Curcumin / BioAv Cancer Research Results

CUR, Curcumin: Click to Expand ⟱

Features:

Curcumin is the main active ingredient in Turmeric. Member of the ginger family.Curcumin is a polyphenol extracted from turmeric with anti-inflammatory and antioxidant properties.
- Has iron-chelating, iron-chelating properties. Ferritin. But still known to increase Iron in Cancer cells.
- GSH depletion in cancer cells, exhaustion of the antioxidant defense system. But still raises GSH↑ in normal cells.
- Higher concentrations (5-10 μM) of curcumin induce autophagy and ROS production
- Inhibition of TrxR, shifting the enzyme from an antioxidant to a prooxidant
- Strong inhibitor of Glo-I, , causes depletion of cellular ATP and GSH
- Curcumin has been found to act as an activator of Nrf2, (maybe bad in cancer cells?), hence could be combined with Nrf2 knockdown
-may suppress CSC: suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).

Curcumin — Curcumin is a turmeric-derived polyphenolic curcuminoid and diarylheptanoid from Curcuma longa, functionally best classified as a natural-product small molecule / nutraceutical candidate with pleiotropic redox, inflammatory, transcriptional, metabolic, and chemosensitizing activity. The standard abbreviation is CUR. It is the principal active pigment of turmeric rhizome, usually studied as purified curcumin, curcuminoid mixtures, turmeric extract, phytosomal curcumin, liposomal curcumin, nanoparticle curcumin, or piperine-enhanced formulations. Its oncology relevance is mechanistically broad but clinically constrained by poor aqueous solubility, rapid metabolism, low free systemic exposure, formulation variability, and insufficient well-powered cancer outcome trials.

Primary mechanisms (ranked):

Suppression of NF-κB / STAT3 inflammatory-survival signaling, reducing cytokine, COX-2, iNOS, anti-apoptotic, invasion, and treatment-resistance programs.
Biphasic redox modulation: ROS buffering in normal/inflamed tissue but ROS↑, GSH depletion, thioredoxin reductase disruption, and oxidative stress amplification in susceptible cancer models at sufficient exposure.
Mitochondrial injury and intrinsic apoptosis, including mitochondrial membrane potential loss, cytochrome-c release, caspase activation, PARP cleavage, and ER-stress/UPR involvement.
PI3K/AKT/mTOR and MAPK pathway modulation, contributing to growth arrest, autophagy modulation, apoptosis sensitization, and reduced survival signaling.
Wnt/β-catenin, Hedgehog/GLI, Notch, and cancer-stem-cell suppression, reducing stemness, EMT, invasion, and recurrence-associated phenotypes in models.
Hypoxia / HIF-1α and glycolysis inhibition, including reduced GLUT1, HK2, LDHA, PKM2, lactate/ECAR, and Warburg-like metabolic support in selected models.
Anti-angiogenic and anti-metastatic modulation, including VEGF, MMPs, uPA, CXCR4/SDF-1, TGF-β/α-SMA, FAK, and EMT-related axes.
Epigenetic and transcriptional reprogramming, including reported HDAC, DNMT, EZH2, Sp-family, p53, and microRNA-related effects.
NRF2 modulation: generally cytoprotective in normal cells but potentially protective for cancer cells when NRF2 is activated; NRF2 suppression/knockdown can increase curcumin-induced ROS stress in some tumor models.
Chemosensitization and radiosensitization, with parallel normal-tissue protective signals reported in some mucositis, dermatitis, oxidative-stress, and radioprotection contexts.

Bioavailability / PK relevance: Conventional oral curcumin has poor systemic bioavailability because of low solubility, low absorption, rapid conjugation, and rapid elimination. Oral trials have used doses up to gram-level daily dosing, but circulating free curcumin is typically low; measured plasma exposure often reflects conjugated curcumin. Piperine, phospholipid/phytosome, micellar, liposomal, nanoparticle, and other enhanced formulations can raise exposure, but each formulation should be treated as a distinct translational entity. Delivery constraints are central for oncology interpretation.

In-vitro vs systemic exposure relevance: Common in-vitro anticancer concentrations, often in the low-to-mid micromolar range and sometimes higher, frequently exceed achievable free plasma exposure from standard oral curcumin. Therefore, direct systemic anticancer claims from cell culture should be weighted cautiously unless supported by tissue-local exposure, enhanced formulation data, local delivery, IV/liposomal delivery, or clinically measured pharmacodynamic biomarkers.

Clinical evidence status: Preclinical evidence is extensive; human oncology evidence is mainly small human, biomarker, pilot, chemoprevention, adjunctive, symptom-management, and formulation trials. Current authoritative oncology summaries judge evidence inadequate to recommend curcumin-containing products as cancer treatment or as routine adjunct anticancer therapy, although symptom-support areas such as oral mucositis, radiation dermatitis, oxidative-status measures, and quality of life have more suggestive but still confirmatory-level evidence.

Clinical studies testing curcumin in cancer patients have used a range of dosages, often between 500 mg and 8 g per day; however, many studies note that doses on the lower end may not achieve sufficient plasma concentrations for a therapeutic anticancer effect in humans.
• Formulations designed to improve curcumin absorption (like curcumin combined with piperine, nanoparticle formulations, or liposomal curcumin) are often employed in clinical trials to enhance its bioavailability.

-Note half-life 6 hrs.
BioAv is poor, use piperine or other enhancers
Pathways:
- induce ROS production at high concentration. Lowers ROS at lower concentrations
curcumin can act as a pro-oxidant when blue light is applied
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: GSH↓ Catalase↓ HO1↓ GPx↓
but conversely is known as a NRF2↑ activator in cancer
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, uPA↓, VEGF↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, TrxR**,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Curcumin Cancer Mechanism Ranking

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	NF-κB / STAT3 inflammatory survival signaling	NF-κB ↓; STAT3 ↓; IL-6/TNF-α/COX-2/iNOS ↓; Bcl-2/Bcl-xL/survivin programs ↓	Inflammatory tone ↓; tissue-protective anti-inflammatory effect likely context-dependent	R/G	Reduced survival, inflammation, invasion, and therapy-resistance signaling	Most central and industry-relevant axis; explains many downstream effects but is not curcumin-specific.
2	Biphasic redox stress and antioxidant buffering	ROS ↑ (dose-dependent); GSH ↓; antioxidant reserve ↓; oxidative apoptosis ↑	ROS ↓; NRF2/SOD/GSH/catalase/HO-1 often ↑ in stress models	R/G	Selective redox pressure in susceptible tumor cells with normal-cell protection in lower-stress settings	Direction depends strongly on concentration, formulation, light exposure, basal redox state, and tumor antioxidant capacity.
3	Thioredoxin reductase and GSH linked redox systems	TrxR inhibition or redox cycling ↑; GSH depletion ↑; oxidative stress ↑	Usually buffered or antioxidant response ↑ at non-toxic exposure	R/G	Collapse of tumor redox compensation	Mechanistically important for ROS amplification and radiosensitization; achievable exposure remains a major constraint.
4	Mitochondrial depolarization and intrinsic apoptosis	ΔΨm ↓; cytochrome-c ↑; caspase-3/9 ↑; PARP cleavage ↑; apoptosis ↑	Generally ↔ or protected under oxidative/inflammatory stress	R/G	Execution of apoptosis after upstream redox and survival-signal disruption	Central cytotoxic endpoint in many cell models; often downstream of ROS, ER stress, AKT/mTOR suppression, or p53 modulation.
5	PI3K / AKT / mTOR and autophagy balance	PI3K ↓; AKT ↓; mTOR ↓; survival signaling ↓; autophagy ↑ or mixed	Stress-adaptive autophagy ↔ or ↑ (context-dependent)	R/G	Growth suppression and apoptosis sensitization	Autophagy may be cytotoxic or protective depending on model and timing; combination logic may require autophagy-state interpretation.
6	Wnt / β-catenin / Hedgehog / Notch stemness signaling	β-catenin ↓; GLI/Hedgehog ↓; Notch ↓; CD133/CD44/OCT4/SOX2-like stemness markers ↓	Generally ↔; possible normal stem-cell effects are tissue/context-dependent	G	Reduced cancer stemness, EMT, self-renewal, and recurrence-associated phenotypes	Important for anti-metastatic and anti-CSC positioning; evidence is mainly preclinical.
7	HIF-1α / glycolysis / Warburg metabolism	HIF-1α ↓; GLUT1 ↓; HK2 ↓; LDHA ↓; PKM2 ↓; lactate/ECAR ↓; ATP stress ↑	Metabolic effects ↔ or adaptive; normal-cell toxicity depends on exposure	G	Reduced hypoxic adaptation and glycolytic energy support	Mechanistically relevant but formulation and tissue exposure are critical; hypoxic tumors may be more relevant than normoxic cell culture.
8	EMT / invasion / metastasis matrix axis	EMT ↓; MMP2/MMP9 ↓; uPA ↓; FAK ↓; CXCR4/SDF-1 ↓; migration/invasion ↓	Inflammation-linked remodeling ↓; wound-healing effects context-dependent	G	Anti-invasive and anti-metastatic phenotype	Strongly supported in models; clinical anti-metastatic efficacy is not established.
9	VEGF / angiogenesis / hypoxia interface	VEGF ↓; HIF-1α ↓; angiogenic signaling ↓	Angiogenesis modulation ↔ or ↓ (context-dependent)	G	Reduced tumor vascular-support signaling	Overlaps with NF-κB, HIF-1α, STAT3, and inflammatory cytokine suppression.
10	Epigenetic and transcriptional reprogramming	HDAC ↓; DNMT1/3A ↓; EZH2 ↓; Sp proteins ↓; p53 ↑ or restored in selected models	Broad transcriptional effects possible; selectivity uncertain	G	Reactivation of growth-control and differentiation-associated programs	Biologically plausible but highly model-dependent; direct target specificity is lower than pathway-level interpretation.
11	Ferroptosis and iron redox stress	Iron/redox stress ↑; lipid peroxidation ↑; GPX4/GSH axis may ↓ (model-dependent)	Iron-chelation and antioxidant protection may occur (context-dependent)	R/G	Potential ferroptosis contribution in susceptible tumor models	Curcumin can behave as an iron chelator, antioxidant, or pro-oxidant depending on exposure, formulation, and cancer redox context.
12	NRF2 cytoprotection risk	NRF2 ↑ may protect tumor cells; NRF2 depletion can enhance curcumin-induced ROS stress in some models	NRF2 ↑ supports antioxidant and anti-inflammatory tissue protection	G	Dual-edged stress-response modulation	Important caution for antioxidant matrix use: NRF2 activation is favorable in normal-cell protection but may be undesirable in NRF2-addicted tumors.
13	Chemosensitization and radiosensitization	Chemo response ↑; radiation response ↑; apoptosis ↑; resistance pathways ↓	Chemo/radiation injury may ↓ in mucositis, dermatitis, and oxidative-stress contexts	R/G	Adjunct sensitization with possible normal-tissue protection	Attractive translational axis, but clinical evidence remains mainly pilot/small-study; interaction risk should be checked per regimen.
14	Clinical Translation Constraint	Free systemic exposure often insufficient for direct cytotoxic extrapolation from in-vitro micromolar data	Enhanced formulations may improve exposure but may also alter safety, liver-risk profile, and interaction potential	G	Bioavailability and formulation dominate translational interpretation	Separate ordinary curcumin, turmeric extract, piperine-enhanced, phytosomal, micellar, liposomal, nanoparticle, and IV/liposomal products where possible.

TSF legend:

P: 0–30 min

R: 30 min–3 hr

G: >3 hr

BioAv, bioavailability: Click to Expand ⟱

Source:

Type: measurement

Bioavailability (usually in %) absorbed by the body.

Scientific Papers found: Click to Expand⟱

2015-

CAP,

CUR,

urea,

Anti-cancer Activity of Sustained Release Capsaicin Formulations

Review,

Var,

AntiCan↑, Several convergent studies show that capsaicin displays robust cancer activity, suppressing the growth, angiogenesis and metastasis of several human cancers.
TumCG↓,
angioG↓,
TumMeta↓,
BioAv↓, clinical applications of capsaicin as a viable anti-cancer drug have remained problematic due to its poor bioavailability and aqueous solubility properties
BioAv↓, capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, nausea and diarrhea and vomiting
BioAv↑, All these hurdles may be circumvented by encapsulation of capsaicin in sustained release drug delivery systems.
selectivity↑, Most importantly, these long-acting capsaicin formulations selectively kill cancer cells and have minimal growth-suppressive activity on normal cells.
EPR↑, The EPR effect is a mechanism by which high–molecular drug delivery systems (typically prodrugs, liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues
eff↓, The efficiency of such extravasation is maximum when the size of the liposomes less than 200 nm The CAP-CUR-GLY-GAL-LIPO were spherical in shape with a narrow range of size distribution ranging from 135–155nm
ChemoSen↑, The chemosensitization and anti-tumor activity of capsaicin involves multiple molecular pathways
Dose∅, oral, Intravenous (IV), and Intraperitoneal (IP) options
Half-Life∅, oral metabolized in 105mins, T1/2in blood=25mins.
eff↑, presence of urea (as a carrier) increased the aqueous solubility of capsaicin by 3.6-fold compared to pure capsaicin

4826-

CUR,

The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management

Review,

Var,

*antiOx↑, Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators
*Inflam↑,
*ROS↓,
Apoptosis↑, Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers
TumCP↓,
BioAv↓, application is limited by its poor bioavailability due to its rapid metabolism and low absorption.
Half-Life↓,
eff↑, curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy.
TumCCA↑, Studies have demonstrated that curcumin can suppress the proliferation of cancer cells by interfering with the cell cycle [21,22]
BAX↑, Curcumin enhances the expression of pro-apoptotic proteins such as Bax, Bak, PUMA, Bim, and Noxa and death receptors such as TRAIL-R1/DR4 and TRAIL-R2/DR5
Bak↑,
PUMA↑,
BIM↑,
NOXA↑,
TRAIL↑,
Bcl-2↓, curcumin decreases the levels of anti-apoptotic proteins like Bcl-2, Bcl-XL, survin, and XIAP
Bcl-xL↓,
survivin↓,
XIAP↓,
cMyc↓, This shift in the balance of apoptotic regulators facilitates the release of cytochrome c from mitochondria [33,35] and activates caspases
Casp↑,
NF-kB↓, Curcumin suppresses the activity of key transcription factors like NF-κB, STAT3, and AP-1 and interferes with critical signal transduction pathways such as PI3K/Akt/mTOR and MAPK/ERK.
STAT3↓,
AP-1↓,
angioG↓, curcumin inhibits angiogenesis and metastasis by downregulating VEGF, VEGFR2, and matrix metalloproteinases (MMPs).
TumMeta↑,
VEGF↓,
MMPs↓,
DNMTs↓, Epigenetic modifications through the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) further contribute to its anticancer properties.
HDAC↓,
ROS↑, curcumin-loaded nanoparticles showed significant cytotoxicity in the SCC25, MDA-MB-231, and A549 cell lines, with a decrease in tumor cell proliferation, an increase in ROS, and an increase in apoptosis.

4829-

CUR,

Dual Action of Curcumin as an Anti- and Pro-Oxidant from a Biophysical Perspective

Review,

Var,

*antiOx↑, therapeutic effects against different disorders, mostly due to its anti-oxidant properties.
ROS↑, However, curcumin can act as a pro-oxidant when blue light is applied, since upon illumination it can generate singlet oxygen
*lipid-P↓, In addition to inhibiting lipid peroxidation, curcumin appears to reduce induciblenitric oxide (NO) synthase (iNOS) activity.
*iNOS↓,
*BioAv↓, poor bioavailability is the key to curcumin’s health-promoting effects,

4651-

CUR,

Targeting cancer stem cells by curcumin and clinical applications

Review,

Var,

CSCs↓, recent research has shown that curcumin can target cancer stem cells (CSCs)
*toxicity↓, safety and tolerability of curcumin have been well-established by numerous clinical studies
*BioAv↝, Importantly, the low bioavailability of curcumin has been dramatically improved through the use of structural analogues or special formulations.
chemoP↑, promising agent in cancer chemoprevention and therapy

4655-

CUR,

Inhibition of Cancer Stem-like Cells by Curcumin and Other Polyphenol Derivatives in MDA-MB-231 TNBC Cells

in-vitro,

BC,

CSCs↓, Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs.
*BioAv↓, curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects

4672-

CUR,

An old spice with new tricks: Curcumin targets adenoma and colorectal cancer stem-like cells associated with poor survival outcomes

vitro+vivo,

CRC,

HCT116

CSCs↓, Curcumin targets proliferating stem cells in human colorectal adenoma models, with activity across all molecular subtypes.
Nanog↓, Evidence suggests these effects involve direct protein binding of curcumin to NANOG, a master regulator of CRC CSCs
BioAv↓, It is well established that curcumin has poor bioavailability, but appreciable concentrations can be detected in gastrointestinal tissue when it is taken orally in its standard form

6218-

CUR,

Exploring the Thioredoxin System as a Therapeutic Target in Cancer: Mechanisms and Implications

Review,

Var,

NF-kB↓, curcumin inhibits, among others, NF-κB and TrxR [177].
TrxR↓,
ROS↑, Several studies show that curcumin leads to an accumulation of ROS in tumor cells, inhibiting metastasis formation and inducing cell death and/or sensitizing the cells to radiation
TumMeta↓,
TumCD↑,
RadioS↑,
BioAv↝, Curcumin exhibits limitations for potential clinical applications due to its poor water solubility. Therefore, analogues have been developed, such as WZ26, which inhibits TrxR and restricts the proliferation and survival of tumor cells
BioAv↑, Phase I trial with theracurmin, a curcumin derivative that demonstrates higher bioavailability than curcumin, it was shown that a combination with irinotecan is safe and well-tolerated in patients with advanced solid tumors

6230-

CUR,

Dual redox effects of 2,6-bis-(4-hydroxyl-3-methoxybenzylidene) cyclohexanone (BHMC) on human liver cancer cells, HepG2 via ROS, glutathione and Nrf2/Keap1 pathway

in-vitro,

Liver,

HepG2

chemoP↑, Curcumin has demonstrated significant potential as a chemoprotective agent by inducing death in malignant cells while exhibiting selective cytotoxicity toward normal cells.
selectivity↑,
*BioAv↓, curcumin has limited bioavailability which hindered its full potential.
*BioAv↑, Thus, 2,6-bis-(4-hydroxyl-3-methoxybenzylidene) cyclohexanone (BHMC), a curcuminoid derivative is produced by eliminating unstable β-diketone component, transformed it with double bonds while retaining the phenolic hydroxyl group.
ROS↑, BHMC triggers greater cytotoxic effect via inducing higher oxidative stress damage through reactive oxygen species (ROS)-mediated pathway.
ROS↓, Further analysis shows that BHMC significantly reduces intracellular ROS levels in HepG2 cells at low concentrations of 15 µM after 18 h and 10 µM after 24 h compared to untreated.
ROS↑, However, at a higher concentration of 20 µM, BHMC induces oxidative stress like curcumin by lowering the ratio of reduced glutathione to glutathione disulfide (GSH/GSSG) and upregulating Nrf2 expression.

6228-

CUR,

A pharmacokinetic study and critical reappraisal of curcumin formulations enhancing bioavailability

Study,

Nor,

 nine healthy males receiving three formulations (AOV, Longvida, and NovaSOL) at about 570 mg, while AOV was also tested at 2280 mg, with and without piperine.

*BioAv↓, Plasma levels of unconjugated curcumin remained below 2 nM in most cases, including high-dose AOV and piperine combinations
*other↓, Therefore, measuring the total of conjugated and unconjugated curcumin is not the correct metric to assess oral bioavailability and emphasis should be on unconjugated curcumin.18

6227-

CUR,

Revisiting Curcumin in Cancer Therapy: Recent Insights into Molecular Mechanisms, Nanoformulations, and Synergistic Combinations

Review,

Var,

Wnt↓, By targeting multiple molecular pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, JAK/STAT3, MAPK, NF-κB, and Notch, curcumin suppresses cancer growth and induces apoptosis.
β-catenin/ZEB1↓,
PI3K↓,
Akt↓,
mTOR↓,
JAK↓,
STAT3↓,
MAPK↓,
NF-kB↓,
NOTCH↓,
TumCG↓,
Apoptosis↑,
GSK‐3β↓, curcumin directly targets β-catenin and key Wnt/β-catenin regulators, including Dvl-2, Dvl-3, and GSK-3β.
cMyc↓, curcumin downregulates downstream oncogenic effectors such as c-Myc and Survivin while upregulating Axin-2, thereby inducing G2/M cell cycle arrest and apoptosis.
survivin↓,
Axin2↑,
TumCCA↑,
PTEN↑, curcumin upregulates PTEN expression, restoring its negative regulatory effect on the PI3K/Akt pathway.
P53↑, Curcumin’s activation and stabilization of p53 have been demonstrated in multiple cancer cell lines
ROS↑, In cervical cancer cells, curcumin induced apoptosis and ROS accumulation. Curcumin treatment elevated cleaved caspase-3 and PARP levels, markers of apoptosis.
Casp3↑,
PARP↑,
Ferroptosis↑, Ferroptosis Induction by Curcumin
angioG↓, Curcumin Inhibits Angiogenesis, Invasion, and Metastasis in Cancer Cells
TumCI↓,
TumMeta↓,
BioAv↓, curcumin’s clinical translation is limited by its poor bioavailability, rapid metabolism, and low systemic stability.
Half-Life↓,
ChemoSen↑, Synergistic Effects of Curcumin with Chemotherapy and Nanoparticle-Based Drug Delivery Systems
CompStab↓, curcumin’s clinical translation is limited by its poor bioavailability, rapid metabolism, and low systemic stability.

6222-

CUR,

Anticancer Molecular Mechanisms of Curcuminoids: An Updated Review of Clinical Trials

Review,

Var,

RadioS↑, curcumin has been shown to enhance the efficacy of the conventional anti‐cancer modalities such as radiation and chemotherapy.
ChemoSen↑,
MMPs↓, By suppressing the expression of matrix metalloproteinases (MMPs), which are enzymes that break down the extracellular matrix and promote cancer cell invasion and metastasis
TumMeta↓,
TumCI↓,
Inflam↓, Inflammation and the advancement of cancer are linked to the NF‐κB signaling pathways, which are also suppressed by curcuminoids.
NF-kB↓,
BioAv↓, curcumin's low bioavailability limits its therapeutic use.
BioAv↑, may be overcome due to recent developments in drug delivery technologies, such as curcumin‐loaded nanoparticles.
MAPK↓, Curcuminoids prevent the activation of a variety of signaling pathways, including the MAPK, PI3K/Akt, and NF‐kB pathways,
PI3K↓,
Akt↓,
*ROS↓, Many studies have pointed out curcumin's potential to reduce oxidative stress markers significantly in various biological models
*MDA↓, significant decrease in the level of MDA in treated animals was observed, which indicated that curcumin treatment delays the process of lipid peroxidation.
*lipid-P↓,
*Half-Life↓, Curcumin has a short biological half‐life and is poorly soluble in water, which allows understanding the low bioavailability of curcumin after oral administration.
mTOR↓, In breast cancer, curcumin mainly targets PI3K/Akt/mTOR

6221-

CUR,

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer

Review,

Var,

NF-kB↓, NF-Kβ suppression from Cur interaction led to the identification of Cur’s immunomodulatory effects
Imm↑, on various cytokines and immune related proteins such as IL-6, TNF-α, and PD-L1 and is suggested as a potential adjuvant treatment for immunotherapy
*TAC↑, In clinical trials, Cur is shown to increase total antioxidant capacity (TAC) and decrease malondialdehyde.53
*MDA↓,
ROS↑, increases overall ROS accumulation in SiHa cervical cancer cells resulting in increased autophagy and G2/M phase cell cycle arrest.54
TumAuto↑,
TumCCA↑,
Keap1↑, activate KEAP1/NRF2/ARE pathways and serve as an effective therapeutic especially in combination with 5-FU
ChemoSen↑,
ER Stress↑, administration of 1g resulted in ROS production, G1 cell cycle phase arrest, and increased ER-stress which was reversed upon addition of NAC, an ROS scavenging agent
eff↓, reversed upon addition of NAC
TrxR↓, Non-small cell lung cancer cell lines showed marked increases in apoptosis and ferroptosis driven by the analogs ability to generate ROS through TrxR inhibition.
STAT3↓, analog WZ26 increased ROS and cell death in cholangiocarcinoma via STAT3 inhibition
*BioAv↓, Studies with doses as high as 12 g/day still resulted in small amounts of traceable plasma Cur, mostly due to low absorption in the small intestine and rapid elimination in the body via the gall bladder.

6219-

CUR,

Natural Products and Altered Metabolism in Cancer: Therapeutic Targets and Mechanisms of Action

Review,

Var,

PI3K↓, blocking the PI3K/Akt pathway and its downstream NF-κB protein expression
Akt↓,
NF-kB↓,
BioAv↑, Piperine is a bioavailability enhancer for several chemotherapeutic agents, such as resveratrol and curcumin.
GSK‐3β↓, blocking the ILK/GSK-3β/slug signaling pathway.
Slug↓,
Cyt‑c↑, 0, 9, 18 of piperine and 36 µM curcumin for 24 h Leukemia (HL60) Release of mitochondrial cytochrome-c, which further initiates caspase-9/3 mediated cell apoptosis.
Casp3↑,
Casp9↑,

6216-

CUR,

Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials

Review,

Var,

TumCG↓, Curcumin can prevent tumor growth, angiogenesis, epithelial–mesenchymal transition, invasion, and metastasis by modulating the expression of tumor-related non-coding RNA (ncRNA)
angioG↓,
EMT↓,
TumCI↓,
TumMeta↓,
*GutMicro↑, curcumin plays a crucial role in regulating the gut microbiota via biotransformation of curcumin and its metabolites.
*BioAv↓, one of the primary drawbacks of taking curcumin alone is its low bioavailability, which appears to be caused by poor absorption, fast metabolism, and excretion
*HO-1↑, Curcumin is an efficient inducer of hemoxygenase-1 and a powerful inhibitor of reactive oxygen-generating enzymes, such as cyclooxygenase (COX), inducible nitric oxygen synthase (iNOS), lipoxygenase, and xanthine dehydrogenase/oxidase
*ROS↓,
*COX2/PTGS2↓,
*iNOS↓,
PKCδ↓, Curcumin is also a powerful inhibitor of protein kinase C (PKC), tyrosine kinase, epidermal growth factor receptor (EGFR), and IB kinase.
EGFR↓,
NF-kB↓, It suppresses NF-κB activation and the expression of oncogenes, such as c-jun, c-fos, c-myc, Akt, PI3K, cyclin-dependent kinase (CDK)
cJun↓,
cFos↓,
cMyc↓,
Akt↓,
PI3K↓,
CDK4↓,
*TNF-α↓, Continuous supplementation with nanocurcumin (two 40 mg capsules/day after a meal) for 3 months suppressed expression of inflammatory tumor necrosis factor-alpha (TNF-α), high sensitive protein with C-reactive protein (CRP), and interleukin-6 (IL-6)
*CRP↓,
*IL6↓,
MMP9↓, curcumin suppressed metastasis to the lung by suppressing NF-κB, MMP-9, COX-2, and vascular endothelial growth factor (VEGF) expression.
VEGF↓,
JAK↓, Curcumin remarkably inhibits JAK/STAT signaling by downregulating pro-inflammatory interleukins, such as IL-1, IL-2, IL-6, IL-8, IL-12, and MCP-1.
STAT↓,
IL1↓,
IL2↓,
IL6↓,
IL8↓,
IL12↓,
MCP1/CCL2↓,
Apoptosis↑, It promotes apoptosis and ER stress by targeting phosphorylated protein kinase-like ER-resident kinase,
ER Stress↑,
5LO↓, inhibiting lipoxygenase and xanthine oxidase activity
XO↓,
*NRF2↑, The expression of nuclear factors erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) is boosted by curcumin
*HO-1↑,
*AChE↓, Curcumin also inhibits the key enzyme acetylcholinesterase (AChE) and p300, a positive regulator of the Wnt/β-catenin pathway
*neuroP↑, Curcumin has also been suggested to prevent and cure neurotoxicity by replenishing dopamine and 3,4-dihydroxyphenylacetic acid levels.
*glucose↓, remarkably lowers blood glucose levels and improves insulin resistance by reducing hepatic glucose synthesis, inhibiting inflammatory reactions produced by hyperglycemia,
*GLUT2↑, boosting glucose transporters 2 (GLUT2), 3 (GLUT3), and 4 (GLUT4) gene expression, enhancing glucose uptake, and activating the AMPK signaling pathway.
*GLUT3↑,
*GLUT4↑,
*GlucoseCon↑,
*AMPK↑,
*BMD↑, Supplementation with nanomicelle curcumin (80 mg) alone or in combination with Nigella sativa oil (1000 mg) for 2–6 months increased plasma levels of miRNA-21 in postmenopausal women with low bone mass density.
*MDA↓, (1000 mg/day) for 8 weeks reduced serum levels of malondialdehyde (MDA) and high-sensitivity CRP (hs-CRP) and increased the total antioxidant capacity in 81 healthy postmenopausal women
*Synergy↑, Loriczova et al. demonstrated that iron (18 mg and 65 mg) supplementation along with curcumin (500 mg) reduces iron-induced systemic inflammation by reducing plasma levels of TNF-α
Synergy↑, high-dose vitamin C (25–100 g/day) along with oral nutrient supplementation including curcumin (1–3 g/day) had improved QoL and survival
P53↑, Curcumin was also reported to induce p53 and Bax expression in patients with colorectal cancer, causing apoptosis and DNA fragmentation and suppressing TNF-α and Bcl-2.
BAX↑,
DNAdam↑,
Bcl-2↓,
CSCs↓, The combination of curcumin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in colorectal liver metastases reduced stem cell markers, such as aldehyde dehydrogenase and CD133.
ALDH↓,
CD133↑,

6215-

CUR,

Curcumin: biochemistry, pharmacology, advanced drug delivery systems, and its epigenetic role in combating cancer

Review,

Var,

*antiOx↑, Curcumin exerts potent antioxidant, anti-inflammatory, and anticancer effects by modulating multiple signaling pathways, including NF-κB, PI3K/Akt, and Wnt/β-catenin.
*Inflam↓,
*BioAv↓, curcumin’s clinical application is limited by poor solubility, rapid metabolism, and low systemic bioavailability.
NF-kB↓, graphical abstract
PI3K↓,
Akt↓,
Wnt↓,
β-catenin/ZEB1↓,
DNMTs↓,
TumCI↓,
TumMeta↓,
*CompStab↑, Advanced drug delivery systems such as nanoparticles, liposomes, and micelles have been developed to address these challenges. These systems enhance curcumin’s solubility, stability, and targeted delivery, improving therapeutic efficacy while minimiz
*BioAv↑, coadministration with piperine, lipid-based formulations, and nanoparticle microencapsulation have been developed. Piperine has been shown to increase curcumin absorption by up to 2000 percent
angioG↓, Curcumin is also known for its antiangiogenic action through its inhibitory activity against vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs)
VEGF↓,
MMPs↓,
*ROS↓, suppresses oxidative stress by scavenging free radicals and enhancing the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase
*SOD↑,
*Catalase↑,
*GSTs↑, timulating phase II detoxifying enzymes such as glutathione S-transferase (GST), UDP-glucuronosyltransferase, and heme oxygenase-1 (HO-1).
*HO-1↑,
*NRF2↑, It also enhances the activity of the transcription factor Nrf2, which regulates genes crucial for cellular redox homeostasis and safeguarding cells against oxidative damage
mTOR↓, 0 to 50 μM, treatment was associated with decreased phosphorylation of Akt kinase (Akt), mammalian target of rapamycin (mTOR), glycogen synthase kinase (GSK3β), Forkhead box protein O1 (FOXO1), and other proteins
GSK‐3β↓,
FOXO1↓,
*radioP↑, Reduced radiation-induced dermatitis and inflammatory cytokine expression (IL-1, IL-6, TNF-α)
*IL1↓,
*IL6↓,
*TNF-α↓,
HATs↓, curcumin has been described as an agent that reduces histone acetylation by inhibiting HAT (histone acetyltransferases), such as the p300/CBP family of proteins
HDAC↓, curcumin has been detected to be an HDI and has the ability to inhibit the expressions of HDACs, like HDAC1, HDAC3, and HDAC8,
ROS↑, Elevating the levels of reactive oxygen species (ROS) in colon adenocarcinoma cells is one of the outcomes of treatment with curcumin, which results in a decline in cell proliferation and viability
ROS↑, at higher concentrations or in the presence of transition metal ions (e.g. Cu2+, Fe2+/Fe3+), curcumin can paradoxically act as a pro-oxidant.
MMP↓, Excess ROS damages mitochondrial membranes, oxidizes nucleic acids, lipids, and proteins, and activates apoptotic cascades via cytochrome c release and caspase activation
Casp↑,
Cyt‑c↑,
COX1↓, curcumin acts as a partial and condition-dependent inhibitor of both COX-1 and COX-2.
COX2/PTGS2↓,
PGE2↓, At lower or therapeutic concentrations, curcumin predominantly downregulates COX-2 and reduces prostaglandin E2 (PGE2) synthesis.
*cytoP450↓, curcumin’s capacity to inhibit cytochrome P450 enzymes may influence the metabolism of numerous medicines over extended durations.
ChemoSen↑, curcumin has been integrated with standard chemotherapy agents, including doxorubicin, cisplatin, and paclitaxel, to enhance cancer treatment efficacy
cardioP↑, co-delivery of curcumin and doxorubicin via nanoparticles improved anticancer effectiveness and decreased cardiotoxicity.
Synergy↑, concurrent treatment of curcumin and resveratrol has demonstrated increased anti-inflammatory and anticancer properties

6214-

CUR,

Curcumin Nanoparticles-related Non-invasive Tumor Therapy, and Cardiotoxicity Relieve

Review,

CardioV,

TumCD↓, Curcumin plays the antitumor effect by directly promoting tumor cell death and reducing tumor cells' invasive ability.
TumCI↓,
*Inflam↓, curcumin has many pharmacological effects, such as anti-inflammation, antioxidation, antitumor, etc.
*antiOx↓,
*AntiTum↓,
NF-kB↓, Curcumin exerts the therapeutic effect mainly by inhibiting the nuclear factor-κB (NF-κB) signal pathway, inhibiting the production of cyclooxygenase-2 (COX-2),
COX2/PTGS2↓,
Casp9↓, promoting the expression of caspase-9, and directly inducing reactive oxygen species (ROS) production in tumor cells.
ROS↑, Curcumin can induce lethal levels of reactive oxygen species (ROS) in tumors
BioAv↑, Curcumin nanoparticles can solve curcumin's shortcomings, such as poor water solubility and high metabolic rate, and can be effectively used in antitumor therapy.
RadioS↑, Figure 1, Curcumin Increases Radiosensitivity of Tumor
ChemoSen↑,
Imm↑,
PhotoS↑, Curcumin Mediates the Antitumor Effect of PDT
sonoS↑, Curcumin Mediates the Antitumor Effect of SDT
5LO↓, down-regulating the activities of cyclooxygenase-2 (COX-2), lipoxygenase (LOX), inducible nitric oxide synthase (iNOS) and so on, reducing the production of proinflammatory cytokines such as IL-2, tumor necrotic factor-α (TNF-α),
iNOS↓,
IL2↓,
TNF-α↓,
Casp9↑, activating intracellular caspase-9 and caspase-3, reducing the expression of p53, inhibiting Bcl2, and promoting the expression of Bax and down-regulating the proportion of Bcl2/Bax
Casp3↑,
Bcl-2↓,
BAX↑,
Apoptosis↑, promote apoptosis by activating caspase-4 and stimulating the Endoplasmic reticulum (ER) stress pathway and mitochondria stress pathway in tumor cells [
ER Stress↑,
cycD1/CCND1↓, It reduces the expression of cyclin D1, cyclin kinase-dependent kinase 2 (CDK2), cdc2/cyclin B complex, and other cell cycle-related proteins,
CDK2↓,
CycB/CCNB1↓,
TumCCA↑, blocks tumor cells from G1 / S phase and G2 / M phase, thus exerting an antitumor effect
MMPs↓, curcumin inhibits tumor invasion and metastasis by inhibiting NF-κB and other signaling pathways, such as chemokine and matrix metalloproteinases (MMPs)
*radioP↑, Curcumin can effectively treat and prevent radiation adverse reactions such as radiation dermatitis and radiation pneumonia by reducing the expression of inflammatory factors such as fibrotic cytokines, TNF-α, and IL-1, inhibiting NF-κB signal path
chemoP↑, Protective Effect of Curcumin on Side Effects of Chemotherapy
hepatoP↑, urcumin alleviates the hepatotoxicity caused by chemotherapy through anti-inflammation and antioxidation, reducing the level of liver fibrosis and blood lipids [
cardioP↑, Using curcumin to reduce the cardiotoxicity of chemotherapy can improve the therapeutic effect of tumors and patients' prognosis and quality of life.
Synergy↑, Curcumin Enhances the Therapeutic Effect of Immunotherapy
PhotoS↑, it has the potential to be a new photosensitizer
eff↑, Curcumin nanoparticles with functions of relieving hypoxia and consuming GSH could improve the ability of curcumin to induce ROS and promote ROS- mediated tumor cell death
ROS↑,
GSH↓,

6211-

CUR,

The effect of curcumin on hypoxia in the tumour microenvironment as a regulatory factor in cancer

Review,

Var,

HIF-1↓, Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF).
VEGF↓, Curcumin suppresses the HIF-1 pathway under hypoxia, which decreases VEGF expression in both tumour and stromal cells and suppresses angiogenesis.
angioG↓, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia.
RadioS↑, continued interest in curcumin is the molecules’ modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours.
ChemoSen↑, Combining cisplatin with curcumin promotes cell apoptosis through the YWHAG pathway and its interaction with HIF-1α, affecting the pentose phosphorylation pathway [
other↝, Cancer patients with hypoxia in their tumours have a poorer prognosis and are at greater risk of metastasis
Apoptosis↑, Curcumin exerts its unique anti-tumour efficacy primarily via pleiotropic functions resulting in apoptosis and decreased tumour cell growth and metastasis
TumCG↓,
TumMeta↓,
BioAv↓, However, due to its low water solubility and low chemical stability, curcumin’s use is limited.
COX2/PTGS2↓, abrogate the proliferation of pancreatic cancer cells through inhibition of COX-2, CD-31, VEGF, and IL-8 and suppression of TGF-β via NF-κB and HIF-1α downregulation
CD31/PECAM-1↓,
IL8↓,
TGF-β↓,
NF-kB↓,
JAK2↓, Curcumin application reduced tumourspheres of H460 cells via inhibition of the JAK2/STAT3 signalling pathway
STAT3↓,
CompStab↓, However, due to its low water solubility and low chemical stability, curcumin’s use is limited.

6209-

CUR,

Curcumin as a complementary treatment in oncological therapy: a systematic review

Review,

Var,

other↝, The findings of the included studies indicate that the administration of curcumin may offer a potential benefit with respect to oral symptoms and weight loss.
eff↓, Overall, 6 studies found no significant effect of curcumin in all or almost all investigated endpoints
*BioAv↓, Due to its low bioavailability, high doses seem necessary when using pure curcumin for it to be detected in the plasma
ChemoSen↓, In vitro or in vivo studies indicate an interaction between curcumin and various chemotherapeutic agents, with curcumin reducing the effect, depending on dosage and time of curcumin administration

6207-

CUR,

Enhancing the Bioavailability and Bioactivity of Curcumin for Disease Prevention and Treatment

Review,

Var,

Review,

AD,

*AntiCan↑, gained increasing interest due to its proposed anti-cancer, anti-obesity, anti-inflammatory, antioxidant, and lipid-lowering effects, in addition to its thermogenic capacity.
*Obesity↓,
*Inflam↓,
*lipid-P↓,
*BioAv↓, intact curcumin in the body may be too low (<1 microM) and not sufficient to affect signaling and gene expression, as observed in vitro with cultured cells (10–20 microM).
*BioAv↑, a myriad of nanoformulations have been developed that either lead to a systemic increase in curcumin or are targeted to specific cells, tissues, or organelles
*BioAv↑, latest generation of curcumin nanoformulations can increase the bioavailability of free curcumin in plasma greater than 100-fold and have superior absorption, cellular uptake, BBB permeability, and tissue distribution
*BioAv↑, In a clinical study, the authors found that 2 g of curcumin administered concomitantly with 20 mg of piperine, an inhibitor of hepatic and intestinal glucuronidation, appeared to promote a significant 2000% increase in the oral bioavailability of cur
*BioAv↑, rats in which piperine pre-administration was performed before receiving curcumin, there was a significant increase in the oral bioavailability of curcumin, especially at 6 h after piperine administration
*BioAv↑, Nanotechnology-based delivery systems such as micelles, liposomes, and polymeric, metal, and solid lipid nanoparticles have also been applied to enhance curcumin bioavailability
*ROS↓, Curcumin was effective against ischemia/reperfusion (I/R) lesions, as well in various experimental models, primarily through antioxidant actions such as scavenging ROSs [153], increasing mitochondrial superoxide dismutase (SOD) activity and decreasin
*mt-SOD↑,
*MDA↓,
*BBB↓, Curcumin has poor bioavailability, especially in the brain, where the BBB further limits its absorption
*Aβ↓, curcumin appears to reduce the production of Aβ also by affecting a second enzyme required for the cleavage of APP
*GSK‐3β↓, the inhibition of GSK3β by curcumin would hinder both Aβ production and tau aggregation
*tau↓,
*neuroG↑, prolonged treatment of aged rats with curcumin stimulates neurogenesis in the hippocampus
*memory↑, chronic curcumin administration improved memory acquisition and consolidation in both adult and aged rats
cardioP↑, curcumin has been investigated to promote cardioprotective effects against chemotherapy-induced cardiotoxicity

6206-

CUR,

Bioavailability of Oral Curcumin in Systematic Reviews: A Methodological Study

Review,

Nor,

*BioAv↓, Numerous factors contribute to the unfavorable pharmacokinetics of curcumin: very low water solubility (approximately 11 ng/mL) [13,14], poor absorption in the gut, fast metabolism as well as low distribution, and fast excretion [15,16
*Half-Life↓,
*BioAv↑, Possible solutions for increasing bioavailability are offered through the reduction in metabolism through the liver by additives such as piperine

6205-

CUR,

Clinical trials on curcumin in relation to its bioavailability and effect on malignant diseases: critical analysis

Review,

Var,

BioAv↓, After oral ingestion, only a small portion of curcumin is absorbed. The absorbed portion is metabolized at a pH of > 7 within 20 min
Half-Life↓, problem of curcumin bioavailability can be attributed to its low absorption, rapid metabolism, short half-life, and low tissue distribution
COX2/PTGS2↓, COX-2 expression levels decreased significantly after oral administration of 8 g curcumin/day
ChemoSen↑, observed benefits of the treatment group with curcumin paclitaxel combination remained (Saghatelyan et al. 2020). A slightly increased PFS was observed in the curcumin group compared to the placebo group.
cachexia↓, average gain in muscle mass of 0.46 kg muscle mass in the patients treated with curcumin, after the interval of 8 weeks (Thambamroong et al. 2022). Patients receiving placebo lost an average of 1.05 kg of muscle mass
NF-kB↓, Inhibition of the NF-κB pathway has also been observed in patients with pancreatic cancer

2817-

CUR,

Neuroprotection by curcumin: A review on brain delivery strategies

Review,

Nor,

*BioAv↝, blood–brain barrier (BBB) is the major obstacle for the delivery of curcumin into the brain, limiting its therapeutic potential.
neuroP↑, Although it appears to possess important neuroprotective properties, the utility of curcumin is limited because of its poor brain bioavailability owing to poor absorption and stability at physiological pH, high rate of metabolism, rapid systemic elim

2816-

CUR,

NEUROPROTECTIVE EFFECTS OF CURCUMIN

Review,

AD,

Review,

Park,

*neuroP↑, Curcumin has an outstanding safety profile and a number of pleiotropic actions with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and anti-protein-aggregate activities.
*Inflam↓,
*antiOx↑,
*BioAv↓, despite concerns about poor oral bioavailability, curcumin has at least 10 known neuroprotective action
*AP-1↓, Curcumin inhibition of AP-1 and NF-κB-mediated transcription occurs at relatively low (<100 nM) doses and might be due to inhibition of histone acetylase (HAT) or activation of histone deacetylase (HDAC) activity
*NF-kB↓,
*HATs↓,
*HDAC↑,
Dose↑, At high doses (>3 µM) that are relevant to colon cancer but unlikely achievable with oral delivery in plasma and tissues outside of the gut, curcumin can act as an alkylating agent,10 a phase II enzyme inducer,11 and stimulate antioxidant response el
*ROS↓, We also found that curcmin reduced oxidative damage, inflammation, and cognitive deficits in rats receiving CNS infusions of toxic Aβ
*cognitive↑,
*Aβ↓, dose-dependently blocked Aβ aggregation at submicromolar concentrations

3574-

CUR,

The effect of curcumin (turmeric) on Alzheimer's disease: An overview

Review,

AD,

*antiOx↑, Curcumin as an antioxidant, anti-inflammatory and lipophilic action improves the cognitive functions in patients with AD
*Inflam↓,
*lipid-P↓,
*cognitive↑,
*memory↑, overall memory in patients with AD has improved.
*Aβ↓, curcumin may help the macrophages to clear the amyloid plaques found in Alzheimer's disease.
*COX2/PTGS2↓, Curcumin is found to inhibit cyclooxygenase (COX-2),
*ROS↓, The reduction of the release of ROS by stimulated neutrophils, inhibition of AP-1 and NF-Kappa B inhibit the activation of the pro-inflammatory cytokines TNF (tumor necrosis factor)-alpha and IL (interleukin)-1 beta
*AP-1↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*SOD↑, It also increased the activity of superoxide dismutase, sodium-potassium ATPase that normally decreased with aging.
*GSH↑, followed by a significant elevation in oxidized glutathione content.
*HO-1↑, curcumin induces hemoxygenase activity.
*IronCh↑, curcumin effectively binds to copper, zinc and iron.
*BioAv↓, Curcumin has poor bioavailability. Because curcumin readily conjugated in the intestine and liver to form curcumin glucuronides.
*Half-Life↝, , serum curcumin concentrations peaked one to two hours after an oral dose
*Dose↝, Peak serum concentrations were 0.5, 0.6 and 1.8 micromoles/L at doses of 4, 6 and 8 g/day respectively.
*BBB↑, Curcumin crosses the blood brain barrier and is detected in CSF
*BioAv↑, Absorption appears to be better with food.
*toxicity∅, A phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for three months found no toxicity from curcumin.
*Synergy↑, Co-supplementation with 20 mg of piperine (extracted from black pepper) significantly increase the bioavailablity of curcumin by 2000%

3576-

CUR,

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease

Review,

AD,

*Inflam↓, known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions.
*antiOx↑,
*memory↑,
*Aβ↓, curcumin prevents Aβ aggregation and crosses the blood-brain barrier,
*BBB↑,
*cognitive↑, curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD
*tau↓, curcumin's effect on inhibition of A and tau,copper binding ability, cholesterol lowering ability, anti-inflammatory and modulation of microglia, acetylcholinesterase (AChE) inhibition, antioxidant properties,
*LDL↓,
*AChE↓,
*IL1β↓, Curcumin reduced the levels of oxidized proteins and IL1B in the brains of APP mice
*IronCh↑, Curcumin binds to redox-active metals, iron and copper
*neuroP↑, Curcumin, a neuroprotective agent, has poor brain bioavailability.
*BioAv↝,
*PI3K↑, They found that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1, and ferritin expression
*Akt↑,
*NRF2↑,
*HO-1↑,
*Ferritin↑,
*HO-2↓, and that it significantly downregulates heme oxygenase 2, ROS, and A40/42 expression.
*ROS↓,
*Ach↑, significant increase in brain ACh, glutathione, paraoxenase, and BCL2 levels with respect to untreated group associated with significant decrease in brain AChE activity,
*GSH↑,
*Bcl-2↑,
*ChAT↑, nvestigation revealed that the selected treatments caused marked increase in ChAT positive cells.

2688-

CUR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Var,

Review,

AD,

*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↑,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
Synergy↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1/CCND1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,

2305-

CUR,

Mitochondrial targeting nano-curcumin for attenuation on PKM2 and FASN

in-vitro,

BC,

MCF7

BioAv↑, This nano-curcumin can readily enter mitochondrion in MCF-7 cancer cells.
PKM2↓, expression of both pyruvate kinase M2 and fatty acid synthase in the MCF-7 cancer cells were noticeably inhibited by CUR@DNA-FeS2-DA
FASN↓,
Glycolysis↓,

2308-

CUR,

Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells

in-vitro,

Liver,

HepG2

GlucoseCon↓, Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production
lactateProd↓,
ECAR↓,
NO↓,
ROS↑, Curcumin favors the ROS production in HepG2 cells in normal as well as hyperglycemic conditions. ROS production was detected in cancer cells treated with curcumin, or doxorubicin, or their combinations in NG or HG medium for 24 h
HK2↓, HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, tr
PFK1↓,
GAPDH↓,
PKM2↓,
LDHA↓,
FASN↓,
GLUT1↓, Curcumin treatment was able to significantly decrease the expression of GLUT1, HKII, and HIF-1α in HepG2 cells either incubated in NG or HG medium.
MCT1↓,
MCT4↓,
HCAR1↓,
SDH↑, Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition
ChemoSen↑, Curcumin Prevents High Glucose-Induced Chemoresistance
ROS↑, Treatment of cells with doxorubicin in presence of curcumin was found to cooperatively augment the ROS level in cells of both NG and HG groups.
BioAv↑, Curcumin Favors Drug Accumulation in Cancer Cells
P53↑, An increased expression of p53 in curcumin-treated cells can be suggestive of susceptibility towards cytotoxic action of anticancer drugs
NF-kB↓, curcumin has therapeutic benefits in hyperglycemia-associated pathological manifestations and through NF-κB inhibition
pH↑, Curcumin treatment was found to resist the lowering of pH of culture supernatant both in NG as well in HG medium.

2654-

CUR,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

ROS↑, ROS induction has been implicated as one of the mechanisms of the anticancer activity of curcumin and its derivatives in various cancers
Catalase↓, Curcumin induces ROS by inhibiting the activity of various ROS-related metabolic enzymes, such as CAT, SOD1, glyoxalase 1, and NAD(P)H dehydrogenase [quinone] 1 [146,149]
SOD1↓,
GLO-I↓,
NADPH↓,
TumCCA↑, ROS accumulation further mediates G1 or G2/M cell cycle arrest [146,147,150,154], senescence [146], and apoptosis.
Apoptosis↑,
Akt↓, downregulation of AKT phosphorylation [145
ER Stress↑, endoplasmic reticulum stress (namely through the PERK–ATF4–CHOP axis)
JNK↑, activation of the JNK pathway [151],
STAT3↓, and inhibition of STAT3 [155].
BioAv↑, Additionally, the combination of curcumin and piperine, a pro-oxidative phytochemical that drastically increases the bioavailability of curcumin in humans

2809-

CUR,

Comparative absorption of curcumin formulations

in-vivo,

Nor,

BioAv↑, co-administration of curcumin with an extract obtained from the black pepper has been shown to increase the absorption (AUC) of curcumin by 1.5-fold.
BioAv↑, Whereas, a complex of curcumin with phospholipids increased absorption by 3.4-fold
BioAv↑, and a formulation of curcumin with a micellar surfactant (polysorbate) has been shown to increase the absorption of curcumin in mice 9.0-fold
BioAv↑, A micro emulsion system of curcumin, which consists of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol P aqueous solution (co-surfactant) has been shown to increase the relative absorption in rats by 22.6-fold
BioAv↑, Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol (PEG) (PLGA-PEG) blend nanoparticles increased curcumin absorption by 15.6- and 55.4-fold, respectively, compared to an aqueous suspension of curcumin in rats
BioAv↓, curcumin are limited by its poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination.
Half-Life↝, Our data indicated that the curcumin half-life was estimated to be 6-7 hours

2814-

CUR,

Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management

Review,

Var,

*BioAv↓, curcumin’s practical application in medicine is hindered by its limited bioavailability. low solubility in water and rapid breakdown in the body
*Inflam↓, anti-inflammatory, antioxidant, and potential anticancer abilities
*antiOx↑,
AntiCan↑,
CK2↓, Curcumin exhibited an IC50 of 2.38 ± 0.15 μM against CK2α
GSK‐3β↓, roles of GSK3β and how they are suppressed by curcumin
EGFR↓, roles of EGFR and how it is inhibited by the curcumin analog, 3a
TOP1↓, unwinding of DNA supercoils by Topo I and Topo II and their inhibition by cyclocurcumin
TOP2↓,
NF-kB↓, The activation of NF-kB signaling and the inhibition of NF-kB’s activity are portrayed in Figure 5.
COX2/PTGS2↓, curcumin itself interacts with COX-2 and potentially inhibits its function
CRP↓, ole of CRP in inducing inflammation and its inhibition by curcumin are depicted in Figure 6.

3590-

CUR,

The Holy Grail of Curcumin and its Efficacy in Various Diseases: Is Bioavailability Truly a Big Concern?

Review,

Var,

Review,

AD,

*BioAv↓, limited systemic bioavailability of curcumin has hindered its development as a potential therapeutic agent
*BioAv↑, recent introduction of unique extraction processes and various delivery methods has resulted in the development of new curcumin formulations and significantly improved its bioavailability.
Dose↑, daily consumption of 3.6 g of curcumin resulted in achieving curcumin concentration in the malignant colorectal tissues ranging from 7 to 20 nmol/g.
*Dose↝, pharmacokinetics of curcumin show that only 0.13–1.35 µg/mL concentration of curcumin was present in the blood from 1 to 2 g/kg when gavaged
*BBB↑, Curcumin has been shown to be detectable in the brain after oral administration
*cognitive↑, urcumin treatment in a mouse model of Alzheimer disease resulted in significant improvement in cognitive function
*BioAv↑, piperine, a major component of black and long peppers, has been shown to inhibit enzymatic conjugation of curcumin allowing greater levels of unconjugated curcumin to be absorbed into portal blood circulation14 and increased curcumin tissue retention

3588-

CUR,

The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies

Review,

AD,

*cognitive↝, Clinical studies are mixed regarding curcumin’s effects on cognitive deficits.
*BioAv↑, Ways to improve curcumin’s bioavailability are required.
*Inflam↓, anti-inflammatory activity can be attributed to the suppression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes via down-regulation of nuclear factor kappa B (NF-κB)
*COX2/PTGS2↓,
*iNOS↓,
*NF-kB↓,
*TNF-α↓, nhibition of several inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-a) or interleukin (IL) -1, -2, -6, -8, and -12 (
*IL1↓,
*IL2↓,
*IL6↓,
*IL8↓,
*IL12↓,
*ROS↓, Curcumin’s ability to scavenge free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), provides its antioxidant capacity
*RNS↓,
*antiOx↑,
*BBB↑, Multiple studies in rodents and humans have shown that curcumin crosses the blood brain barrier (BBB)
*BioAv↓, drawback is the low bioavailability due to poor solubility, low absorption, rapid metabolism, and rapid excretion
*cognitive↑, The researchers detected a significant cognitive improvement at both doses compared to the untreated group, while a significant dose-response effect was found throughout time with higher doses of curcumin producing greater cognitive improvement
*memory↑, supplementation may improve memory and result in a number of biochemical alternations leading to suppressed tau aggregation
*tau↓,
*Synergy↑, Combined curcumin and piperine showed superiority, in a dose dependent manner,

3586-

CUR,

PI,

Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers

in-vivo,

NA,

rats

*BioAv↑, Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. T

3577-

CUR,

Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study

Trial,

AD,

2 grams/day, or 4 grams/day of oral curcumin for 24 weeks.

*cognitive∅, unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound.
*BioAv↑, The levels of native curcumin measured in plasma were low (7.32 ng/mL).

3578-

CUR,

SIL,

Curcumin, but not its degradation products, in combination with silibinin is primarily responsible for the inhibition of colon cancer cell proliferation

in-vitro,

CRC,

DLD1

Synergy↑, combination of curcumin and silymarin exhibited synergistic anticancer activity.
BioAv↓, Despite the low bioavailability of curcumin and the relatively low daily dietary intake (Shen et al. 2016, Teiten et al. 2010, Tsuda 2018), the beneficial effect of curcumin observed could be due to other phytochemicals present in the diet and act sy
TumCG↓, curcumin and silibinin in combination inhibit cell growth significantly

3579-

CUR,

AgNPs,

Metal–Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin

Review,

NA,

*IronCh↑, It is well established that curcumin strongly chelates several metal ions, including boron, cobalt, copper, gallium, gadolinium, gold, lanthanum, manganese, nickel, iron, palladium, platinum, ruthenium, silver, vanadium, and zinc.
*BioAv↑, Metal–curcumin complexes increase the solubility, cellular uptake, and bioavailability and improve the antioxidant, anti-inflammatory, antimicrobial, and antiviral effects of curcumin.
*antiOx↑,
*Inflam↓,
*BioAv↑, complexes of curcumin with transition metals may provide another approach to overcome the issues associated with curcumin.
ROS↑, curcumin–metal complexes with liposomes present enhanced cellular uptake and ROS generation in cancer cells and thus cause increased cytotoxicity
*neuroP↑, Since curcumin has the ability to cross the blood–brain barrier due to its hydrophobic nature, it can strongly chelate the metal ions in the brain and prevent metal-induced neurotoxicity.
*Synergy↑, Curcumin with silver nanoparticle formates also increases the solubility and stability of curcumin in complexes. Curcumin reduces and caps the silver nanoparticles, which increases its stability and solubility in water

3582-

CUR,

PI,

Therapeutic and Preventive Effects of Piperine and its Combination with Curcumin as a Bioenhancer Against Aluminum-Induced Damage in the Astrocyte Cells

*Synergy↑, In conclusion, the results of the study showed that the use of different concentrations of piperine, curcumin, and their combination had significantly higher % cell viability on aluminum-induced damage in astrocyte cells compared to the damaged contr
*IL6↓, decrease in the amount of IL-6 and TGF-β cytokines also supported that piperine increased the effectiveness of curcumin.
*TGF-β↓,
*BioAv↑, bioavailability-enhancing property of piperine on curcumin was shown for the first time in the literature.

3585-

CUR,

Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer

Study,

NA,

*BioAv↑, curcumin entrapped nanoparticles demonstrate at least 9-fold increase in oral bioavailability when compared to curcumin administered with piperine as absorption enhancer.

1487-

CUR,

Relationship and interactions of curcumin with radiation therapy

Review,

Var,

RadioS↑, overall level of evidence for curcumin as a radiosensitizer and radioprotector is low, it must be recognized that risks of adverse effects are exceedingly low, and clinicians may need to judge the yet-unproven rewards with low toxicity risks.
ChemoSen↑,
NF-kB↓, suppressing NF-κB
radioP↑, substantial volume of evidence exists that curcumin is a radiosensitizer of multiple cancers as well as a radioprotector of several normal tissues.
BioAv↓, Further research is greatly needed to strengthen curcumin’s major weakness - poor gastrointestinal absorption leading to low oral bioavailability.
*toxicity↓, curcumin is extremely safe and not harmful to the cancer patient undergoing radio(chemo)therapy.

146-

CUR,

EGCG,

Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in PC3 prostate cancer cells

in-vitro,

Pca,

PC3

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

DU145

P21↑, The protein expressions of p21 were significantly increased by the co-treatment of EGCG and curcumin, whereas it was not changed by the treatment with each individual compound.
TumCCA↑, treatments of EGCG and curcumin arrested both S and G2/M phases of PC3 cells.
TumCP↓, EGCG inhibited PC3 cell proliferation to 11.2 and 24.3% at 50 and 100 μM, respectively.
BioAv↓, While curcumin has versatile anticancer properties, its poor absorption and low bioavailability are the challenges for its developmentas chemopreventive agent (33). The low bioavailability of EGCG is also confirmed i

125-

CUR,

Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway

in-vitro,

adrenal,

H295R

 10 µg/mL

CYP17A1↓,
CYP19↓,
*Nrf1↑, Curcumin has been shown to modulate molecular signaling pathways, such as the aryl hydrocarbon receptor, the induction of Nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of nuclear factor kappa-light-chain-enhancer of activated B
*NF-kB↓,
angioG↓, Curcumin can also inhibit angiogenesis and induce apoptosis on cancerous cells
Apoptosis↑,
AR↓, Curcumin has been shown to downregulate the androgen receptor in prostate cancer cells [11]
toxicity↓, Human trials using up to 8000 mg of curcumin found no evidence of toxicity [52].
BioAv↑, An important formulation has been the use of curcumin with piperine, which has been found to enhance the bioavailability as well as effects of curcumin

6770-

CUR,

A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

Review,

Nor,

*AntiBio↑, Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported.
*Bacteria↓, These results demonstrated promising antibacterial activity for different curcumin derivatives as well.
*AntiViral↑, Antiviral Activity
*BioAv↓, optimum potential of curcumin is limited because of poor oral bioavailability and insufficient solubility in aqueous solvents leading to poor absorption, fast metabolism, and quick systemic elimination
*Half-Life↓,

6417-

RES,

CUR,

Curcumin and Resveratrol Synergy: A Multi-Target Strategy Against Neurodegenerative Disease Pathology

Review,

AD,

*neuroP↑, synergistic approach with curcumin and resveratrol represents a promising strategy for developing novel neuroprotective agents for a range of neurological disorders.
*NRF2↝, compounds operate through multiple molecular pathways, including the modulation of the Nrf2/ARE signalling pathway, inhibition of NF-κB, and regulation of key proteins involved in amyloid-beta plaque formation and tau phosphorylation.
*ARE↝,
*NF-kB↓,
*Aβ↓,
*ROS↓, combined use has demonstrated enhanced efficacy in mitigating oxidative stress and neuroinflammation in various preclinical models.
*Inflam↓,
*BioAv↓, major challenges, such as poor bioavailability, and discusses advanced delivery strategies like nanomedicine to enhance their efficacy

4904-

Sal,

CUR,

Co-delivery of Salinomycin and Curcumin for Cancer Stem Cell Treatment by Inhibition of Cell Proliferation, Cell Cycle Arrest, and Epithelial–Mesenchymal Transition

in-vitro,

Var,

CSCs↓, We determined CD44-targeting co-delivery nanoparticles are highly efficacious against BCSCs by inducing G1 cell cycle arrest and limiting epithelial–mesenchymal transition.
TumCCA↑,
EMT↓,
other↝, anti-cancer mechanism of salinomycin is associated with dysregulation of metal ions
TumAuto↑, activation of autophagy-mediated cell death, and inhibition of stem cell maintenance
Iron↑, recent study found that salinomycin and its derivative, ironomycin, exhibited a potent and selective activity against breast cancer stem cells (BCSCs) by accumulating and sequestering iron to induce ferroptosis,
Ferroptosis↑,
BioAv↓, challenging to efficiently deliver salinomycin (Sal) to tumor sites due to its hydrophobicity, unfavorable pharmacokinetic profile, and cytotoxicity during systemic drug administration
ROS↑, Our previous studies showed that conjugation of salinomycin with gold nanoparticles can efficiently induce ferroptotic cell death of BCSCs by increasing the generation of ROS, mitochondrial dysfunction, and lipid oxidation with higher iron accumulati
lipid-P↑,
GPx4↓, and GPX-4 inactivation
Synergy↑, Salinomycin and curcumin were loaded onto poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles via double emulsion method to form nanoparticles . salinomycin and curcumin showed improved therapeutic efficiency against BCSCs

6220-

Se,

CUR,

Rad,

Selenium-Curcumin-PEG Nanoparticles Radiosensitization for Intensity-Modulated Radiation Therapy of Lung Tumor Cells: In Vitro Synergistic Combination Therapy

in-vitro,

Lung,

A549

RadioS↑, The combination of Se-Cur-PEG NPs (50 µg mL-1) with IMRT (4 Gy) resulted in a significant enhancement in cell death compared to either treatment alone, indicating a strong synergistic effect (CI=1.21) and a notable sensitizer enhancement ratio (SER=
TumCD↑,
ROS↑, Intracellular ROS generation analysis confirmed that Se-Cur-PEG NPs amplified IMRT-induced oxidative stress, contributing to increased cancer cell toxicity.
Imm↑, Selenium, a trace element with powerful antioxidant and anticancer properties, enhances oxidative stress in tumor cells, sensitizing them to radiation while modulating immune responses and inhibiting angiogenesis
angioG↓,
BioAv↑, Polyethylene glycol improves the biocompatibility and stability of nanoparticles, prolonging circulation time and enabling efficient tumor targeting by minimizing immune clearance
TumCP↓, Curcumin, a bioactive polyphenol, provides a broad spectrum of anticancer effects, including the inhibition of cell proliferation, induction of apoptosis, and suppression of metastasis.
Apoptosis↓,
TumMeta↓,
CompStab↑, Polyethylene glycol improves the biocompatibility and stability of nanoparticles, prolonging circulation time and enabling efficient tumor targeting by minimizing immune clearance

4752-

SeNPs,

CUR,

Chemo,

Curcumin-Modified Selenium Nanoparticles Improve S180 Tumour Therapy in Mice by Regulating the Gut Microbiota and Chemotherapy

in-vitro,

Cerv,

HeLa

 6.86 nm

in-vitro,

sarcoma,

S180

8.4 μg/mL

tumCV↓, Cur/Se nanoparticles showed higher cytotoxicity against HeLa and S180 tumour cells.
ROS↑, Cur/Se nanoparticles significantly delivered more curcumin into the HeLa tumour cells and induced greater ROS production.
*GutMicro↑, Cur and Cur/Se nanoparticles significantly reduced the relative abundances of Rikenellaceae_RC9_gut_group, Enterorhabdus and Bilophila and increased the relative abundance of Lachnospiraceae_UCG-006.
BioAv↑, Cur/Se nanoparticles could increase the bioactivity of curcumin and improve cancer therapy by regulating the gut microbiota.
other↝, The Cur/Se nanoparticles were prepared by reducing sodium selenite with curcumin in one step
Dose↝, The IC50 values of Cur and Cur/Se nanoparticles were 33.0 μg/mL and 8.4 μg/mL, respectively, against S180

139-

Tomatine,

CUR,

Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells

in-vitro,

Pca,

PC3

NF-kB↓, synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells.
Bcl-2↓,
p‑Akt↓, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination
p‑ERK↓, ERK1/2
TumCG↓, α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer.
Apoptosis↑, α-Tomatine and curcumin induce apoptosis in PC-3 cells
PCNA↓, Combined treatment with α-tomatine and curcumin had a more potent effect on decreasing the number of PCNA positive cells than either agent used alone
BioAv↓, However, the bioavailability of curcumin is low

6460-

TUR,

CUR,

Neuroprotective Effect of Turmeric Extract in Combination with Its Essential Oil and Enhanced Brain Bioavailability in an Animal Model

in-vivo,

AD,

*memory↑, Aluminum impairs spatial learning and memory, which was significantly reversed with TE+EO by 28.6% (25 mg/kg) and 39.4% (50 mg/kg).
*lipid-P↓, A significant reduction in aluminum-induced lipid peroxidation was observed
*GSH↑, Also, the levels of glutathione, acetylcholinesterase, and catalase were improved with TE+EO.
*AChE↑, Our study results show that the levels of AChE decreased in response to Al, and TE+EO elevated it to the normal levels.
*Catalase↑,
*BioAv↑, The enhancement of brain and plasma bioavailability even at low dose (HED 142 mg in 70 kg adult) was due to the presence of turmerones in TE+EO, which acts as inhibitors of the p-glycoprotein pathway, the significant bottleneck in curcumin absorpti
*P-gp/ABCB1↓,
*BioAv↑, curcumin alone vs. curcuminoids with turmerones, which showed a sixfold increase in the bioavailability with the latter
*SOD↑, increase in the levels of GSH, CAT, SOD, and total proteins.
*BBB↑, The observed effect of TE+EO could be linked with its ability to cross the blood-brain barrier, bind to redox metal ions, and neutralize free radicals.
*ROS↓,

Showing Research Papers: 1 to 49 of 49

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 49

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1, antiOx↑, 10, ARE↝, 1, Catalase↑, 2, GSH↑, 3, GSTs↑, 1, HO-1↑, 5, HO-2↓, 1, lipid-P↓, 5, MDA↓, 5, Nrf1↑, 1, NRF2↑, 3, NRF2↝, 1, RNS↓, 1, ROS↓, 13, SOD↑, 4, mt-SOD↑, 1, TAC↑, 1,

Metal & Cofactor Biology(tgid=2) ⓘ

Ferritin↑, 1, IronCh↑, 3,

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1, cytoP450↓, 1, glucose↓, 1, GlucoseCon↑, 1, GSK‐3β↓, 1, LDL↓, 1,

Cell Death(tgid=5) ⓘ

Bcl-2↑, 1, iNOS↓, 3,

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↑, 1, PI3K↑, 1,

Transcription & Epigenetics(tgid=7) ⓘ

HATs↓, 1, HDAC↑, 1, other↓, 1,

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

neuroG↑, 1,

Migration(tgid=13) ⓘ

AP-1↓, 2, TGF-β↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↑, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↓, 1, BBB↑, 5, GLUT2↑, 1, GLUT3↑, 1, GLUT4↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 3, IL1↓, 2, IL12↓, 1, IL1β↓, 2, IL2↓, 1, IL6↓, 4, IL8↓, 1, Inflam↓, 11, Inflam↑, 1, NF-kB↓, 5, TNF-α↓, 4,

Synaptic & Neurotransmission(tgid=18) ⓘ

Ach↑, 1, AChE↓, 2, AChE↑, 1, ChAT↑, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 5, tau↓, 3,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 17, BioAv↑, 20, BioAv↝, 3, CompStab↑, 1, Dose↝, 2, Half-Life↓, 3, Half-Life↝, 1, P-gp/ABCB1↓, 1, Synergy↑, 5,

Clinical Biomarkers(tgid=22) ⓘ

BMD↑, 1, CRP↓, 1, Ferritin↑, 1, IL6↓, 4,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1, AntiTum↓, 1, cognitive↑, 6, cognitive↝, 1, cognitive∅, 1, memory↑, 6, neuroP↑, 5, Obesity↓, 1, radioP↑, 2, toxicity↓, 2, toxicity∅, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiBio↑, 1, AntiViral↑, 1, Bacteria↓, 1, GutMicro↑, 2,
Total Targets: 87

Scientific Paper Hit Count for: BioAv, bioavailability

49 Curcumin
2 Piperine
1 Capsaicin
1 urea
1 Silymarin (Milk Thistle) silibinin
1 Silver-NanoParticles
1 EGCG (Epigallocatechin Gallate)
1 Resveratrol
1 salinomycin
1 Selenium
1 Radiotherapy/Radiation
1 Selenium NanoParticles
1 Chemotherapy
1 Tomatine
1 Turmerones

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#:65  Target#:792  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Curcumin / BioAv Cancer Research Results

Curcumin Cancer Mechanism Ranking

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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