HMGB1 Cancer Research Results

HMGB1, High Mobility Group Box 1: Click to Expand ⟱

Source:

Type:

HMGB1 is a nuclear protein that plays key roles in DNA architecture and regulation of transcription; however, when released extracellularly it can act as a damage-associated molecular pattern (DAMP), influencing immune responses and affecting tumor progression.

Overexpression of HMGB1, particularly when associated with increased extracellular release, is frequently correlated with enhanced tumor aggressiveness, metastasis, and poorer survival across several cancer types including breast, colorectal, lung, ovarian, and pancreatic cancers.
• Its critical involvement in inflammation and immune modulation makes HMGB1 an attractive candidate for targeted therapeutic intervention as well as a potential prognostic marker.

Scientific Papers found: Click to Expand⟱

2393-

Cela,

Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect

in-vivo,

Sepsis,

mice

in-vitro,

Nor,

RAW264.7

OS↑, Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS
PKM2↓, Cel bound to Cys424 of pyruvate kinase M2 (PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis (Warburg effect).
Glycolysis↓,
Warburg↓,
Inflam↓, Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.
HMGB1↓, Cel directly binds PKM2 and HMGB1
ALAT↓, pretreatment with Cel followed by LPS significantly reduced serum levels of ALT, AST and urea (
AST↓,
TNF-α↓, Cel pretreatment also decreased the serum levels of TNF-α, IL-1β and IL-6
IL1β↓,
IL6↓,

6303-

Cro,

Crocetin treatment inhibits proliferation of colon cancer cells through down-regulation of genes involved in the inflammation

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

DU145

NF-kB↓, Treatment of the DU-145 cells with crocetin caused a significant reduction in the expression levels of NF-κB, VEGF and MMP-9.
VEGF↓,
MMP9↓,
Inflam↓, significant reduction in the expression of genes involved in inflammation including, HMGB1, IL-6 and IL-8 on treatment of DU-145 cells with crocetin.
HMGB1↓,
IL6↓,
IL8↓,
TumCG↓, Crocetin inhibits growth of colon cancer cells and prevents tube formation through induction of apoptosis.
Apoptosis↑,

1601-

Cu,

The copper (II) complex of salicylate phenanthroline induces immunogenic cell death of colorectal cancer cells through inducing endoplasmic reticulum stress

in-vitro,

CRC,

i-CRT↓, Cu(sal)phen induced the release of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), the main molecular markers of ICD (immunogenic cell death)
ICD↑,
i-ATP↓,
i-HMGB1↓,
ER Stress↑, accumulation of ROS and inducing ERS
ROS↑,
DCells↑, promoted the maturation of dendritic cells (DCs)
CD8+↑, and activation of CD8+T cells
IL12↑, secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ)
IFN-γ↑,
TGF-β↓, while downregulating transforming growth factor-β (TGF-β) levels

7193-

EGb 761,

5-FU,

Ginkgo biloba extract 761 enhances 5-fluorouracil chemosensitivity in colorectal cancer cells through regulation of high mobility group-box 3 expression

in-vitro,

CRC,

SW480

in-vitro,

CRC,

SW-620

*antiOx↑, Although the standard ginkgo biloba extract EGb 761 exhibits antioxidative, anti-apoptotic, and anticancer properties, there is no research focusing on the chemopreventive effects of EGb 761 in colorectal cancer (CRC).
AntiCan↑,
ChemoSen↑, We found that combined EGb 761 and 5FU treatment significantly elevated the chemosensitivity of CRC cells to 5FU in 5FU-resistant (5FUR) CRC cells
selectivity↑, whereas no obvious cytotoxicity of EGb 761 was observed in parental cells.
EMT↓, EGb 761 notably attenuated drug resistance through inhibition of epithelial-mesenchymal transition (EMT) factors (increased E-cadherin and decreased vimentin).
E-cadherin↑,
Vim↓,
HMGB1↓, we found that EGb 761 significantly inhibited 5FU-induced upregulation of high mobility group-box 3 (HMGB3) expression in 5FUR CRC cells both at mRNA and protein levels.
other↝, GBE contains over 60 biologically active substances, the most important of which are terpentins, flavonoids, carboxylic acids, and L-ascorbic acid.
chemoPv↑, It has also been reported that EGb 761 has chemopreventive effects in estrogen receptor-independent breast cancer through anti-proliferative and apoptosis-inducing activities

5519-

EP,

Nanosecond Pulsed Electric Fields (nsPEFs) for Precision Intracellular Oncotherapy: Recent Advances and Emerging Directions

Review,

Var,

MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,

7012-

Fuc,

Fucoidan: A promising natural therapeutic agent for protecting human kidney health

Review,

EC,

*RenoP↑, Fucoidan exhibits significant anti-inflammatory effects in kidney protection.
*Inflam↓,
*antiOx↑, Antioxidant properties effectively reduce oxidative stress in renal tissues.
*ROS↓,
*BloodF↑, Enhances renal function by improving blood flow and diuresis.
*diuretic↑,
*BioAv↓, High-MW fucoidans often display stronger anticoagulant and viscosity-modulating effects. However, they may have limited oral bioavailability,
*BioAv↑, whereas low- to medium-MW fractions show improved tissue penetration, more favorable absorption, and can retain potent anti-inflammatory and anti-fibrotic activities, making them attractive for chronic kidney disease applications
*MAPK↓, (LMWF) has been reported in models of renal ischemia-reperfusion injury, where it inhibits the MAPK signaling pathway and subsequently reduces inflammation and fibrosis
*ERK↑, fucoidan can activate the ERK/MAPK signaling pathway, which plays a crucial role in preserving the endothelial glycocalyx in CKD
*NLRP3↓, fucoidan attenuates NLRP3 inflammasome activation and subsequent podocyte pyroptosis, ultimately leading to improved renal function and reduced inflammation in diabetic kidney disease (DKD)
*NRF2↑, By inhibiting ROS-generating systems (e.g., NADPH oxidase) and activating Nrf2-dependent transcription of antioxidant genes, fucoidan limits mitochondrial dysfunction and prevents oxidative injury to podocytes and tubular epithelial cells
*MDA↓, fucoidan nanoparticles significantly reduced levels of malondialdehyde (MDA), a marker of lipid peroxidation and oxidative stress, while simultaneously upregulating the levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx)
*SOD↑,
*GPx↑,
*Catalase↑, Altogether, fucoidan directly reduces renal oxidative stress by scavenging reactive oxygen species and upregulating endogenous antioxidant defenses (e.g., SOD, CAT, GPx) in tubular and glomerular cells, by suppressing upstream ROS generation
*lipid-P↓, fucoidan limits lipid peroxidation and DNA damage, thereby preserving podocyte integrity and tubular epithelial viability
*DNAdam↓,
*Fibrosis↓, Inhibition of fibrosis
*JAK2↓, fucoidan combats renal fibrosis is via the restriction of the JAK2/STAT3 signaling pathway.
*STAT3↓,
*uricA↓, By reducing serum uric acid levels, fucoidan significantly inhibits the activation of JAK2/STAT3, consequently decreasing the expression of key fibrotic markers such as collagen I and α-smooth muscle actin (α-SMA)
*COL1↓,
*α-SMA↓,
*SIRT1↑, fucoidan’s anti-fibrotic effects are further attributed to its activation of protective pathways such as Sirt-1, GLP-1R, and Nrf2/HO-1(
*HO-1↑,
*GLP-1R↑,
*HMGB1↓, Stimulating these protective pathways results in the inhibition of pro-fibrotic signaling cascades, including the HMGB1/RAGE/NF-κB/TGF-β1 pathway
*RAGE↓,
*NF-kB↓,
*TGF-β1↓,
*PI3K↓, Fucoidan also exhibits potential in curtailing the inflammatory processes associated with renal fibrosis through its inhibitory effects on the PI3K/Akt/NF-κB signaling cascade.
*Akt↓,
*GutMicro↑, research has elucidated the important role of gut microbiota in mediating the protective effects of fucoidan, suggesting that modulation of microbial communities may underlie its benefits in renal health
*SCFAs↑, Fucoidan’s positive impact on gut microbiota includes enhancing the production of short-chain fatty acids (SCFAs), especially butyrate, which are known to support gut integrity and overall health (
*Buty↑,
*IBI↑, Fucoidan's ability to enhance SCFA production has been linked to improved intestinal barrier integrity, a crucial factor in preventing the translocation of harmful substances into the bloodstream, which can exacerbate kidney injury
*TJ↑, Studies indicate that fucoidan can upregulate the expression of tight junction proteins, crucial for maintaining the integrity of the intestinal epithelium
*Dose↝, national approval in China for renal indications, indicate that fucoidan is generally safe at oral doses of 50–300 mg/day and up to 1–3 g/day in short‑ to mid‑term studies, with no major hematologic, hepatic, or renal toxicity reported.

7489-

H2,

Molecular Hydrogen in the Treatment of Respiratory Diseases

Review,

Asthma,

*antiOx↑, Molecular hydrogen is gaining increasing attention as an antioxidant, anti-inflammatory, and antiapoptotic agent.
*Inflam↓,
*Apoptosis↓,
*Dose↓, It reaches a maximum level of about 0.78 mM (≈1.6 mg/L) at room temperature with a loss of about 2–5% per 3 min
*Dose↝, It is produced (and consumed) by bacteria of the gut microbiota .The most prominent bacterial phyla involved in this process are the Firmicutes and Bacteroidetes phyla, which include the anaerobic Clostridium species
*eff↑, hydrogen mixed with oxygen at a ratio of 96%-to-4%, known as the Hydrox gas mixture, was used by deep-sea divers to prevent decompression sickness and allow diving to depths of up to 500 m
*ROS↓, The antioxidant activity of H2 is based on two processes: a direct scavenging of the most toxic reactive oxygen and nitrogen species (ROS/RNS),
*RNS↓,
*NRF2↑, H2 activates the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway, a key transcription factor involved in oxidative stress-related responses, including cytoprotective, antioxidant, and detoxifying enzymes such as HO-1
*HO-1↑,
*Fenton↓, removal of free heme and inhibition of the Fenton reaction
*NLRP3↓, the activation of the Nrf2 pathway has been shown to inhibit the NLRP3 (NLR family pyrin domain containing 3) inflammasome,
*NADPH↓, H2 suppresses the activation of the NADPH oxidase pathway and downregulates the expression of NOX2 and NOX4
*NOX4↓,
*NOX↓,
*MPO↓, H2 has been shown to reduce the overactivation of myeloperoxidase (MPO)
*NF-kB↓, would further suppress the NFκB
*TNF-α↓, figure 3
*IL6↓,
*IL1β↓,
*HMGB1↓,
*IL4↑,
*IL10↑,
*M2 MC↑, Additionally, H2 promotes the polarization of macrophages from the proinflammatory M1 type to the anti-inflammatory M2 type
*Treg lymp↝, It also inhibits Th2 responses, restores regulatory T cells (Treg), and, thus, normalizes an overactivated immune system
*Bcl-2↑, upregulate the antiapoptotic factors, including Bcl-2 and Bcl-xl.
*Bcl-xL↑,
*PI3K↑, phenomenon is likely facilitated by the activation of the PI3K/Akt and JAK2/STAT3 signaling pathways
*Akt↑,
*JAK2↑,
*STAT3↑,
*Dose↑, The consumption of certain prebiotics, especially those rich in dietary fiber, indigestible starches, and sugars (lactulose), has been demonstrated to enhance intestinal H2 production through the activity of intestinal flora
*CD4+↑, H2 increased the population of CD4+CD25+Foxp3+ Treg cells, which are often decreased in allergic rhinitis (AR)
*CD25+↑,
*FOXP3↑,
*MDA↓, H2 administration attenuated oxidative stress expressed as lower MDA and other lipid peroxidation markers along with an enhancement in the expression and activity of endogenous antioxidant enzymes such as SOD or CAT
*SOD↑,
*Catalase↑,
*Casp3↓, inhibition of proapoptotic processes like the caspase 3 and 9 pathways
*Casp9↓,
*TBARS↓, drinking of HRW by patients with asthma and COPD leads to an increase in blood oxygen saturation, vitamin E levels, along with lower oxidative stress markers such as thiobarbituric acid reactive substances (TBARS), MDA,
*SpO2↑,
*VitE↓,
*OS↑, COPD:In general, H2 administration has been found to lead to enhanced survival and reduced weight loss [110], improved lung function and static lung compliance, and decreased arterial blood pressure
*Weight↑,
*DNAdam↓, reduction in levels of oxidative DNA damage markers
*PGE2↓, H2 reduced elevated inflammatory markers, including IL-1β, IL-6, TNF-α, prostaglandin E2 (PGE2) [29,65,71,128,130], macrophage protein 1α 2 (MP1α), and monocyte chemoattractant protein-1 (MCP-1)
*MCP1/CCL2↓,
*lipid-P↓, Further, a reduction in oxidative stress markers such as lipid peroxidation and proapoptotic markers, including Bax and caspase-3, was observed.
*TumCP↓, H2-rich medium reduced the colony size and formation of tongue cancer cells and decreased proliferation in human fibrosarcoma and esophageal cancer cells, as well as A549 cells
*tumCV↓, decrease in cell viability, migration, and invasion
*TumCMig↓,
*TumCI↓,
TumW↓, A reduction in tumor weight and size, as well as a lower number of cells of squamous cell carcinoma, was revealed by animal studies.
TumVol↓,
selectivity↑, Notably, as previously reported, H2 administration exhibited no effect on healthy animals or non-cancerous cell lines
QoL↑, Patients reported improved quality of life with better physical status and fewer pulmonary symptoms
ChemoSen↑, In combination with conventional (such as cis-platin) and modern (including antibodies like nivolumab) therapeutics, H2 enhanced drug activity, resulting in enhanced outcomes and improved disease control
chemoP↑, and reduced side effects of the treatment, such as nephrotoxicity, weight loss, insomnia, pain, or hearing loss in the case of radiotherapy
radioP↑, radioprotective effects of H2 are primarily attributed to its hydroxyl radical scavenging activity
ROS↑, As indicated by Yang et al., the latter include the activation of the ROS/NLRP3/caspase-3/gasdermin D-mediated pyroptotic pathways
NLRP3↑,
Casp3↑,
VEGF↓, suppression of vascular endothelial growth factor (VEGF) expression
Wnt↓, H2 result in the suppression of the overactivated Wnt/beta-catenin signaling pathways, which further leads to suppression of tumor progression
β-catenin/ZEB1↓,

2508-

H2,

Molecular hydrogen is a promising therapeutic agent for pulmonary disease

Review,

Var,

Review,

Sepsis,

*ROS↓, inhalation of 2% molecular hydrogen results in the selective scavenging of hydroxyl free radical (·OH) and peroxynitrite anion (ONOO-), significantly improving oxidative stress injury caused by cerebral ischemia/reperfusion (I/R)
eff↝, Molecular hydrogen can exert biological effects on almost all organs, including the brain, heart, lung, liver, and pancreas.
*Inflam↓, including roles in the regulation of oxidative stress and anti-inflammatory and anti-apoptotic effects
*NRF2↑, By stimulating nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the basal and induces expression of many antioxidant enzymes
*HO-1↑, hydrogen can increase the expression of heme oxygenase-1 (HO-1)
*SOD↑, increases the activity of the antioxidant enzymes SOD, CAT, and myeloperoxidase (MPO)
*Catalase↑,
*MPO↑,
*ASK1↓, Molecular hydrogen can block the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway
*NADPH↓, thereby inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and decreasing free radical production
*Sepsis↓, Emerging evidence suggests that hydrogen can prevent sepsis, providing a novel treatment strategy for sepsis-induced ALI.
*HMGB1↓, Hydrogen attenuates tissue injury and dysfunction by inhibiting HMGB-1.
ROS↑, it has been shown that hydrogen pretreatment enhances ROS and the expression of pyroptosis-related proteins, stimulates NLRP3 inflammasome/gasdermin D (GSDMD) activation, and inhibits endometrial cancer
NLRP3↑,
GSDMD↑,
chemoP↑, Hydrogen can alleviate the side effects of conventional anti-cancer therapies, such as chemotherapy and radiotherapy, and improve quality of life
eff↑, It significantly improves the physical status of patients, reduces fatigue, insomnia, anorexia, and pain, and decreases elevated tumor markers.

2503-

H2,

Brain Metastases Completely Disappear in Non-Small Cell Lung Cancer Using Hydrogen Gas Inhalation: A Case Report

Case Report,

Lung,

TumVol↓, Hydrogen-gas monotherapy was started to control the tumor a month later. After 4 months, the size of multiple brain tumors was reduced significantly
OS↑, After 1 year, all brain tumors had disappeared, and there were no significant changes in metastases in the liver and lung.
Dose↝, The hydrogen oxygen nebulizer (AMS-H-03, Asclepius Meditec, Shanghai, China) generates 3 L/min hydrogen gas by hydrocephalus electrolysis. As measured by gas chromatography, the gas generated consisted of 67% hydrogen and 33% oxygen.
Dose↝, Using a special mask, the patient continued to inhale hydrogen for 3–6 hrs a day at rest, with no interruption even after the obvious relief of symptoms.
CEA↓, dropped from 29.44 to 12 ng/mL in 12 months (figure 3)
CA125↓, dropped from 150 to 60 u/mL (figure 3)
CYFRA21-1↓, dropped from 12 to 6 ng/mL (figure 3)
SIRT1↓, several scholars have demonstrated that hydrogen can suppress SIRT1 signaling in different model
COX2/PTGS2↓, hydrogen exerts neuroprotective effects by reducing cyclooxygenase-2 activity25 or activating expression of anti-apoptotic protein kinase B.
IL1β↓, Hydrogen inhalation can down-regulate the expression of various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, intracellular adhesion molecule-1, high mobility group box-1, nuclear factor-kappa B, and prosta
IL6↓,
TNF-α↓,
HMGB1↓,
NF-kB↓,
EP2↓, and prostaglandin-E2

1266-

LE,

Glycyrrhizin suppresses epithelial-mesenchymal transition by inhibiting high-mobility group box1 via the TGF-β1/Smad2/3 pathway in lung epithelial cells

in-vitro,

Lung,

A549

in-vitro,

Nor,

BEAS-2B

HMGB1↓,
EMT↓,
TumCMig↓,
p‑SMAD2↓,
p‑SMAD3↓,

2338-

QC,

Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury

Review,

Nor,

*SIRT1↑, Quercetin increased SIRT1 expression in lung tissue, inhibited NLRP3 inflammasome activation, and reduced the release of pro-inflammatory factors (TNFα, IL-1β, and IL-6), preventing the up-regulation of nuclear PKM2 in the lung.
*NLRP3↓,
*Inflam↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*PKM2↓, preventing the up-regulation of nuclear PKM2 in the lung.
*HO-1↑, Quercetin increased HO-1 expression in the lungs of a septic lung injury mouse model
*ROS↓, puncture in rats, showing that early administration of Quercetin reduced the levels of oxidative stress markers, such as xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA), and increased the levels of antioxidant enzymes in lung tiss
*NO↓,
*MDA↓,
*antiOx↑,
*COX2/PTGS2↓, Quercetin also reduced the expression of COX-2, HMGB1, and iNOS expression and NF-κB p65 phosphorylation
*HMGB1↓,
*iNOS↓,
*NF-kB↓,

3349-

QC,

HMGB1_Protein_Expression">Quercetin Exerted Protective Effects in a Rat Model of Sepsis via Inhibition of Reactive Oxygen Species (ROS) and Downregulation of High Mobility Group Box 1 (HMGB1) Protein Expression

in-vivo,

Sepsis,

rats

*Sepsis↓, results showed that quercetin reduced the tissue edema, congestion, and hemorrhage, increased the alveolar volume, and helped to maintain the lung anatomy of septic rats.
*ROS↓, Admistration of quercetin at the dosage of 15 and 20 mg/kg to septic rats caused significant reduction in the ROS levels.
*SOD↑, The results showed that administration of quercetin at the dosage of 15 and 5 mg/kg to septic rats caused a significant increase in SOD, CAT, and APX expression levels
*Catalase↑,
*HMGB1↓, quercetin caused a significant decrease in HMGB1 protein levels
*Inflam↓, quercetin was found to reduce the inflammation associated with sepsis
*TAC↑, significant increase in the expression of antioxidant enzymes.

3003-

RosA,

Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases

Review,

Var,

Review,

AD,

Review,

Park,

*Inflam↓, anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes,
*antiOx↑,
*neuroP↑,
*IL6↓, diabetic rat model treated with RA, there is an anti-inflammatory activity reported. This activity is achieved through the inhibition of the expression of various proinflammatory factors, including in IL-6, (IL-1β), tumour
*IL1β↓,
*NF-kB↓, inhibiting NF-κB activity and reducing the production of prostaglandin E2 (PGE2), nitric oxide (NO), and cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
*PGE2↓,
*COX2/PTGS2↓,
*MMP↑, RA inhibits cytotoxicity in tumour patients by maintaining the mitochondrial membrane potential
*memory↑, amyloid β(25–35)-induced AD in rats was treated with RA, which mitigated the impairment of learning and memory disturbance by reducing oxidative stress
*ROS↓,
*Aβ↓, daily consumption of RA diminished the effect of neurotoxicity of Aβ25–35 in mice
*HMGB1↓, SH-SY5Y in vitro and ischaemic diabetic stroke in vivo, and the studies revealed that a 50 mg/kg dose of RA decreased HMGB1 expression
TumCG↓, Rosemary and its extracts have been shown to exhibit potential in inhibiting the growth of cancer cells and the development of tumours in various cancer types, including colon, breast, liver, and stomach cancer
MARK4↓, Another study reported the inhibition of Microtubule affinity regulating kinase 4 (MARK4) by RA
Zeb1↓, Fig 4 BC:
MDM2↓,
BNIP3↑,
ASC↑, Skin Cancer
NLRP3↓,
PI3K↓,
Akt↓,
Casp1↓,
E-cadherin↑, Colon Cancer
STAT3↓,
TLR4↓,
MMP↓,
ICAM-1↓,
AMPK↓,
IL6↑, PC and GC
MMP2↓,
Warburg↓,
Bcl-xL↓, CRC: Apoptosis induction caspases ↑, Bcl-XL ↓, BCL-2 ↓, Induces cell cycle arrest, Inhibition of EMT and invasion, Reduced metastasis
Bcl-2↓,
TumCCA↑,
EMT↓,
TumMeta↓,
mTOR↓, Inhibits mTOR/S6K1 pathway to induce apoptosis in cervical cancer
HSP27↓, Glioma ↓ expression of HSP27 ↑ caspase-3
Casp3↑,
GlucoseCon↓, GC: Inhibited the signs of the Warburg effect, such as high glucose consumption/anaerobic glycolysis, lactate production/cell acidosis, by inhibiting the IL-6/STAT3 pathway
lactateProd↓,
VEGF↓, ↓ angiogenic factors (VEGF) and phosphorylation of p65
p‑p65↓,
GIT1↓, PC: Increased degradation of Gli1
FOXM1↓, inhibiting FOXM1
cycD1/CCND1↓, RA treatment in CRC cells inhibited proliferation-induced cell cycle arrest of the G0/G1 phase by reducing the cyclin D1 and CDK4 levels,
CDK4↓,
MMP9↓, CRC cells, and it led to a decrease in the expressions of matrix metalloproteinase (MMP)-2 and MMP-9.
HDAC2↓, PCa cells through the inhibition of HDAC2

2354-

SK,

PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation

in-vivo,

Sepsis,

mice

PKM2↓, Shikonin is a potent PKM2 inhibitor in cancer cells and macrophages
*PKM2↓,
*IL1β↓, Shikonin dose-dependently inhibited IL-1β, IL-18 and HMGB1 release in activated BMDMs following treatment with NLRP3 inflammasome activator (for example, ATP) or AIM2 inflammasome activator
*IL18↓,
*HMGB1↓,
*Casp1↓, shikonin significantly inhibited caspase-1 activation triggered by stimulation with ATP
*NLRP3↓, pharmacologic inhibition of PKM2 by shikonin selectively suppresses NLRP3 and AIM2 inflammasome activation.
*AIM2↓,
*p‑eIF2α↓, Shikonin inhibited EIF2AK2 phosphorylation (Fig. 6a) and caspase-1 activity (Fig. 6b) in PMs obtained from mice subjected to lethal endotoxemia or polymicrobial sepsis.
*Sepsis↓,

1284-

SK,

Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy

in-vitro,

Melanoma,

RPMI-8226

in-vitro,

Melanoma,

U266

Ferroptosis↑, SHK treatment leads to the ferroptosis of MM cells
LDH↓,
ROS↑, Cellular mitochondrial lipid ROS also increased after SHK treatment
Iron↑,
lipid-P↑,
ATP↓, extracellular release of Adenosine 5’-triphosphate (ATP) and High mobility group protein B1 (HMGB1
HMGB1↓,
GPx4↓, Additionally, the ferroptosis markers GPX4 and solute carrier family 7 member 11 (xCT/SLC7A11) were downregulated at both the transcriptional and translational levels after SHK treatment
MDA↑, SHK treatment led to an increase in MDA content in cells. In contrast, the levels of SOD and GSH decreased in cells
SOD↓,
GSH↓,

7909-

VT,

Vitexin Inhibits Gastric Cancer Growth and Metastasis through HMGB1-mediated Inactivation of the PI3K/AKT/mTOR/HIF-1α Signaling Pathway

vitro+vivo,

GC,

mice

tumCV↓, Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner.
TumCMig↓,
TumCI↓,
EMT↓,
PI3K↓, Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression.
Akt↓,
Hif1a↓,
HMGB1↓,
TumCG?, Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression.

7887-

VT,

IVT,

Dietary Flavonoids Vitexin and Isovitexin: New Insights into Their Functional Roles in Human Health and Disease Prevention

Review,

AD,

Review,

Var,

*antiOx↑, antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective mechanisms.
*Inflam↓,
*AntiCan↑,
*Bacteria↓,
*neuroP↑, cardiovascular protection, blood sugar regulation, anti-obesity, anticancer, antioxidant, anti-inflammatory, and neuroprotective properties.
*Obesity↓,
*cardioP↑, Vitexin exerts a cardioprotective effect against DOX-induced cardiac toxicity by reducing oxidative stress, lowering cardiac inflammatory cytokines, increasing FOXO3a, and inhibiting caspase-3 activation.
*ROS↓, Sprague-Dawley rat hearts, H9c2 cells 10 μM Reducing ROS levels; improving mitochondrial activity, mitochondrial membrane potential, and ATP content; markedly increasing MFN2 expression and reducing the recruitment of Drp1 in mitochondria.
*MMP↑,
*ATP↑,
*MFN2↑,
*DRP1/DNM1L↓,
*FOXO3↑, Protect against DOX-induced acute cardiotoxicity Rats 30 mg/kg Vitexin induced elevated FOXO3a protein expression levels, by suppressing oxidative stress
*NRF2↑, vitexin activated nuclear factor-erythroid 2-related factor 2 (Nrf2) in HUVEC under high glucose.
*Ferroptosis↓, Diabetic nephropathy HK-2 cells/DN rat 0–40 μM Vitexin could alleviate diabetic nephropathy by attenuated ferroptosis via activating GPX4
*GPx4↑,
TumCP↓, Gastric cancer Nude mice/GC cells 2 mg/kg 10–160 μM Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway.
HMGB1↓,
PI3K↓,
Akt↓,
Hif1a↓,
CDK1↓, Colon cancer HCT-116 cells 1–300 μM Inhibit colon cancer HCT-116 cell proliferation by suppressing CDK1/cyclin B expression, leading to cell cycle arrest in the G2/M phase.
CycB/CCNB1↓,
TumCCA↑,
Apoptosis↑, Isovitexin Colon cancer Promoted apoptosis and suppressed cell proliferation by activating the p53 signaling pathway.
P53↑,
NF-kB↓, Non-small cell lung cancer cells A549/ H1299 cells, nude mice 1–120 μM Suppressed NF-κB, AKT and ERK activation. [24] Vitexin A549 cells, nude mice 0–40 μM Reduced the levels of p-PI3K, p-Akt, and p-mTOR.
ERK↓,
p‑PI3K↓,
miR-34a↑, Isovitexin Hepatocarcinoma SK-Hep-1 cells Mediated miR-34a upregulation induces apoptosis and suppresses the stemness of SK-SC.
Apoptosis↑,
CSCs?,
*MAPK↓, Isovitexin Acute lung injury RAW 264.7 cells 0–50 μM Inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways.
*HO-1↑,
*hepatoP↑, EAH mice 5 mg/kg Vitexin ameliorated hepatic injury in EAH mice through activation of the AMPK/AKT/GSK-3β pathway and upregulation of the Nrf2 gene.
*AMPK↑,
*Akt↑,
*GSK‐3β↑,
*chemoP↑, Vitexin exerts a cardioprotective effect against DOX-induced cardiac toxicity by reducing oxidative stress, lowering cardiac inflammatory cytokines, increasing FOXO3a, and inhibiting caspase-3 activation.
*Casp3↓,
*IRes↝, Vitexin and isovitexin flavonoids not only affected the absorption of peripheral glucose in insulin and non-insulin sensitive tissues but also showed the potential to restore insulin resistance in HepG2 cells by enhancing cellular uptake of glucose.
*GlucoseCon↑,
ChemoSen↑, When combined with doxorubicin (Dox), vitexin can reduce tumor growth and show synergistic effects in in vivo tests, increasing antitumor efficacy.
*GSH↑, Vitexin also increased Nrf2 expression and boosted GSH and antioxidant enzymes such as SOD, CAT, GPx, and GST.
*SOD↑,
*ATF2↑,
*GPx↑,
*GSTs↑,
*AntiAge↑, In Caenorhabditis elegans, studies have shown that vitexin and isovitexin, as putative SKN-1/Nrf2 activators, increase lifespan and support a healthy lifespan.
*Stroke↓, It has been demonstrated that vitexin protects against a cerebral ischemia/reperfusion (I/R)-induced increase in the permeability of brain endothelial cells
*AChE↓, vitexin treatment significantly inhibited acetylcholinesterase activity and markedly downregulated the expression of ace-1 and ace-2.
*ACE/ACE1↓,
*ACE2↓,
*GutMicro↑, Vitexin and isovitexin have also shown promising potential in modulating intestinal microbiota and in turn play a significant role in regulating various diseases such as overweight
*MPO↓, Vitexin can also resist Helicobacter pylori infection, which may be related to its anti-myeloperoxidase (MPO) enzyme activity and inhibition of H- and K-ATPase activity
*H+/K+-ATPase↓,
*AntiDiabetic↑, Antidiabetic Vitexin and Isovitexin Inhibits α-glucosidase/α-amylase, promotes GLUT4, modulates gut microbiota
*GLUT4↑,
*Obesity↓, Anti-obesity Vitexin Activates AMPKα, inhibits C/EBPα, FAS, activates Hedgehog signaling
*HH↓,
*RenoP↑, vitexin protects the kidneys and prevents the formation of kidney stones by inhibiting pyroptosis, apoptosis, epithelial–mesenchymal transition (EMT), and macrophage activation.
*BioAv↓, Vitexin and isovitexin have poor absorption in the gastrointestinal tract, with significant first-pass effects in the intestine (approximately 94%), stomach (30%), and liver (50%), resulting in a lower bioavailability (F) (approximately 5%).
*BioAv↝, The absorption and metabolism processes of vitexin and isovitexin in the human body are complex, and their bioavailability is influenced by multiple factors, including the action of the gut microbiota, interactions with dietary components, first-pass
*BioAv↑, The vitexin-loaded bilayer nanoparticles are designed by assembling soybean peptides and coating them with a goblet cell-targeting peptide. They significantly increase the bioaccessibility and bioavailability of vitexin

Showing Research Papers: 1 to 17 of 17

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 1,
Total Targets: 132

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

ACE/ACE1↓, 1, ACE2↓, 1, Buty↑, 1, diuretic↑, 1, GLP-1R↑, 1, H+/K+-ATPase↓, 1, IRes↝, 1, SCFAs↑, 1, SpO2↑, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 6, Catalase↑, 4, Fenton↓, 1, Ferroptosis↓, 1, GPx↑, 2, GPx4↑, 1, GSH↑, 1, GSTs↑, 1, HO-1↑, 5, lipid-P↓, 2, MDA↓, 3, MFN2↑, 1, MPO↓, 2, MPO↑, 1, NOX4↓, 1, NRF2↑, 4, RNS↓, 1, ROS↓, 7, SOD↑, 5, TAC↑, 1, TBARS↓, 1, uricA↓, 1, VitE↓, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1, DRP1/DNM1L↓, 1, MMP↑, 2,

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1, GlucoseCon↑, 1, NADPH↓, 2, PKM2↓, 2, SIRT1↑, 3,

Cell Death(tgid=5) ⓘ

Akt↓, 1, Akt↑, 2, Apoptosis↓, 1, ASK1↓, 1, ATF2↑, 1, Bcl-2↑, 1, Bcl-xL↑, 1, Casp1↓, 1, Casp3↓, 2, Casp9↓, 1, Ferroptosis↓, 1, iNOS↓, 1, MAPK↓, 2,

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

p‑eIF2α↓, 1,

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 2,

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

ERK↑, 1, FOXO3↑, 1, GSK‐3β↑, 1, HH↓, 1, PI3K↓, 1, PI3K↑, 1, STAT3↓, 1, STAT3↑, 1,

Migration(tgid=13) ⓘ

COL1↓, 1, Fibrosis↓, 1, RAGE↓, 1, TGF-β1↓, 1, TJ↑, 1, Treg lymp↝, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 1, α-SMA↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↑, 1, NO↓, 1,

Barriers & Transport(tgid=15) ⓘ

GLUT4↑, 1, IBI↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

AIM2↓, 1, CD25+↑, 1, CD4+↑, 1, COX2/PTGS2↓, 2, FOXP3↑, 1, HMGB1↓, 7, IL10↑, 1, IL18↓, 1, IL1β↓, 4, IL4↑, 1, IL6↓, 3, Inflam↓, 7, JAK2↓, 1, JAK2↑, 1, M2 MC↑, 1, MCP1/CCL2↓, 1, NF-kB↓, 4, PGE2↓, 2, TNF-α↓, 2,

Cellular Microenvironment(tgid=17) ⓘ

NOX↓, 1,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1, NLRP3↓, 4,

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

BloodF↑, 1, GutMicro↑, 2, IL6↓, 3, RAGE↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 2, AntiCan↑, 1, AntiDiabetic↑, 1, cardioP↑, 1, chemoP↑, 1, hepatoP↑, 1, memory↑, 1, neuroP↑, 2, Obesity↓, 2, OS↑, 1, RenoP↑, 2, Weight↑, 1,

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1, Sepsis↓, 3,
Total Targets: 127

Scientific Paper Hit Count for: HMGB1, High Mobility Group Box 1

3 Hydrogen Gas
2 Quercetin
2 Shikonin
2 Vitexin
1 Celastrol
1 Crocetin
1 Copper and Cu NanoParticles
1 Ginkgo biloba-EGb 761
1 5-fluorouracil
1 Electrical Pulses
1 Fucoidan
1 Licorice
1 Rosmarinic acid
1 Isovitexin

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#:1059  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HMGB1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

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) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

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) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

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) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

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) ⓘ

Home Page