
*IFN-γ↓,
*GSH↑,
*SREBP1↓,
*ZO-1↑,
*TLR4↓,
BAX↑, anti cancer
Bcl-2↓,
XIAP↓,
Fas↑,
Casp8↑,
Beclin-1↑,
*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
*Casp1↓,
*IL1β↓,
*IL18↓,
*NLRP3↓,
*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
*SOD↑,
*NRF2↑, luteolin promoted the activation of the Nrf2/ antioxidant response element (ARE) pathway and NF-κB cell apoptosis pathway, thereby reversing the decrease in Nrf2 levels(lead induced liver injury)
*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
*AST↓,
*iNOS↓,
*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
*HO-1↑,
*NQO1↑,
*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
*CHOP↓,
*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
*antiOx↑,
*GutMicro↑, luteolin could significantly enrich more than 10% of intestinal bacterial species, thereby increasing the abundance of ZO-1, down regulating intestinal permeability and plasma lipopolysaccharide

4231- Lut,    Luteolin and its antidepressant properties: From mechanism of action to potential therapeutic application
- Review, AD, NA
*PSD95↑, upregulating the expression of synaptophysin, postsynaptic density protein 95, brain-derived neurotrophic factor, B cell lymphoma protein-2, superoxide dismutase, and glutathione S-transferase; and decreasing the expression of malondialdehyde, caspa
*BDNF↑,
*SOD↑,
*GSTA1↑,
*MDA↑,
*Casp3↓,
*Mood↑, antidepressant effects of luteolin are mediated by various mechanisms, including anti-oxidative stress, anti-apoptosis, anti-inflammation, anti-endoplasmic reticulum stress, dopamine transport, synaptic protection, hypothalamic–pituitary–adrenal axi
*antiOx↑,
*Apoptosis↓,
*Inflam↓,
*ER Stress↓,

3261- Lyco,    Lycopene and Vascular Health
- Review, Stroke, NA
*Inflam↓, main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabolic profile, and reduce arterial stif
*antiOx↑, It is a much more potent antioxidant than alpha-tocopherol (10 × more potent) or beta-carotene (twice as potent)
*AntiAg↑, lycopene, protecting against myocardial infarction and stroke, is its antiplatelet activity
*cardioP↑, favorable effect in patients with subclinical atherosclerosis, metabolic syndrome, hypertension, peripheral vascular disease, stroke and several other cardiovascular disorders
*SOD↑, Lycopene modulates also the production of antioxidant enzymes, such as superoxide dismutase and catalase
*Catalase↑,
*ROS↓, By reducing oxidative stress and reactive oxygen species, lycopene increases the bioavailability of nitric oxide (NO), improves endothelium-dependent vasodilation and reduces protein, lipids, DNA, and mitochondrial damage (
*mtDam↓,
*cardioP↑, Lycopene exerts a cardioprotective effect against atrazine induced cardiac injury due to its anti-inflammatory effect, by blocking the NF-kappa B pathway and NO production
*NF-kB↓,
*NO↓,
*COX2↓, downregulation of cyclooxygenase 2,
*LDL↓, significant reductions in total and LDL cholesterol were revealed only at doses of, at least, 25 mg lycopene/day
*eff↑, It was noticed that lycopene can potentiate the antiplatelet effect of aspirin, which requires low lycopene diet
*ER Stress↓, Lycopene protects the cardiomyocytes by relieving ERS
*BioAv↑, Lycopene is very bioavailable in the presence of oil, especially in monounsaturated oils, other dietary fats and processed tomato products
*eff↑, Lycopene can increase the antioxidant properties of vitamin C, E, polyphenols and beta-carotene in a synergistic way
*MMPs↓, figure 3, secretion of MMPs
*COX2↓,
*RAGE↓,

3459- MF,    EFFECT OF PULSED ELECTROMAGNETIC FIELDS ON ENDOPLASMIC RETICULUM STRESS
- in-vitro, Cerv, HeLa
GRP78/BiP↑, the expression of BiP, Grp94 and CHOP were increased in HeLa cells upon PEMF exposure.
GRP94↑,
CHOP↑,
ER Stress↓, Our main findings are that PEMF exposure (8 Hz and meant flux density of 0.56 mT) is able to reduce the elevated activity of ER stress markers induced by tunicamycin, in HepG2 cell line.

2053- PB,    4-Phenyl butyric acid prevents glucocorticoid-induced osteoblast apoptosis by attenuating endoplasmic reticulum stress
- in-vitro, ostP, 3T3
*ER Stress↓, 4-PBA attenuated ER stress and mitochondrial dysfunction induced by Dex in MC3T3-E1 cells.
*mtDam↓,
*Apoptosis↓, 4-PBA reduces apoptosis induced by Dex and ER stressors in osteoblast cells
eff↑, inhibiting ER stress. This new discovery is of great significance for molecular intervention against GC-induced osteoporosis.

2052- PB,    Lipid-regulating properties of butyric acid and 4-phenylbutyric acid: Molecular mechanisms and therapeutic applications
- Review, NA, NA
*HDAC↓, BA appears to function as a histone deacetylase (HDAC) inhibitor while PBA acts as a chemical chaperone and/or a HDAC inhibitor.
*Half-Life↑, In humans, the plasma concentration of BA decreased quickly with a half-life of approximately 5 min once the infusion had ended
*Half-Life↑, The mean half-lives of PBA, PAA and PAGN in blood plasma were 0.7, 1.2 and 1.7 h, respectively, after an intravenous infusion of sodium phenylbutyrate to human subjects and 1, 1.8 and 2.8 h in serum, respectively, after an oral PB 9 to 45 g/day
*lipoGen↓, in vivo studies have shown that PBA ameliorated fructose-induced hepatosteatosis by inhibiting lipogenesis.
*ER Stress↓, PBA blocked fructose-driven expression of SREBP1c and its target genes by attenuating ER stres
*FAO↑, BA and PBA promote fatty acid β-oxidation
*ROS↓, Moreover, PBA prevented palmitate-induced autophagy-dependent reactive oxygen species (ROS) formation further supporting the protective role of PBA against lipotoxicity.
*BioAv↑, The absolute bioavailability of PBA averaged 78% in human subjects following the oral administrations of 9-45 g/day

2051- PB,    Beneficial Effects of Sodium Phenylbutyrate Administration during Infection with Salmonella enterica Serovar Typhimurium
- in-vivo, Inf, NA
*Inf↓, PBA has a previously undiscovered protective role in host mucosal defense during infection
*GutMicro↑, PBA to Taconic mice resulted in the increase of intestinal Lactobacillales and segmented filamentous bacteria (SFB)
*IL17↑, increase of interleukin 17 (IL-17) production by intestinal cells
*Inflam↓, lower levels of inflammation
*ER Stress↓, PBA also plays a role in the reduction of endoplasmic reticulum (ER) stress caused by the unfolded protein response (UPR), thereby suppressing oxidative stress in several animal models
*ROS↓,
*OS↑, PBA was shown to increase the life span of flies, which was associated with both a global increase in histone acetylation and a marked alteration of gene expression
*Bacteria↓, PBA administration was shown to inhibit the growth of Helicobacter pylori and Escherichia coli
*Neut↑, these results indicated that PBA treatment reduces intestinal inflammation, the recruitment of neutrophils to the gut
*toxicity↓, PBA, which has been safely used in children and adults for the past 20 years to treat urea cycle disorders

2056- PB,    Endoplasmic Reticulum Stress Induces ROS Production and Activates NLRP3 Inflammasome Via the PERK-CHOP Signaling Pathway in Dry Eye Disease
- in-vitro, Nor, HCE-2
*ROS↓, We found that 4-PBA reduces ROS production and NLRP3 inflammasome activation, along with a decline in IL-1β expression.
*NLRP3↓,
*IL1β↓,
*TXNIP↑, activation of the TXNIP/NLRP3-IL1β signaling pathway
*ER Stress↓, In multiple studies, 4-PBA was shown to effectively suppress ER stress

2057- PB,    Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER–mitochondria crosstalk in SiHa cells
- in-vitro, Cerv, SiHa
ROS↓, Pretreatment with N-acetyl cysteine (ROS scavenger) or 4-phenylbutyric acid (4-PBA; ER stress inhibitor) significantly alleviated apoptosis, mitochondrial ROS production, mitochondrial dysfunction and ER stress response in a dose-dependent manner.
tumCV∅, There was no difference in cell viability between the SiHa cells treated with 2 mM 4-PBA for 6 h and cell in the untreated control group
cl‑PARP↓, Surprisingly, 4-PBA pretreatment attenuated the levels of cleaved PARP and caspase-3 in T. vaginalis-infected SiHa cells in a dose-dependent manner
cl‑Casp3↓,
MMP∅, T. vaginalis induced MMP depolarization in the SiHa cells; however, these changes in fluorescence were suppressed by 4-PBA pretreatment
ER Stress↓, pretreatment with the ER stress inhibitor 4-PBA was found to significantly attenuate the levels of ER stress-related proteins in T. vaginalis-infected cells

2058- PB,    Induction of Human-Lung-Cancer-A549-Cell Apoptosis by 4-Hydroperoxy-2-decenoic Acid Ethyl Ester through Intracellular ROS Accumulation and the Induction of Proapoptotic CHOP Expression
- in-vitro, Lung, A549
ER Stress↓, Pretreatment with 4-phenylbutyric acid (PBA), an inhibitor of endoplasmic reticulum stress, also suppressed A549-cell death (38.4 ± 1.1%).

2048- PB,    Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo
- in-vitro, OS, CAL27 - in-vitro, Oral, HSC3 - in-vitro, OS, SCC4 - in-vivo, NA, NA
*NH3↓, Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been reported to be an ammonia scavenger, histone deacetylase inhibitor, and an endoplasmic reticulum stress inhibitor
*HDAC↓,
*ER Stress↓,
Apoptosis?, SPB could significantly promote cell apoptosis
Bcl-2↓, BCL-2 was downregulated
cl‑Casp3↑, cleavage of caspase-3 was increased
TGF-β↑, transforming growth factor-β (TGFB) related epithelial-mesenchymal transition (EMT) was inhibited by SPB
N-cadherin↓, decreased mesenchymal marker N-cadherin and increased epithelial marker E-cadherin.
E-cadherin↑,
TumVol↓, SPB induced remarkably tumor regression with decreased tumor volume
eff↑, phenylbutyrate improved the sensitivity of cisplatin for cell cycle arrest by inhibiting the FA/BRCA pathway in cancer cells.

2028- PB,    Potential of Phenylbutyrate as Adjuvant Chemotherapy: An Overview of Cellular and Molecular Anticancer Mechanisms
- Review, Var, NA
HDAC↓, Phenylbutyrate is one of the first drugs encountered in cancer therapy as a histone deacetylase inhibitor (HDACI).
TumCCA↑, phenylbutyrate treatment that results in reduced proliferation and cell-cycle arrest in G1 or G2 phases.
P21↑, common sequela of phenylbutyrate treatment is the upregulation of p21,
Dose↝, In prostate cancer, phenylbutyrate at clinically achievable concentrations (0.1 mM-8 mM),
Telomerase↓, butyrate or its derivatives was also evident in several other types of cancers and was associated with loss of telomerase activity
IGFBP3↑, Upregulation of insulin-like growth factor binding protein 3 (IGFBP-3) is another unique antiproliferative mechanism of sodium butyrate in breast cancer cells
p‑p38↑, Phenylbutyrate and its derivatives upregulated p21, gelsolin, phosphorylated p38, JNK, and ERK (MAPK pathway members), Bax, caspases-3,
JNK↑,
ERK↑,
BAX↑,
Casp3↑,
Bcl-2↓, downregulated Bcl-X L , Bcl-2, cytochrome c, FAK, and survivin
Cyt‑c↝,
FAK↓,
survivin↓,
VEGF↓, Butyrate treatment reduced the level of vascular endothelial growth factor (VEGF)
angioG↓,
DNArepair↓, Inhibition of DNA Repair.
TumMeta↓,
HSP27↑, Moreover, butyrate treatment in colorectal cancer cells resulted in an acute stress response that was associated with HSP27 activation, activation of ASK1 (MAP3K) and p38 MAPK pathway consequently.
ASK1↑,
ROS↑, Also it resulted in elevated cellular levels of reactive oxygen species (ROS) in oral and tongue cancer cells.
eff↑, phenylbutyrate enhanced the cytotoxicity of temozolamide in malignant glioma cells via suppression of the endoplasmic reticulum stress revealed by the decreased expression of GRP78 and GADD153.
ER Stress↓,
GRP78/BiP↓,
CHOP↑, GADD153
AR↓, Sodium butyrate treatment of prostate cancer cells was associated with downregulation of androgen receptor
other?, lots of references in this paper.

2034- PB,    Protective effects of 4-phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress
- in-vitro, Nor, SH-SY5Y
*ER Stress↓, Moreover, these compounds protected cells against ER stress-induced neuronal cell death.
*ChemChap↓, The cytoprotective effect correlated with the in vitro chemical chaperone activity.
*cytoP↑,
*cellD↓, 3-PPA and 4-PBA significantly suppressed neuronal cell death caused by ER stress induced by the overexpression of Pael-R
*neuroP↑, These results suggest that terminal aromatic substituted fatty acids are potential candidates for the treatment of neurodegenerative diseases.

2041- PB,    The Effect of Glucose Concentration and Sodium Phenylbutyrate Treatment on Mitochondrial Bioenergetics and ER Stress in 3T3-L1 Adipocytes
- in-vitro, Nor, 3T3
*mitResp↓, Treatment of adipocytes with sodium phenylbutyrate relieved mitochondrial stress through a reduction in mitochondrial respiration.
*ER Stress↓, sodium phenylbutyrate (PBA), an agent that reduces ER stress in adipocytes
MMP↓, Sodium phenylbutyrate (PBA) reduces protein succination and mitochondrial membrane potential in adipocytes matured in high glucose
GlucoseCon↓, PBA inhibits adipocyte maturation and glucose uptake
OCR↓, We observed that PBA reduced adipocyte glucose uptake (Figure 5 D), suggesting that overall the OCR is lower due to decreased metabolic flux coupled with selective reductions in mitochondrial protein content
CHOP↑, Both normal and high glucose adipocytes proceed through adipogenesis by activation of the UPR but only in high glucose is this accompanied by increased protein succination and CHOP production.

2651- PLB,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
ROS↑, Various studies have shown that plumbagin is a potent inducer of ROS
TrxR↓, The mechanism underlying ROS induction by plumbagin has predominantly been attributed to inhibition of the antioxidant enzymes TrxR
GSR↓, and glutathione reductase
ER Stress↓, mediates its anticancer effect by inducing ER stress-mediated apoptosis
TumCCA↑, S/G2 and G2/M cell cycle arrest
MMP↓, and mitochondrial membrane depolarization in an ROS-dependent manner
NF-kB↓, plumbagin was found to inhibit the NF-κB [57], PI3K/AKT/mTOR [58] and MKP1/2 [59] pathways in non-small cell lung cancer, bladder cancer, and lymphoma,
PI3K↓,
Akt↓,
mTOR↓,
MKP1↓,
MKP2↓,
ChemoSen↑, improve the efficacy of existing chemotherapeutic strategies

4297- QC,    Quercetin attenuates tau hyperphosphorylation and improves cognitive disorder via suppression of ER stress in a manner dependent on AMPK pathway
- in-vitro, AD, SH-SY5Y
*AMPK↑, administration of quercetin enhanced AMPK activity, inhibited IRE1α and PERK phosphorylation, NLRP3 expression and tau phosphorylation
*IRE1↓,
*p‑PERK↓,
*p‑tau↓,
*cognitive↑, and improved cognitive disorder in mice exposed to high fat diets
*antiOx↑, exert anti-oxidative, anti-ER stress, anti-inflammatory activities and regulating glucose homeostasis, which can prevent neurodegenerative disorders, diabetes, and obesity
*ER Stress↓,
*Inflam↓,
*neuroP↑,
*TXNIP↓, Quercetin and quercetin-3-O-glucuronide suppressed ER stress with decreased phosphorylation of IRE1α and PERK, thereby inhibited TXNIP and NLRP3 inflammasome activation,
*NLRP3↓, effectively protected neuronal cells from inflammatory insult by blocking ER stress/NLRP3 inflammasome activation.

3337- QC,    Endoplasmic Reticulum Stress-Relieving Effect of Quercetin in Thapsigargin-Treated Hepatocytes
- in-vitro, NA, HepG2
*Inflam↓, quercetin exerts anti-inflammatory and anti–insulin resistance actions by suppressing UPR in cells experiencing ER stress
*UPR↓,
*GRP58↓, (GRP78) and the downstream proteins such as X-box binding protein 1 (XBP1). The increased expression was significantly inhibited by quercetin, indicating that this compound can relieve ER stress
*XBP-1↓,
*ER Stress↓, previous reports as well as our results, we suggest that quercetin can inhibit ER stress in hepatocytes
*antiOx↑, Quercetin, a well-known antioxidant, is one of the most abundant flavonols in vegetables and fruits and has been shown to have many pharmacological actions
TNF-α↓, Quercetin suppressed the increased expression of TNF-α significantly and dose-dependently
p‑eIF2α↓, quercetin treatment suppressed the phosphorylation of eIF2α, IRE1α and JNK and the mRNA expression of XBP-1, GRP78 and CHOP
p‑IRE1↓,
p‑JNK↓,
CHOP↓,

3361- QC,    Quercetin ameliorates testosterone secretion disorder by inhibiting endoplasmic reticulum stress through the miR-1306-5p/HSD17B7 axis in diabetic rats
- in-vivo, Nor, NA - in-vitro, NA, NA
*BG↓, Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose, and inhibited oxidative stress.
*ROS↓,
*SOD↑, Both doses of quercetin reduced reactive oxygen species and malondialdehyde levels, and increased superoxide dismutase level in HG-treated cells.
*MDA↓,
*ER Stress↓, quercetin inhibits endoplasmic reticulum stress
*iNOS↓, Quercetin could eliminate the upregulation of iNOS, ET-1, and AR mRNA levels in HG-treated cells
*CHOP↓, HG treatment increased CHOP and Grp78 mRNA and protein levels in HG-treated cells, and two doses (5 or 10 μM) of quercetin all decreased these levels
*GRP78/BiP↓,
*antiOx↓, Quercetin is a natural polyphenol compound with anti-inflammatory [37], anti-oxidant [38], and blood sugar lowering properties
*Inflam↓,
*JAK2↑, Our results in vitro showed that quercetin treatment upregulated the phosphorylation levels of JAK2 and STAT3 in HG treated cells. (activating of the JAK2/STAT3 pathway could inhibit ER stress)
*STAT3?,

3363- QC,    The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation
- in-vitro, Nor, HBMECs
*Apoptosis↓, Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis.
*angioG↑,
*NRF2↑, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression.
*Keap1↓,
*ATF6↓,
*GRP78/BiP↓,
*CLDN5↑, quercetin could increase the expression of Claudin-5 and Zonula occludens-1.
*ZO-1↑,
*MMP↑, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis.
*BBB↑, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.
*ROS↓, Quercetin Could Inhibit Oxidative Stress
*ER Stress↓, In our study, ER stress was activated by H/R, and the levels of ATF6 and GRP78 were increased. Quercetin at 1 μmol/L was able to significantly reduce the protein levels of both, inhibit ER stress, and protect HBMECs from H/R injury

3365- QC,    Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1/AMPK pathways
- in-vivo, Sepsis, NA
*ER Stress↓, quercetin could inhibit the level of ER stress as evidenced by decreased mRNA expression of PDI, CHOP, GRP78, ATF6, PERK, IRE1α
*PDI↓,
*CHOP↓,
*GRP78/BiP↓,
*ATF6↓,
*PERK↓,
*IRE1↓,
*MMP↑, and improve mitochondrial function, as presented by increased MMP, SOD level and reduced production of ROS, MDA.
*SOD↑,
*ROS↓,
*MDA↓,
*SIRT1↑, quercetin upregulated SIRT1/AMPK mRNA expression.
*AMPK↑,
*Sepsis↓, quercetin could protect against sepsis-induced ALI by suppressing oxidative stress-mediated ER stress and mitochondrial dysfunction via induction of the SIRT1/AMPK pathways.

3366- QC,    Quercetin Attenuates Endoplasmic Reticulum Stress and Apoptosis in TNBS-Induced Colitis by Inhibiting the Glucose Regulatory Protein 78 Activation
- in-vivo, IBD, NA
*Apoptosis↓, quercetin improved TNBS-induced histopathological alterations, apoptosis, inflammation, oxidative stress, and ER stress
*Inflam↓,
*ROS↓,
*ER Stress↓, suggests that quercetin has a regulatory effect on ER stress-mediated apoptosis, and thus may be beneficial in treating IBD.
*TNF-α↓, Quercetin reduced the TNF-α and MPO levels associated with colitis
*MPO↓,
*p‑JNK↓, The HSCORE values of p-JNK (p < 0.001), caspase-12 (p < 0.001), and GRP78 (p = 0.004) were lowered in the quercetin group when compared to the colitis group
*Casp12↓,
*GRP78/BiP↓,
*antiOx↑, protective effect of quercetin in IBD, attributed to its antioxidant properties and NF-kB inhibition
*NF-kB↓,

3020- RosA,    Protective Effect of Rosmarinic Acid on Endotoxin-Induced Neuronal Damage Through Modulating GRP78/PERK/MANF Pathway
- in-vivo, Nor, NA - in-vitro, NA, SH-SY5Y
*cognitive↑, 20 and 40 mg/kg RA significantly improve endotoxin-induced cognitive dysfunction without dose differences
*PERK↓, 40 mg/kg RA treatment significantly decreased the hippocampal level of PERK protein
*GRP78/BiP↓, 120 μM RA pretreatment significantly inhibited LPS-conditioned culture-induced GRP78, PERK, and MANF upregulation in vitro.
*ER Stress↓, improving cognitive impairment and suppressing the endoplasmic reticulum stress mediated by the GRP78/IRE1α/JNK pathway.

3023- RosA,    Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis
- in-vivo, Sepsis, NA
*GPx4↑, RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement,
*Inflam↓, decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice.
*ER Stress↓,
*Ferroptosis↓, the anti-ferroptosis effect of RA in LPS-induced septic
*Sepsis↓,
*GRP78/BiP↓, Previously, we reported that RA markedly ameliorated septic-associated mortality and lung injury via inhibiting GRP78/IRE1α/JNK pathway-mediated ERS
*IRE1↓,
JNK↓,

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

3180- SFN,    Exploring the therapeutic effects of sulforaphane: an in-depth review on endoplasmic reticulum stress modulation across different disease contexts
- Review, Var, NA
*cardioP↑, broad range of protective functions of sulforaphane, improving various diseases, such as cardiovascular, central nervous system, liver, eye, and reproductive diseases, as well as diabetes, cancer, gastroenteritis, and osteoarthritis,
*ER Stress↓, through the amelioration of ER stress in both in vivo and in vitro studies.
GRP78/BiP↑, Sulforaphane significantly increased the level of Bip/GRP78, and XBP-1 protein expression and enhanced the rate of HepG2 cells apoptosis.
XBP-1↑,
Apoptosis↑,
*NRF2↑, Mitigates oxidative stress and ER stress in vascular cells, contributing to cardioprotection
UPR↑, SFN can drive the UPR into an overactivated state(ai)

2217- SK,    Shikonin Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis to Attenuate Renal Ischemia/Reperfusion Injury by Activating the Sirt1/Nrf2/HO-1 Pathway
- in-vivo, Nor, NA - in-vitro, Nor, HK-2
*ER Stress↓, shikonin alleviated ER stress-induced apoptosis in I/R mice
*SIRT1↑, shikonin activated Sirt1/Nrf2/HO-1 signaling post-I/R
*NRF2↑,
*HO-1↑,
*eff↓, inhibition of Sirt1 limited shikonin-mediated protection against ER stress-stimulated apoptosis in both animal and cellular models.
*RenoP↑, Shikonin pretreatment alleviates renal I/R injury through activating Sirt1/Nrf2/HO-1 signaling to inhibit ER stress-mediated apoptosis.
*GRP78/BiP↓, The current study revealed that shikonin significantly downregulated GRP78, CHOP, caspase-12, Bax, and cleaved caspase-3 proteins levels in renal tissues of I/R mice and H/R-challenged HK-2 cells
*CHOP↓,
*Casp12↓,
*BAX↓,
*cl‑Casp3↓,

3950- Taur,    Taurine Supplementation as a Neuroprotective Strategy upon Brain Dysfunction in Metabolic Syndrome and Diabetes
- Review, Diabetic, NA - Review, Stroke, NA - Review, AD, NA
*Ca+2↝, taurine homeostasis can impact a number of biological processes, such as osmolarity control, calcium homeostasis, and inhibitory neurotransmission, and have been reported in both metabolic and neurodegenerative disorders.
*neuroP↑, taurine can afford neuroprotection in individuals with obesity and diabetes.
*other↝, Notably, both methionine and cysteine produced from protein degradation can generate taurine as an end-product
*pH↝, Taurine might counteract extreme mitochondrial pH fluctuations and help preserve mitochondrial physiology.
*ROS∅, Taurine is not able to act as a radical scavenger
eff↑, Taurine also decreased the activity of glutathione peroxidase and manganese-superoxide dismutase upon tamoxifen toxicity, which contributed to decreasing mitochondrial oxidative stress, measured through lipid peroxidation, protein carbonyl content, a
*MMP↑, In sum, taurine supplementation is proposed to improve the function of the mitochondria, contributing to the preservation of mitochondrial membrane potential, proton gradient, and matrix pH that are critical for energy metabolism and efficient oxidat
*Apoptosis↓, Taurine was found to prevent apoptosis upon many noxious challenges
*other↝, The most striking neuroprotective effects of taurine were observed on the reduction of apoptotic rates and the improvement of neurological outcomes upon brain ischemia.
*ER Stress↓, prevention of mitochondrial and endoplasmic reticulum (ER) stress.
*Bcl-xL↓, reduction of anti-apoptotic Bcl-xL and the increase of the pro-apoptotic Bax, preventing cytochrome C release from the mitochondria, and inhibiting the activation of calpain and caspase-3
*BAX↑,
*Cyt‑c↑,
*cal2↓,
*Casp3↓,
*UPR↓, prevent ischemia/hypoxia-induced endoplasmic reticulum (ER) stress by inhibiting the unfolded protein response via transcription factor 6 (ATF6), protein kinase R-like ER kinase (PERK), and inositol-requiring enzyme 1 (IRE1) pathways
*other↝, Altogether, one might speculate that taurine loss in patients with AD is linked to worsened cognitive deterioration.
*NF-kB↓, ameliorated the diabetes-induced increase of the transcription factor NF-κβ, involved in inflammatory processes, and the diabetes-induced reduction of Nrf2 and glucose transporters Glut1 and Glut3 in the brain.
*NRF2↑,
*GLUT1↑,
*GLUT3↑,
*memory↑, In mice fed a fat-rich diet, which develop metabolic syndrome, we recently demonstrated that 3% (w/v) taurine supplemented in the drinking water for 2 months prevented memory impairment

3146- VitC,    Vitamin C protects against hypoxia, inflammation, and ER stress in primary human preadipocytes and adipocytes
- in-vivo, Nor, NA
*Obesity↓, These findings indicate that Vitamin C can reduce obesity-associated cellular stress and thus provide a rationale for future investigations.
*ER Stress↓, Vitamin C prevented the increase in hypoxia (Fig. 1A–B), significantly reduced the induction of ER stress
*Inflam↓, nd ameliorated the increased expression of inflammatory genes
Hif1a↓, Vitamin C treatment for 24 and 48 h significantly reducing induction of HIF1α protein by 30–40% and VEGFA and GLUT1 mRNA by 40–80%
VEGF↓,
GLUT1↓,
GRP78/BiP↓, significantly reversing the effects of TNFα+PA pre-treatment only on GRP78 induction, by 30–40%

3147- VitC,    Vitamin C modulates the metabolic and cytokine profiles, alleviates hepatic endoplasmic reticulum stress, and increases the life span of Gulo−/− mice
- in-vivo, Nor, NA
*OS↑, life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo−/− mice.
*ER Stress↓,
*GRP78/BiP↓, There was a decrease in GRP78 in Gulo−/− mice treated with 0.4% ascorbate


Showing Research Papers: 1 to 50 of 53
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 53

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSR↓, 1,   H2O2↑, 1,   ROS↓, 1,   ROS↑, 4,   TrxR↓, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 1,   CDC25↓, 1,   MMP↓, 3,   MMP∅, 1,   OCR↓, 1,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   GlucoseCon↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis?, 1,   Apoptosis↑, 1,   ASK1↑, 1,   BAX↑, 3,   Bcl-2↓, 3,   Casp3↓, 1,   Casp3↑, 2,   cl‑Casp3↓, 1,   cl‑Casp3↑, 1,   Casp8↑, 3,   Casp9↑, 2,   Cyt‑c↝, 1,   Fas↑, 1,   JNK↓, 3,   JNK↑, 1,   p‑JNK↓, 1,   MAPK↑, 1,   MDM2↓, 1,   MKP1↓, 1,   MKP2↓, 1,   p27↑, 1,   p‑p38↑, 1,   survivin↓, 2,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

other?, 1,   tumCV∅, 1,  

Protein Folding & ER Stress ⓘ

CHOP↓, 2,   CHOP↑, 3,   p‑eIF2α↓, 2,   ER Stress↓, 8,   GRP78/BiP↓, 2,   GRP78/BiP↑, 3,   GRP94↑, 1,   HSP27↑, 1,   p‑IRE1↓, 1,   PERK↓, 1,   p‑PERK↓, 1,   UPR↑, 1,   XBP-1↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   DNArepair↓, 1,   cl‑PARP↓, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   E2Fs↓, 1,   P21↑, 2,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   ERK↑, 1,   HDAC↓, 1,   IGFBP3↑, 1,   mTOR↓, 2,   NOTCH1↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TOP2↓, 1,  

Migration ⓘ

AP-1↓, 1,   Cdc42↑, 1,   E-cadherin↑, 2,   FAK↓, 1,   LRP1↑, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   PKCδ↓, 1,   RAGE↓, 1,   SMAD3↓, 1,   p‑SMAD4↓, 1,   TGF-β↑, 2,   TIMP2↑, 1,   TumCP↓, 1,   TumMeta↓, 2,   uPA↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   Hif1a↓, 1,   VEGF↓, 3,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR4↓, 1,   IL8↓, 1,   NF-kB↓, 3,   TNF-α↓, 2,  

Protein Aggregation ⓘ

BACE↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   ChemoSen↑, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 5,   Half-Life↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   HER2/EBBR2↓, 1,   RAGE↓, 1,  

Functional Outcomes ⓘ

TumVol↓, 2,  
Total Targets: 119

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 13,   Catalase↑, 3,   Ferroptosis↓, 1,   GPx↑, 2,   GPx4↑, 1,   GSH↑, 2,   GSTA1↑, 1,   HO-1↓, 1,   HO-1↑, 3,   Keap1↓, 1,   lipid-P↓, 2,   MDA↓, 5,   MDA↑, 1,   MPO↓, 2,   NQO1↑, 1,   NRF2↑, 8,   ROS↓, 22,   ROS∅, 1,   mt-ROS↓, 1,   SOD↑, 10,   TBARS↓, 1,  

Mitochondria & Bioenergetics ⓘ

Insulin↑, 1,   mitResp↓, 1,   MMP↑, 3,   mtDam↓, 2,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 2,   AMPK↑, 4,   FAO↑, 1,   LDL↓, 1,   lipoGen↓, 1,   NH3↓, 1,   PPARα↑, 1,   SIRT1↑, 4,   SREBP1↓, 1,  

Cell Death ⓘ

Akt↑, 1,   Apoptosis↓, 10,   BAX↓, 2,   BAX↑, 1,   Bcl-2↑, 1,   Bcl-xL↓, 1,   Casp1↓, 1,   Casp12↓, 5,   Casp3↓, 4,   cl‑Casp3↓, 2,   Casp9↓, 1,   cellD↓, 1,   Cyt‑c↓, 1,   Cyt‑c↑, 1,   Ferroptosis↓, 1,   GRP58↓, 1,   iNOS↓, 3,   JNK↓, 1,   p‑JNK↓, 1,   MLKL↓, 1,   RIP1↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,   other↑, 2,   other↝, 5,  

Protein Folding & ER Stress ⓘ

ATF6↓, 3,   ChemChap↓, 1,   CHOP↓, 10,   eIF2α↓, 1,   p‑eIF2α↓, 1,   ER Stress↓, 42,   GRP78/BiP↓, 11,   HSP70/HSPA5↑, 1,   HSP90↑, 1,   IRE1↓, 5,   PERK↓, 5,   p‑PERK↓, 2,   UPR↓, 4,   XBP-1↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 2,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3II↑, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   p16↓, 1,   p‑PARP↓, 1,   TP53↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 2,   Jun↓, 1,   mTOR↓, 1,   mTOR↑, 1,   PI3K↑, 1,   STAT3?, 1,   STAT3↑, 1,  

Migration ⓘ

AntiAg↑, 2,   APP↓, 1,   Ca+2↓, 1,   Ca+2↝, 1,   cal2↓, 1,   E-cadherin↓, 1,   MMPs↓, 1,   RAGE↓, 1,   Rho↓, 1,   ROCK1↓, 1,   TXNIP↓, 3,   TXNIP↑, 1,   Zeb1↓, 1,   ZO-1↓, 1,   ZO-1↑, 2,  

Angiogenesis & Vasculature ⓘ

angioG↑, 3,   ATF4↓, 3,   CLDN5↑, 1,   p‑eNOS↑, 1,   Hif1a↑, 1,   NO↓, 2,   PDI↓, 1,   VEGF↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↑, 1,   GLUT3↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IFN-γ↓, 1,   IL10↓, 1,   IL10↑, 2,   IL17↑, 1,   IL18↓, 1,   IL1β↓, 4,   IL2↓, 1,   IL6↓, 4,   IL8↓, 1,   Inflam↓, 22,   JAK2↑, 2,   Neut↑, 1,   NF-kB↓, 3,   TLR4↓, 1,   TNF-α↓, 4,  

Cellular Microenvironment ⓘ

pH↝, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BDNF↑, 1,   monoA↑, 1,   PSD95↑, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 3,   NLRP3↓, 4,  

Hormonal & Nuclear Receptors ⓘ

RAAS↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 3,   Dose↝, 1,   eff↓, 1,   eff↑, 2,   Half-Life↑, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 2,   ALP↓, 1,   AST↓, 2,   BG↓, 2,   BP↓, 1,   GutMicro↑, 5,   IL6↓, 4,   RAGE↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,   AntiTum↑, 1,   cardioP↑, 7,   cognitive↑, 8,   cytoP↑, 1,   hepatoP↑, 3,   memory↑, 6,   Mood↑, 1,   neuroP↑, 11,   Obesity↓, 1,   OS↑, 3,   RenoP↑, 3,   toxicity↓, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,   Inf↓, 1,   Sepsis↓, 2,  
Total Targets: 171

Scientific Paper Hit Count for: ER Stress, endoplasmic reticulum (ER) stress signaling pathway
10 Phenylbutyrate
6 Berberine
6 Quercetin
4 Vitamin C (Ascorbic Acid)
3 Rosmarinic acid
2 Crocetin
2 Hydrogen Gas
1 Allicin (mainly Garlic)
1 Apigenin (mainly Parsley)
1 Artemisinin
1 Bacopa monnieri
1 Celastrol
1 Cinnamon
1 Coenzyme Q10
1 EGCG (Epigallocatechin Gallate)
1 Emodin
1 Ferulic acid
1 hydrogen sulfide
1 Luteolin
1 Lutein
1 Lycopene
1 Magnetic Fields
1 Plumbagin
1 Sulforaphane (mainly Broccoli)
1 Shikonin
1 Taurine
1 Vitamin K2
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#:103  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

Home Page