| Features: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Anthocyanins — Anthocyanins (ACNs) are a structurally diverse class of water-soluble flavonoid pigments (glycosylated anthocyanidins) abundant in berries, purple/red grapes, cherries, red cabbage, and other deeply colored plants. They function as pleiotropic redox- and inflammation-modulating polyphenols with context-dependent signaling effects that can shift from antioxidant/anti-inflammatory tone at nutritionally relevant exposures to stress-signaling/pro-apoptotic effects in tumor models at higher concentrations. Classification: dietary polyphenols (flavonoids; anthocyanidin O-glycosides). Standard abbreviations: ACNs; often specified as C3G (cyanidin-3-O-glucoside) or as “total anthocyanins.” A key translation nuance is that circulating parent ACNs are typically low and transient, while phase-II conjugates and gut microbiota–derived phenolic acids (e.g., protocatechuic acid from cyanidin glycosides) plausibly mediate a meaningful fraction of systemic biology. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral bioavailability of intact parent anthocyanins is generally modest with rapid appearance and clearance; extensive phase-II metabolism (glucuronidation/sulfation/methylation) and prominent gut microbiota catabolism generate phenolic acid metabolites that may dominate systemic exposure. Local gastrointestinal exposures can be substantially higher than plasma levels, making “GI-local” mechanisms more plausible than “systemic parent-compound” mechanisms for many endpoints. In-vitro vs systemic exposure relevance: Many anticancer in-vitro studies use ~10–100+ µM parent anthocyanins/extract equivalents, which often exceed achievable circulating parent anthocyanin concentrations after dietary intake; therefore, mechanistic claims that require high micromolar parent exposure should be treated as (high concentration only) unless supported by metabolite biology or GI-local relevance. Clinical evidence status: Human evidence is strongest for cardiometabolic and inflammation-related biomarkers (multiple RCTs/meta-analyses). For cancer, evidence is predominantly preclinical and epidemiologic/biomarker-level in humans; there is no established oncology indication or regulatory approval as an anticancer drug. For cognition/brain aging, small RCTs with anthocyanin-rich foods/supplements show signal in select domains, but overall evidence remains exploratory. "Anthocyanins are a class of water‐soluble flavonoids, which show a range of pharmacological effects, such as prevention of cardiovascular disease, obesity control and antitumour activity. Their potential antitumour effects are reported to be based on a wide variety of biological activities including antioxidant; anti‐inflammation; anti‐mutagenesis; induction of differentiation; inhibiting proliferation by modulating signal transduction pathways, inducing cell cycle arrest and stimulating apoptosis or autophagy of cancer cells; anti‐invasion; anti‐metastasis; reversing drug resistance of cancer cells and increasing their sensitivity to chemotherapy."Anthocyanins are flavonoid pigments with multi-target pleiotropic effects in cancer models, primarily through modulation of ROS balance, NF-κB signaling, PI3K/Akt/mTOR inhibition, apoptosis induction, and anti-angiogenic activity. Their effects are often context-dependent and dose-dependent: low physiologic exposures tend to support antioxidant and anti-inflammatory tone, whereas higher concentrations in vitro can induce oxidative stress and apoptosis in tumor cells. They also influence tumor microenvironment dynamics including VEGF signaling, MMP activity, and inflammatory cytokines. Bioavailability is modest, and metabolites (phenolic acids) likely contribute significantly to biological effects. Evidence in humans remains supportive but not definitive. • Anthocyanins are a class of water-soluble flavonoid pigments responsible for the red, purple, and blue hues in many fruits, vegetables, and flowers (e.g., berries, red grapes, and eggplants). • Anthocyanins can effectively scavenge free radicals and reduce oxidative stress, thereby protecting cellular components like DNA, lipids, and proteins from oxidative damage—a factor linked to carcinogenesis. • Their antioxidant capacity helps in neutralizing reactive oxygen species (ROS), which can otherwise promote mutations and tumor initiation. • Anthocyanins have been shown to inhibit pro-inflammatory cytokines (e.g., TNF-α, IL-6) and enzymes (e.g., COX-2), reducing the inflammatory signals associated with cancer progression. • They may modulate pathways such as NF-κB, MAPK, and PI3K/Akt, contributing to the downregulation of genes involved in survival and proliferation of cancer cells. • Anthocyanins have been found to inhibit the formation of new blood vessels (angiogenesis) essential for tumor growth and metastatic spread. Anthocyanins: ranked cancer-relevant pathway effects
TSF legend: P: 0–30 min; R: 30 min–3 hr; G: >3 hr Anthocyanins and Alzheimer’s disease — Anthocyanin-rich foods/supplements have small-human-trial signals suggesting modest improvements in selected cognitive domains and/or brain function proxies in at-risk or impaired cohorts, plausibly mediated through vascular/inflammatory tone, oxidative stress buffering, and microbiome–metabolite signaling (rather than sustained high circulating parent anthocyanins). Overall, evidence remains exploratory and heterogeneous across preparations, doses, and endpoints. Clinical evidence status: Small RCTs/pilot trials (food-based and some purified preparations) with mixed but promising signals; not an established disease-modifying therapy. Anthocyanins: non-cancer mechanisms relevant to Alzheimer’s disease
|
| 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. -mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related) "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 Mevalonate 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 Combined effect research -Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2) Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference -generated from AI and Cancer database ROS rating: +++ strong | ++ moderate | + weak | ± mixed | 0 none NRF2: ↓ suppressed | ↑ activated | ± mixed | 0 none Conditions: [D] dose [Fe] metal [M] metabolic [O₂] oxygen [L] light [F] formulation [T] tumor-type [C] combination
|
| 3864- | ACNs, | Anthocyanins Potentially Contribute to Defense against Alzheimer’s Disease |
| - | Review, | AD, | NA |
| 3969- | ACNs, | Blueberry Supplementation in Midlife for Dementia Risk Reduction |
| - | Human, | AD, | NA |
| - | in-vivo, | AD, | NA |
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#:31 Target#:275 State#:% Dir#:1
wNotes=0 sortOrder:rid,rpid