RenoP Cancer Research Results
RenoP, K,Renoprotection: Click to Expand ⟱
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Protects kidneys
-Same as nephroprotective
Opposite is : Nephrotoxicity is toxicity in the kidneys
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Scientific Papers found: Click to Expand⟱
*eff↑, Treatment with AgNPs led to a notable reduction in damages of liver, kidney, lung, stomach and duodenum.
*RenoP↑,
*hepatoP↑,
*MDA↓, AgNPs treated groups reduced the levels of tissues MDA and increased the levels of tissues SOD and GSH.
*SOD↑,
*GSH↑,
*TNF-α↓, The expression levels of TNF-α mRNA and IL-1β mRNA were reduced in the rats treated by silver nanoparticles.
*IL1β↓,
*Dose↝, The treated group received a single oral dose of 5.5 mg/kg of Ag NPs. 5 to 12 nm
*eff↑, Ag NPs treatment in septic mice significantly decreased liver enzyme activities, total protein, and serum albumin.
*RenoP↑, Ag NPs significantly enhanced kidney function, as indicated by a significant decrease in the levels of creatinine, urea, and uric acid.
*antiOx↑, Ag NPs showed a powerful antioxidant effect via the considerable reduction of malondialdehyde and nitric oxide levels and the increase in antioxidant content.
*MDA↓,
*NO↓,
*hepatoP↑, hepatoprotective effect of Ag NPs may be attributed to their antioxidant properties
*toxicity↝, The Ag NPs dose is 1/10 of LD50, which is 5.5 mg/kg.
*GSH↑, GSH, SOD, GST, and CAT of the septic group. Meanwhile, the Ag NPs-treated mice showed a significant (p < 0.05) increase in all four parameters.
*SOD↑,
*GSTs↑,
*Catalase↑,
*BioAv↑, another key property of allicin is its hydrophobicity, which allows it to be absorbed easily through the cell membrane without causing any physical or chemical damage to the phospholipid bilayer, thereby allowing its rapid metabolism to produce pharm
*cardioP↑, Allicin exhibits protective effects in multiple organ systems, including the brain, intestines, lungs, liver, kidneys, prostate, and heart.
*hepatoP↑,
*RenoP↑,
*Half-Life↝, half-life (t1/2)of allicin was 227 min–260 min. Because allicin is eliminated from the body by the respiratory tract, the concentration of allicin in lung tissue is significantly lower than that in the blood
*BioAv↓, We believe that the bioavailability of allicin is relatively low for the following reasons: At first, allicin is characterized by a distinctive garlic odor and chemical instability. It can be easily degraded under room temperature.
*neuroP↑, Neuroprotective activity
*cognitive↑, On the other hand, allicin improves cognitive deficits via Protein kinase R-like endoplasmic reticulum kinase (PERK)/Nuclear factor erythroid-2-related factor 2 (NRF2) signaling pathway and c-Jun N-terminal kinase (JNK) signaling pathways
*ROS↓, They found that allicin suppressed ROS generation and decreased lipid peroxidation in 6-hydroxydopamine (6-OHDA)-induced Pheochromocytoma 12 (PC12) cells
*lipid-P↓,
*DNArepair↑, Allicin not only directly protects DNA, but also indirectly protects DNA through antioxidant activity and regulation of oxidizing enzymes
*ChemoSen↑, Allicin combined with other chemotherapy drugs showed a better anti-cancer effect
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*antiOx↑, Allicin may exert anti-apoptotic and antioxidative effects to promote renal function recovery in I/R renal tissues and H/R treated NRK-52E cells.
*RenoP↑,
*MDA↓, Allicin ameliorated the increase in MDA content and the reduction in SOD activity induced by renal IRI in groups D, E and F
*SOD↑,
*RenoP↑, We focus on various animal models of kidney injury by which the underlying renoprotective mechanisms of ALA have been unraveled
*ROS↓, ALA’s renal protective actions that include decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating renal fibrosis, and attenuating nephron cell death.
*antiOx↑,
*Inflam↓,
*Sepsis↓, figure 1
*IronCh↑, ALA can also chelate metals such as zinc, iron, and copper and regenerate endogenous antioxidants—such as glutathione—and exogenous vitamin antioxidants—such as vitamins C and E—with minimal side effects
*BUN↓, ALA can decrease acute kidney injury by lowering serum blood urea nitrogen, creatinine levels, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), thereby decreasing endothelin-1 vasoconstriction, neutrophil dif
*creat↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*MDA↓, pretreatment with ALA decreased MDA content and ameliorated renal oxidative stress
*NRF2↑, activate the Nrf2 signaling pathway, leading to upregulation of the second-phase cytoprotective proteins such as heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1)
*HO-1↑,
*NQO1↑,
*chemoP↑, ALA has also been shown to lower plasma creatinine levels and urine output, increase creatinine clearance and urine osmolality, and normalize sodium excretion in cisplatin kidney injury
*eff↑, ALA can also minimize renal toxicity induced by gold nanoparticles, which are often used as drug carriers
*NF-kB↓, Enhancing autophagy, inhibiting NF-KB, attenuating mitochondrial oxidative stress
*antiOx↑, α-LA has been widely used as an antioxidant compound in many multivitamin formulations, food supplements, anti-aging formulas, and even in human and pet food recipes
*IronCh↑, potential role in the chelation of metals and in restoring normal levels
of intracellular glutathione (GSH) after depletion caused by toxicants,
*GSH↑,
*BBB↑, ALA, which can pass through the blood-brain barrier (BBB
Apoptosis↑, increased level of apoptosis, mitochondrial membrane depolarization, ROS production, lipid peroxidation, poly-(ADP)-ribose polymerase 1 (PARP1), caspase 3 and 9 expression levels in simultaneous ALA (0.05 mM) and cisplatin(0.025 mM)-treated MCF7
MMP↓,
ROS↑,
lipid-P↑,
PARP1↑,
Casp3↑,
Casp9↑,
*NRF2↑, ALA's ability to activate Nfr2 in GSH production
*GSH↑,
*ROS↓, administration of ALA has been shown to reduce oxidative stress
RenoP↑, ALA also reduced lipid peroxidation in the kidneys caused by the anticancer drug cisplatin,
ChemoSen↑, ALA enhances the functions of various anticancer drugs such as 5-fluorouracil in CRC [146] and cisplatin in MCF-7 cells
*BG↓, ALA was shown to lower the blood glucose levels in patients with type 2 diabetes
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neuroP↑, APG has a protective role against DOX-induced nephrotoxicity
ChemoSen∅, without weakening DOX cytotoxicity in malignant tumors.
RenoP↑, potential protective agent against renal injury. attenuate renal toxicity in cancer patients treated with DOX.
selectivity↑, APG maintained the cytotoxicity of DOX to tumor cells but not to renal cells. APG alone exhibited a prominent cytotoxic effect on 4T1 cells (Fig. 9E), but not on normal renal cells, at the same concentration
chemoP↑, Furthermore, APG revealed a dose-dependent improvement in normal renal cells against DOX-induced injury (Fig. 9E), with an exacerbation observed in 4T1 cells
ROS↑, Our in vivo study revealed that DOX caused a severe reduction in SOD activity and GSH levels, accompanied
by an increase in MDA, leading to the overproduction of ROS and induction of oxidative injuries.
*ROS∅, Noteworthily, these changes were suppressed by APG(meaning on normal cells), consistent with several previous reports
*antiOx↑, APG has a similar antioxidative role as NAC and scavenges DOX-induced oxygen radicals and inhibits apoptosis significantly, implying that antioxidative stress is one of the main mechanisms through which APG protects renal tubular cells against DOX cy
*toxicity↓, We confirmed that APG mitigated the toxicity of DOX on normal renal cells by inhibiting oxidative stress, inflammation, and apoptosis.
*RenoP↑, ashwaganda WSE as a valid candidate for evaluation of therapeutic potential for the treatment of chronic renal dysfunction.
*NF-kB↓, WSE completely prevented TNF-α-induced increases in CCL5, while attenuating the increase in CCL2 expression and NF-κB activation.
*MCP1↓,
*RANTES↓,
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*RenoP↑, WFA ameliorated renal damage, improved kidney function, and decreased levels of creatinine, BUN, UA, and XOD in PO-induced hyperuricemic mice.
*hepatoP↑,
*creat↓,
*BUN↓,
*uricA↓,
*Apoptosis↓, WFA markedly inhibited renal apoptosis, accompanied by changes of apoptosis-related proteins.
*α-SMA↓, Notably reduced α-SMA expression was observed after WFA administration, with WFA 10 mg/kg group presenting the most significant inhibitory effect.
TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,
AntiCan↑, assess the anticancer effect of melatonin (MEL) and ascorbyl palmitate-loaded pluronic nanoparticles (APnp) combination on Ehrlich ascites carcinoma
(EAC)-bearing mice.
TumCG↓, MEL alone showed a decrease in tumor growth by 48%, while in the case of using MEL combined with APnp, it displayed inhibition of tumor growth by 62%
Apoptosis↑, It also induced apoptosis and DNA damage.
DNAdam↑,
TumCCA↑, Besides, mediated cell cycle arrest.
IL6↓, IL-6/STAT3
pathway was inactivated to a greater extent after our combination treatment.
STAT3↓,
TumCP↓, antiproliferative effect of MEL and APnp via decreased expression of Ki-67
Ki-67↓,
TumCI↓, Our combination of MEL and APnp was able to inhibit cancer cell invasion and metastasis by decreasing the protein expression of MMP-9.
TumMeta↓,
MMP9↓,
eff↑, The synergy score was 21.06 ( > 10 indicates synergistic effect)
*Catalase↑, Administration of MEL alone or MEL+ APnp treated mice showed a significant and highly significant increase, respectively (P<0.05, P<0.01) in the antioxidant enzyme activities of CAT and SOD, and GSH.
*SOD↑,
*GSH↑,
*MDA↓, Figure 2 demonstrated a highly significant and extremely significant reduction, respectively (P<0.01, P<0.001) in the MDA and NO levels compared to the EAC control
group.
*NO↓,
*antiOx↑, Figure 2 demonstrated a highly significant and extremely significant reduction,
respectively (P<0.01, P<0.001) in the MDA and NO levels compared to the EAC control
group.
*hepatoP↑, combined MEL and
APnp- treated animals displayed a noteworthy amelioration for all examined organs when
compared to the control EAC inoculated group, Figure 3.
*RenoP↑,
*RenoP↑, Baicalein alleviated cisplatin- and folic acid-induced renal dysfunction and pathological damage and improved cisplatin-induced HK2 cell injury
*12LOX↓, Mechanistically, baicalein reduced the expression of 12-lipoxygenase (ALOX12), which inhibits phospholipid peroxidation and ferroptosis in AKI
*Ferroptosis↓,
*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.
*RenoP↑, Thus, we concluded that baicalein executed a kidney-protection action in hyperuricemia and therefore may be used as a therapeutic alternative for hyperuricemic nephropathy.
*uricA↓, Baicalein lowered UA and protected kidney against hyperuricemia
*ROS↓, Baicalein prevented renal oxidative stress in hyperuricemia mice.
EMT↓, Baicalein inhibits hyperuricemia-induced epithelial-mesenchymal transition (EMT) process
RenoP↑, Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function
*iNOS↑, Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear tra
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*MAPK↓, baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys
*ERK↓,
*JNK↓,
*antiOx↑, Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys.
*NRF2↓,
*HO-1↑,
*Cyt‑c∅, inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP
*Casp3∅,
*Casp9∅,
*PARP∅,
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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↓, 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↓,
*Inflam↓, Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis
*antiOx↑,
*Ferroptosis↓,
*RenoP↑, Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice.
*DNMT1↓, Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation.
*DNMTs↓,
*KLF4↑,
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Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1↓,
PGE2↓,
COX2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB/CCNB1↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents
*Inflam↓, including anti-inflammatory, antioxidative, anti-apoptotic, antiproliferative, and antihypertensive.
*antiOx↑,
*ER Stress↓, BBR can decrease apoptosis and inflammation following different pathological conditions, which might be mediated by targeting ER stress pathways.
*cardioP↑, protective potential of BBR against several diseases, such as metabolic disorders, cancer, intestinal diseases, cardiovascular, liver, kidney, and central nervous system diseases, in both in vivo and in vitro studies.
*RenoP↑,
*hepatoP↑,
*AChE↓, Berberine (9) has gained considerable attention due to its wide pharmacological potentials and several biological properties, such as acetylcholinesterase and butyrylcholinesterase inhibitory, antioxidant, monoamine oxidase oxidase,
*Aβ↓, amyloid-b peptide level-reducing, cholesterol- lowering and renoprotective activities
*LDL↓,
*RenoP↑,
*BChE↓,
*eff↑, Above all, the berberine-pyrocatechol hybrid (14) showed a strong AChE inhibitor activity (IC50 of 123 ± 3 nM)
[34]
*BACE↓, Curcumin: inhibite the rBACE1 activity [42]. In addition, it has made good inhibitory effect on acetylcholinesterase activity
*AChE↓, EGCG promoted brain health, prevented AD progression, and inhibited the AChE activity [52,53].
*eff↑, EGCG could enhance the effect of huperzine A on inhibiting AChE.
*RenoP↑, BA pretreatment alleviated excessive glomerular hemorrhage and inflammatory cell infiltration in kidneys caused by T-2 toxin.
*SOD?, Moreover, pretreatment with BA mitigated T-2 toxin-induced renal oxidative damage by up-regulating the activities of SOD and CAT, and the content of GSH, while down-regulating the accumulation of ROS and MDA
*Catalase↑,
*GSH↑,
*ROS↓,
*MDA↓,
*IL1β↓, decreasing the mRNA expression of IL-1β, TNF-α and IL-10, and increasing IL-6 mRNA expression
*TNF-α↓,
*IL10↓,
*IL6↑,
*NRF2↑, pretreatment with BA could activate Nrf2 signaling pathway.
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AntiTum↑, BA is considered a future promising antitumor compound
Cyt‑c↑, BA stimulated mitochondria to release cytochrome c and Smac and cause further apoptosis reactions
Smad1↑,
Sepsis↓, Administration of 10 and 30 mg/kg of BA significantly improved survival against sepsis and attenuated lung injury.
NF-kB↓, BA inhibited nuclear factor-kappa B (NF-κB) expression in the lung and decreased levels of cytokine, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9)
ICAM-1↓,
MCP1↓,
MMP9↓,
COX2↓, In hPBMCs, BA suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PEG2) production by inhibiting extracellular regulated kinase (ERK) and Akt phosphorylation and thereby modulated the NF-κB signaling pathway
PGE2↓,
ERK↓,
p‑Akt↓,
*ROS↓, BA significantly decreased the mortality of mice against endotoxin shock and inhibited the production of PEG2 in two of the most susceptible organs, lungs and livers [80]. Moreover, BA reduced reactive oxygen species (ROS) formation
*LDH↓, and the release of lactate dehydrogenase
*hepatoP↑, hepatoprotective effect of BA from Tecomella undulata.
*SOD↑, Pretreatment of BA prevented the depletion of hepatic antioxidants superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) and ascorbic acid (AA) and decreased the CCl4-induced LPO level
*Catalase↑,
*GSH↑,
*AST↓, A also attenuated the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) plasma level,
*ALAT↓,
*RenoP↑, BA also exhibits renal-protective effects. Renal fibrosis is an end-stage renal disease symptom that develops from chronic kidney disease (CKD).
*ROS↓, BA protected against this ischemia-reperfusion injury in a mice model by enhancing blood flow and reducing oxidative stress and nitrosative stress
*α-SMA↓, Moreover, BA reduced the expression of α-smooth muscle actin (α-SMA) and collagen-I
*RenoP↑, Our results revealed that low doses of boron (up to 160 mg) had positive effect, while high doses (especially 640 mg) caused negative effect on the development of the kidney
*ROS↓, The low doses regulate the oxidative and enzyme activity in the kidney.
*antiOx↑, boron at low doses upregulated the expression of genes involved in the antioxidant pathway
*Apoptosis↓, low levels of boron (up to 160 mg) inhibited the cell apoptosis, regulate the enzyme activity, and improved the antioxidant system, thus may encourage the development of the ostrich chick's kidney
*NRF2↑, maximum localization of Nrf2 in 80 mg/L BA dose group
*HO-1↑, As the boron concentration increased, the expression of Nrf2, GCLc, and HO-1 genes upregulated
*MDA↓, In comparison to those of the group 1, MDA content (lipid peroxidation marker) was significantly decreased by 26.02 and 48.12% in the 40 and 80 mg/L BA groups
*lipid-P↓,
*GPx↓, GSH-PX activity of ostrich chick kidney tissue was slightly increased in the 40 and 80 mg/L BA groups,
*Catalase↑, supplementation of low doses of boron in the ostrich drinking water has resulted in stimulation of antioxidant capacity of GR, CAT, and SOD significantly.
*SOD↑,
*ALAT↓, boron supply in low doses (especially 80 mg/L BA) showed decrease levels in the activity of ALT, AST, and ALP.
*AST↓,
*ALP↓,
*ROS↓, decreased inflammation and oxidative stress caused by cisplatin
*Inflam↓,
RenoP↑, boric acid and borax reduced apoptotic damage in kidney tissue,
*AntiCan↑, capsaicin possesses anti-cancer, anti-inflammatory, and antioxidant properties and is used as a topical analgesic
*Inflam↓,
*antiOx↑,
*TRPV1↑, Studies demonstrate that capsaicin directly activates TRPV1 by binding to intracellular sites within the channel protein
*AMPK↑, Moreover, capsaicin and TRPV1 can activate the AMPK pathway [82, 83]
*SIRT1↑, elevating SIRT1 levels
*NADPH↓, suppressing NADPH oxidase and reducing reactive oxygen species
*ROS↓,
*MAPK↓, inhibiting MAPK pathways
*eNOS↑, activating eNOS
*Wnt/(β-catenin)↓, inhibiting the Wnt/β-catenin signaling pathway
RenoP↑, Furthermore, TRPV1 activation decreases renal perfusion pressure while increasing glomerular filtration rate and the excretion of sodium/water, thereby modulating renal hemodynamics and excretory functions
*IL1β↓, capsaicin ameliorated LPS-induced cytotoxicity in vitro and attenuated the release of interleukin (IL)-1β and IL-18.
*IL18↓,
*TRPV1↑, Molecularly, capsaicin activated transient receptor potential cation channel subfamily V member 1 –mitochondrial uncoupling protein 2 axis and inhibited caspase-1-mediated pyroptosis
*ROS↓, capsaicin alleviated LPS-induced ROS production and mitochondrial membrane potential disruption and inhibited apoptosis.
*MMP↑,
*Apoptosis↓,
*RenoP↑, These findings suggest that capsaicin shows a protective effect in in vitro acute kidney injury model.
*Inflam↓, Capsaicin ameliorates LPS-induced cytotoxicity and inflammation response in HK-2 cells
*UCPs↑, Capsaicin alleviates LPS-induced pyroptosis in HK-2 cells by activating TRPV1/UCP2 axis
RenoP↑, observed experimental benefits in preventing acute kidney injury
AntiTum↑, anti-tumoral properties of capsaicin on different types of cancer cells are well-acknowledged
AMPK↑, activating the AMPK/mTOR
mTOR↑,
PD-1↓, capsaicin promotes the inhibition of the PD-L1/PD-1 checkpoint
PD-L1↓,
*Bacteria↓, Carvacrol, either alone or in combination with other compounds, has a strong antimicrobial effect on many different strains of bacteria and fungi that are dangerous to humans
*Inflam↓, Carvacrol also exerts strong anti-inflammatory properties by preventing the peroxidation of polyunsaturated fatty acids by inducing SOD, GPx, GR, and CAT, as well as reducing the level of pro-inflammatory cytokines in the body.
*SOD↑,
*GPx↑,
*GSR↑,
*Catalase↑,
*toxicity↓, Carvacrol is considered a safe compound despite the limited amount of data on its metabolism in humans.
*Pain↓, carvacrol has been used as a substitute for cretol and carbolic acid in the treatment of toothache, sensitive dentine, and alveolar abscess, and as an antiseptic in the pulp canals of the teeth
*other↑, because it has much greater activity as a mosquito repellent than the commercial preparation, N,N-diethyl-m-methylbenzamide
*cardioP↑, other biological activities, including cardio-, reno-, and neuroprotective [20]; immune response-modulating [21]; antioxidant; anti-inflammatory [22];
*RenoP↑,
*neuroP↑,
*antiOx↑,
*AntiDiabetic↑, antidiabetic; hepatoprotective [28]; and anti-obesity properties
*hepatoP↑,
*Obesity↓,
*AntiAg↑, figure 1
*BioAv↓, challenges surrounding the wider use of carvacrol in food or feed are its unpleasant and pungent taste at higher doses; low bioavailability;
BioAv↝, sensitivity to the surrounding environment, such as in processing conditions (e.g., heat or other ingredients); and the acidic environment in the digestive tract.
*OS↑, pneumonia. Administration of carvacrol to mice (10, 25, 50 mg/kg) was associated with increased survival and significantly reduced bacterial load
MMP↓, carvacrol was found to cause greater membrane depolarization and increased oxidative stress in E. coli cells;
ROS↑,
*MDA↓, In studies conducted in guinea pigs, carvacrol concentrations of 120 and 240 μg/mL have been shown to reduce malondialdehyde levels compared to the control group
*lipid-P↓, Carvacrol prevents lipid peroxidation by inducing SOD, GPx, GR, and CAT [85,86].
*COX2↓, A decrease in COX-2 gene expression was found at carvacrol concentrations of 0.008% and 0.016%
*Dose↝, Phase I clinical trial, carvacrol was administered to healthy subjects at 1 and 2 mg/kg/day for 1 month, and no critical adverse reactions
*lipid-P↓, Carvacrol also attenuated lipid peroxidation by reducing malondialdehyde (MDA) levels, while boosting total antioxidant capacity and improving inflammatory status.
*MDA↓,
*antiOx↑,
*Inflam↑,
RenoP↑, Moreover, restoration of liver and kidney function was observed through normalization of serum ALT, AST, urea, and creatinine levels
hepatoP↑,
*ALAT↓,
AST↓,
creat↓,
chemoPv↑, Preclinical studies have demonstrated the chemopreventive and therapeutic potential of Carvacrol in several malignancies, including breast cancer, melanoma, hepatocellular carcinoma, cervical cancer, and non-small cell lung cancer
Cyt‑c↑, markedly enhanced cytochrome c expression
FADD↑, . Carvacrol-injected therapy markedly elevated FADD expression
P53↑, Carvacrol receiving rat’s up-regulated P53 concentrations markedly that reached their peak in the injected (## P ≤ 0.01 vs. tumor and **P ≤ 0.01 vs. normal) as well as oral and mixed groups
*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,
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*Aβ↓, chlorogenic acid can reduce Aβ plaques in Alzheimer’s disease model mice by 37%, indicating its neuroprotective potential.
*neuroP↑,
*cardioP↑, Similarly, CGAs offer protection to the cardiovascular system, gastrointestinal tract, kidneys, and liver, while additionally preventing metabolic syndrome and displaying anticancer and antimicrobial capabilities.
*GastroP↑,
*RenoP↑,
*hepatoP↑,
*Obesity↓,
*Bacteria↓,
*BioAv↑, hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase, HQT in tomatoes significantly enhances CGA accumulation without significantly altering the levels of other soluble phenolic botanical drugs.
*BioAv↑, Mechanistic studies have shown that dietary fats (such as soybean oil and coconut oil) can significantly enhance the permeability of CGA in the Caco-2 monolayer by increasing cell membrane fluidity
*BioAv↑, Following oral administration of CGA, the acidic environment in the stomach helps maintain the structural stability of CGA, with approximately one-third of the dose entering the blood system through passive diffusion in the small intestine, while the
*ROS↓, CGA pretreatment markedly diminished ROS caused by PD toxins
*GutMicro↑, CGA works with the gut microbiota and its metabolites to alleviate post-infectious irritable bowel syndrome (PI-IBS)
*IBI↑, CGA increases intestinal damage repair, decreases MCT-1 and TFF-3 expression, and suppresses NF-κB expression
*MCT1↓,
*NF-kB↓,
*DNMT1↓, Liver Cancer, DNMT1 protein expression↓
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*antiOx↑, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective
*Inflam↓, inhibitory effect of chrysin on inflammation and oxidative stress is also important in Parkinson’s disease
*hepatoP↑,
*neuroP↑,
*BioAv↓, Accumulating data demonstrates that poor absorption, rapid metabolism, and systemic elimination are responsible for poor bioavailability of chrysin in humans that, subsequently, restrict its therapeutic effects
*cardioP↑, cardioprotective [69], lipid-lowering effect [70]
*lipidLev↓,
*RenoP↑, Renoprotective
*TNF-α↓, chrysin reduces levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).
*IL2↓,
*PI3K↓, induction of the PI3K/Akt signaling pathway by chrysin contributes to a reduction in oxidative stress and inflammation during cerebral I/R injury
*Akt↓,
*ROS↓,
*cognitive↑, Chrysin (25, 50, and 100 mg/kg) improves cognitive capacity, inflammation, and apoptosis to ameliorate traumatic brain injury
eff↑, chrysin and silibinin is beneficial in suppressing breast cancer malignancy via decreasing cancer proliferation
cycD1/CCND1↓, chrysin and silibinin induced cell cycle arrest via down-regulation of cyclin D1 and hTERT
hTERT/TERT↓,
VEGF↓, Administration of chrysin is associated with the disruption of hypoxia-induced VEGF gene expression
p‑STAT3↓, chrysin is capable of reducing STAT3 phosphorylation in hypoxic conditions without affecting the HIF-1α protein level.
TumMeta↓, chrysin is a potent agent in suppressing metastasis and proliferation of breast cancer cells during hypoxic conditions
TumCP↓,
eff↑, combination therapy of breast cancer cells using chrysin and metformin exerts a synergistic effect and is more efficient compared to chrysin alone
eff↑, combination of quercetin and chrysin reduced levels of pro-inflammatory factors, such as IL-1β, Il-6, TNF-α, and IL-10, via NF-κB down-regulation.
IL1β↓,
IL6↓,
NF-kB↓,
ROS↑, after chrysin administration, an increase occurs in levels of ROS that, subsequently, impairs the integrity of the mitochondrial membrane, leading to cytochrome C release and apoptosis induction
MMP↓,
Cyt‑c↑,
Apoptosis↑,
ER Stress↑, in addition to mitochondria, ER can also participate in apoptosis
Ca+2↑, Upon chrysin administration, an increase occurs in levels of ROS and cytoplasmic Ca2+ that mediate apoptosis induction in OC cells
TET1↑, In MKN45 cells, chrysin promotes the expression of TET1
Let-7↑, Chrysin is capable of promoting the expression of miR-9 and Let-7a as onco-suppressor factors in cancer to inhibit the proliferation of GC cells
Twist↓, Down-regulation of NF-κB, and subsequent decrease in Twist/EMT are mediated by chrysin administration, negatively affecting cervical cancer metastasis
EMT↓,
TumCCA↑, nduction of cell cycle arrest and apoptosis via up-regulation of caspase-3, caspase-9, and Bax are mediated by chrysin
Casp3↑,
Casp9↑,
BAX↑,
HK2↓, Chrysin administration (15, 30, and 60 mM) reduces the expression of HK-2 in hepatocellular carcinoma (HCC) cells to impair glucose uptake and lactate production.
GlucoseCon↓,
lactateProd↓,
Glycolysis↓, In addition to glycolysis metabolism impairment, the inhibitory effect of chrysin on HK-2 leads to apoptosis
SHP1↑, upstream modulator of STAT3 known as SHP-1 is up-regulated by chrysin
N-cadherin↓, Furthermore, N-cadherin and E-cadherin are respectively down-regulated and up-regulated upon chrysin administration in inhibiting melanoma invasion
E-cadherin↑,
UPR↑, chrysin substantially diminishes survival by ER stress induction via stimulating UPR, PERK, ATF4, and elF2α
PERK↑,
ATF4↑,
eIF2α↑,
RadioS↑, Irradiation combined with chrysin exerts a synergistic effect
NOTCH1↑, Irradiation combined with chrysin exerts a synergistic effect
NRF2↓, in reducing Nrf2 expression, chrysin down-regulates the expression of ERK and PI3K/Akt pathways—leading to an increase in the efficiency of doxorubicin in chemotherapy
BioAv↑, chrysin at the tumor site by polymeric nanoparticles leads to enhanced anti-tumor activity, due to enhanced cellular uptake
eff↑, Chrysin- and curcumin-loaded nanoparticles significantly promote the expression of TIMP-1 and TIMP-2 to exert a reduction in melanoma invasion
*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,
*neuroP↑, Chrysin mitigates neurotoxicity, neuroinflammation, and oxidative stress.
*Inflam↓,
*ROS↓,
NF-kB↓, Chrysin treatment maintains the antioxidant armory and suppresses the activation of redox-active transcription factor NF-kB
*PCNA↓, Chrysin supplementation downregulated the expression of PCNA, COX-2, and NF-kB
*COX2↓,
ChemoSen↑, Chrysin is effective in attenuating cisplatin-induced expression of both COX-2 and iNOS
Hif1a↓, DU145: Chrysin suppressed the expression of HIF-1a of tumor cells in vitro and inhibited tumor cell-induced angiogenesis in vivo
angioG↓,
*chemoPv↑, Chrysin as an effective chemopreventive agent having the capability to obstruct DEN initiated and Fe-NTA promoted renal cancer in the rat model
PDGF↓, Chrysin functionally suppresses PDGF-induced proliferation and migration in VSMCs
*memory↑, Chrysin is effective in attenuating memory impairment, oxidative stress, acting as an antiaging agent
*RenoP↑, protected the kidney from damage
*PPARα↑, Chrysin significantly inhibits AGE-RAGE mediated oxidative stress and inflammation through PPAR-g activation
*lipidLev↓, Chrysin was able to decrease plasma lipids concentration because of its antioxidant properties
*hepatoP↑, Chrysin shows promising hepatoprotective and antihyperlipidemic effects, which are evidenced by the decreased
levels of triglycerides, free fatty acids, total cholesterol, phospholipids, low-density lipoprotein-C, and very low-density lipoprotein
*cardioP⇅, Chrysin significantly ameliorated myocardial damage
*BioAv↓, despite its therapeutic potential, the bioavailability of chrysin and probably other flavonoids in humans is extremely low, mainly due to poor absorption, rapid metabolism, and rapid systemic elimination.
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*AntiAge↑, supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics.
*cardioP↑, Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ10
*Inflam↓, Administration of CoQ10 in doses ranging from 60 to 500 mg/day for a 1-week to 4-month intervention period significantly decreased production of inflammatory cytokines
*antiOx↑,
*lipid-P↓, The concentrations of CoQ10 in the plasma of elderly people are positively correlated with levels of physical activity and cholesterol concentrations (Del Pozo-Cruz et al., 2014a,b), as well as with lower lipid oxidative damage.
*QoL↑, Older individuals given a combination of selenium and CoQ10 over a 4-year period reported an improvement in vitality, physical performance, and quality of life
*neuroP↑, health benefits in elderly people by preventing chronic oxidative stress associated with cardiovascular and neurodegenerative diseases
*Dose↝, the highest dose for CoQ10 supplementation is 1200 mg daily according to well-designed randomized, controlled human trials, although doses as high as 3000 mg/day have been used in shorter clinical trials
*BP↓, These authors interpreted the results to indicate a significant reduction in systolic blood pressure without improvements in other CVD risk factors, such as diastolic blood pressure, total cholesterol, LDL- and high-density lipoprotein (HDL)-choleste
*IGF-1↑, elderly healthy participants who received selenium and CoQ10 supplementation for over 4 years, an increase in insulin-like growth factor 1 (IGF-1) and postprandial insulin-like growth factor-binding protein 1 (IGFBP-1) levels
*IGFBP1↑,
*eff↑, A combination of CoQ10 with red yeast rice, berberina, policosanol, astaxanthin, and folic acid significantly decreased total cholesterol, LDL-cholesterol, triglycerides, and glucose in the blood while increasing HDL-cholesterol levels
*LDL↓,
*HDL↑,
*eff↑, 60 patients suffering from statin-associated myopathy were enrolled in a 3-month study to test for efficacy of CoQ10 and selenium treatment. A consistent reduction in their symptoms, including muscle pain, weakness, cramps, and fatigue was observed
*other↑, Because of its capacity to reduce the side-effects of statins, CoQ10 has been proposed to prevent and/or slow the progression of frailty and sarcopenia in the elderly chronically treated with statins.
*RenoP↑, experiments performed on rats showed a promising protective effect of ubiquinol in the kidneys
*ROS↓, 65 patients undergoing hemodialysis, supplementation with high amounts of CoQ10 (1200 mg/day) lowered F2-isoprostane plasma levels indicative of a reduction in oxidative stress
*TNF-α↓, low grade inflammation, respond well to CoQ10 supplementation with significant decrease in TNF-α plasma levels without having an effect on C-reactive protein and IL-6 production
*IL6↓, Another study reported that CoQ10 therapy in doses ranging from 60 to 300 mg/day caused no significant decrease in C-reactive protein while eliciting a significant reduction in IL-6 levels
*other↝, Preclinical studies demonstrated that CoQ can preserve mitochondrial function and reduce the loss of dopaminergic neurons in the case of Parkinson's disease
*other∅, There was no improvement observed in oxidative stress or neurodegeneration markers in a randomized clinical trial in Alzheimer's Disease patients with CoQ10 supplementation at a dose of 400 mg/day for 16 weeks
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*RenoP↑, EGCG improved kidney function, reduced albuminuria and body weight, and alleviated renal pathological damage.
*NLRP3↓, EGCG treatment reduced the expression of the NLRP3 inflammasome and its associated proteins, including TXNIP, ASC, caspase‐1, and IL‐1β, as well as the levels of ROS and inflammatory factors such as TNF‐α, IL‐6, and IL‐18.
*TXNIP↓,
*ASC↓,
*Casp1↓,
*IL1β↓,
*ROS↓,
*TNF-α↓,
*IL6↓,
*IL18↓,
*antiOx↑, antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy.
*Inflam↓,
*neuroP↑, neuroprotective strategy against AD due to its promising antioxidant and anti-inflammatory properties.
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B), a key mediator of proinflammatory cytokine signaling pathway, which promotes the synthesis of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), leading to neuroinflammation
*NLRP3↓, also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1),
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK↓, Ferulic acid was also able to affect the mitogen activated protein kinases (MAPKs) pathway, by inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK)
*p38↓,
*JNK↓,
*IL6↓, reduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) mRNA expression
*IL8↓,
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen
*RenoP↑, renal protective effects by enhancing the CAT activity and PPAR γ gene expression
*Catalase↑,
*PPARγ↑,
*ROS↓, it was able to scavenge free radicals, inhibit the generation of reactive oxygen species (ROS)
*Fenton↓, inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu)
*IronCh↑,
*SOD↑, increasing the activity of the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes
*MDA↓, lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker,
*lipid-P↓,
*NRF2↑, ferulic acid has been found associated to the modulation of several signaling pathways, and to an increased expression of the nuclear translocation of the transcription factor NF-E2-related factor (Nrf2)
*HO-1↑, Particularly, Nrf2 binds the antioxidant responsive element (ARE) in the promoter region of the heme oxygenase-1 (HO-1) gene,
*ARE↑,
*Bil↑, production of bilirubin, which acts as an efficient ROS scavenger, in human umbilical vein endothelial cells (HUVEC) under radiation-induced oxidative stress
*radioP↑,
*GCLC↑, HO-1 upregulation, an increased expression of other antioxidant genes, such as glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic
*GCLM↑,
*NQO1↑,
*Half-Life↝, highest plasma concentration varies greatly depending on the investigated species: it is reached at 24 min and 2 min after ingestion in humans and rats, respectively
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*Aβ↓, ferulic acid was able to inhibit the aggregation of Aβ25–35, Aβ1–40, and Aβ1–42 and to destabilize pre-aggregated Aβ.
*BDNF↑, up-regulation of brain-derived neurotrophic factor (BDNF) gene were observed after treatment with ferulic acid
*Ca+2↓, prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*lipid-P↓,
*PGE2↓,
*cognitive↑, highlighted that ferulic administration (0.002–0.005% in drinking water) for 28 days improved the trimethyltin-induced cognitive deficit: an increase in the choline acetyltransferase activity was hypothesized as a possible mechanism of action.
*ChAT↑,
*memory↑, Another study showed that ferulic acid, administered intragastrically (30 mg/kg) for 3 months, improved memory in the transgenic APP/PS1 mice, and reduced Aβ deposits,
*Dose↝, 4-week prospective, open-label trial, in which patients (n = 20) assumed daily Feru-guard® (3.0 g/day), was designed.
*toxicity↓, Salau et al. [130] did not find signs of toxicity of ferulic acid in hippocampal neuronal cell lines HT22 cells, thus concluding that the substance seems to be safe in healthy brain cells
*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h
*neuroP↑, As a hydrophobic agent, FIS readily penetrates cell membranes and accumulates in cells to exert neuroprotective, neurotrophic and antioxidant effects
*antiOx↑,
*Inflam↓, FIS treatment may include alleviating inflammation, cell apoptosis and oxidative stress
RenoP↑, alleviates cell apoptosis and inflammation in acute kidney injury
COX2↓, FIS induces apoptosis in various tumor cells by, for example, inhibiting cyclooxygenase-2, inhibiting the Wnt/EGFR/NF-κB pathway, activating the caspase-3 cascade
Wnt↓,
EGFR↓,
NF-kB↓,
Casp3↑,
Ca+2↑, activating the caspase-3 and Ca2+ dependent endonuclease, and activating the caspase-8/caspase-3 dependent pathway via ERK1/2.
Casp8↑,
TumCCA↑, FIS controls the cell cycle and inhibits cyclin-dependent kinases (CDKs) in human cancer cell lines,
CDK1↓,
PI3K↓, by inhibition of PI3K/Akt/mTOR signaling [20], mitogen-activated protein kinases (MAPK) [21], and nuclear transcription factor (NF-κB)
Akt↓,
mTOR↓,
MAPK↓,
*P53↓, FIS inhibits aging by reducing p53, p21 and p16 expression in mouse and human tissues
*P21↓,
*p16↓,
mTORC1↓, FIS induces autophagic cell death by inhibiting both the mTORC1 and mTORC2 pathways
mTORC2↓,
P53↑, FIS significantly increases the expression of p53 and p21 proteins and lowers the levels of cyclin D1 [27,28], cyclin A, CDK4 and CDK2, thus contributing to cell-cycle arrest.
P21↑,
cycD1/CCND1↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
BAX↑, FIS also increases Bax [27,28] and Bak [27] protein expression, but reduces the levels of Bcl-2 [27,28], Bcl-xL [27] and PCNA [28], and then starts the mitochondrial apoptotic pathway.
Bcl-2↓,
PCNA↓,
HER2/EBBR2↓, FIS reduces HER2 tyrosine phosphorylation in a dose-dependent manner and aids in proteasomal degradation of HER2 rather than lysosomal degradation
Cyt‑c↑, FIS cells causes destabilization of the mitochondrial membrane and an increase in cytochrome c levels, which is consistent with the loss of mitochondrial membrane integrity.
MMP↓,
cl‑Casp9↑,
MMP2↓, FIS reduces the enzymatic activity of both MMP-2 and MMP-9.
MMP9↓,
cl‑PARP↑, cell membrane, mitochondrial depolarization, activation of caspase-7, -8 and -9, and cleavage of PARP
uPA↓, interestingly, the promoter activity of the uPA gene is suppressed by FIS
DR4↑, induces upregulation of DR4 and DR5 death receptor expression in a dose-dependent manner
DR5↑,
ROS↓, FIS induces an increase in intracellular Ca2+ but reduces the production of ROS in WEHI-3 cells (myelomonocytic leukemia)
AIF↑, It also increases the levels of caspase-3 and AIF mRNA, but also increases necrosis markers including RIP3 and PARP1
CDC25↓, FIS reduces the expression of cdc25a, but increases the expression of p-p53, Chk1, p21 and p27, which may lead to a G0/G1 arrest.
Dose↑, FIS in concentrations from 0 to 10 μM does not affect cell viability; however, its use at concentrations of 20–40 μM significantly reduces the viability of lung cancer cells
CHOP↑, CaKi : FIS induces upregulation of CHOP expression and ROS production
ROS↑, NCI-H460 :FIS increases the ER stress signaling FIS increases the level of mitochondrial ROS FIS induces mitochondrial Ca2+ overloading and ER stress FIS induced ER stress-mediated cell death via activation of the MAPK pathway
cMyc↓, FIS influences proliferation related genes such as cyclin D1, c-myc and cyclooxygenase (COX)-2 by downregulating them.
cardioP↑, cardioprotective activity
*Half-Life↓, Except the thigh muscle required a longer time to saturate, the other organs need 5–10 min to reach Cmax (maximum hydrogen concentration).
*ROS↓, regulate several key players in cancer, including ROS, and certain antioxidant enzymes
*selectivity↑, hydrogen gas could selectively scavenge the most cytotoxic ROS, •OH, as tested in an acute rat model of cerebral ischemia and reperfusion
*SOD↑, the expression of superoxide dismutase (SOD) (48), heme oxyganase-1 (HO-1) (49), as well as nuclear factor erythroid 2-related factor 2 (Nrf2) (50), increased significantly, strengthening its potential in eliminating ROS.
*HO-1↑,
*NRF2↑,
*chemoP↑, reduce the adverse effects in cancer treatment while at the same time doesn't abrogate the cytotoxicity of other therapy, such as radiotherapy and chemotherapy
*radioP↑,
ROS↑, Interestingly, due the over-produced ROS in cancer cells (38), the administration of hydrogen gas may lower the ROS level at the beginning, but it provokes much more ROS production as a result of compensation effect, leading to the killing of cancer
*Inflam↓, By regulating inflammation, hydrogen gas can prevent tumor formation, progression, as well as reduce the side effects caused by chemotherapy/radiotherapy
eff↑, More importantly, hydrogen-rich water didn't impair the overall anti-tumor effects of gefitinib both in vitro and in vivo, while in contrast, it antagonized the weight loss induced by gefitinib and naphthalene, and enhanced the overall survival rate
*TNF-α↓, hydrogen-rich saline treatment exerted its protective effects via inhibiting the inflammatory TNF-α/IL-6 pathway, increasing the cleaved C8 expression and Bcl-2/Bax ratio, and attenuating cell apoptosis in both heart and liver tissue
*IL6↓,
*cl‑Casp8↑,
*Bax:Bcl2↓,
*Apoptosis↓,
*cardioP↑,
*hepatoP↑,
*RenoP↑, Hydrogen-rich water also showed renal protective effect against cisplatin-induced nephrotoxicity in rats.
*chemoP↑, nother study showed that both inhaling hydrogen gas (1% hydrogen in air) and drinking hydrogen-rich water (0.8 mM hydrogen in water) could reverse the mortality, and body-weight loss caused by cisplatin via its anti-oxidant property
eff↝, More importantly, hydrogen didn't impair the anti-tumor activity of cisplatin against cancer cell lines in vitro and in tumor-bearing mice
chemoP↑, hydrogen-rich water combinational treatment group exhibited no differences in liver function during the treatment, probably due to its antioxidant activity, indicating it a promising protective agent to alleviate the mFOLFOX6-related liver injury
radioP↑, consumption of hydrogen-rich water reduced the radiation-induced oxidative stress while at the same time didn't compromise anti-tumor effect of radiotherapy
eff↑, Hydrogen Gas Acts Synergistically With Thermal Therapy
TumCG↓, in vivo study showed that under hydrogen gas treatment, tumor growth was significantly inhibited, as well as the expression of Ki-67, VEGF and SMC3
Ki-67↓,
VEGF↓,
selectivity↑, H2-silica could concentration-dependently inhibit the cell viability of human esophageal squamous cell carcinoma (KYSE-70) cells, while it need higher dose to suppress normal human esophageal epithelial cells (HEEpiCs), indicating its selective profi
*RenoP↑, We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats.
*ROS↓,
*Apoptosis↓,
*ER Stress↓, endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated
*CHOP↓,
*Casp12↓,
*GRP78/BiP↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑, higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated.
*Beclin-1↑,
*p62↓,
*mTOR↓, Inhibition of mTOR may be involved in the upregulation of autophagy by H2
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*P-gp↓, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6),
*ROS↓,
*TNF-α↓,
*IL10↓,
*IL6↓,
eIF2α↑, Bcl-2, phosphorylated eIF2α, CHOP,GRP78, Bax, cleaved caspase-9 and phosphorylated PERK
CHOP↑,
GRP78/BiP↑,
BAX↑,
cl‑Casp9↑,
p‑PERK↑,
ER Stress↑, endoplasmic reticulum stress and proteins in apoptosis in 95-D and A549 cells
Apoptosis↑,
MMPs↓, decrease in levels of matrix metal-mloproteinases, P-glycoprotein expression, the formation of mammosphere, H3K27 methyltransferase, c-FLIP, level of CXCR4 receptor,pluripotency-factors, Twist-1, class I histone deacetylases, steroid receptor co
cFLIP↓,
CXCR4↓,
Twist↓,
HDAC↓,
BMPs↑, enhancement in Bax protein, and (BMP7), as well as interference with an activator of transcription 3 (STAT3), (mTOR), (EGFR), (NF-kB) and Shh
p‑STAT3↓, secreased the phosphorylation of STAT3
mTOR↓,
EGFR↓,
NF-kB↓,
Shh↓,
VEGF↓, induce apoptosis, and regulate the vascular endothelial growth factor-A expression (VEGF-A)
tumCV↓, human glioma cell lines (U251 and U-87 MG) through inhibition of colony formation, glioma cell viability, cell migration, invasion, suppression of ERK and AKT signalling cascades, apoptosis induction, and reduction of Bcl-2 expression.
TumCMig↓,
TumCI↓,
ERK↓,
Akt↓,
Bcl-2↓,
Nestin↓, increased the Bax expression, lowered the CD133, EGFR, and Nesti
CD133↓,
p‑cMET↑, HKL through the downregulating the phosphorylation of c-Met phosphorylation and stimulation of Ras,
RAS↑,
chemoP↑, Cheng and coworker determined the chemopreventive role of HKL against the proliferation of renal cell carcinoma (RCC) 786â0 cells
through multiple mechanism
*NRF2↑, , HKL also effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in in vivo
and in vitro model
*NADPH↓, (HUVECs) such as inhibition of NADPH oxidase activity, suppression of p22 (phox) protein expression, Rac-1 phosphorylation, reactive oxygen species production, inhibition of degradation of Ikappa-B-alpha, and suppression of activity of of NF-kB
*p‑Rac1↓,
*ROS↓,
*IKKα↑,
*NF-kB↓,
*COX2↓, Furthermore, HKL treatment the inhibited cyclooxygenase (COX-2) upregulation, reduces prostaglandin E2 production, enhanced caspase-3 activity reduction
*PGE2↓,
*Casp3↓,
*hepatoP↑, compound also displayed hepatoprotective action against oxidative injury in tert-butyl hydroperoxide (t-BHP)-injured AML12
liver cells in in vitro model
*antiOx↑, compound reduces the level of acetylation on SOD2 to stimulate its antioxidative action, which results in reduced reactive oxygen
species aggregation in AML12 cells
*GSH↑, HKL prevents oxidative damage induced by H2O2 via elevating antioxidant enzymes levels which includes glutathione and catalase and promotes translocation and activation transcription factor Nrf2
*Catalase↑,
*RenoP↑, imilarly, the compound protects renal reperfusion/i-schemia injury (IRI) in adult male albino Wistar rats via reducing theactivities of serum alkaline phosphatase (ALP), aspartate aminotrans-
ferase (AST) and alanine aminotransferase (ALT)
*ALP↓,
*AST↓,
*ALAT↓,
*neuroP↑, Several reports and works have shown that HKL displays some neuroprotective properties
*cardioP↑, Cardioprotection
*HO-1↑, the expression level of heme oxygenase-1 (HO-1)was remarkably up-regulated and miR-218-5p was significantly down-regulated in septic mice treated with HKL
*Inflam↓, anti-inflammatory action of
HKL at dose of 10 mg/kg in the muscle layer of mice
*RenoP↑, luteolin protects the kidney against I/R injury via reducing oxidative stress, increasing antioxidant enzymes and reducing expression of Nrf2 and miR320.
*ROS↓,
*antiOx↑,
*NRF2↓, luteolin protects the kidney against I/R injury via reducing oxidative stress, increasing antioxidant enzymes and reducing expression of Nrf2 and miR320.
*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↓,
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*antiOx↑, Anti‐oxidative mechanism of lycopene
*ROS↓, Lycopene inhibits ROS generation and subsequent oxidative stress by inducing antioxidant enzymes (SOD, CAT, GSH, GSH‐Px, and GST) and limiting MDA level and lipid peroxidation (LPO).
*SOD↑,
*Catalase↑,
*GSH↑,
*GSTs↑,
*MDA↓,
*lipid-P↓,
*NRF2↑, Lycopene also prevents ROS release by upregulating Nrf2‐mediated HO‐1 levels and inhibiting iNOS‐activated NO generation
*HO-1↑,
*iNOS↓,
*NO↓,
*TAC↑, upregulating total antioxidant capacity (TAC) and direct inhibition of 8‐OHdG, NOX4.
*NOX4↓,
*Inflam↓, Anti‐inflammatory mechanism of lycopene.
*IL1↓, IL‐1, IL‐6, IL‐8, IL‐1β, and TNF‐α release.
*IL6↓,
*IL8↓,
*IL1β↓,
*TNF-α↓,
*TLR2↓, prevents inflammation by inhibiting toll‐like receptors TLR2 and TLR4 and endothelial adhesion molecules VCAM1 and ICAM‐1.
*TLR4↓,
*VCAM-1↓,
*ICAM-1↓,
*STAT3↓, inhibiting STAT3, NF‐κB, ERK pathway, and IL‐6 and TNF‐α release.
*NF-kB↓,
*ERK↓,
*BP↓, Another clinical study demonstrated that consumption of raw tomato (200 g/day) could prevent type 2 diabetes‐associated cardiovascular diseases by lowering systolic and diastolic blood pressure, upregulating ApoA1, and downregulating ApoB levels
ROS↓, lycopene suppresses the metastasis of the SK‐HEP‐1 cell line by NOX‐4 mRNA expression inhibition and the reactive ROS intracellular activity inhibition
PGE2↓, Lycopene is also used to treat colorectal cancer cells in humans, and the introduction of lycopene decreases the prostaglandin E2 and nitric oxide levels
cardioP↑, Lycopene‐rich foods can be highly beneficial in preventing cardiovascular diseases as lycopene is a potential source of antioxidants
*neuroP↑, beneficial role of lycopene on aging‐related neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, has been confirmed in both experimental and clinical trials
*creat↓, Several pre‐clinical studies reported that lycopene treatment significantly reduced serum urea and serum creatinine, as well as reversed various toxic chemical‐induced nephrotoxicity and oxidative damage by exhibiting excellent antioxidative properti
*RenoP↑,
*CRM↑, its potency in treating aging disorders and its role as a mimic of caloric restriction.
eff↑, Our study shows that lycopene supplementation does not modify the main hallmarks of cancer, but it increases circulating lycopene concentration in patients under cancer therapy, which could have a positive impact on potential clinical and molecular o
cardioP↑, A systematic review and meta-analysis reported that tomato and lycopene supplementation have positive effects on cardiovascular risk factors
eff?, lycopene supplementation may have benefits in the oncology population during cancer treatment.
PSA↓, Lycopene supplementation improved PSA levels in patients with an intermediate risk of cancer
RenoP↑, Surprisingly, lycopene has been shown to improve renal makers of nephrotoxicity after cisplatin treatment
*antiOx↑, As one of the most potent antioxidants, its capacity to neutralise singlet oxygen is double that of ?-carotene, ten times greater than that of ?-tocopherol, and one hundred and twenty-five times more effective than glutathione
*ROS⇅, lycopene acts as an antioxidant in systems that produce singlet oxygen but behaves as a pro-oxidant in systems that create peroxide
*Dose↝, In low doses, it acts as an antioxidant, but at high doses, it acts as a pro-oxidant
*eff↑, In situation where there is an imbalance between antioxidant defences and ROS production, such as during inflammation or exposure to environmental toxins [91], lycopene may switch from its antioxidant role to a pro-oxidant role
*LDL↓, Wistar rats given a high-fat diet and 50mg/kg body weight of lycopene daily for 3mths had significant reductions in plasma total cholesterol, triglycerides, and lLDL levels but increased HDL cholesterol
*RenoP↑, shown to protect the kidney against chemically induced damage
*Inflam↓, evidence is plentiful demonstrating the anti-inflammatory effects of lycopene both in vitro and in vivo
neuroP↑, mice with Alzheimer's disease induced by ? amyloid, lycopene reduced oxidative stress, decreased neuronal loss, improved synaptic plasticity, and inhibited neuroinflammation
Rho↓, lycopene treatment was demonstrated to have the potential to mitigate vascular arteriosclerosis in allograft transplantation by inhibiting Rho-associated kinases
*ROS↓, uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances
*Fenton↓, reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions
*antiOx↑, credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant
*toxicity∅, uncommonly high-safety profile of melatonin also bolsters this conclusion.
*GPx↑, melatonin was found to stimulate antioxidative enzymes including glutathione peroxidase and glutathione reductase
*GSR↑,
*GSH↑, melatonin upregulates the synthesis of glutathione
*NO↓, neutralize nitrogen-based toxicants, i.e., nitric oxide
*Iron↓, Melatonin chelates both iron (III) and iron (II), which is the form that participates in the Fenton reaction to generate the hydroxyl radical
*Copper↓, copper-chelating ability of melaton
*IL1β↓, significant reductions in plasma cardiac troponin 1, interleukin 1 beta, inducible nitric oxide synthase (iNOS) and caspase 3 due to melatonin
*iNOS↓,
*Casp3↓,
*BBB↑, melatonin readily crosses the blood-brain barrier;
*RenoP↑, Published reports haveshown that the lung,231, 232 liver, 233- 235 kidney,236 pancreas,237 intestine,238 urinary bladder,239,240 corpus cavernosum,241 skeletal muscle242, 243 spinal cord244, 245 and stem cells246 are alsoprotected by melatonin.
chemoP↑, Melatonin has not been found to interfere with the efficacy of prescription drugs. Doxorubicin, if given it in combination with melatonin may allow the use of a larger dose with greater efficacy.
*Ca+2↝, Moreover, melatonin regulates free Ca2+ movement intracellularly
eff↑, elatonin was found to exaggerate the cancer inhibiting actions of pitavastatin270 and pravastatin271 against breast cancer in experimental studies
*PKCδ?, major targets by which melatonin reduces methamphetamine-related neuronal damage is due to the inhibition of the PKCδ gene
ChemoSen↑, at least some cases melatonin reduces the toxicity of these pharmacological agents in normal cells256, 289, 290 while enhancing the cancer-killing actions (also, see below) of conventional chemotherapeutic agents.256, 291-293
eff↑, TRAIL was combined with melatonin for the treatment of A172 and U87 human glioblastoma cells, however, apoptotic cell death was greatly exaggerated over that caused by TRAIL alone
Akt↓, in GBM: observed effect was related to a modulation of protein kinase c which reduced Akt activation resulting in a rise in death receptor 5 (DR5) levels;
DR5↑,
selectivity↑, The pro-oxidant action of melatonin is common in cancer cells while in normal cells the indoleamine is a powerful antioxidant.
ROS↑, cancer cells
eff↑, human lung adenocarcinoma cells (SK-LV-1) showed that melatonin also increased their sensitivity to the chemotherapy, cisplatin.
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*antiOx↑, rich in antioxidants
*ROS↓, MO leaves also protect against oxidative stress [14], inflammation [15], hepatic fibrosis [16], liver damage [17], hypercholesterolemia [18,19], bacterial activity [20], cancer [14] and liver injury [21].
*hepatoP↑, methanol extract of MO leaves has a hepatoprotective effect, which might be due to the presence of quercetin
*lipid-P↓, reductions in lipids and lipid peroxidation levels in the liver of rats
*ALAT↓, MO leaves have been shown to reduce plasma ALT, AST, ALP and creatinine [82,83] and to ameliorate hepatic and kidney damage induced by drugs.
*AST↓,
*ALP↓,
*creat↓,
*RenoP↑,
NF-kB↓, MO was shown to contain the growth of pancreatic cancer cells, by inhibiting NF-ĸB signaling as well as increasing the efficacy of chemotherapy, by enhancing the effect of the drug in these cells
ChemoSen↑,
*memory?, MO, have been demonstrated to enhance memory by nootropics activity and protect against the oxidative stress present in AD
*antiOx↑, biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions.
*RenoP↑,
*hepatoP↑,
*radioP↑, Two studies have shown that extracts of M. oleifera can provide radioprotection in mice.
*eff↑, leaves are widely used as a basic food because of their high nutrition content
*toxicity↓, authors concluded that consumption of M. oleifera leaves at doses of up to 2000 mg/kg were safe.
*ROS↓, Chumark et al. (2008) demonstrated the free radical scavenging ability of an aqueous extract of M. oleifera leaves in several in vitro systems, and also showed that the extract inhibited lipid peroxidation in both in vitro and ex vivo systems.
*lipid-P↓,
*DNAdam↓, inhibit oxidative damage to DNA
*Catalase↑, increased the antioxidant enzymes catalase and superoxide dismutase while decreasing lipid peroxidases
*SOD↑,
*GPx↑, increases in the antioxidant enzymes glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase, and glutathione S‐transferase (Sreelatha and Padma, 2010).
*GSR↑,
*GSTs↑,
*AST↓, M. oleifera leaves protects against liver damage as demonstrated by reductions in tissue histopathology and serum activities of marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)
*ALAT↓,
*ALP↓,
*Bil↓, extract decreased drug‐induced levels of AST, ALT, ALP, and bilirubin
Showing Research Papers: 1 to 50 of 81
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 81
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
ATF3↑, 1, GSR↑, 1, HO-1↓, 1, HO-1↑, 1, lipid-P↑, 3, NQO1↑, 1, NRF2↓, 2, NRF2↑, 2, ROS↓, 2, ROS↑, 11, mt-ROS↑, 1, SIRT3↑, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, CDC2↓, 2, CDC25↓, 4, mitResp↓, 1, MMP↓, 7, MMP↑, 1, XIAP↓, 2,
Core Metabolism/Glycolysis ⓘ
ALAT↓, 1, AMPK↑, 2, cMyc↓, 2, GlucoseCon↓, 1, Glycolysis↓, 2, HK2↓, 2, lactateProd↓, 1, LDH↓, 1, LDHA↓, 1, LDL↓, 1, NADPH↑, 1, PCK1↓, 1, PDK1↓, 1, PPARα↓, 1, TCA↓, 1,
Cell Death ⓘ
Akt↓, 5, p‑Akt↓, 1, Apoptosis↑, 5, BAX↑, 7, Bcl-2↓, 7, Bcl-xL↓, 2, Casp↑, 1, Casp3↓, 1, Casp3↑, 4, cl‑Casp3↑, 1, Casp8↑, 2, Casp9↑, 3, cl‑Casp9↑, 3, cFLIP↓, 1, Chk2↓, 1, Chk2↑, 1, Cyt‑c↑, 8, Diablo↑, 1, DR4↑, 1, DR5↑, 3, FADD↑, 1, Fas↑, 2, FasL↑, 1, HEY1↓, 1, hTERT/TERT↓, 2, IAP1↓, 1, IAP2↓, 1, iNOS↓, 1, JNK↑, 1, MAPK↓, 3, MAPK↑, 2, Mcl-1↓, 2, MDM2↓, 1, p38↑, 1, p‑p38↓, 1, survivin↓, 2, TumCD↑, 1,
Kinase & Signal Transduction ⓘ
HER2/EBBR2↓, 1,
Transcription & Epigenetics ⓘ
H3↑, 1, p‑H3↓, 1, other↓, 1, tumCV↓, 1,
Protein Folding & ER Stress ⓘ
CHOP↑, 3, eIF2α↑, 2, p‑eIF2α↑, 1, ER Stress↑, 4, GRP78/BiP↑, 2, HSP90↓, 1, PERK↑, 1, p‑PERK↑, 1, UPR↑, 2, XBP-1↓, 1,
Autophagy & Lysosomes ⓘ
ATG5↑, 1, Beclin-1↑, 1, BNIP3↑, 1, LC3II↑, 1, LC3s↑, 1, TumAuto↑, 1,
DNA Damage & Repair ⓘ
ATM↑, 2, CHK1↓, 1, CHK1↑, 1, DNAdam↑, 2, P53↑, 5, PARP↑, 2, cl‑PARP↑, 2, PARP1↑, 1, PCNA↓, 2, γH2AX↑, 1,
Cell Cycle & Senescence ⓘ
CDK1↓, 2, CDK2↓, 3, CDK4↓, 5, cycA1/CCNA1↓, 2, CycB/CCNB1↓, 2, cycD1/CCND1↓, 5, cycE/CCNE↓, 1, cycE/CCNE↑, 1, P21↑, 3, RB1↑, 1, p‑RB1↓, 1, TumCCA↑, 7,
Proliferation, Differentiation & Cell State ⓘ
CD133↓, 1, CD44↓, 1, p‑cMET↑, 1, CSCs↓, 2, EMT↓, 4, EMT↑, 1, ERK↓, 4, FOXO3↑, 1, GSK‐3β↑, 1, HDAC↓, 2, Let-7↑, 1, mTOR↓, 4, mTOR↑, 1, mTORC1↓, 2, mTORC2↓, 2, Nanog↓, 1, Nestin↓, 1, NOTCH↓, 1, NOTCH1↑, 2, OCT4↓, 1, PI3K↓, 1, RAS↓, 2, RAS↑, 1, Shh↓, 1, SHP1↑, 1, SOX2↓, 1, STAT3↓, 4, p‑STAT3↓, 2, TOP1↓, 1, TumCG↓, 2, Wnt↓, 1,
Migration ⓘ
AP-1↓, 1, Ca+2↑, 4, CLDN1↓, 1, E-cadherin↑, 3, ER-α36↓, 1, FAK↓, 1, Fibronectin↓, 1, Ki-67↓, 3, MMP-10↓, 1, MMP1↓, 1, MMP13↓, 2, MMP2↓, 4, MMP3↓, 1, MMP7↓, 1, MMP9↓, 6, MMPs↓, 3, N-cadherin↓, 2, PDGF↓, 1, Rho↓, 3, ROCK1↓, 1, Slug↓, 2, Smad1↑, 1, Snail↓, 2, TET1↑, 2, TGF-β↓, 1, TumCI↓, 4, TumCMig↓, 2, TumCP↓, 4, TumMeta↓, 3, Twist↓, 3, uPA↓, 4, Vim↓, 2, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 4, ATF4↑, 2, EGFR↓, 3, Hif1a↓, 3, PDGFR-BB↓, 1, VEGF↓, 7, VEGFR2↓, 1,
Immune & Inflammatory Signaling ⓘ
CD4+↓, 1, COX2↓, 5, COX2↑, 1, CXCR4↓, 1, ICAM-1↓, 1, IL1↓, 1, IL10↓, 1, IL1β↓, 2, IL6↓, 4, Inflam↓, 1, JAK1↓, 1, MCP1↓, 2, NF-kB↓, 11, PD-1↓, 1, PD-L1↓, 1, PGE2↓, 4, PSA↓, 1, TLR4↓, 1, TNF-α↓, 3,
Drug Metabolism & Resistance ⓘ
BioAv↓, 2, BioAv↑, 2, BioAv↝, 1, ChemoSen↑, 5, ChemoSen∅, 1, Dose↑, 1, Dose↝, 1, eff?, 1, eff↑, 18, eff↝, 1, Half-Life↓, 1, RadioS↑, 1, selectivity↑, 3,
Clinical Biomarkers ⓘ
ALAT↓, 1, ALP↓, 1, AST↓, 1, BMPs↑, 1, creat↓, 1, E6↓, 1, E7↓, 1, EGFR↓, 3, HER2/EBBR2↓, 1, hTERT/TERT↓, 2, IL6↓, 4, Ki-67↓, 3, LDH↓, 1, PD-L1↓, 1, PSA↓, 1,
Functional Outcomes ⓘ
AntiCan↓, 1, AntiCan↑, 2, AntiTum↑, 4, cardioP↑, 4, chemoP↑, 5, chemoPv↑, 1, hepatoP↑, 2, neuroP↑, 4, radioP↑, 1, RenoP↑, 13,
Infection & Microbiome ⓘ
Sepsis↓, 1,
Total Targets: 243
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 27, ARE↑, 1, Bil↓, 1, Bil↑, 1, Catalase↑, 12, Copper↓, 1, Fenton↓, 2, Ferroptosis↓, 3, GCLC↑, 1, GCLM↑, 1, GPx↓, 1, GPx↑, 6, GSH↑, 11, GSR↑, 3, GSTs↑, 3, HDL↑, 2, HO-1↓, 1, HO-1↑, 8, Iron↓, 1, Keap1↓, 1, lipid-P↓, 12, MDA↓, 12, NOX4↓, 1, NQO1↑, 3, NRF2↓, 2, NRF2↑, 11, Prx↑, 1, ROS↓, 29, ROS⇅, 1, ROS∅, 1, SOD?, 1, SOD↑, 13, SOD1↑, 1, SOD2↑, 1, TAC↑, 1, UCPs↑, 1, uricA↓, 2,
Metal & Cofactor Biology ⓘ
IronCh↑, 3,
Mitochondria & Bioenergetics ⓘ
MMP↑, 1, mtDam↓, 1,
Core Metabolism/Glycolysis ⓘ
12LOX↓, 1, ALAT↓, 7, AMPK↑, 1, p‑AMPK↑, 1, BUN↓, 2, CRM↑, 1, glucose↝, 1, GLUT2↑, 1, HMG-CoA↓, 1, LDH↓, 1, LDL↓, 3, lipidLev↓, 2, NADPH↓, 2, PPARα↑, 1, PPARγ↑, 1, SIRT1↑, 1,
Cell Death ⓘ
Akt↓, 1, Akt↑, 1, Apoptosis↓, 8, BAX↓, 3, Bax:Bcl2↓, 1, Bcl-2↑, 2, Casp1↓, 1, Casp12↓, 1, Casp3?, 1, Casp3↓, 4, Casp3∅, 1, cl‑Casp8↑, 1, Casp9↓, 2, Casp9∅, 1, Cyt‑c∅, 1, Fas↓, 2, Ferroptosis↓, 3, HGF/c-Met↑, 1, iNOS↓, 6, iNOS↑, 1, JNK↓, 2, MAPK↓, 3, p‑MAPK↓, 1, MCT1↓, 1, p38↓, 1, TRPV1↑, 2,
Transcription & Epigenetics ⓘ
other↑, 2, other↝, 1, other∅, 1,
Protein Folding & ER Stress ⓘ
CHOP↓, 1, CHOP↑, 1, ER Stress↓, 2, GRP78/BiP↓, 1, GRP78/BiP↑, 1, GRP94↑, 1,
Autophagy & Lysosomes ⓘ
Beclin-1↑, 1, LC3‑Ⅱ/LC3‑Ⅰ↑, 1, p62↓, 1,
DNA Damage & Repair ⓘ
DNAdam↓, 1, DNArepair↑, 1, DNMT1↓, 2, DNMTs↓, 1, p16↓, 1, P53↓, 1, PARP∅, 1, PCNA↓, 1,
Cell Cycle & Senescence ⓘ
P21↓, 1,
Proliferation, Differentiation & Cell State ⓘ
ERK↓, 2, p‑ERK↑, 1, IGF-1↑, 1, IGFBP1↑, 1, KLF4↑, 1, mTOR↓, 1, PI3K↓, 1, STAT3↓, 1, Wnt/(β-catenin)↓, 1,
Migration ⓘ
AntiAg↑, 1, Ca+2↓, 1, Ca+2↝, 1, PKCδ?, 1, p‑Rac1↓, 1, TXNIP↓, 1, VCAM-1↓, 2, α-SMA↓, 2,
Angiogenesis & Vasculature ⓘ
eNOS↑, 1, NO↓, 5,
Barriers & Transport ⓘ
BBB↑, 2, GastroP↑, 1, IBI↑, 1, P-gp↓, 1,
Immune & Inflammatory Signaling ⓘ
ASC↓, 1, COX2↓, 7, ICAM-1↓, 2, IKKα↑, 1, IL1↓, 2, IL10↓, 3, IL18↓, 2, IL1β↓, 9, IL2↓, 1, IL6↓, 9, IL6↑, 1, IL8↓, 2, Inflam↓, 19, Inflam↑, 1, MCP1↓, 1, NF-kB↓, 9, PGE2↓, 3, RANTES↓, 1, TLR2↓, 1, TLR4↓, 3, TNF-α↓, 14,
Synaptic & Neurotransmission ⓘ
AChE↓, 2, BChE↓, 1, BDNF↑, 1, ChAT↑, 1,
Protein Aggregation ⓘ
AGEs↓, 1, Aβ↓, 3, BACE↓, 1, NLRP3↓, 2,
Drug Metabolism & Resistance ⓘ
BioAv↓, 4, BioAv↑, 5, BioAv↝, 1, ChemoSen↑, 1, Dose↝, 5, eff↑, 9, Half-Life↓, 1, Half-Life↝, 2, selectivity↑, 1,
Clinical Biomarkers ⓘ
ALAT↓, 7, ALP↓, 4, AST↓, 7, BG↓, 1, Bil↓, 1, Bil↑, 1, BP↓, 2, creat↓, 4, GutMicro↑, 2, IL6↓, 9, IL6↑, 1, LDH↓, 1,
Functional Outcomes ⓘ
AntiAge↑, 1, AntiCan↑, 1, AntiDiabetic↑, 1, cardioP↑, 9, cardioP⇅, 1, chemoP↑, 3, chemoPv↑, 1, cognitive↑, 4, hepatoP↑, 18, memory?, 1, memory↑, 2, neuroP↑, 13, Obesity↓, 2, OS↑, 1, Pain↓, 1, QoL↑, 1, radioP↑, 3, RenoP↑, 37, toxicity↓, 5, toxicity↝, 1, toxicity∅, 1,
Infection & Microbiome ⓘ
Bacteria↓, 2, Sepsis↓, 1,
Total Targets: 199
Scientific Paper Hit Count for: RenoP, K,Renoprotection
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#:1175 State#:% Dir#:2
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