Database Query Results : Piperine, , ROS

PI, Piperine: Click to Expand ⟱
Features:
Compound of black pepper that boosts bioavailability of curcumin
ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Melavonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day
-Dipyridamole typically 200mg 2x/day
-Lycopene typically 100mg/day range

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

Scientific Papers found: Click to Expand⟱
3598- PI,    Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer's disease
- in-vivo, AD, NA
*ROS↓, increased oxidative-nitrosative stress, an altered neurotransmission and an elevated neuroinflammation in hippocampus, as well as significant cognitive deficits. All these alterations can be ameliorated by piperine
*Inflam↓,
*cognitive↑,
*Aβ↓, Previous studies have suggested that piperine also provides benefits against Aβ and tau pathologies.
*tau↓,

3596- PI,    Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress
- in-vivo, Nor, NA
*TBARS↑, Simultaneous supplementation with black pepper or piperine lowered TBARS and CD levels and maintained SOD, CAT, GPx, GST, and GSH levels to near those of control rats.
*SOD↑,
*Catalase↑,
*GSTs↑,
*GPx↑,
*GSH↑,
*ROS↓, can reduce high-fat diet induced oxidative stress to the cells.

3595- PI,    Black pepper and health claims: a comprehensive treatise
- Review, Var, NA - Review, AD, NA
*antiOx↑, Black pepper (Piper Nigrum L.) is an important healthy food owing to its antioxidant, antimicrobial potential and gastro-protective modules
*ROS↓, The free-radical scavenging activity of black pepper and its active ingredients might be helpful in chemoprevention and controlling progression of tumor growth.
*chemoP↑,
TumCG↓,
*cognitive↑, piperine assist in cognitive brain functioning, boost nutrient's absorption and improve gastrointestinal functionality
*MMPs↓, They postulated that inhibition of interlukon, matrix metalloproteinase, prostaglandin E2, and activator protein 1 are possible routes for their said properties
*PGE2↓,
*AP-1↓,
*5LO↓, Piperine along with some other components can inhibit the expression of enzymes like 5-lipoxygenase and COX-1 that are responsible for leukotriene and prostaglandin biosynthesis.
*COX1↓,
*other↑, It is widely accepted that black pepper is instrumental to prevent and cure gastrointestinal problems. The black pepper enhances the production of hydrochloric acid from stomach thus improving digestion through stimulation of histamine H2 recepto
*other↑, black pepper has diaphoretic (promotes sweating), and diuretic (promotes urination) properties
*other↑, Moreover, it protects intestinal membranes from gastric secretions and ROS damage owing to antioxidant potential.
*SOD↑, black pepper significantly enhanced the activities of antioxidant enzymes, that is, SOD, CAT, GR, and GST.
*Catalase↑,
*GSTs↑,
*GSR↑,
*other↑, black pepper and its active ingredients improve expression of some digestive enzymes along with increase in the secretion of saliva
*Weight↓, piperine intake may decrease body weight
*BioEnh↑, The black pepper and piperine improve the bioavailability of many drugs.
*BioAv↑, Piperine also boosts the bioavailability of important phyto- chemicals contained in other foods, for example, bioactive com- ponents present in curcumin and green tea
*eff↑, The combination of piperine (2.5 mg/kg, i.p., 21 days) with curcumin (20 and 40 mg/kg, i.p., 21 days) showed improved anti-immobility, neurotransmitter enhancing, and monoamine oxidase inhibitory (MAO-A) effects of curcumin
*CYP3A2↓, combination of curcumin and piperine is most likely to inhibit CYP3A, CYP2C9, UGT, and SULT metabolism within the intestinal mucosa (Volak et al., 2008)
*neuroP↑, Neuroprotective Potential of Black Pepper
*BP↓, Piperine (20 mg/kg/day) decreased the blood pressure caused by the blockage of voltage-dependent calcium channels
*other↑, black pepper oil is one of the strongest appetizer; inhalation stimulates the swallowing in post stroke patients with dysphagia.

3587- PI,    Piperine: A review of its biological effects
- Review, Park, NA - Review, AD, NA
*hepatoP↑, piperine has also been documented for its hepatoprotective, anti-allergic, anti-inflammatory, and neuroprotective properties
*Inflam↓,
*neuroP↑,
*antiOx↑, antiangiogenesis, antioxidant, antidiabetic, antiobesity, cardioprotective,
*angioG↑,
*cardioP↑,
*BioAv↑, nano-encapsulation and resulting piperine-loaded nanoparticles enhance the bioavailability of piperine via oral administration
*P450↓, piperine inactivates cytochrome P450 (CYP) 3A (CYP3A), which plays a critical role in drug metabolism
*eff↑, enhances the anti-inflammatory effects when combined with resvera- trol
*BioAv↑, piperine increases the bioavailability of various compounds such as ciprofloxacin, norfloxacin, metronidazole, oxytetracycline, nimesulide, pentobarbitone, phenytoin, resveratrol, beta-carotene, curcumin, gallic acid, tiferron, nevirapine, and sparte
E-cadherin↓, Downregulates the E-cadherin (E-cad), estrogen receptor (ER), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP- 9), vascular endothelial growth factor (VEGF) levels, and c-Myc.
ER(estro)↓,
MMP2↓,
MMP9↓,
VEGF↓,
cMyc↓,
BAX↑, Increases the expressions of Bax and p53.
P53↑,
TumCG↓, Lowers the tumor growth and elevates survival time
OS↑,
*cognitive↑, piperine ameliorated the neuro-chemical, neuroinflammatory, and cognitive alterations caused by chronic exposure to galactose
*GSK‐3β↓, piperine reversed D-Gal-induced GSK-3β activation through modulating PKC and PI3K/AKT pathways, s
*GSH↑, Piperine stimulates glutathione levels in rats' striatum, reduced caspase-3 and 9 activation, and diminished release of cytochrome-c from mitochondria along with a reduction in lipid peroxidation
*Casp3↓,
*Casp9↓,
*Cyt‑c↓,
*lipid-P↓,
*motorD↑, piperine also caused improvement in motor coordination and balance behavior along with reduction in contralateral rotations.
*AChE↓, significantly amended impaired memory and hippo-campus neurodegeneration and lowered lipid peroxidation and acetylcholinesterase enzyme
*memory↑,
*cardioP↑,
*ROS↓, fig 6
*PPARγ↑,
*ALAT↓, piperine lowers alanine aminotransferase (ALT), AST, and ALP levels in sera of cholesterol-fed albino mice
*AST↓,
*ALP↓,
*AMPK↑, reversed the downregulation of AMPK signaling molecules, which are responsible for fatty acid oxidation, insulin signaling, and lipogenesis in mouse liver.
*5HT↑, t causes a significant decrease in serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) contents in the hippocampus and frontal cortex.
*SIRT1↑, , it may enhance the SIRT1 expression in cells and SIRT1 activity enhancing its potential to prevent SIRT1-mediated disease
*eff↑, combination ther- apy of resveratrol and piperine as an approach to enhance the biologi- cal effects with respect to cerebral blood flow and improved cognitive functions

1257- PI,    Piperlongumine attenuates bile duct ligation-induced liver fibrosis in mice via inhibition of TGF-β1/Smad and EMT pathways
- ex-vivo, LiverDam, NA
*Fibronectin↓,
*α-SMA↓,
*COL1↓, collagen1a
*COL3A1↓,
*TGF-β↓,
*EMT↓,
*MMP2↓, PL produced a significant attenuation of the BDL-induced increase in MMP-2, α-SMA, collagen1a, and collagen3a expressio
*α-SMA↓,
*Smad7↑, Smad7 protein expression was decreased in BDL mice whereas upon PL treatment, it increased significantly
*E-cadherin↑, oral administration of PL demonstrated a dose-dependent increase in expression of E-cadherin and reduction in vimentin and fibronectin expression
*Vim↓,
*hepatoP↑, Our study displays that PL treatment is capable of restoring liver enzymes, suggesting a hepatoprotective potential of PL in liver injury markers
*antiOx↑, PL showed powerful antioxidant effects by attenuating oxidative-nitrosative stress and increasing intracellular antioxidant GSH levels in BDL liver.
*GSH↑,
*ROS↓,

1256- PI,    Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models
- in-vitro, adrenal, PHEO - in-vivo, NA, NA
Apoptosis↑,
ROS↑,
TumCMig↓,
TumCI↓,
EMT↓,
angioG↓,
Necroptosis↑,
MAPK↑,
ERK↑, 8 fold

1254- PI,  VitC,    Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS–STAT3 pathway
- in-vivo, GC, NA
STAT3⇅, PL effectively suppressed STAT3 activation while VC caused abnormal activation of STAT3.
eff↑, combination of PL and VC exhibited a stronger apoptotic effect compared with either agent alone
ROS↑, PL and VC effectively induced apoptosis of GC cells through oxidative stress.
Apoptosis↑, 15 µM PL and 3 mM VC caused more than 60% apoptosis in two GC cell lines.

1946- PL,  PI,    Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling
- in-vitro, Liver, NA
eff↑, Among these, compound 9m exerted the most potent antiproliferative activity against drug-resistant Bel-7402/5-FU human liver cancer 5-FU resistant cells (IC50 = 0.8 μM), which was approximately 10-fold lower than piperlongumine (IC50 = 8.4 μM).
toxicity↓, Further, 9m showed considerably lower cytotoxicity against LO2 human normal liver epithelial cells compared to Bel-7402/5-FU.
TrxR↓, Mechanistically, compound 9m inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, reduced mitochondrial transmembrane potential (MTP
ROS↑,
MMP↓,
p38↑, Finally, 9m activated significantly the p38 signaling pathways and suppressed the Akt/mTOR signaling pathways.
Akt↓,
mTOR↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   angioG↓,1,   Apoptosis↑,2,   BAX↑,1,   cMyc↓,1,   E-cadherin↓,1,   eff↑,2,   EMT↓,1,   ER(estro)↓,1,   ERK↑,1,   MAPK↑,1,   MMP↓,1,   MMP2↓,1,   MMP9↓,1,   mTOR↓,1,   Necroptosis↑,1,   OS↑,1,   p38↑,1,   P53↑,1,   ROS↑,3,   STAT3⇅,1,   toxicity↓,1,   TrxR↓,1,   TumCG↓,2,   TumCI↓,1,   TumCMig↓,1,   VEGF↓,1,  
Total Targets: 27

Results for Effect on Normal Cells:
5HT↑,1,   5LO↓,1,   AChE↓,1,   ALAT↓,1,   ALP↓,1,   AMPK↑,1,   angioG↑,1,   antiOx↑,3,   AP-1↓,1,   AST↓,1,   Aβ↓,1,   BioAv↑,3,   BioEnh↑,1,   BP↓,1,   cardioP↑,2,   Casp3↓,1,   Casp9↓,1,   Catalase↑,2,   chemoP↑,1,   cognitive↑,3,   COL1↓,1,   COL3A1↓,1,   COX1↓,1,   CYP3A2↓,1,   Cyt‑c↓,1,   E-cadherin↑,1,   eff↑,3,   EMT↓,1,   Fibronectin↓,1,   GPx↑,1,   GSH↑,3,   GSK‐3β↓,1,   GSR↑,1,   GSTs↑,2,   hepatoP↑,2,   Inflam↓,2,   lipid-P↓,1,   memory↑,1,   MMP2↓,1,   MMPs↓,1,   motorD↑,1,   neuroP↑,2,   other↑,5,   P450↓,1,   PGE2↓,1,   PPARγ↑,1,   ROS↓,5,   SIRT1↑,1,   Smad7↑,1,   SOD↑,2,   tau↓,1,   TBARS↑,1,   TGF-β↓,1,   Vim↓,1,   Weight↓,1,   α-SMA↓,2,  
Total Targets: 56

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
8 Piperine
1 Vitamin C (Ascorbic Acid)
1 Piperlongumine
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:133  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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