BAX Cancer Research Results

BAX, Apoptosis regulator BAX: Click to Expand ⟱
Source:
Type: Proapototic protein
BAX is a member of the Bcl-2 gene family.
Pro-apoptotic protein that forms heterodimers with anti-apoptotic BCL2 proteins; involved in various cellular activities and regulated by p53; mediates the release of cytochrome c from mitochondria.
Scientific Papers found: Click to Expand⟱
7407- Amla,    Functional and Nutraceutical Significance of Amla (Phyllanthus emblica L.): A Review
- Review, Nor, NA
*Inflam↓, amla has been proven to have anti-hyperglycemic, hypoglycemic, anti-inflammatory, anti-hyperlipidemic, and antioxidant activities
*antiOx↑,
*GSH↑, a study using the extract from amla leaves (200–400 mg/kg BW) indicated a similar protective effect in diabetic mice by reducing inducing the activity of GSH, GPx, SOD, and CAT activity and also reducing lipid peroxidation
*GPx↑,
*SOD↑,
*Catalase↑,
*lipid-P↓, significant reduction in the peroxidation level and increased antioxidant status were observed in subjects that consumed 250 mg (twice a day) for 60 days
*ROS↓, polyphenols (especially tannins and flavonoids) present in this fruit extract significantly reduced oxidative stress by scavenging NOx.
*cardioP↑, Fruit Gallic acid Cardioprotective activity
*AntiDiabetic↑, Fruit Ellagic acid Antidiabetic activity
*neuroP↑, Fruit Emblicanin A and B Neuroprotective activity
*GastroP↑, Fruit Tannins and gallic acid Gastrointestinal protective activity
*COX2/PTGS2↓, inhibited the enhanced mitochondrial COX-2, MDA, and Bax expressions in the liver
*MDA↓,
*BAX↓,
*TG/TAG↓, Figure 2
*HDL↑,
*LDL↓,
*HMG-CoA↓,
*Dose↝, At the human level, a 500 mg dose of P. emblica L. extract (twice a day) for three months reduced the high sensitive C-reactive protein (CRP), total cholesterol, and LDL levels in Class I obese subjects
*CRP↓,
DNAdam↑, Particularly for amla extracts, DNA fragmentation, increased activity of caspase-3, 7, and 8, and up-regulation of Fas protein were observed in the HeLa cell line,
Casp3↑,
Casp7↑,
Casp8↑,
Fas↑,
TumCI↓, This study also indicated that P. emblica L. decreased the invasiveness of MDA-MB-231 cells (in vitro Matrigel invasion study), and no cytotoxicity was seen in normal lung fibroblasts (MRC5)
selectivity↑,

2478- Ba,    The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria- and caspase-3-dependent pathway
- in-vitro, BC, MDA-MB-231
Bcl-2↓, Baicalein induced apoptosis in a time-dependent effect through the inhibition of Bcl-2 expression, increased the levels of Bax
BAX↓,
Cyt‑c↑, promoted the cytochrome c release and caspase-3 activation.
Casp3↑,
Ca+2↓, baicalein induced apoptosis via Ca2+ production, mitochondria-dependent and caspase-3 activation in MDA-MB-231 cells.

2629- Ba,    Baicalein, a Component of Scutellaria baicalensis, Attenuates Kidney Injury Induced by Myocardial Ischemia and Reperfusion
- in-vivo, Nor, NA
*RenoP↑, Intravenous pretreatment with baicalein (in doses of 3, 10, or 30 mg/kg), however, significantly reduced the increases in the creatinine level, renal histological damage, and apoptosis induced by myocardial ischemia and reperfusion.
*Apoptosis↓,
*TNF-α↓, In addition, the increases in the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6, and of tumor necrosis factor-α in the kidneys were significantly reduced
*IL1↓,
*Bcl-2↑, Western blot analysis revealed that baicalein significantly increased Bcl-2 and reduced Bax in the kidneys
*BAX↓,
*Akt↑, inhibition of apoptosis, possibly through the reduction of tumor necrosis factor-α production, the modulation of Bcl-2 and Bax, and the activation of Akt and extracellular signal-regulated kinases 1 and 2.

2626- Ba,    Molecular targets and therapeutic potential of baicalein: a review
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
AntiCan↓, anticancer, antidiabetic, antimicrobial, antiaging, neuroprotective, cardioprotective, respiratory protective, gastroprotective, hepatic protective, and renal protective effects
*neuroP↑,
*cardioP↑, Cardioprotective action of baicalein
*hepatoP↑,
*RenoP↑, baicalein’s capacity to lessen cisplatin-induced nephrotoxicity is probably due, at least in part, to the attenuation of renal oxidative and/or nitrative stress
TumCCA↑, Baicalein induces G1/S arrest in lung squamous carcinoma (CH27) cells by downregulating CDK4 and cyclin D1, as well as upregulating cyclin E
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↑,
BAX↑, SGC-7901 cells showed that when baicalein was administered, Bcl-2 was downregulated and Bax was increased
Bcl-2↓,
VEGF↓, Baicalein inhibits the synthesis of vascular endothelial growth factor (VEGF), HIF-1, c-Myc, and nuclear factor kappa B (NF-κB) in the G1 and S phases of ovarian cancer cell
Hif1a↓,
cMyc↓,
NF-kB↓,
ROS↑, Baicalein produced intracellular reactive oxygen species (ROS) and activated BNIP3 to slow down the development and hasten the apoptosis of MG-63,OS cell
BNIP3↑,
*neuroP↑, Baicalein exhibits neuroprotective qualities against amyloid (AN) functions by preventing AN from aggregating in PC12 neuronal cells to cause A𝛽-induced cytotoxicity
*cognitive↑, baicalein encourages non-amyloidogenic processing of APP, which lowers the generation of A𝛽 and enhances cognitive function
*NO↓, baicalein effectively reduced NO generation and iNOS gene expression
*iNOS↓,
*COX2/PTGS2↓, Baicalein therapy significantly decreased the expression of COX-2 and iNOS, as well as PGE2 and NF-κB, indicating a protective effect against cerebral I/R injury.
*PGE2↓,
*NRF2↑, Baicalein therapy markedly elevated nuclear Nrf2 expression and AMPK phosphorylation in the ischemic cerebral cortex
*p‑AMPK↑,
*Ferroptosis↓, Baicalein suppressed ferroptosis associated with 12/15-LOX, hence lessening the severity of post-traumatic epileptic episodes generated by FeCl3
*lipid-P↓, HT22 cells were damaged by ferroptosis, which is mitigated by baicalein may be due to its lipid peroxidation inhibitor
*ALAT↓, Baicalin lowers the raised levels of hepatic markers alanine transaminase (ALT), aspartate aminotransferase (AST)
*AST↓,
*Fas↓, Baicalin has also been shown to suppress apoptosis, decrease FAS protein expression, block the caspase-8 pathway, and decrease Bax protein production
*BAX↓,
*Apoptosis↓,

2689- BBR,    Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells
- in-vitro, Nor, PC12 - in-vitro, AD, NA - in-vitro, Stroke, NA
*ROS↓, In both cell lines, pretreatment with berberine (especially at low concentrations) significantly decreased ROS generation, lipid peroxidation, and DNA fragmentation, while improving glutathione content and SOD activity in glutamate-injured cells.
*lipid-P↓,
*DNAdam↓, Berberine significantly diminished glutamate-induced DNA fragmentation
*GSH↑,
*SOD↑,
*eff↑, This is relevant to berberine treatment in neurodegenerative disorders, such as dementia (Alzheimer’s disease), seizures, and stroke.
*cl‑Casp3↓, Berberine significantly decreased cleaved caspase-3 and bax/bcl-2 expressions in the glutamate-injured cells
*BAX↓,
*neuroP↑, the current study demonstrated that berberine exerts neuroprotective effects against glutamate-induced N2a and PC12 cytotoxicity via antioxidant and anti-apoptotic mechanisms
*Dose↝, the protective effect of berberine was more significant at lower concentrations and decreased with increasing concentration.
*Ca+2↓, Nadjafi et al demonstrated that berberine protects OLN-93 oligodendrocytes against ischemic-induced cell death by attenuating the intracellular Ca2+ overload similar to the NMDA or the AMPA/kainate receptors antagonists

5631- BCA,    Perspectives Regarding the Role of Biochanin A in Humans
- Review, Var, NA - Review, AD, NA
*BioAv↓, Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption
*Inflam↓, various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects.
AntiCan↑,
*neuroP↑, many studies have focused on the effect of BCA on neurodegenerative diseases, especially PD and AD
chemoPv↑, BCA Has Chemopreventive Activity Against Various Cancers
Dose↝, BCA is metabolized in the gut to GEN or formononetin, which is converted to daidzein and then to equol (Knight and Eden, 1996).
*SOD↑, BCA also has a gastroprotective effect through the enhancement of cellular metabolic cycles, as evidenced by increases in superoxide dismutase (SOD) and nitric oxide (NO) activity, decreases in the malondialdehyde (MDA) and Bax levels, and increases
*MDA↓,
*BAX↓,
*HSP70/HSPA5↑, and increases in Hsp70 expression
*AntiDiabetic↑, BCA is well known for its antidiabetic and hypolipidemic effects.
*Insulin↑, BCA increases the circulating insulin levels and improves insulin sensitivity, leading to body weight control, an increase in liver glycogen, and a decrease in plasma glucose
*TNF-α↓, BCA inhibits the production of inflammatory mediators, such as TNF-α, interleukin-1β (IL-1β), IL-6, iNOS, COX-2, MMP-9, and NO, in various inflammatory responses
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2/PTGS2↓,
*MMP9↓,
*ROS↓, BCA scavenges ROS and increases SOD activity
*PGE2↓, BCA significantly reduces the synthesis of prostaglandin E2 and/or thromboxane B2 by inhibiting COX-2 expression
*BACE/β-secretase↓, BCA effectively inhibits the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)
*BioAv↑, Various attempts have been made to improve the solubility and bioavailability of BCA, including the use of liposomes
P-gp/ABCB1⇅, Interestingly, BCA has been found to stimulate P-gp in some studies (An and Morris, 2010). Therefore, the effect of BCA on P-gp may be substrate dependent.

5653- BNL,    Borneol hinders the proliferation and induces apoptosis through the suppression of reactive oxygen species-mediated JAK1 and STAT-3 signaling in human prostate cancer cells
- in-vitro, Pca, PC3
ROS↑, BNL treatment with PC-3 cells induces cytotoxicity, increases ROS production, and causes apoptotic morphological changes in a concentration-dependent manner.
TumCP↓, BNL significantly reduced the expression of cell proliferation markers such as cyclin-D1, cyclin-D2 and cyclin-E1 (P<0.05) compared to untreated PC-3 control cells.
cycD1/CCND1↓,
cycE1↓,
Apoptosis↑, BNL treatment enhanced apoptosis rates by observed overexpression of Bcl-2-associated X protein (Bax), caspase-3
BAX↓,
Casp3↑,
Bcl-2↓, and down regulation B-cell leukemia/lymphoma 2 (Bcl-2) (P<0.05) expression in PC-3 cells.
IL6↓, Additionally, BNL reduced interleukin-6, JAK1, and STAT3 phosphorylation ((P<0.05) in PC-3 cells
JAK1↓,
STAT3↓, Thus, BNL may be a therapeutic agent against prostate cancer by blocking the STAT3 signaling axis.

6542- BSB,    Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol
- Review, Var, NA - Review, Park, NA - Review, AD, NA
AntiCan↑, Numerous experimental studies demonstrated pharmacological properties of α-Bisabolol including anticancer, antinociceptive, neuroprotective, cardioprotective, and antimicrobial.
*neuroP↑,
*cardioP↑,
*AntiBio↑,
*BioAv↑, Given the polypharmacological effects and pleiotropic properties, along with favorable pharmacokinetics, and dietary availability and safety, α-Bisabolol can be used as a dietary agent, nutraceutical or phytopharmaceutical agent or as an adjuvant wit
*toxicity↓,
*BioAv↑, integrated in many cosmetic formulations due to its skin soothing effects, well documented dermal absorption
*motorD↑, improvement in locomotor activity, a reduction in the expression of thiol and a reinstate of the activity of mitochondrial complex-I.
*SOD↑, α-Bisabolol also increased the mRNA level of antioxidants proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product.
*Catalase↑,
*Keap1↑,
*MDA↓, α-Bisabolol attenuated oxidative insult by reducing malondialdehyde (MDA), restoring depleted glutathione (GSH) and improving SOD and CAT activity.
*GSH↑,
*IL1β↓, attenuated neuroinflammation by reducing glial cells activation and subsequent release of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and mediators (iNOS and COX-2).
*IL6↓,
*TNF-α↓,
*iNOS↓,
*COX2/PTGS2↓,
*lipid-P↓, α-Bisabolol restored mitochondrial function by preventing mitochondrial lipid peroxidation, cytochrome-C release and most importantly preserving Complex-I activity
*Cyt‑c↓,
*ROS↓, The study concluded that α-Bisabolol safeguarded against the induced upsurge of ROS and nitrite.
*MMP↑, α-Bisabolol treatment also restored mitochondrial membrane potential (MMP) validating its antioxidant effect.
*antiOx↑,
*AChE↓, showed a significant reduction in AChE activity and an ability to avert Ach depletion.
*Apoptosis↓, α-Bisabolol protected cells from Aβ triggered apoptosis by reducing Bax and Caspase-3 and increasing Bcl-2 activity.
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BACE/β-secretase↓, α-Bisabolol inhibitory activity on BACE1 and found a decrease in BACE1 activity following α-Bisabolol treatment
*BChE↓, AChE, BuChE, β-secretase actions were decreased significantly in cells pretreated with α-Bisabolol
*eff↑, The compound clearly illustrated a potent anti-AchE activity of 95.869% similar to the activity of donepezil, a standard drug. I
*Aβ↓, The compound also disaggregated Aβ25–35 peptide and protected against its induced toxicity by increasing neuro2a cells viability [
*ATP↑, figure 2
RadioS↑, α-Bisabolol and Anticancer Effects, figure 3
Cyt‑c↑,
Casp3↑,
Casp8↑,
Casp9↑,
Apoptosis↑,
PARP↑,
BAX↑,
BID↑,
NF-kB↑,
Fas↑,
EGFR↑,
TIMP2↑,
XIAP↓,
COX2/PTGS2↓,
Bak↓,
Bcl-2↓,
P53↑, The expression of p53 (a transcription factors whose products might lead to apoptosis), NF-κB and Fas was increased following α-Bisabolol treatment, indicating their function in mediating α-Bisabolol-induced apoptosis in the cancer cell line.
HER2/EBBR2↓,
FGF↓,
CEA↓,
Akt↓,
TumCCA↑, α-Bisabolol suppresses the cellular proliferation at G2/M cell cycle phase.
*Imm↑, reported that α-Bisabolol boosted the immunity response by T-cell subsets (CD4 and CD8) supplementation in treated mice.
*CD4+↑,
*CD8+↑,
*BBB↑, ↑ BBB penetration
*Pain↓, α-Bisabolol based mouthwash to that of chlorhexidine in reducing pain during brushing
*cardioP↑, α-Bisabolol and Cardioprotection, figure 5
*TBARS↓, rats co-treated with α-Bisabolol showed reduced LOOH and TBARS and increased SOD, CAT and GSH.
*SOD↑,
*Catalase↑,
*GSH↑,
*AntiBio↑, α-Bisabolol demonstrated an antibacterial effect against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa as well as a synergism against S. aureus, when combined with the antibiotic norfloxacin and against E. coli when combined with
*AntiFungal↑, ↓ fungal growth
*GastroP↑, α-Bisabolol and Gastroprotection. oral administration of α-Bisabolol was realized to attenuate gastric damage and to provide cytoprotection in stomach.
*RenoP↑, The nephroprotective effects of α-Bisabolol and the underlying mechanisms are summarized in Table 10.
*creat↓, ↓ creatinine, urea, uric acid
*uricA↓,
*Inflam↓, Anti-Inflammatory Effects of α-Bisabolol
*iNOS↓, ↓ iNOS, COX-2, TNF-α, p65 PGE2, nitrite, IL-6, ↓ MMP13
*COX2/PTGS2↓,
*TNF-α↓,
*IL6↑,
*MMP13↓,

6553- BSB,    Pharmacological and biological effects of alpha-bisabolol: An updated review of the molecular mechanisms
- Review, Nor, NA
*ROS↓, Various therapeutic and biological properties of α-bisabolol in preventing oxidative stress, inflammatory disorders, infections, neurodegenerative diseases, cancers, and metabolic disorders have been reported.
*Inflam↓,
*Inf↓,
*neuroP↑,
*RNS↓, The antioxidant mechanism of α-bisabolol is mainly associated with the reduction of ROS/RNS, MDA, and GSH depletion, MPO activity, and augmentation of SOD and CAT.
*MDA↓,
*GSH↑,
*MPO↓,
*SOD↑,
*Catalase↑,
*Bcl-2↑, upregulating the expression of bcl-2 and suppression of bax, P53, APAF-1, caspase-3, and caspase-9 activity indicates the anti-apoptotic effects of α- bisabolol.
*BAX↓,
*P53↓,
*APAF1↓,
*Casp3↓,
*Casp9↓,
*TNF-α↓, It possesses anti-inflammatory effects via reduction of TNF-α, IL-1β, IL-6, iNOS, and COX-2 and suppresses the activation of ERK1/2, JNK, NF-κB, and p38.
*IL1β↓,
*IL6↓,
*iNOS↓,
*COX2/PTGS2↓,
*ERK↓,
*JNK↓,
*NF-kB↓,
*p38↓,
*cognitive↑, improves cognitive function via downregulation of bax, cleaved caspases-3 and 9 levels, β-secretase, cholinesterase activities, and upregulation of bcl-2 levels.
*BChE↓,

1640- CA,  MET,    Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle Anaplerosis while Metformin Downregulates HIF-1α-Induced Glycolytic Enzymes in Human Cervical Squamous Cell Carcinoma Lines
- in-vitro, Cerv, SiHa
GLS↓, downregulation of Glutaminase (GLS) and Malic Enzyme 1 (ME1)
NADPH↓, CA alone and co-treated with Met caused significant reduction of NADPH
ROS↑, increased ROS formation and enhanced cell death
TumCD↑,
AMPK↑, activation of AMPK
Hif1a↓, Met inhibited Hypoxia-inducible Factor 1 (HIF-1α). CA treatment at 100 μM for 24 h also inhibited HIF-1α
GLUT1↓,
GLUT3↓,
HK2↓,
PFK↓, PFKFB4
PKM2↓,
LDH↓,
cMyc↓, Met suppressed the expression of c-Myc, BAX and cyclin-D1 (CCND1) a
BAX↓,
cycD1/CCND1↓,
PDH↓, CA at a concentration of 100 µM caused inhibition of PDK activity
ROS↑, CA Regulates TCA Cycle Supply via Pyruvate Dehydrogenase Complex (PDH), Induces Mitochondrial ROS Generation and Evokes Apoptosis
Apoptosis↑,
eff↑, both drugs inhibited the expression of ACLY and FAS, but the greatest effect was detected after co-treatment
ACLY↓,
FASN↓,
Bcl-2↓,
Glycolysis↓, Met acts as a glycolytic inhibitor under normoxic and hypoxic conditions

2807- CHr,    Evidence-based mechanistic role of chrysin towards protection of cardiac hypertrophy and fibrosis in rats
- in-vivo, Nor, NA
*antiOx↑, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic
Inflam↓,
*cardioP↑, Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways
*GSH↑, CHY at the highest dose (60 mg/kg) significantly bolstered the antioxidant status :GSH, SOD and CAT
*SOD↑,
*Catalase↑,
*GAPDH↑, significant increase in GAPDH levels was observed in CHYP group in comparison with normal group
*BAX↓, Decrease in apoptotic (Bax), increase in anti-apoptotic (Bcl-2)
*Bcl-2↑,
*PARP↓, expression of downstream signalling proteins, that is, PARP, cytochrome-C and caspase-3 were following the similar pattern. however at CHY 60 mg/kg treatment group, the levels were remarkably (P < 0·001) reduced.
*Cyt‑c↓,
*Casp3↓,
*NOX4↓, Whereas, lower levels of Nox-4 and higher levels of Nrf-2, HO-1 and HSP-70 were observed in CHYP group
*NRF2↑,
*HO-1↑,
*HSP70/HSPA5↑,

6631- Cic,    Chicoric acid is a potent anti-atherosclerotic ingredient by anti-oxidant action and anti-inflammation capacity.
- in-vitro, Nor, NA
*MMP↑, chicoric acid mitigates apoptotic features caused by oxLDL, such as the subsequent break down of mitochondrial transmembrane potential and the activation of Bax, which promote DNA strand breaks and activate caspase-3.
*BAX↓,
*DNAdam↓,
*Casp3↓,
*NF-kB↓, attenuated the oxLDL activation of NF-κB,
*antiOx↑, anti-oxidant action and anti-inflammation capacity
*Inflam↓,

6623- Cic,  MTX,    Chicoric acid prevents methotrexate hepatotoxicity via attenuation of oxidative stress and inflammation and up-regulation of PPARγ and Nrf2/HO-1 signaling
- in-vivo, Nor, NA
*antiOx↑, Chicoric acid (CA) is a natural antioxidant with promising hepatoprotective activity.
*hepatoP↑,
*ROS↓, Pre-treatment with CA suppressed reactive oxygen species and lipid peroxidation and enhanced antioxidants in MTX-induced rats.
*lipid-P↓,
*TAC↑,
*NRF2↑, CA upregulated hepatic Nrf2, HO-1, NQO-1, and PPARγ, and attenuated inflammation.
*HO-1↑,
*NQO1↑,
*PPARγ↑,
*Inflam↓,
*Apoptosis↓, CA inhibited apoptosis by increasing Bcl-2 expression and suppressing Bax, cytochrome c, and caspase-3 in MTX-administered rats.
*Bcl-2↑,
*BAX↓,
*Cyt‑c↓,
*Casp3↓,

6141- Cin,    The role and mechanism of cinnamaldehyde in cancer
- Review, Var, NA
Apoptosis↑, Cinnamaldehyde has diverse anti-cancer mechanisms, including inducing apoptosis by activating caspases and damaging mitochondrial function, inhibiting tumor angiogenesis, anti-proliferation, anti-inflammatory and antioxidant.
Casp↑,
mtDam↑,
angioG↓,
TumCP↓,
*Inflam↓,
*antiOx↑,
*ROS↓, In addition, cinnamaldehyde also acts as a reactive oxygen species scavenger, reducing oxidative stress and preventing DNA damage and genomic instability.
*DNAdam↓,
ROS↑, studies have shown that CA can enhance intracellular reactive oxygen species (ROS) levels by inducing mitochondrial dysfunction
*Bcl-2↑, CA exhibits a noteworthy upregulation of B-cell lymphoma protein 2 (Bcl-2) expression (a marker of antiapoptosis), while simultaneously downregulating Bax expression
*BAX↓,
*NF-kB↓, CA has been found to inhibit the activation of nuclear factor-kappa B (NF-κB)
ChemoSen↑, CA enhances the effectiveness of oxaliplatin by promoting apoptosis both in vitro and in vivo
ICAM-1↓, CA down-regulated the expression of adhesion molecules Intercellular adhesion molecule-1 (ICAM-1) and Vascular cell adhesion molecule-1 (VCAM-1)
VCAM-1↓,
PI3K↓, CA downregulates various components of the p PI3K/AKT/mTOR pathway in oral cancer cell lines
Akt↓,
mTOR↓,
BioAv↝, he estimated oral bioavailability of CA was found to be less than 20% for both the 250 and 500 mg/kg doses

3630- Cro,    Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis
- in-vivo, AD, NA
*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

3631- Cro,    Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease
- in-vitro, AD, HT22 - in-vivo, AD, NA
*ROS↓, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells.
*Ca+2↓, crocin strongly inhibited the overload of Ca2+ compared with the l-Glu-damaged HT22 cells,
*BAX↓, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase-3
*BAD↓,
*Casp3↓,
*cognitive↑, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test,
*memory↑,
*Aβ↓, Crocin improved cognitive abilities of AD mice, and reduced Aβ deposition in their brains
*GPx↑, crocin was able to reduce the Aβ1-42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase,
*SOD↑,
*ChAT↑,
*Ach↑,
*AChE↓, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice.
*ROS↓,
*p‑Akt↑, crocin upregulated the phosphorylation levels of Akt and mTOR in 24-h l-Glu-exposed cells.
*p‑mTOR↑,
*neuroP↑, crocin-mediated neuroprotection of l-Glu-damaged HT22 cells.

3205- EGCG,    The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas
- Review, Var, NA - Review, AD, NA
Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP/DDIT3↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,

6780- EGCG,    The pharmacological activity of epigallocatechin-3-gallate (EGCG) on Alzheimer's disease animal model: A systematic review
- Review, AD, NA
*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

6819- EMD,    Recent advances in the therapeutic potential of emodin for human health
- Review, Nor, NA
AntiCan↑, It has therapeutic effects in cancer, diabetes, neurodegenerative diseases or chronic inflammatory diseases.
*AntiDiabetic↑, anticancer, neuroprotective, antidiabetic, antioxidant and anti-inflammatory.
*neuroP↑,
*Inflam↓,
*antiOx↑,
*BioAv↓, Because its bioavailability is low, there are limitations in clinical therapeutic use.
*BioAv↑, combined administration of emodin and piperine has been observed to clinically improve emodin pharmacokinetics, increasing 221 % of the area under the curve (AUC), 258 % the maximum concentration (Cmax), and decreasing 230 % the clearance related to
*SOD↑, fig 2 antioxidant
*GPx↑,
*GSH↑,
*NRF2↑,
*ROS↓,
*lipid-P↓,
*Cyt‑c↓,
*BAX↓, fig 2 antiinflammatory
*Bcl-2↓,
*iNOS↓,
*NO↓,
*IL6↓,
*IL10↓,
*IL17↓,
*IFN-γ↓,
*NF-kB↓,
*LC3II↓,
*Akt↓,
*Beclin-1↓,
*AMPK↓, fig 2 neuroprotective
*TNF-α↓,
*PGE2↓,
*Apoptosis↓,
*Casp3↓,
*Casp9↓,
*P53↓,
*P21↓,
*NAD↓, neuronal oxidative stress
*ATP↓,
*CHOP/DDIT3↓,
*GADD34↓,
*ATF4↓,
tumCV↓, fig 2 anticancer
Apoptosis↑,
TumCG↓,
TumCI↓,
TumMeta↓,
CSCs↓, glioma stem cells ↓b-catenin, ↓Notch-1, ↓STAT3
NOTCH1↓,
STAT3↓,
eff↑, emodin combined with curcumin ↓proliferation, ↑miR-34a
miR-34a↓,
*neuroP↑, Neuroprotective LPS-stimulated mouse ↓Nrf-2, NQO1, ↓TNF-α,↓↓ IL-6, ↓NO, ↓PGE2
*BDNF↓, model of chronic stress mice in vivo ↓progression of behavioral impairments in mice ↓consumption of sucrose, ↓plasmatic corticosterone, ↓mRNA, ↓BDNF,
*hepatoP↑, Hepatoprotective rats in vivo ↓ethanol-mediated liver steatosis ↓ ALT, ↓AST, ↓ TGL
*ALAT↓,
*AST↓,
TG/TAG↓,
ROS↑, However, at higher concentrations, emodin significantly increased ROS generation and reduced cell viability.
Slug↓, expression levels of Slug (a transcription factor) were also suppressed with emodin treatment.
EMT↓, results suggested that emodin suppressed the epithelial-mesenchymal transition of cancer cells through the ILK/GSK-3β/Slug signaling pathway
Glycolysis↓, In addition, emodin inhibited glycolysis via ROS-induced inactivation of the PI3K/AKT signaling pathway.
ChemoSen↑, The study by Peng et al. [130] also showed chemosensitizing effects of emodin to cisplatin in A549 (2–20 µM, for 48 h) and H460 (0.5–10 µM) non-small cell lung cancer cells.
P-gp/ABCB1↓, The sensitization mechanism was mediated by the inhibition of P-glycoprotein (Pgp), a drug-resistant protein related to the efflux pump mechanism.
Ki-67↓, The significant reduction of Ki-67 and proliferating cell nuclear antigen (PCNA) protein levels supported the antiproliferative effect of emodin in animal models.
PCNA↓,
ER Stress↑, findings suggested that emodin exerts its apoptotic effects in a process mediated by ER stress and the activation of the TRIB3/NF-κB pathway in lung cancer cells.
TRIB3↑,
NF-kB↑,
TumMeta↑, Emodin (40 mg/kg for 7 days) significantly decreased the metastatic recurrence of breast cancer after surgery in the lungs by reducing the formation of epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC).
*Imm↓, emodin may be developed as an immunosuppressive agent in case of immune activation, autoimmune disorders even in organ transplantation
*toxicity↝, An excess of emodin due to its laxative effects causes intestinal pain and severe diarrhea with subsequent electrolyte imbalance and dehydration [157]. Therefore, treatment should begin when symptoms appear, with special attention to electrolyte leve

6828- EMD,    Neuroprotective effect of emodin against Alzheimer's disease via Nrf2 signaling in U251 cells and APP/PS1 mice
- in-vitro, AD, U251
*MMP↑, emodin ameliorated the dissipation of the mitochondrial membrane potential, inhibited the over-accumulation of reactive oxygen species, enhanced the expression levels of nuclear factor-erythroid-2-related factor 2 (Nrf2), haemeoxygenase-1, superoxide
*ROS↓,
*NRF2↑,
*HO-1↑,
*SOD↑, superoxide dismutase 1, Bcl-2 and catalase in addition to decreasing the expression levels of Bax.
*Bcl-2↑,
*Catalase↑,
*BAX↓,
*memory↑, In APP/PS1 mice, an 8-week course of emodin administration improved spatial memory and learning ability and decreased anxiety.
*ANXi↓,
*Aβ↓, decreased the deposition of Aβ, phosphorylated-τ and 4-hydroxy-2-nonenal in APP/PS1 mice
*antiOx↑, In addition, emodin exhibits antioxidative effects: In viral myocarditis, emodin alleviates oxidative stress by increasing myocardial SOD expression levels whilst decreasing malondialdehyde expression levels
*MDA↓,

6886- FA,  MTX,    Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats
- in-vivo, Nor, NA
*hepatoP↑, Liver injury is one of the adverse effects of methotrexate (MTX). Ferulic acid (FA) is an antioxidant phytochemical that confers hepatoprotective efficacy;
*ROS↓, FA prevented all histological alterations, ameliorated liver function markers, suppressed oxidative stress, and boosted antioxidants in MTX-induced rats.
*TNF-α↓, FA reduced serum TNF-α and IL-1β, and hepatic NF-κB p65, Bax, and caspase-3,
*IL1β↓,
*NF-kB↓,
*p65↓,
*BAX↓,
*Casp3↓,
*NRF2↑, In conclusion, FA prevented MTX hepatotoxicity by activating Nrf2/HO-1 signaling and PPARγ, and attenuating oxidative stress, inflammation, and cell death.
*HO-1↑,
*PPARγ↑,
*Inflam↓,

1656- FA,    Ferulic Acid: A Natural Phenol That Inhibits Neoplastic Events through Modulation of Oncogenic Signaling
- Review, Var, NA
tyrosinase↓,
CK2↓,
TumCP↓,
TumCMig↓,
FGF↓,
FGFR1↓,
PI3K↓,
Akt↓,
VEGF↓,
FGFR1↓,
FGFR2↓,
PDGF↓,
ALAT↓,
AST↓,
TumCCA↑, G0/G1 phase arrest
CDK2↓,
CDK4↓,
CDK6↓,
BAX↓,
Bcl-2↓,
MMP2↓,
MMP9↓,
P53↑,
PARP↑,
PUMA↑,
NOXA↑,
Casp3↑,
Casp9↑,
TIMP1↑,
lipid-P↑,
mtDam↑,
EMT↓,
Vim↓,
E-cadherin↓,
p‑STAT3↓,
COX2/PTGS2↓,
CDC25↓,
RadioS↑,
ROS↑,
DNAdam↑,
γH2AX↑,
PTEN↑,
LC3II↓,
Beclin-1↓,
SOD↓,
Catalase↓,
GPx↓,
Fas↑,
*BioAv↓, ferulic acid stability and limited solubility in aqueous media continue to be key obstacles to its bioavailability, preclinical efficacy, and clinical use.
cMyc↓,
Beclin-1↑, ferulic acid by elevating the levels of the apoptosis and autophagy biomarkers, including beclin-1, Light chain (LC3-I/LC3-II), PTEN-induced putative kinase 1 (PINK-1), and Parkin
LC3‑Ⅱ/LC3‑Ⅰ↓,

7035- GA,    Gallic acid attenuates LPS-induced inflammation in Caco-2 cells by suppressing the activation of the NF-κB/MAPK signaling pathway
- in-vitro, IBD, Caco-2
*Inflam↓, Gallic acid (GA) is renowned for its remarkable biological activity, encompassing anti-inflammatory and antioxidant properties.
*antiOx↑,
*CLDN1↓, Our findings demonstrate that 5 μg/mL GA restores the downregulation of the mRNA and protein levels of Claudin-1, Occludin, and ZO-1 and decreases the expressions of inflammatory factors such as IL-6, IL-1β and TNF-α induced by LPS.
*OCLN↓,
*ZO-1↓,
*IL6↓,
*IL1β↓,
*TNF-α↓,
*BAX↓, downregulating the mRNA levels of pro-apoptotic factors ( Bax, Bad, Caspase-3, Caspase-8, and Caspase-9)
*BAD↓,
*Casp3↓,
*Casp8↓,
*ROS↓, GA also reduces the levels of reactive oxygen species increased by LPS and restores the activity of antioxidant enzymes, namely, superoxide dismutase and catalase, as well as the level of glutathione.
*SOD↑,
*Catalase↑,
*GSH↑,
*TJ↑, GA increases the expressions of tight junction proteins, reduces cell apoptosis, relieves oxidative stress and suppresses the activation of the NF-κB/MAPK pathway
*Apoptosis↓,
*NF-kB↓,
*MAPK↓,

7040- GA,    Effects of gallic acid on acrylamide-induced endoplasmic reticulum stress, neuroinflammation and neuronal apoptosis in rats
- Trial, AD, NA
*SOD↑, GA treatment, particularly at 100 mg/kg, markedly ameliorated these biochemical, molecular, and histopathological alterations.
*GSH↑,
*GPx↑,
*Catalase↑,
*MDA↓,
*TNF-α↓, TNF-α, IL-1β, IL-6), neuronal nitric oxide synthase (nNOS), and apoptosis-related gene expression (Bax and caspase-3).
*IL1β↓,
*BAX↓,
*Casp3↓,
*BDNF↑, while BDNF, Nrf2, and HO-1 immunoreactivity decreased in the ACR group (markedly ameliorated)
*NRF2↑,
*HO-1↑,

7275- GGB,    Protective Effect of Ginkgolide B against Cognitive Impairment in Mice via Regulation of Gut Microbiota
- in-vivo, AD, NA
*cognitive↑, Our results showed that GB significantly alleviated cognitive dysfunction, neurodegeneration, and neuropathological changes in AD model mice
*neuroP↑,
*RAGE↓, Moreover, GB treatment remarkably reduced the levels of RAGE and Bax and increased the level of Bcl-2 in AD model mice.
*BAX↓,
*Bcl-2↑,
*GutMicro↑, GB treatment reversed the decreased abundance of Lactobacillus and the increased abundance of Bacteroidales, Muribaculaceae, and Alloprevotella, which led to reconstruction of gut microbiota.

7277- GGB,    Ginkgolide B inhibits hydrogen peroxide-induced apoptosis and attenuates cytotoxicity via activating the PI3K/Akt/mTOR signaling pathway in H9c2 cells
- in-vitro, Nor, H9c2
*cardioP↑, GB protected against hydrogen peroxide-induced cytotoxicity and cell apoptosis in H9c2 cardiac cells
*Bcl-2↑, GB upregulated the expression level of the anti-apoptotic protein Bcl-2 and downregulated the expression levels of the pro-apoptotic proteins cleaved caspase-3 and Bax in hydrogen peroxide-treated H9c2 cells.
*cl‑Casp3↓,
*BAX↓,
*PI3K↑, GB pretreatment activated the PI3K/Akt/mTOR signaling pathway and caused an increase in the phosphorylation levels of Akt and mTOR in hydrogen peroxide-treated H9c2 cells.
*Akt↑,
*mTOR↑,

7279- GGB,  Rad,    Radioprotective effect of Ginkgolide B on brain: the mediating role of DCC/MST1 signaling
- in-vivo, Nor, NA
*cognitive↑, X-ray-treated mice exhibited cognitive impairment and depression-like behavior, which was ameliorated by GB treatment.
*radioP↑,
*ROS↓, GB also reduced the ROS production and the number of TUNEL-positive cells in the hippocampus
*p‑Akt↑, GB increased the protein levels of p-AKT and Bcl2, while decreased the protein levels of MST1, p-p38, p-JNK, cleaved-caspase-3 and Bax both in vivo and in vitro.
*Bcl-2↑,
*Mst1↓,
*p‑p38↓,
*JNK↓,
*cl‑Casp3↓,
*BAX↓,

7256- Gink,    Neuroprotective effect of ginkgetin in experimental cerebral ischemia/reperfusion via apoptosis inhibition and PI3K/Akt/mTOR signaling pathway activation
- in-vivo, Stroke, NA
*Stroke↓, Our results showed that administration of ginkgetin remarkably reduced brain infarction volumes and neurologic deficits;
*Apoptosis↓, reducing apoptotic cell numbers, downregulating the levels of cleaved caspase-3 and Bax, and upregulating the level of Bcl-2 in rats subjected to IR injury in a dose-dependent manner.
*Casp3↓,
*BAX↓,
*Bcl-2↑,
*p‑Akt↑, high-dose ginkgetin treatment (100 mg/kg) significantly increased the phosphorylations of Akt and mTOR.
*p‑mTOR↑,

7338- Gra,    Pharmacological Activities of Soursop (Annona muricata Lin.)
- Review, Var, NA
AntiCan↑, A.muricata’s activities were shown to include anticancer (25%), antiulcer (17%), antidiabetic (14%), antiprotozoal (10%), antidiarrhea (8%), antibacterial (8%), antiviral (8%), antihypertensive (6%), and wound healing (4%).
*AntiDiabetic↑,
*Diar↓,
*Bacteria↓,
*AntiViral↑,
*Wound Healing↑,
MMP2↓, Fruit, stem, seed, and twigs Inhibits MMP-2 and MMP-9, which play an important role in cancer progression, in HT1080 fibrosarcoma cells.
MMP9↓,
MMP↓, Disrupts MMP function, reactive oxygen species (ROS) generation, and G0/G1 cell cycle arrest in HL-60 leukemia cells.
ROS↑,
TumCCA↑,
BAX↑, Increases Bax expression and decreases Bcl-2 expression, cell cycle arrest at G0/G1 phase in A-549 lung cancer cells.
Bcl-2↓,
Casp3↑, Induces apoptosis by enhancing the expression of caspase-3 in MDA-MB-231 breast cancer cells.
*BAX↓, Antiulcer Leaf, Downregulates Bax and malondialdehyde (MDA) expression.Upregulates CAT, SOD, GSH, NO, PGE2, glycogen, and Hsp70 expression.
*MDA↓,
*Catalase↑,
*SOD↑,
*GSH↑,
*NO↑,
*PGE2↑,
*HSP70/HSPA5↑,

3764- H2,    Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model
- in-vivo, AD, NA
*memory↑, However, after H2 treatment, memory deficits were ameliorated.
*Aβ↓, H2 treatment also decreased AD-related biomarkers, such as Apo-E, Aβ-40, p-tau, and Bax and OS markers such as ROS, NO, Ca2+, and MDA in both serum and brain.
*p‑tau↓,
*BAX↓,
*ROS↓,
*NO↓,
*Ca+2↓,
*MDA↓,
*Catalase↓, In contrast, catalase and GPx activities were significantly increased in the TMT-only group and decreased after H2 gas treatment in serum and brain
*GPx↓,
*TNF-α↓, (G-CSF), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) were found to be significantly decreased after H2 treatment in both serum and brain lysates
*Bcl-2↑, In contrast, Bcl-2 and vascular endothelial growth factor (VEGF) expression levels were found to be enhanced after H2 treatment.
*VEGF↑,
*Inflam↓, 2% H2 gas inhalation in TMT-treated mice exhibits memory enhancing activity and decreases the AD, OS, and inflammatory-related markers.
*cognitive↑,

7499- H2S,    Hydrogen sulfide slows down progression of experimental Alzheimer's disease by targeting multiple pathophysiological mechanisms
*TNF-α↓, decrease in tumor necrosis factor-α level, up-regulation of Bcl-2, and down-regulation of BAX and the downstream executioner caspase-3, also occurred in the hippocampus of 3xTg-AD mice after treatment with Tabiano's spa-water, thus suggesting that it
*Bcl-2↑,
*BAX↓,
*Casp3↓,
*Inflam↓, thus suggesting that it is also able to modulate inflammation and apoptosis.
*Apoptosis↓,
*memory↑, long-term treatments with sodium hydrosulfide and/or Tabiano's spa-water significantly protected against impairment in learning and memory in rat models of AD induced

2867- HNK,    Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway
- in-vitro, Nor, C2C12
*antiOx↑, known to have antioxidant activity, but its mechanism of action remains unclear.
*ROS↓, honokiol inhibited hydrogen peroxide (H2O2)-induced DNA damage and mitochondrial dysfunction, while reducing reactive oxygen species (ROS) formation.
*Bcl-2↑, up-regulation of Bcl-2 and down-regulation of Bax,
*BAX↓,
Casp9∅, in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose)
Casp3∅,
cl‑PARP∅,
Cyt‑c?, e blocking of cytochrome c release to the cytoplasm

5052- HPT,    Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells
- in-vitro, OS, U2OS
Apoptosis↑, Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells.
ROS↑, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells.
Casp3↑,
mtDam↑, Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax.
Cyt‑c↑,
Bcl-2↓,
Bcl-xL↓,
Bak↑,
BAX↓,
ER Stress↑, Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity.
Ca+2↝,
cal2↑,

7565- HYP,    Potential Implications of Hyperoside on Oxidative Stress-Induced Human Diseases: A Comprehensive Review
- Review, AD, NA
*Inflam↓, exhibits a multitude of biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects and neuroprotective effects,
*antiOx↑,
*neuroP↑,
*lipid-P↓, Anti-oxidant Saccharomyces Cerevisiae 5, 20 mg/L Decreased LPO and the level of ROS
*ROS↓,
*IL1β↓, HT22 cells 20 μM Alleviates the level of IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF.
*IL6↓,
*IL8↓,
*TNF-α↓,
*MDA↓,
*BAX↓,
*Casp3↓,
*Catalase↑,
*SOD↑,
*GSH↑,
*BDNF↑,
*TrkB↑,
*NGF↑,
*BDNF↑, Male Albino Swiss mice 0.94 mg/kg, 3.75 mg/kg Mediated by monoaminergic system and the upregulation of BDNF level
*NF-kB↓, Inhibited the activation of NF-κB, lessened the expression of iNOS,
*AChE↓, ICR mice 2.5 mg/kg Inhibited AchE activity
*H2S↑, SD rats 1, 10, 100 μM Upregulation of H2S,
Casp3↑, Anti-lung cancer A549 cells, Balb/c-nude mice 15, 20, 25 μM in vitro 15, 20, 25 mg/kg in vivo Activation of caspase-3 to motivate apoptosis and inactivation of NF-κB to inhibit inflammatory
Apoptosis↑,
NF-kB↓,
AMPK↑, A549 cells 10, 50, 100 μM Upregulation of AMPK signal pathway and HO-1 expression to suppressed the survival and proliferation of A549 cells
HO-1↑,
MAPK↑, A549 cells, H466 cells, C57BL/6J mice – Upregulated the expression of p38 MAPK, caspase 3, caspase 9, cleaved caspase 3, cleaved caspase 9 and Bax, downregulated the expression of Cu/Zn SOD, CAT, Nrf2, NQO1, HO-1 and Bcl-2
cl‑Casp3↑,
cl‑Casp9↑,
BAX↑,
SOD?,
Catalase↓,
NRF2↓,
NQO1↓,
HO-1↓,
Bcl-2↓,
TumCCA↑, A549 cells 10, 20, 50, 100, 200, 400 μg/mL Inhibited the process of G1/S phase to inhibit proliferation
FOXO1↑, NCI-H1975 cells, PC-9 cells, Nude male mice 30, 60, 90, 120, 150 μM in vitro, 25 mg/kg in vivo Upregulation of FoxO1
TumAuto↑, A549 cells 0.5, 1, 2 mM Induced autophagy through inhibiting the Akt/mTOR/p70S6K signal pathway
Akt↓,
mTOR↓,
P70S6K↓,
BMP7/OP1↓, HepG2 cells 5, 10, 20, 40, 80 μM Inhibiting the BMP-7
*cardioP↑, Cardiovascular Protective Effect
*hepatoP↑, Hepatoprotective
*antiCG↑, The report indicates hyperoside possesses antithrombotic activities and offer bases for development of a novel anticoagulant
*AntiThr↑,
*Diar↓, Antidiarrheal Activity
*AntiFungal↑, Antifungal Activity
*CYP2D6↓, hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and might cause herb-drug interactions when co-administrated with CYP2D substrates.
*PDGFR-BB↓, In diabetic rats’ model, hyperoside inhibited the platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor-B receptor (PDGFR-β) ligand binding
*PDGFRB↓,
*toxicity↓, In research conducted in Wistar rats, the researchers demonstrated that in a long-term oral administration lasted for 6 months, hyperoside has a good safety. And the possible target organ of toxicity is kidney and the damage is reversible
*Half-Life↑, hyperoside also showed a long half-life for 4 hours and the safety experiments also proves that it has good safety.

7561- HYP,    Hyperoside Exerts Therapeutic Effects on Parkinson's Disease by Mitigating Oxidative Stress through Activation of Nrf2/HO-1 Pathway
- in-vivo, Park, NA
*motorD↑, HYP intervention improved motor abilities, increased TH, Nrf2, HO-1, and Bcl-2 expressions, and reduced Bax expression
*NRF2↑,
*HO-1↑,
*Bcl-2↑,
*BAX↓,
*GSH↑, It also elevated GSH, GSH-Px, SOD, and CAT levels, decreased MDA, and reduced neuronal apoptosis
*GPx↑,
*SOD↑,
*Catalase↑,
*MDA↓,
*Apoptosis↓,

7560- HYP,    Hyperoside: A Review of Its Structure, Synthesis, Pharmacology, Pharmacokinetics and Toxicity
- Review, Nor, NA - Review, AD, NA
*RenoP↓, Thirdly, long-term use of hyperoside is toxic to the kidneys, but the damage is reversible
Casp3↑, Up-regulates caspase-3, caspase-8, Bax, p53 and MDA contents; decreases GSH, SOD and CAT activities; decreases VEGF and Bcl-2 levels; and inhibits cell growth. HeLa 100 μmol/L
Casp8↑,
MDA↑,
GSH↓,
SOD↓,
Catalase↓,
VEGF↓,
Bcl-2↓,
TumCG↓,
p‑Akt↓, Down-regulates BMP-7 expression, AKT phosphorylation and PI3K expression; induces cell cycle arrest; and inhibits cell proliferation. Human HepG2 5, 10, 20, 40 and 80 μM
PI3K↓,
TumCCA↑,
TumCP↓,
BMP7/OP1↓,
*ZO-1↑, up-regulates ZO-1 and claudin5 protein expression; maintains the integrity of the blood–brain barrier; and may protect neural function in CIR-injured mice. CIR injury induced by MCAO in mice 50 mg/kg
*BBB↝,
*p‑Akt↑, increases the phosphorylation of AKT and GSK-3β; alleviates early brain injury after subarachnoid haemorrhage; and promotes nerve function recovery in rats.
*GSK‐3β↑,
*SOD↑, increases SOD and CAT activities and GSH content; increases SIRT1 gene expression; down-regulates NF-κB mRNA
*Catalase↑,
*GSH↑,
*SIRT1↑,
*NF-kB↓,
*IL1β↓, Down-regulates IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax and caspase-3 levels; increases CAT, SOD and GSH activities; up-regulates Bcl-2, BDNF, TrkB, SIRT1 and NGF expression; reduces LPS-induced inflammation, oxidative stress and apoptosis; and protec
*IL6↓,
*IL8↓,
*TNF-α↓,
*ROS↓,
*MDA↓,
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BDNF↑,
*TrkB↑,
*NGF↑,
*Apoptosis↓,
*cardioP↑, Cardioprotective Activity of Hyperoside.
*AST↓, Decreases the levels of AST, CK, CK-MB and c-TnT in rats; the rate of cardiomyocyte apoptosis;
*hepatoP↑, Hepatoprotective Activity of Hyperoside.
*AST↓, Decreases liver index, AST, ALT, MDA and Bach1 complex levels and alleviates the pathological damage of acute liver injury mice.
*ALAT↓,
*MDA↓,
*BACH1↓,
*neuroP↑, Brain-Protective Activity of Hyperoside.
*Stroke↓, Down-regulates TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, TLR4, COX-2, NF-κB, caspase-3, caspase-9, Bax and Bcl-2 expression and prevents CIR injury. Middle cerebral artery occlusion/reperfusion rat model
*ICAM-1↓,
*VCAM-1↓,
*TLR4↓,
*COX2/PTGS2↓,
*RenoP↑, Renal-Protective Activity of Hyperoside.
*NLRP3↓, Suppresses NLRP3, caspase-1 and ASC expression and prevents acute kidney injury induced by lipopolysaccharide. Mouse acute kidney injury model
*Casp1↓,
*ASC↓,
*BioAv↓, low oral bioavailability
*BioAv↑, hyperoside is compatible with other traditional Chinese medicines and they can improve its bioavailability and oral absorption.
*toxicity↓, Firstly, an acute toxicity test of hyperoside showed that its LD50 > 5000 mg/kg

7864- isoO,    Isoorientin Inhibits Amyloid β25-35-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway
- in-vitro, AD, BV2
*iNOS↓, ISO inhibited the expression of iNOS and COX-2 induced by Aβ25–35.
*COX2/PTGS2↓,
*TNF-α↓, And, it inhibited the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).
*IL6↓,
*ROS↓, ISO reduced the ROS production in Aβ25–35-induced BV2 cells and inhibited NF-κB activation.
*NF-kB↓,
*Apoptosis↓, ISO Blocks Aβ25–35-Induced Apoptosis in BV2 Microglial Cells
*Bcl-2↑, anti-apoptotic protein Bcl-2 was decreased, while the level of pro-apoptotic protein BAX was increased upon treatment of BV2 cells with 20 μM Aβ25–35. However, ISO reversed the expression of Bcl-2 and BAX
*BAX↓,
*cl‑Casp9↓, expression of cleaved caspases-9 and -3 as well as PARP, which are markers of apoptosis. Aβ promoted the cleavage of these proteins, whereas ISO treatment abrogated these effects
*cl‑Casp3↓,
*cl‑PARP↓,
*NeuroI↓, ISO ameliorated neuronal inflammation via inhibition of ROS generation and blockade of NF-kB activity

7870- isoO,    Anti-oxidative stress and cognitive improvement of a semi-synthetic isoorientin-based GSK-3β inhibitor in rat pheochromocytoma cell PC12 and scopolamine-induced AD model mice via AKT/GSK-3β/Nrf2 pathway
- vitro+vivo, AD, PC12
*GSK‐3β↓, The flavonoid isoorientin (ISO) and its synthetic derivatives TFGF-18 selectively inhibit glycogen synthase kinase-3β (GSK-3β), a potential target of AD treatment
*BAX↓, TFGF-18 inhibited neuronal damage and the expressions of Bax, caspase3 and cleaved-caspase3, and increased the expression of Bcl-2 in vitro and in vivo.
*Casp3↓,
*cl‑Casp3↓,
*Bcl-2↑,
*MDA↓, The level of MDA and ROS were decreased while the activities of SOD and GPx were increased by TFGF-18.
*ROS↓,
*SOD↑,
*GPx↑,
*p‑Akt↑, Moreover, TFGF-18 increased the p-AKT, p-GSK-3β (Ser9), Nrf2, HO-1, p-CREB, and BDNF expression reduced by H2O2 and SCOP
*p‑GSK‐3β↑,
*NRF2↑,
*p‑CREB↑,
*BDNF⇅,

2907- LT,    Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems
- in-vitro, Nor, NA
*ROS↓, Intracellular ROS levels and damage to cellular components such as lipids and DNA in H2O2-treated cells were significantly decreased by luteolin pretreatment.
*Casp9↓, Luteolin suppressed active caspase-9 and caspase-3 levels while increasing Bcl-2 expression and decreasing Bax protein levels.
*Casp3↓,
*Bcl-2↑,
*BAX↓,
*GSH↑, luteolin restored levels of glutathione that was reduced in response to H2O2.
*SOD↑, luteolin enhanced the activity and protein expressions of superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1.
*Catalase↑,
*GPx↑,
*HO-1↑,
*antiOx↑, upregulating antioxidant enzymes.
*lipid-P↓, protective effect of luteolin against lipid peroxidation
*p‑γH2AX↓, showed that luteolin pretreatment diminished expression levels of phospho-H2A.X in H2O2-exposed cells
eff↑, promising therapeutic agent for management and treatment of conditions such as COPD and pulmonary fibrosis.

3531- Lyco,    Lycopene attenuates the inflammation and apoptosis in aristolochic acid nephropathy by targeting the Nrf2 antioxidant system
- in-vivo, Nor, NA
*NRF2↑, After LYC intervened in the body, it activated Nrf2 nuclear translocation and its downstream HO-1 and NQO1 antioxidant signaling pathways
*HO-1↑, Lycopene activates Nrf2-HO-1 antioxidant pathway to inhibit oxidative stress injury induced by AAI exposure in NRK52E cells
*NQO1↑,
*ROS↓, LYC inhibited ROS production by renal tubular epithelial cells, and alleviated mitochondrial damage.
*mtDam↓,
*Bcl-2↑, LYC was able to up-regulate the expression of Bcl-2, down-regulate Bax expression and inhibit the activation of cleaved forms of Caspase-9 and Caspase-3, which finally attenuated the apoptosis
*BAX↓,
*Casp9↓,
*Casp3↓,
*Apoptosis↓,
*RenoP↑, Interestingly, there was a significant improvement in damaged renal tissue in mice with AAN after lycopene intervention
*lipid-P↓, lycopene significantly decreased the expression of AAI-induced lipid peroxidation product (MDA), and increased the expression of antioxidant enzyme systems (T-AOC, SOD, and GSH-PX)
*SOD↑,
*GPx↑,
*Inflam↓, Lycopene improves inflammatory responses in the kidneys of AAN mice
*TNF-α↓, TNF-α, IL-6, IL-10, was increased and the expression of IL-12 was decreased in the kidneys of model mice compared with the control group. However, LYC intervention reversed the expression of these genes in a dose-dependent manner
*IL6↓,
*IL10↓,

3263- Lyco,    Lycopene protects against myocardial ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening
- in-vitro, Nor, H9c2 - in-vitro, Stroke, NA
*Apoptosis↓, LP pretreatment significantly increased cell viability, reduced myocardial infarct size and decreased the apoptosis rate.
*MMP↑, decrease of ΔΨm were attenuated by LP and the expressions of cytochrome c, APAF-1, cleaved caspase-9 and cleaved caspase-3 were also decreased by LP
*Cyt‑c↓,
*APAF1↓,
*cl‑Casp9↓,
*cl‑Casp3↓,
*Bcl-2↑, LP treatment markedly increased Bcl-2 expression, decreased Bax expression and the Bax/Bcl-2 ratio.
*BAX↓,
cardioP↑, myocardial ischemia-reperfusion injury (MIRI). LP protects against MIRI by inhibiting MPTP opening, partly through the modulation of Bax and Bcl-2.

3277- Lyco,    Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent
- Review, Var, NA
antiOx↑, lycopene provides a strong antioxidant activity that is 100 times more effective than α-tocopherol and more than double effective that of β-carotene
TumCP↓, In vivo and in vitro experiments have demonstrated that lycopene at near physiological levels (0.5−2 μM) could inhibit cancer cell proliferation [[22], [23], [24]], induce apoptosis [[25], [26], [27]], and suppress metastasis [
Apoptosis↑,
TumMeta↑,
ChemoSen↑, lycopene can increase the effect of anti-cancer drugs (including adriamycin, cisplatin, docetaxel and paclitaxel) on cancer cell growth and reduce tumour size
BioAv↓, low water solubility and bioavailability of lycopene
Dose↝, The concentration of lycopene in plasma (daily intake of 10 mg lycopene) is approximately 0.52−0.6 μM
BioAv↓, significant decrease in lycopene bioavailability in the elderly
BioAv↑, oils and fats favours the bioavailability of lycopene [80], while large molecules such as pectin can hinder the absorption of lycopene in the small intestine due to their action on lipids and bile salt molecules
SOD↑, GC: 50−150 mg/kg BW/day ↑SOD, CAT, GPx ↑IL-2, IL-4, IL-10, TNF-α ↑IgA, IgG, IgM ↓IL-6
Catalase↑,
GPx↑,
IL2↑, lycopene treatment significantly enhanced blood IL-2, IL-4, IL-10, TNF-α levels and reduced IL-6 level in a dose-dependent manner.
IL4↑,
IL1↑,
TNF-α↑,
GSH↑, GC: ↑GSH, GPx, GST, GR
GPx↑,
GSTA1↑,
GSR↑,
PPARγ↑, ↑GPx, SOD, MDA ↑PPARγ, caspase-3 ↓NF-κB, COX-2
Casp3↑,
NF-kB↓,
COX2/PTGS2↓,
Bcl-2↑, AGS cells Lycopene 5 μM ↑Bcl-2 ↓Bax, Bax/Bcl-2, p53 ↓Chk1, Chk2, γ-H2AX, DNA damage ↓ROS Phase arrest
BAX↓,
P53↓,
CHK1↓,
Chk2↓,
γH2AX↓,
DNAdam↓,
ROS↓,
P21↑, CRC: ↑p21 ↓PCNA, β-catenin ↓COX-2, PGE2, ERK1/2 phosphorylated
PCNA↓,
β-catenin/ZEB1↓,
PGE2↓,
ERK↓,
cMyc↓, AGS cells: ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS
cycE/CCNE↓,
JAK1↓,
STAT3↓,
SIRT1↑, Huh7: ↑SIRT1 ↓Cells growth ↑PARP cleavage ↓Cyclin D1, TNFα, IL-6, NF-κB, p65, STAT3, Akt activation ↓Tumour multiplicity, volume
cl‑PARP↑,
cycD1/CCND1↓,
TNF-α↓,
IL6↓,
p65↓,
MMP2↓, SK-Hep1 human hepatoma cells Lycopene 5, 10 μM ↓MMP-2, MMP-9 ↓
MMP9↓,
Wnt↓, AGS cells Lycopene 0.5 μM, 1 μM ↓Wnt-1, c-Myc, cyclin E ↓Jak1/Stat3, Wnt/β-catenin alteration ↓ROS

520- MF,    Exposure to a 50-Hz magnetic field induced mitochondrial permeability transition through the ROS/GSK-3β signaling pathway
- in-vitro, Nor, NA
*MPT↑, MPT induced by MF exposure was mediated through the ROS/GSK-3β signaling pathway.
*Cyt‑c↑, induced Cyt-c release
*ROS↑, cells exposed to the MF showed increased intracellular reactive oxidative species (ROS) levels and glycogen synthase kinase-3β (GSK-3β) dephosphorylation at 9 serine residue (Ser(9))
*p‑GSK‐3β↑,
*eff↓, attenuated by ROS scavenger (N-acetyl-L-cysteine, NAC) or GSK-3β inhibitor
*MMP∅, no significant effect on mitochondrial membrane potential (ΔΨm)
*BAX↓, Bax declined around 15% which was statistically significant while the total level of Bcl-2 reminded unchanged in cells
*Bcl-2∅,

194- MF,    Electromagnetic Field as a Treatment for Cerebral Ischemic Stroke
- Review, Stroke, NA
*BAD↓,
*BAX↓,
*Casp3↓,
*Bcl-xL↑,
*p‑Akt↑,
*MMP9↓, EMF significantly decreased levels of IL-1β and MMP9 in the peri-infarct area at 24 h and 3rd day of the experiment
*p‑ERK↑, ERK1/2
*HIF-1↓,
*ROS↓, n a similar experiment, ELF-MF (50 Hz/1 mT) increased cell viability and decreased intracellular ROS/RNS in mesenchymal stem cells submitted to OGD conditions and 3 h ELF-MF exposure
*VEGF↑,
*Ca+2↓,
*SOD↑,
*IL2↑,
*p38↑,
*HSP70/HSPA5↑,
*Apoptosis↓, PEMF decreased apoptosis
*ROS↓, Nevertheless, in the presence of ischemia, EMF decreased NO and ROS concentrations.
*NO↓,

4112- MF,    Novel protective effects of pulsed electromagnetic field ischemia/reperfusion injury rats
- in-vivo, Stroke, NA
*cardioP↑, in vivo results showed that per-treatment of PEMF could significantly improve the cardiac function in I/R injury group
*Bcl-2↑, up-regulating the expression of anti-apoptosis protein B-cell lymphoma 2 (Bcl-2) and down-regulating the expression of pro-apoptosis protein (Bax)
*BAX↓,
*ROS↓, PEMF treatment could significantly reduce the apoptosis and reactive oxygen species (ROS) levels in primary neonatal rat cardiac ventricular myocytes (NRCMs) induced by hypoxia/reoxygenation (H/R)

6775- Neem,  Nimb,    Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment
- Review, Nor, NA
*antiOx↑, its role as health-promoting effect is attributed because it is rich source of antioxidant.
P53↑, anticancer management through the modulation of various molecular pathways including p53, pTEN, NF-κB, PI3K/Akt, Bcl-2, and VEGF
PTEN↑, figure 2
NF-kB↓,
PI3K↓,
Akt↓,
Bcl-2↓,
VEGF↓,
*Inflam↓, Neem also plays role as anti-inflammatory via regulation of proinflammatory enzyme activities including cyclooxygenase (COX), and lipoxygenase (LOX) enzyme.
*COX2/PTGS2↓,
*5LO↝,
*Wound Healing↑, figure 1
*Imm↑,
*hepatoP↑,
*AntiDiabetic↑,
*neuroP↑,
*AntiViral↑,
*Bacteria↑,
*AntiBio↑,
*AntiFungal↑,
cMyc↓, figure 2
BAX↓,
IAP1↓, Nimbolide downregulated cell survival proteins, including I-FLICE, cIAP-1, cIAP-2, Bcl-2, Bcl-xL, survivin, and X-linked inhibitor of apoptosis protein, and upregulated the proapoptotic proteins p53 and Bax
IAP2/BIRC3↓,
Bcl-xL↓,
survivin↓,
XIAP↓,
angioG↓, ethanolic fraction of neem leaf (EFNL) treatment effectively inhibited the expression of proangiogenic genes,

1680- PBG,    Protection against Ultraviolet A-Induced Skin Apoptosis and Carcinogenesis through the Oxidative Stress Reduction Effects of N-(4-bromophenethyl) Caffeamide, a Propolis Derivative
- in-vitro, Nor, HS68
*ROS↓, K36H reduced UVA-induced intracellular reactive oxygen species generation
*NRF2↑, increased nuclear factor erythroid 2–related factor 2 translocation into the nucleus to upregulate the expression of heme oxygenase-1, an intrinsic antioxidant enzyme.
*HO-1↑,
*cJun↓, K36H inhibited UVA-induced activation of extracellular-signal-regulated kinases and c-Jun N-terminal kinases,
*MMP1↓, reduced the overexpression of matrix metalloproteinase (MMP)-1 and MMP-2
*MMP2↓,
*p‑cJun↓, K36H inhibited the phosphorylation of c-Jun and downregulated c-Fos expression
*cFos↓,
*BAX↓, K36H attenuated UVA-induced Bax and caspase-3 expression and upregulated antiapoptotic protein B-cell lymphoma 2 expression.
*Casp3↓,
*DNAdam↓, K36H reduced UVA-induced DNA damage.
*iNOS↓, K36H also downregulated inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-6 expression as well as the subsequent generation of prostaglandin E2 and nitric oxide.
*COX2/PTGS2↓,
*IL6↓,
*PGE2↓,
*NO↓,

1672- PBG,    The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers
- Review, BC, NA
ChemoSen↓, 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects.
RadioS↑,
Inflam↓, immunomodulatory, anti-inflammatory, and anti-cancer properties.
AntiCan↑,
Dose∅, Indonesia: IC50 = 4.57 μg/mL and 10.23 μg/mL
mtDam↑, Poland: propolis induced mitochondrial damage and subsequent apoptosis in breast cancer cells.
Apoptosis?,
OCR↓, China: CAPE inhibited mitochondrial oxygen consumption rate (OCR) by reducing basal, maximal, and spare respiration rate and consequently inhibiting ATP production
ATP↓,
ROS↑, Iran: inducing intracellular ROS production, IC50 = 65-96 μg/mL
ROS↑, Propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating the occurrence of ROS-associated necrosis.
LDH↓,
TP53↓, Interestingly, a reduced expression of apoptosis-related genes such as TP53, CASP3, BAX, and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, CAPE: inducing oxidative stress through upregulation of e-NOS and i-NOS levels
eNOS↑,
iNOS↑,
eff↑, The combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone
hTERT/TERT↓, downregulation of the mRNA levels of hTERT and cyclin D1
cycD1/CCND1↓,
eff↑, Synergism with bee venom was observed
eff↑, Statistically significant decrease was found in the MCF-7 cell viability 48 h after applying different combinations of cisplatin (3.12 μg/mL) and curcumin (0.31 μg/mL) and propolis (160 μg/mL)
eff↑, Nanoparticles of chrysin had significantly higher cytotoxicity against MCF-7 cells, compared to chrysin
eff↑, Propolis nanoparticles appeared to increase cytotoxicity of propolis against MCF-7 cells
STAT3↓, Chrysin also inhibited the hypoxia-induced STAT3 tyrosine phosphorylation suggesting the mechanism of action was through STAT3 inhibition.
TIMP1↓, Propolis reduced the expression of TIMP-1, IL-4, and IL-10.
IL4↓,
IL10↓,
OS↑, patients supplemented with propolis had significantly longer median disease free survival time (400 mg, 3 times daily for 10 d pre-, during, and post)
Dose∅, 400 mg, 3 times daily for 10 d pre-, during, and post
ER Stress↑, endoplasmic reticulum stress
ROS↑, upregulating the expression of Annexin A7 (ANXA7), reactive oxygen species (ROS) level, and NF-κB p65 level, while simultaneously reducing the mitochondrial membrane potential.
NF-kB↓,
p65↓,
MMP↓,
TumAuto↑, propolis induced autophagy by increasing the expression of LC3-II and reducing the expression of p62 level
LC3II↑,
p62↓,
TLR4↓, propolis downregulates the inflammatory TLR4
mtDam↑, propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating ROS-associated necrosis in MDA MB-231cancer cells
LDH↓,
ROS↑,
Glycolysis↓, inhibit the proliferation of MDA-MB-231 cells by targeting key enzymes of glycolysis, namely glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA),
HK2↓,
PFK↓,
PKM2↓,
LDH↓,
IL10↓, propolis significantly reduced the relative number of CD4+, CD25+, FoxP3+ regulatory T cells expressing IL-10
HDAC8↓, Chrysin, a propolis bioactive compound, inhibits HDAC8
eff↑, combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone.
eff↑, Propolis also upregulated the expression of catalase, HTRA2/Omi, FADD, and TRAIL-associated DR5 and DR4 which significantly enhanced the cytotoxicity of doxorubicin in MCF-7 cells
P21↑, Chrysin, a propolis bioactive compound, inhibits HDAC8 and significantly increases the expression of p21 (waf1/cip1) in breast cancer cells, leading to apoptosis.

2430- PBG,    The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation
- in-vitro, BC, MDA-MB-231
TumCP↓, CP extract exhibited antiproliferative and cytotoxic effects on MDA MB-231 cells, what may be probably related to PI3K/Akt and ERK1/2 pathways.
TP53↓, decreased expression of apoptosis-related genes (TP53, CASP3, BAX and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, These results suggested that CP cytotoxic effects on MDA MB-231 cells might be associated with the intracellular ROS production
eff↓, CP-induced ROS generation was reduced after cotreatment with the antioxidant NAC, which increased the percentage of viable cells, suggesting that CP-induced necrotic-related cell death could be associated with ROS production
MMP↓, Necrosis death is associated with mitochondrial dysfunction and our propolis sample reduced the MMP and increased LDH levels.
LDH↑,
ATP↓, rupture of mitochondrial membrane, loss of adenosine triphosphate (ATP),
Ca+2↑, excessive ROS production, intracellular [Ca+2] elevation, osmotic shock,

1944- PL,    Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress
- in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2
ER Stress↑, PL induces a lethal endoplasmic reticulum (ER) stress response in HCC cells
TrxR1↓, PL treatment reduces TrxR1 activity and tumor cell burden in vivo
ROS↑, and increasing intracellular ROS levels
eff↓, Interestingly, pretreatment with NAC, a specific ROS inhibitor, for 2 h apparently suppressed PL-induced increases in ROS levels
Bcl-2↓, PL treatment decreased the levels of the antiapoptotic proteins Bcl-2 and procaspase3 and increased the levels of the proapoptotic proteins Bax and cleaved caspase-3 in a dose-dependent manner.
proCasp3↓,
BAX↓,
cl‑Casp3↑,
TumCCA↑, PL Induces ROS-Dependent G2/M Cell Cycle Arrest in HCC Cells
p‑PERK↑, PL increased the expression of p-PERK and ATF4 in a dose-dependent manner.
ATF4↑,
TumCG↓, PL Inhibits HUH-7 Xenograft Tumor Growth Accompanied by Increased ROS Levels and Decreased Trxr1 Activity
lipid-P↑, PL treatment increased the levels of the product of lipid peroxidation (MDA) in tumor tissues ( Figure 6H ), suggesting increased ROS levels
selectivity↑, In normal cells, TrxR1 can protect against oxidant stress


Showing Research Papers: 1 to 50 of 65
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 65

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

BMP7/OP1↓, 2,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↓, 3,   Catalase↑, 1,   GPx↓, 1,   GPx↑, 2,   GSH↓, 1,   GSH↑, 1,   GSR↑, 1,   GSTA1↑, 1,   HO-1↓, 1,   HO-1↑, 1,   lipid-P↑, 2,   MDA↑, 1,   NQO1↓, 1,   NRF2↓, 1,   ROS↓, 1,   ROS↑, 17,   SOD?, 1,   SOD↓, 2,   SOD↑, 1,   TrxR1↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 2,   CDC25↓, 1,   FGFR1↓, 2,   MMP↓, 3,   MMP↑, 1,   mtDam↑, 5,   OCR↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACLY↓, 1,   ALAT↓, 1,   AMPK↑, 2,   cMyc↓, 5,   FASN↓, 1,   GLS↓, 1,   Glycolysis↓, 3,   HK2↓, 2,   lactateProd↓, 1,   LDH↓, 4,   LDH↑, 1,   NADPH↓, 1,   PDH↓, 1,   PFK↓, 2,   PKM2↓, 2,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 5,   p‑Akt↓, 2,   Apoptosis?, 1,   Apoptosis↑, 9,   BAD↑, 1,   Bak↓, 1,   Bak↑, 2,   BAX↓, 10,   BAX↑, 4,   Bcl-2↓, 12,   Bcl-2↑, 1,   Bcl-xL↓, 2,   BID↑, 1,   Casp↑, 1,   Casp3↓, 2,   Casp3↑, 11,   Casp3∅, 1,   cl‑Casp3↑, 2,   proCasp3↓, 1,   Casp7↑, 1,   Casp8↓, 1,   Casp8↑, 4,   Casp9↑, 2,   Casp9∅, 1,   cl‑Casp9↑, 1,   Chk2↓, 1,   CK2↓, 1,   Cyt‑c↑, 3,   Cyt‑c?, 1,   Fas↑, 4,   hTERT/TERT↓, 1,   IAP1↓, 1,   IAP2/BIRC3↓, 1,   iNOS↑, 1,   MAPK↑, 1,   Myc↓, 1,   NOXA↑, 1,   PUMA↑, 1,   survivin↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   ER Stress↑, 5,   GRP78/BiP↑, 1,   p‑PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   Beclin-1↓, 1,   Beclin-1↑, 2,   BNIP3↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↓, 1,   LC3B↑, 1,   LC3II↓, 1,   LC3II↑, 2,   p62↓, 1,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

CHK1↓, 1,   DNAdam↓, 1,   DNAdam↑, 2,   P53↓, 1,   P53↑, 3,   PARP↑, 3,   cl‑PARP↑, 1,   cl‑PARP∅, 1,   PCNA↓, 2,   TP53↓, 3,   γH2AX↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 2,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 1,   cycE/CCNE↑, 1,   cycE1↓, 1,   P21↓, 2,   P21↑, 2,   TumCCA↑, 7,  

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

CSCs↓, 1,   EMT↓, 2,   ERK↓, 1,   FGF↓, 2,   FGFR2↓, 1,   FOXO1↑, 1,   HDAC8↓, 1,   IGF-1R↑, 1,   miR-34a↓, 1,   mTOR↓, 2,   NOTCH1↓, 1,   NOTCH3↓, 1,   P70S6K↓, 1,   PI3K↓, 4,   PTEN↑, 2,   STAT3↓, 4,   p‑STAT3↓, 1,   TumCG↓, 3,   tyrosinase↓, 1,   Wnt↓, 1,   Wnt↑, 1,  

Migration(tgid=13) ⓘ

Ca+2↓, 1,   Ca+2↑, 1,   Ca+2↝, 1,   cal2↑, 1,   CEA↓, 1,   E-cadherin↓, 1,   Ki-67↓, 1,   MMP2↓, 3,   MMP9↓, 3,   PDGF↓, 1,   Slug↓, 1,   TIMP1↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TRIB3↑, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 6,   TumMeta↓, 1,   TumMeta↑, 2,   VCAM-1↓, 1,   Vim↓, 1,   Zeb1↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 2,   ATF4↑, 2,   EGFR↑, 1,   eNOS↑, 1,   Hif1a↓, 2,   VEGF↓, 5,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,   GLUT3↓, 1,   P-gp/ABCB1↓, 1,   P-gp/ABCB1⇅, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 3,   ICAM-1↓, 1,   IL1↑, 1,   IL10↓, 2,   IL2↑, 1,   IL4↓, 1,   IL4↑, 1,   IL6↓, 2,   Inflam↓, 2,   JAK1↓, 2,   NF-kB↓, 5,   NF-kB↑, 2,   p65↓, 2,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 1,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 1,   ChemoSen↓, 1,   ChemoSen↑, 3,   Dose↝, 2,   Dose∅, 2,   eff↓, 2,   eff↑, 11,   RadioS↑, 3,   selectivity↑, 2,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   CEA↓, 1,   EGFR↑, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 1,   IL6↓, 2,   Ki-67↓, 1,   LDH↓, 4,   LDH↑, 1,   Myc↓, 1,   TG/TAG↓, 1,   TP53↓, 3,   TRIB3↑, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↓, 1,   AntiCan↑, 5,   cardioP↑, 1,   chemoPv↑, 1,   OS↑, 1,  
Total Targets: 228

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 3,   antiCG↑, 1,   CYP2D6↓, 1,   NeuroI↓, 1,   Stroke↓, 2,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 15,   Catalase↓, 1,   Catalase↑, 13,   Ferroptosis↓, 1,   GPx↓, 1,   GPx↑, 9,   GSH↑, 14,   HDL↑, 1,   HO-1↑, 9,   Keap1↑, 1,   lipid-P↓, 9,   MDA↓, 14,   MPO↓, 2,   NOX4↓, 1,   NQO1↑, 2,   NRF2↑, 11,   RNS↓, 1,   ROS↓, 28,   ROS↑, 1,   SOD↑, 21,   TAC↑, 1,   TBARS↓, 1,   uricA↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   ATP↑, 1,   Insulin↑, 1,   MMP↑, 4,   MMP∅, 1,   MPT↑, 1,   mtDam↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 3,   AMPK↓, 1,   p‑AMPK↑, 1,   p‑CREB↑, 1,   GAPDH↑, 1,   glucose↓, 1,   H2S↑, 1,   HMG-CoA↓, 1,   LDL↓, 2,   NAD↓, 1,   PPARγ↑, 2,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Akt↑, 2,   p‑Akt↑, 6,   APAF1↓, 2,   Apoptosis↓, 15,   BAD↓, 3,   BAX↓, 40,   Bcl-2↓, 1,   Bcl-2↑, 24,   Bcl-2∅, 1,   Bcl-xL↑, 1,   Casp1↓, 1,   Casp3↓, 20,   cl‑Casp3↓, 6,   Casp8↓, 1,   Casp9↓, 4,   cl‑Casp9↓, 2,   Cyt‑c↓, 6,   Cyt‑c↑, 1,   Fas↓, 1,   Ferroptosis↓, 1,   GADD34↓, 1,   iNOS↓, 9,   JNK↓, 3,   MAPK↓, 1,   p38↓, 1,   p38↑, 1,   p‑p38↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach↑, 1,   AntiThr↑, 1,   cJun↓, 1,   p‑cJun↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 3,   GRP78/BiP↓, 2,   HSP70/HSPA5↑, 4,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↓, 1,   LC3II↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 4,   P53↓, 2,   PARP↓, 1,   cl‑PARP↓, 1,   p‑γH2AX↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

P21↓, 1,  

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

cFos↓, 1,   ERK↓, 1,   p‑ERK↑, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↑, 2,   Mst1↓, 1,   mTOR↑, 1,   p‑mTOR↑, 2,   PDGFRB↓, 1,   PI3K↑, 1,  

Migration(tgid=13) ⓘ

5LO↝, 1,   BACH1↓, 1,   Ca+2?, 1,   Ca+2↓, 4,   CLDN1↓, 1,   MMP1↓, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP9↓, 2,   RAGE↓, 1,   TJ↑, 1,   VCAM-1↓, 1,   ZO-1↓, 1,   ZO-1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↓, 1,   HIF-1↓, 1,   NO↓, 6,   NO↑, 1,   PDGFR-BB↓, 1,   VEGF↑, 2,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,   BBB↝, 1,   GastroP↑, 2,   OCLN↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

ASC↓, 1,   CD4+↑, 1,   COX2/PTGS2↓, 11,   CRP↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IL1↓, 1,   IL10↓, 2,   IL17↓, 1,   IL1β↓, 8,   IL2↑, 1,   IL6↓, 10,   IL6↑, 1,   IL8↓, 2,   Imm↓, 1,   Imm↑, 2,   Inflam↓, 17,   NF-kB↓, 10,   p65↓, 1,   PGE2↓, 4,   PGE2↑, 1,   TLR4↓, 1,   TNF-α↓, 16,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 4,   BChE↓, 2,   BDNF↓, 1,   BDNF↑, 4,   BDNF⇅, 1,   ChAT↑, 1,   NGF↑, 3,   tau↓, 1,   p‑tau↓, 1,   TrkB↑, 2,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 4,   BACE/β-secretase↓, 2,   NLRP3↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 4,   BioAv↑, 6,   Dose↑, 1,   Dose↝, 3,   eff↓, 1,   eff↑, 2,   Half-Life↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 3,   AST↓, 4,   creat↓, 1,   CRP↓, 1,   GutMicro↑, 1,   IL6↓, 10,   IL6↑, 1,   RAGE↓, 1,   TG/TAG↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 5,   ANXi↓, 1,   cardioP↑, 10,   cognitive↑, 6,   hepatoP↓, 1,   hepatoP↑, 7,   memory↑, 6,   motorD↑, 2,   neuroP↑, 16,   Pain↓, 1,   radioP↑, 1,   RenoP↓, 1,   RenoP↑, 5,   toxicity↓, 3,   toxicity↝, 1,   Wound Healing↑, 2,  

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 3,   AntiViral↑, 2,   Bacteria↓, 1,   Bacteria↑, 1,   CD8+↑, 1,   Diar↓, 2,   Inf↓, 1,  
Total Targets: 200

Scientific Paper Hit Count for: BAX, Apoptosis regulator BAX
4 Shikonin
4 Thymoquinone
3 Baicalein
3 Ginkgolide B
3 Hyperoside
3 Lycopene
3 Magnetic Fields
3 Propolis -bee glue
2 α-Bisabolol / Chamomile oil
2 Cichoric acid / Chicoric acid
2 methotrexate
2 Crocetin
2 EGCG (Epigallocatechin Gallate)
2 Emodin
2 Ferulic acid
2 Gallic acid
2 isoorientin
2 Quercetin
2 Resveratrol
1 Phyllanthus emblica/Emblica officinalis/Amla / Indian Gooseberry
1 Berberine
1 Biochanin A
1 borneol
1 Caffeic acid
1 Metformin
1 Chrysin
1 Cinnamon
1 Radiotherapy/Radiation
1 Ginkgetin
1 Graviola
1 Hydrogen Gas
1 hydrogen sulfide
1 Honokiol
1 Hyperthermia
1 Luteolin
1 Neem
1 Nimbolide
1 Piperlongumine
1 Parthenolide
1 Rosmarinic acid
1 doxorubicin
1 Vitexin
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#:26  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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