GRP78/BiP Cancer Research Results

GRP78/BiP, HSPA5: Click to Expand ⟱

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Type:

GRP78 (Pgp, BiP or ERp72) is a central regulator of endoplasmic reticulum (ER) function due to its roles in protein folding and assembly, targeting misfolded protein for degradation, ER Ca(2+)-binding and controlling the activation of trans-membrane ER stress sensors.
-GRP78 protein, a marker for endoplasmic reticulum stress
-GRP78’s role as a master regulator of the unfolded protein response (UPR) and cellular stress responses
The association of P-gp and inhibition of cell death in cancerous cells has also been reported in several studies including in hepatocellular, colorectal, prostate cancer, and gastric cancer. Although counterintuitive due to its prominent role in cancer resistance, P-gp has been linked to favorable prognosis.
ERp72 can promote cancer cell proliferation, migration, and invasion by regulating various signaling pathways, including the PI3K/AKT and MAPK/ERK pathways. Additionally, ERp72 can also inhibit apoptosis (programmed cell death) in cancer cells, which can contribute to tumor progression. Overexpressed in: Breast, lung colorectal, prostrate, ovarian, pancreatic.

-GRP78 is frequently upregulated in a variety of solid tumors and hematological malignancies.
-Overexpression of GRP78 in cancer cells is often regarded as a marker of increased ER stress due to the reduced oxygen and nutrient supply typically encountered in the tumor microenvironment.
-Elevated GRP78 levels can contribute to tumor cell survival by enhancing the adaptive UPR, allowing cancer cells to cope with therapeutic and metabolic stress.

Scientific Papers found: Click to Expand⟱

2635-

Api,

CUR,

Synergistic Effect of Apigenin and Curcumin on Apoptosis, Paraptosis and Autophagy-related Cell Death in HeLa Cells

in-vitro,

Cerv,

HeLa

TumCD↑, Treatment with a combination of apigenin and curcumin increased the expression levels of genes related to cell death in HeLa cells 1.29- to 27.6-fold.
eff↑, combination of curcumin and apigenin showed a synergistic anti-tumor effect
TumAuto↑, autophagic cell death, as well as ER stress-associated paraptosis
ER Stress↑,
Paraptosis↑,
GRP78/BiP↓, GRP78 expression was down-regulated, and massive cytoplasmic vacuolization was observed in HeLa cells
Dose↝, combined use of 0.09 μg/μl curcumin and 0.06 μg/μl apigenin showed a synergistic anti-tumor effect

2678-

BBR,

Berberine as a Potential Agent for the Treatment of Colorectal Cancer

Review,

CRC,

*Inflam↓, BBR exerts remarkable anti-inflammatory (94–96), antiviral (97), antioxidant (98), antidiabetic (99), immunosuppressive (100), cardiovascular (101, 102), and neuroprotective (103) activities.
*antiOx↑,
*cardioP↑,
*neuroP↑,
TumCCA↑, BBR could induce G1 cycle arrest in A549 lung cancer cells by decreasing the levels of cyclin D1 and cyclin E1
cycD1/CCND1↓,
cycE/CCNE↓,
CDC2↓, BBR also induced G1 cycle arrest by inhibiting cyclin B1 expression and CDC2 kinase in some cancer cells
AMPK↝, BBR has been suggested to induce autophagy in glioblastoma by targeting the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/ULK1 pathway
mTOR↝,
Casp8↑, BBR has been revealed to stimulate apoptosis in leukemia by upregulation of caspase-8 and caspase-9
Casp9↑,
Cyt‑c↑, in skin squamous cell carcinoma A431 cells by increasing cytochrome C levels
TumCMig↓, BBR has been confirmed to inhibit cell migration and invasion by inhibiting the expression of epithelial–mesenchymal transition (EMT)
TumCI↓,
EMT↓,
MMPs↓, metastasis-related proteins, such as matrix metalloproteinases (MMPs) and E-cadherin,
E-cadherin↓,
Telomerase↓, BBR has shown antitumor effects by interacting with microRNAs (125) and inhibiting telomerase activity
*toxicity↓, Numerous studies have revealed that BBR is a safe and effective treatment for CRC
GRP78/BiP↓, Downregulates GRP78
EGFR↓, Downregulates EGFR
CDK4↓, downregulates CDK4, TERT, and TERC
COX2/PTGS2↓, Reduces levels of COX-2/PGE2, phosphorylation of JAK2 and STAT3, and expression of MMP-2/-9.
PGE2↓,
p‑JAK2↓,
p‑STAT3↓,
MMP2↓,
MMP9↓,
GutMicro↑, BBR can inhibit tumor growth through meditation of the intestinal flora and mucosal barrier, and generally and ultimately improve weight loss. BBR has been reported to modulate the composition of intestinal flora and significantly reduce flora divers
eff↝, BBR can regulate the activity of P-glycoprotein (P-gp), and potential drug-drug interactions (DDIs) are observed when BBR is coadministered with P-gp substrates
*BioAv↓, the efficiency of BBR is limited by its low bioavailability due to its poor absorption rate in the gut, low solubility in water, and fast metabolism. Studies have shown that the oral bioavailability of BBR is 0.68% in rats
BioAv↑, combining it with p-gp inhibitors (such as tariquidar and tetrandrine) (196, 198), and modification to berberine organic acid salts (BOAs)

2763-

BetA,

Betulinic Acid Inhibits the Stemness of Gastric Cancer Cells by Regulating the GRP78-TGF-β1 Signaling Pathway and Macrophage Polarization

in-vitro,

GC,

GRP78/BiP↓, The results indicated that BA inhibited not only GRP78-mediated stemness-related protein expression and GRP78-TGF-β-mediated macrophage polarization
TGF-β↓, BA Inhibits the Expression of GRP78, TGF-β1, and Stemness Markers in Human Gastric Cancer Cells
ChemoSen↑, BA is a promising candidate for clinical application in combination-chemotherapy targeting cancer stemness.
CSCs↓,
SMAD2↓, BA inhibited TGF-β/Smad2/3 signaling, TGF-β1 secretion, and OCT4 expression in a dose-dependent manner
SMAD3↓,
OCT4↓,

3524-

Bor,

Boric Acid Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice

*Inflam↓, Furthermore, BA exhibited anti-inflammatory properties by suppressing inflammatory cytokines within the lung tissue.
*SOD↑, BA ingestion caused upregulation in SOD and a decrease in MDA contents in lung tissue homogenates.
*MDA↓,
*GRP78/BiP↓, BA downregulated the levels of GRP78 and CHOP compared to the LPS group.
*CHOP/DDIT3↓,
*NRF2↑, Remarkably, BA also upregulated transcription and protein expression of Nrf2 and HO-1 compared to the LPS group.
*HO-1↑,

5880-

CAR,

In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis

vitro+vivo,

Lung,

A549

nude mice, present study commenced to formulate CANE by an energy intensive ultrasonication method.

in-vitro,

Nor,

BEAS-2B

in-vitro,

Lung,

PC9

Dose↝, prepare a carvacrol nanoemulsion (CANE) using an ultrasonication technique and further evaluation of its anticancer potential against human lung adenocarcinoma A549 cells. (160nm)
mt-ROS↑, The CANE induced reactive oxygen species (ROS) production in A549 cells,
p‑JNK↑, leading to activation of key regulators of apoptosis such as p-JNK, Bax and Bcl2 as well as release of cytochrome C, and activation of the caspase cascade.
BAX↑,
Cyt‑c↑,
Casp↑,
AntiTum↑, CANE displayed a strong antitumor potential in vivo using an athymic nude mice model.
ER Stress↑, Abnormally high ROS levels create ER stress with the involvement of three major signaling proteins IRE1-α, PERK and ATF-6
LDH↑, higher LDH activity, which is a well-established biomarker released by damaged cells, was observed in CANE-treated cells
selectivity↑, CANE displayed no cytotoxicity up to 100 µg/ml against normal bronchial epithelium cells (BEAS-2B)
Apoptosis↑, Induction of apoptosis and ROS production in the presence of CANE
DNAdam↑, potential role on DNA damage and chromatin condensation
IRE1↑, We observed a higher expression of IRE1-α in CANE treated cells
XBP-1↑, similar expression pattern for XBP-1
CHOP/DDIT3↓, down-regulation of CHOP, p-eIF2α, and GRP78 was observed in CANE-treated cells
p‑eIF2α↓,
GRP78/BiP↓,
Ca+2↑, increase of Ca+2 levels in CANE-treated cells. A 2.5 fold higher Ca+2 was observed at 100 μg/ml CANE treated cells
MMP↓, CANE severely altered mitochondrial membrane potential (Δψm) in a dose-dependent manner.
Bcl-2↓, up- and down-regulation of pro-apoptotic (Bax) and anti-apoptotic (Bcl2) proteins
Casp3↑, higher levels of cleaved caspase-9 and caspase-3 in cells treated with CANE in a dose-dependent manner
Casp9↑,
eff↓, To confirm this, A549 cells were first treated with N-acetyl-L-cysteine NAC (5 mM), a strong scavenger of ROS, prior to CANE (100 µg/ml) treatment and observed a marked reduction in ROS generation
TumW↓, A significant (p < 0.05) 34.2 and 62.1% reduction in tumor weight was observed in the mice treated with 50 and 100 mg/Kg CANE, orally three times in a week
Weight↑, body weights of 100 mg/kg CANE treated mice remained static up to the second week and increased further up to 4 weeks
eff↑, ultrasonication consider as simple, cost-effective, clean and prompt aseptic technique16, wherein large droplets ruptured into small droplets by ultrasound leading to the formation of nano-scale droplets
eff↑, We selected polysorbate 80 as a surfactant (HLB, 15), which is regarded as safe for using in pharmaceutical and food industries1

6300-

Cro,

Interaction of saffron and its constituents with Nrf2 signaling pathway: A review

Review,

Nor,

Review,

Arthritis,

*antiOx↑, many pharmacological properties such as anti-oxidant, anti-inflammatory, antitumor, antigenotoxic, anti-depressant, hepatoprotective, cardioprotective, and neuroprotective.
*Inflam↓,
*AntiTum↑,
*hepatoP↑,
*cardioP↑,
*neuroP↑,
*NRF2↑, review indicate that saffron and its constituents could induce the Nrf2 signaling pathway leading to its anti-oxidant and therapeutic effects.
*NF-kB↓, ↓Arthritic pain, inflammation, oxidative stress, NF-κB, iNOS, COX-2, IL-6, IL-10, IL-1β, and TNF-α ↑Nrf2 and HO-1
*iNOS↓,
*COX2/PTGS2↓,
*IL6↓,
*IL10↓,
*IL1β↓,
*TNF-α↓,
*HO-1↑,
ROS↑, ↑Cytotoxicity in cancer cells, ROS, oxidative stress, Nrf2, HO-1, NQO1, and NQO2 ↓LDHA, membrane potential, and ATP level in vitro/A549, HepG2, HCT-116, HeLa, and SK-OV-3 cancer cell lines
NQO1↑,
NRF2↑,
HO-1↑,
NQO2↑,
LDHA↓,
ATP↓,
*hepatoP↑, Hepatoprotective effects ↑SOD, CAT, GPx, and Nrf2 ↓ROS
*SOD↑,
*Catalase↑,
*GPx↑,
*NRF2↑,
*ROS↓,
*cardioP↑, ↓Cardioprotective, ER stress, GRP78, CHOP, apoptosis, and miR-34a ↑Nrf2, HO-1, and Sirt1
*ER Stress↓,
*GRP78/BiP↓,
*CHOP/DDIT3↓,
*Apoptosis↓,
*miR-34a↓,
*SIRT1↑,
chemoP↑, chemoprotective-protective effects of crocin is its anti-inflammatory and anti-oxidant functions

3630-

Cro,

Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis

in-vivo,

AD,

Rats

*memory↑, learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin.
*Bcl-2↑, Bcl2 in PFC and hippo of AD model group was significantly decreased (P<0.01), while those of Bax, Caspase3, GRP78, and CHOP were significantly increased .Resveratrol and crocin could significantly reverse
*BAX↓,
*Casp3↓,
*GRP78/BiP↓,
*CHOP/DDIT3↓,
*Dose↝, We also reported that the higher dose (40 mg/kg and 80 mg/kg) of crocin performed significantly better than lower dose (20 mg/kg), but no difference was found between 40 mg/kg and 80 mg/kg crocin

3202-

EGCG,

Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity

in-vitro,

Cerv,

HeLa

100uM

in-vitro,

HCC,

QGY-7703

PARP16↓, (EGCG) as a potential inhibitor of PARP16.
p‑PERK↓, EGCG suppressed the ER stress-induced phosphorylation of PERK and the transcription of unfolded protein response-related genes,
Apoptosis↑, leading to dramatically increase of cancer cells apoptosis
eIF2α↓, EGCG suppressed the phosphorylation of PERK and eIF2α induced by ER stress.
UPR↓, UPR-related gene was dramatically induced by BFA and TUN, and this induction was suppressed by treatment of Hela cells with EGCG, further suggesting that EGCG suppressed the UPR induced by ER stress.
ER Stress↑, EGCG can dramatically inhibit the activity of PARP16, and then suppressed the ER stress-induced PERK phosphorylation, leading to dramatical increase of the ER stress-induced apoptosis of cancer cells.
eff↑, These results indicate that EGCG can be used in combination with ER stress-induced drugs to treat the cancer cell.
GRP78/BiP↓, EGCG had previously been found to bind to the ATP-binding domain of glucose regulate protein 78 (GRP78),

3203-

EGCG,

(-)- Epigallocatechin-3-gallate induces GRP78 accumulation in the ER and shifts mesothelioma constitutive UPR into proapoptotic ER stress

NA,

MM,

ROS↑, We have previously shown that (-)-epigallocatechin-3-gallate (EGCG) enhances ROS production and alters Ca2+ homeostasis in cell lines deriving from therapy-recalcitrant malignant mesothelioma (MMe).
Ca+2↝,
GRP78/BiP↑, Exposure to EGCG further increased GRP78 in the ER, and induced ATF4, spliced XBP1, CHOP, and EDEM expressions, combined with a reduction of cell surface GRP78 and a rise in caspase 3 and 8 activities.
ATF4↑,
XBP-1↑,
CHOP/DDIT3↑,
Casp3↑,
Casp8↑,
*GRP78/BiP↓, n non-cancer mouse retinal pigment epithelial cells,EGCG has been found to downregulate GRP78 and UPR signaling (Karthikeyan et al., 2017).
*UPR↓,
UPR↑, However, if ER homeostasiscannot be re-established, the UPR switches its signaling toward irreversible ER stress with the activation of apoptosis (

3206-

EGCG,

Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration

Review,

AMD,

*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/DDIT3↓,
*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.

6780-

EGCG,

The pharmacological activity of epigallocatechin-3-gallate (EGCG) on Alzheimer's disease animal model: A systematic review

Review,

AD,

*neuroP↑, Regulation of α-, β-, γ-secretase activity, inhibition of tau phosphorylation, anti-oxidation, anti-inflammation, anti-apoptosis, and inhibition of AchE activity are reported as the main neuroprotective mechanisms.
*tau↓,
*antiOx↑,
*Inflam↓,
*Apoptosis↓,
*AChE↓,
*TNF-α↓, Inhibiting TNF-α/JNK pathway
*JNK↓,
*NGF↑, Increasing the level of NGF. EGCG (2 mg/kg) mouse
*SOD↑, figure 7
*GPx↑, EGCG enhanced the activity of T-SOD and GSH-Px and reduced MDA content in the hippocampus.
*MDA↓,
*NO↓,
*ROS↓,
*iNOS↓,
*COX2/PTGS2↓, anti apoptosis
*BAX↓, EGCG prevented LPS-induced elevation of GFAP, iNOS, and COX-2.
*CHOP/DDIT3↓,
*GRP78/BiP↓,
*Bcl-2↑,
*Dose↑, The highest safe dose for more than a month of treatment allowed by FDA is 800 mg of EGCG daily with food.
*BioAv↑, In preclinical and phase I clinical trials, it has been shown that bioavailability of EGCG is increased when it is consumed on a fasting basis.
*hepatoP↓, However, the rate of hepatotoxicity is also increased

7265-

Gink,

Ginkgetin targets GRP78 to induce dual pathways of ER stress and immune activation in osteosarcoma

vitro+vivo,

OS,

patient-derived xenograft models

GRP78/BiP↓, we identified the natural compound ginkgetin (Gink) as a novel GRP78 inhibitor.
TumCP↓, In vitro, Gink suppressed osteosarcoma cell proliferation, migration, and invasion while inducing apoptosis and autophagy by activating the PERK-eIF2α-ATF4 pathway.
TumCMig↓,
TumCI↓,
Apoptosis↑,
TumAuto↑,
PERK↑,
eIF2α↑,
ATF4↑,
TumCG↓, Gink treatment markedly attenuated tumor growth and metastasis.
TumMeta↓,
eff↑, synergizing with anti-PD1 therapy to enhance CD8+ T-cell activity

7482-

H2,

Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application

Review,

Var,

Review,

IBD,

Review,

Stroke,

Review,

Sepsis,

Review,

AD,

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.

2507-

H2,

Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis

in-vivo,

NA,

Sprague-Dawley rats

*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/DDIT3↓,
*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

2869-

HNK,

Nature's neuroprotector: Honokiol and its promise for Alzheimer's and Parkinson's

Review,

AD,

Review,

Park,

*neuroP↑, neuroprotective, anti-oxidant, anti-apoptotic, neuromodulating, anti-inflammatory, and many more qualities, honokiol,
*Inflam↓,
*motorD↑, degradation of dopaminergic neurons in Parkinson's disease and improving motor function.
*Aβ↓, Alzheimer's disease, honokiol showed promise in lowering the production of amyloid-beta (Aβ) plaques, phosphorylating tau, and enhancing cognitive performance
*p‑tau↓,
*cognitive↑,
*memory↑, prevented Acetylcholinesterase activity from elevation as well as improved acetylcholine levels, and improved learning, and memory deficits via increased ERK1/2 and Akt phosphorylation
*ERK↑,
*p‑Akt↑,
*PPARγ↑, honokiol has been reported to elevate PPARγ levels in APPswe/PS1dE9 mice as PPARγ is related to ani-inflammatory
*PGC-1α↑, honokiol boosted the expression of PGC1α and PPARγ
*MMP↑, as well as reduced elevated mitochondrial membrane potential and mitochondrial ROS
*mt-ROS↓,
*SIRT3↑, Honokiol has been found as a dual SIRT-3 activator and PPAR-γ agonist that reduced oxidative stress markers within cells and changed the AMPK pathway
*IL1β↓, honokiol prevented restraint stress-induced cognitive dysfunction by reducing the hippocampus's production of IL-1β, TNF-α, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)
*TNF-α↓,
*GRP78/BiP↓,
*CHOP/DDIT3↓,
*NF-kB↓, Additionally, the neuroprotective benefits of honokiol in mice with Aβ-induced learning and memory impairment have been attributed to the inactivation of NF-κB
*GSK‐3β↓, Treatment of honokiol in PC12 cells resulted in reduced GSK-3β and induced β-catenin which effectively showed the neuroprotective and anti-oxidant effect in AD therapy
*β-catenin/ZEB1↑,
*Ca+2↓, , anti-apoptotic effect via reduced caspase 3 levels, and protected membrane injury by reduced calcium level has been investigated in PC12 cells of AD models
*AChE↓, protective effects by serving as an antioxidant, reduced AchE levels, repaired neurofibrillary tangles, reduced NF-kB which downregulates Aβ plaque
*SOD↑, fig1
*Catalase↑,
*GPx↑,

7761-

ISL,

Targeting digestive system cancers with isoliquiritigenin: a comprehensive review of antitumor mechanisms

Review,

Var,

Apoptosis↑, via the regulation of apoptosis, autophagy, cell cycle arrest, redox homeostasis, and tumor microenvironment (TME) remodeling.
TumAuto↑,
TumCCA↑,
ROS↑, ROS ↑, JNK ↑, p38 ↑, ERK ↓, STAT3 ↓, NF-κB ↓, IκB ↑, Bcl-2 ↓, Bax ↑, Cleaved caspase-3 ↑, Cleaved PARP ↑, p21 ↑, p27 ↓, Cyclin B1 ↓, CDK1/2 ↓
JNK↑,
p38↑,
STAT3↑,
NF-kB↓,
IκB↑,
Bcl-2↓,
BAX↑,
cl‑Casp3↑,
cl‑PARP↑,
P21↑,
p27/CDKN1B↑,
CycB/CCNB1↑,
CDK1↓,
CDK2↓,
GRP78/BiP↓, ISL also modulates the TME by downregulating GRP78 and inhibiting the PI3K/AKT/mTOR signaling pathway, thereby promoting apoptosis and autophagy
PI3K↓,
Akt↓,
mTOR↓,
eff↑, ISL-17 is a newly synthesized analog of ISL designed to improve its pharmacological properties.
GLUT4↓, ISL inhibits GLUT4-mediated glucose uptake, reduces lactate production and secretion, and suppresses both mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis.
lactateProd↓,
OXPHOS↓,
Glycolysis↓,
BioAv↑, ISL-loaded nanoliposomes represent a novel drug delivery system with excellent self-assembly and biocompatibility properties.
ENO1↓, ISL nanoliposomes suppress the expression of key glycolytic enzymes including Enolase 1 (ENO1), Aldolase A (ALDOA), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4).
ALDOA↓,
LDHA↓,
MCT4↓,
RadioS↑, ISL also enhances the radiosensitivity of HCC cells by modulating oxidative stress pathways.
Ferroptosis↑, ISL promotes ferroptosis by modulating iron metabolism and enhancing oxidative stress.
i-Iron↑, ISL treatment significantly elevated intracellular ferrous ion (Fe2+) levels, along with a marked increase in ROS and lipid peroxidation.
BioAv↑, Optimization of ISL delivery via two advanced nanocarrier systems has significantly addressed its poor aqueous solubility and limited bioavailability.
Half-Life↓, Furthermore, like many flavonoids, ISL suffers from poor oral bioavailability and rapid metabolic clearance.

7787-

ISL,

Dietary compound isoliquiritigenin targets GRP78 to chemosensitize breast cancer stem cells via β-catenin/ABCG2 signaling

in-vitro,

BC,

β-catenin/ZEB1↓, isoliquiritigenin (ISL) blocked β-catenin transcription activity with the highest inhibition ratio.
ChemoSen↑, ISL could have synergistic effects with chemotherapeutic drugs to inhibit breast cancer cell proliferation and colony formation.
CSCs↓, In addition, ISL could significantly limit the side population and CSC ratios in breast cancer cells, accompanied by inhibited self-renewal and multidifferentiation abilities
ABCG2↓, ISL could inhibit β-catenin/ABCG2 signaling by activating the proteasome degradation pathway
Proteasome↓,
GRP78/BiP↓, functional studies demonstrated that ISL could dock into the ATP domain of GRP78 and thereby inhibit its ATPase activity, resulting in its dissociation from β-catenin
selectivity↑, with little toxicity in normal tissues and mammary stem cells.

2028-

PB,

Potential of Phenylbutyrate as Adjuvant Chemotherapy: An Overview of Cellular and Molecular Anticancer Mechanisms

Review,

Var,

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/DDIT3↑, GADD153
AR↓, Sodium butyrate treatment of prostate cancer cells was associated with downregulation of androgen receptor
other?, lots of references in this paper.

4701-

PTS,

RES,

Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene

Review,

Var,

CSCs↓, Resveratrol and pterostilbene target CSCs
E-cadherin↑, " E-cadherin, # NF-jB, # EMT-associated molecules (Twist1,vimentin)
NF-kB↓,
EMT↓,
GRP78/BiP↓, GRP78
CD133↓, CD133
COX2/PTGS2↓, COX-2,
β-catenin/ZEB1↓,
NOTCH↓, Notch

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,

40 male Sprague Dawley rats, which were subsequently administered with 20 or 50 mg/kg of quercetin.

in-vitro,

NA,

Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 μM quercetin.

*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/DDIT3↓, 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

 (0.1, 0.5, 1 μmol/L)

*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

3364-

QC,

Quercetin Protects Human Thyroid Cells against Cadmium Toxicity

in-vitro,

Nor,

*MDA↓, MDA production was increased significantly after incubation with CdCl 2 1 and 10 μM compared with untreated cells (p < 0.001). This effect was significantly attenuated when the cultures were supple‐ mented with quercetin
*GRP78/BiP↓, A significant increase in GRP78 protein expression was detected in Nthy‐ori‐3‐1 cells exposed to 0.1 or 1 μM of CdCl 2 for 2 h compared with untreated cells. Again, this action was reversed by pretreatment with quercetin 5 μM

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,

*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/DDIT3↓,
*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,

24 Wistar Albino rats

*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,

 20 and 40 mg/kg RA

mice

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.

3021-

RosA,

Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway

in-vivo,

Sepsis,

mice

*eff↑, RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury.
*SOD↑, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity.
*MDA↓,
*GRP78/BiP↓, LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment.
*IRE1↓,
*JNK↓,
*Sepsis↓,

3023-

RosA,

Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis

in-vivo,

Sepsis,

*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↓,

3024-

RosA,

rmMANF prevents sepsis-associated lung injury via inhibiting endoplasmic reticulum stress-induced ferroptosis in mice

in-vivo,

Sepsis,

*Ferroptosis↓, rmMANF pretreatment inhibits ferroptosis by suppressing GRP78/PERK/ATF4 axis.
*GRP78/BiP↓,
*PERK↓,
*ATF4↓,
*Sepsis↓,
*GSH↑, LPS administration mice exhibited elevated MDA immunoactivity, total iron level, and declined GSH level, and SOD, CAT activities, while these effects of LPS were effectively against by rmMANF pretreatment
*SOD↑,
*Catalase↑,

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,

*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/DDIT3↓,
*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

3333-

SIL,

Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP-1 in mice

in-vivo,

NA,

mice

*GRP78/BiP↓, silymarin attenuated NAFLD by decreasing the ER stress proteins GRP78 and XBP-1.
*XBP-1↓,

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,

mice

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/DDIT3↓,
*Casp12↓,
*BAX↓,
*cl‑Casp3↓,

3146-

VitC,

Vitamin C protects against hypoxia, inflammation, and ER stress in primary human preadipocytes and adipocytes

in-vivo,

Nor,

*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,

mice

*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

3149-

VitC,

Hepatoprotective benefits of vitamin C against perfluorooctane sulfonate-induced liver damage in mice through suppressing inflammatory reaction and ER stress

in-vivo,

Nor,

mice

*hepatoP↑, Hepatoprotective benefits of vitamin C against perfluorooctane sulfonate-induced liver damage in mice
*ALAT↓, showed in reductions of serological levels of transaminases (ALT and AST), lipids (TG and TC), fasting glucose and insulin, inflammatory cytokines (TNF-α and IL6)
*AST↓,
*TNF-α↓,
*IL6↓,
*ER Stress↓, Further, intrahepatic expressions of endoplasmic reticulum (ER) stress-based ATF6, eIF2α, GRP78, XBP1 proteins were down-regulated by treatments of VC.
*ATF6↓,
*eIF2α↓,
*GRP78/BiP↓,
*XBP-1↓,
*Inflam↓, suppressing hepatocellular inflammatory reaction and ER stress.

3110-

VitC,

Vitamin C Attenuates Oxidative Stress, Inflammation, and Apoptosis Induced by Acute Hypoxia through the Nrf2/Keap1 Signaling Pathway in Gibel Carp (Carassius gibelio)

in-vivo,

Nor,

Gibel Carp

*IL2↑, Moreover, the levels of the inflammatory cytokines (tnf-α, il-2, il-6, and il-12) were increased by enhancing the Nrf2/Keap1 signaling pathway
*IL6↑,
*IL12↑,
*NRF2↑,
*Catalase↑, Upregulation of the antioxidant enzymes activity (CAT, SOD, and GPx); T-AOC;
*SOD↑,
*GPx↑,
*GRP78/BiP↓, The expression of GRP78 protein in the liver and endoplasmic reticulum stress and apoptosis induced by hypoxia were inhibited by VC.
*ER Stress↓,

Showing Research Papers: 1 to 35 of 35

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 35

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 2,
Total Targets: 152

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

compII↑, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1, antiOx↑, 5, Catalase↑, 5, Ferroptosis↓, 2, GPx↑, 5, GPx4↑, 1, GSH↑, 1, HO-1↑, 4, Keap1↓, 1, MDA↓, 7, MPO↓, 2, NRF2↑, 7, ROS↓, 9, mt-ROS↓, 1, SIRT3↑, 1, SOD↑, 10,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1, compIII↑, 1, MMP↑, 4, PGC-1α↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 2, AMPK↑, 1, LDL↓, 1, PPARγ↑, 1, SIRT1↑, 3,

Cell Death(tgid=5) ⓘ

Akt↑, 1, p‑Akt↑, 1, Apoptosis↓, 6, BAX↓, 4, Bcl-2↑, 3, Casp12↓, 6, Casp3↓, 3, cl‑Casp3↓, 1, Casp9↓, 1, Cyt‑c↓, 1, Ferroptosis↓, 2, GranB/GZMB↓, 1, iNOS↓, 3, JNK↓, 2, p‑JNK↓, 2, MLKL↓, 1, p38↓, 1, RIP1↓, 1,

Kinase & Signal Transduction(tgid=6) ⓘ

CaMKII ↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

ATF6↓, 4, CHOP/DDIT3↓, 12, eIF2α↓, 1, p‑eIF2α↓, 1, ER Stress↓, 16, GRP78/BiP↓, 24, IRE1↓, 5, PERK↓, 5, UPR↓, 2, XBP-1↓, 3,

Autophagy & Lysosomes(tgid=9) ⓘ

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

DNA Damage & Repair(tgid=10) ⓘ

p‑PARP↓, 1,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↑, 1, GSK‐3β↓, 1, miR-34a↓, 1, mTOR↓, 2, PI3K↑, 1, STAT3?, 1,

Migration(tgid=13) ⓘ

APP↓, 1, Ca+2↓, 2, E-cadherin↓, 1, Rho↓, 1, ROCK1↓, 1, TGF-β↑, 1, Zeb1↓, 1, ZO-1↓, 1, ZO-1↑, 1, β-catenin/ZEB1↑, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↑, 1, ATF4↓, 2, CLDN5↑, 1, NO↓, 1, PDI↓, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1, IBI↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 1, COX2/PTGS2↓, 2, IFN-γ↓, 1, IL10↓, 1, IL10↑, 2, IL12↑, 1, IL1β↓, 4, IL2↑, 1, IL4↓, 1, IL6↓, 4, IL6↑, 1, Imm↑, 1, Inflam↓, 11, JAK2↑, 1, LPS↓, 1, NF-kB↓, 3, TNF-α↓, 7,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 2, NGF↑, 1, tau↓, 1, p‑tau↓, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2, BACE/β-secretase↓, 1, NLRP3↓, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1, BioAv↑, 1, BioAv↝, 1, Dose↑, 1, Dose↝, 3, eff↓, 1, eff↑, 2,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 2, AST↓, 2, BG↓, 1, creat↓, 1, GutMicro↑, 2, IL6↓, 4, IL6↑, 1, Urea↓, 1,

Functional Outcomes(tgid=23) ⓘ

antiPs↑, 1, AntiTum↑, 1, cardioP↑, 4, cognitive↑, 3, hepatoP↓, 1, hepatoP↑, 5, memory↑, 2, motorD↑, 1, neuroP↑, 6, Obesity↓, 2, OS↑, 1, RenoP↑, 3, toxicity↓, 1,

Infection & Microbiome(tgid=24) ⓘ

Sepsis↓, 5,
Total Targets: 137

Scientific Paper Hit Count for: GRP78/BiP, HSPA5

5 Quercetin
5 Rosmarinic acid
4 EGCG (Epigallocatechin Gallate)
4 Vitamin C (Ascorbic Acid)
2 Crocetin
2 Hydrogen Gas
2 Isoliquiritigenin
1 Apigenin (mainly Parsley)
1 Curcumin
1 Berberine
1 Betulinic acid
1 Boron
1 Carvacrol
1 Ginkgetin
1 Honokiol
1 Phenylbutyrate
1 Pterostilbene
1 Resveratrol
1 Silymarin (Milk Thistle) silibinin
1 Shikonin

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#:356  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

GRP78/BiP Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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