condition found tbRes List
ALA, Alpha-Lipoic-Acid: Click to Expand ⟱
Features: antioxidant, energy production in cell mitochondria
Alpha-Lipoic-Acid: also known as lipoic acid or thioctic acid (reduced form is dihydrolipoic acid).
"Universal antioxidant" because it is both water- and fat-soluble and can neutralize free radicals.
-Treatment sometimes as ALA/N (alpha-lipoic acid/low-dose naltresone)
-Also done in IV
-Decreases ROS production, but also has pro-oxidant role.
Normal adult can take 300 milligrams twice a day with food, but they should always take a B-complex vitamin with it. Because B complex vitamins, especially thiamine, and biotin, and riboflavin, are depleted during this metabolic process.
α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
-It seems a paradox that LA functions as both antioxidant and prooxidant. LA functions the pro-oxidant only in special cancer cells, such as A549 and PC9 cells which should show high-level NRF2 expression and high glycolytic level. Through inhibiting PDK1 to further prohibit NRF2; LA functions as anticancer prooxidant.

α-lipoic acid possesses excellent silver chelating properties.

- ALA acts as pro-Oxidant only in cancer cells:#278 - Pro-Oxidant Dose margin >100uM:#304

- Bioavailability: 80-90%, but conversion to EPA/DHA is 5-10% (and takes longer time).
- AI (Adequate Intake): 1.1-1.6g/day.
- human studies have shown that ALA levels decline significantly with age
- 1g of ALA might achieve 500uM in the blood.
- ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
- Pilot studies or observational interventions have used flaxseed supplementation (rich in ALA) in doses providing roughly 3–4 g of ALA daily.
- Flaxseed oil is even more concentrated in ALA – typical 50–60% ALA by weight.
- single walnut may contain 300mg of ALA
- chia oil contains 55-65% ALA.
- α-LA can also be obtained from the diet through the consumption of dark green leafy vegetables and meats
- ALA is more stable in chia seeds, (2grams of ALA per tablespoon)
- ALA degrades when exposed to heat, light, and air. (prone to oxidation)

-Note half-life 1-2 hrs.
BioAv 30-40% from walnuts, 60-80% from supplements. Co-ingestion with fat improves absorption. Both fat and water soluble
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- small indication of inhibiting Cancer Stem Cells : CSC↓, CD24↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


GlucoseCon, Glucose Consumption: Click to Expand ⟱
Source:
Type:
Glucose consumption is often elevated in cancer cells due to an increased reliance on glycolysis for energy production, even in the presence of oxygen. This phenomenon, known as the Warburg effect, is a metabolic shift that allows cancer cells to rapidly proliferate and survive in nutrient-poor environments.

The increased glucose consumption in cancer cells can be detected using positron emission tomography (PET) scans, which measure the uptake of a glucose analog labeled with a radioactive tracer.
Scientific Papers found: Click to Expand⟱
3437- ALA,    Revisiting the molecular mechanisms of Alpha Lipoic Acid (ALA) actions on metabolism
- Review, Var, NA
*IronCh↑, ALA functions as a metabolic regulator, metal chelator, and a powerful antioxidant.
*antiOx↑,
*ROS↓, It quenches reactive oxygen species (ROS), restores exogenous and endogenous antioxidants such as vitamins and Glutathione (GSH), and repairs oxidized proteins
*GSH↑,
*NF-kB↓, inhibition of the activation of nuclear factor kappa B (NF-κB)
*AMPK⇅, activation of peripheral AMPK and inhibition of hypothalamic AMPK
*FAO↑, ALA has been found to activate peripheral AMPK, thereby enhancing fatty acid oxidation and glucose uptake in muscle cells
*GlucoseCon↑,
*PI3K↑, It stimulates glucose uptake by increasing the activity of PI3K and Akt which are crucial for the translocation of glucose transporters like GLUT4 to the cell membrane, mimicking the action of insulin
*Akt?,

3447- ALA,    Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells
- in-vitro, AD, SH-SY5Y
*ATP↑, Incubation with ALA showed a significant increase in ATP levels in both SH-SY5Y-APP695 and SH-SY5Y-MOCK cells.
*MMP↑, MMP levels were elevated in SH-SY5Y-MOCK cells, treatment with rotenone showed a reduction in MMP, which could be partly alleviated after incubation with ALA in SH-SY5Y-MOCK cells.
*ROS↓, ROS levels were significantly lower in both cell lines treated with ALA.
*GlucoseCon↑, benefits to diabetic neuropathy and impaired glucose uptake, and the regeneration of glutathione (GSH) and vitamins C and E
*GSH↑,
*neuroP↑, ALA seems to have a positive effect on neurodegenerative diseases such as AD
*cognitive↑, ALA improves cognitive performance and could be considered as a promising bioactive substance for AD by affecting multiple mechanisms such as:
*Ach↑, (1) impaired acetylcholine production;
*Inflam↓, (2) hydroxyl radical formation, ROS production, and neuroinflammation;
*Aβ↓, (3) impaired amyloid plaque formation;
OXPHOS↓, ALA has also been shown to restore the expression of OXPHOS complexes in HepG2 cells, ranging in a concentration between 0.5–2 mM

3441- ALA,    α-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice
- in-vivo, AD, NA
*tau↓, α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research
*GlucoseCon↑, chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brain
*GLUT3↑,
*GLUT4↑,
*VEGF↑,
*HO-1↑,
*Glycolysis↑, LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1).
*HK1↑, Our results indicated that the activity of HK was significantly increased after 10 mg/kg LA treatment.
*PGC-1α↑,
*Hif1a↑, found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment.
*neuroP↑,

3439- ALA,    The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles
- in-vitro, NA, NA
*ROS↓, At 96 h after culture, a decrease in ROS and an increase in TAC were observed in ALA group compared to control group (p < 0.05).
*TAC↑,
*eff↑, ALA (100 uM) improves the in vitro development of follicles. This effect may be mediated by decreasing ROS concentration and increasing follicular TAC level during the culture period.‎‎‎
*SOD↑, ALA administration significantly elevated plasma total antioxidant status and could increase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in the brain tissues of male rat exposed to restraint stress
*GPx↑,
*Catalase↑,
*GlucoseCon↑, ALA enhances glucose uptake by cells,
*antiOx↑, Taken together, our study indicates that ALA has an excellent antioxidant activity,

3438- ALA,    The Potent Antioxidant Alpha Lipoic Acid
- Review, NA, NA - Review, AD, NA
*antiOx↑, Both of alpha lipoic acid and its reduced form have been shown to possess anti-oxidant, cardiovascular, cognitive, anti-ageing, detoxifying, anti-inflammatory, anti-cancer, and neuroprotective pharmacological properties
*cardioP↑,
*cognitive↑, Alpha lipoic acid has the ability to decrease cognitive impairment and may be a successful therapy for Alzheimer’s disease and any disease related dementias
*AntiAge↑,
*Inflam↓,
*AntiCan↑,
*neuroP↑, ALA has neuroprotective effects in experimental brain injury caused by trauma and subarachnoid hemorrhage
*IronCh↑, Also, the ability of ALA to chelate metals can produce an antioxidant effect
*ROS↑, DHLA can exert a pro-oxidant effect of donating its electrons for the reduction of iron, which can then break down peroxide to the prooxidant hydroxyl radical via the Fenton reaction [10]. So, ALA and its reduced form DHLA, can promote antioxidant pr
*Weight↓, α-lipoic acid supplementation at a dose of 300 mg/day might help to could help to promote weight loss and fat mass reduction in healthy overweight/obese women following an energy-restricted balanced diet
*Ach↑, Alpha lipoic acid increases the production of Acetylcholine (Ach) via activating choline acetyl transferase and increases glucose uptake, hence, supplying more acetyl-CoA for the production of Ach of each
*ROS↓, also scavenges reactive oxygen species, thereby increasing the concentration levels of reduced Glutathione (GSH).
*GSH↑,
*lipid-P↓, Alpha lipoic acid can scavenge lipid peroxidation products as hydroxynonenal and acrolein.
*memory↑, learning and memory in the passive avoidance test partially through its antioxidant activity.
*NRF2↑, α-LA treatment has been shown to increase Nrf2 nuclear localization
*ChAT↑, Alpha lipoic acid increases the production of Acetylcholine (Ach) via activating choline acetyl transferase and increases glucose uptake, hence, supplying more acetyl-CoA for the production of Ach of each
*GlucoseCon↑,
*Acetyl-CoA↑,

3436- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights Author links open overlay panel
- in-vitro, BC, MCF-7
ChemoSen↑, LA also enhanced the sensitivity of breast cancer spheroids to doxorubicin (Dox), demonstrating a synergistic effect.
PI3K↓, LA inhibits PI3K/AKT signaling in breast cancer spheroids
Akt↓,
ATP↓, found that LA markedly reduced both ATP levels and glucose uptake
GlucoseCon↓,
ROS↑, LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
Glycolysis↓,
CSCs↓,
IGF-1R↓, LA inhibits IGF-1R via furin downregulation, synergizes with other anticancer drugs like paclitaxel and cisplatin, and enhances radiosensitivity in breast cancer
Furin↓,
RadioS↑,

3434- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
tumCV↓, significant dose-dependent reduction in cell viability, with the half-maximal inhibitory concentration (IC50) of LA to be 3.2 mM for MCF-7 cells and 2.9 mM for MDA-MB-231 cells
PI3K↓, LA significantly inhibited PI3K, p-AKT, p-p70S6K and p-mTOR levels
p‑Akt↓,
p‑P70S6K↓,
mTOR↓,
ATP↓, LA markedly reduced both ATP levels and glucose uptake (Fig. 4A and 4B). LA also induced ROS generation in both MCF-7 and MDA-MB231 spheroids
GlucoseCon↓,
ROS↑,
PKM2↓, LA downregulated the expression of PKM2 and LDHA in the spheroids, indicating an inhibition of glycolysis in BCSCs
LDHA↓,
Glycolysis↓,
ChemoSen↑, LA enhances chemosensitivity of spheroids to Dox treatment

3271- ALA,    Decrypting the potential role of α-lipoic acid in Alzheimer's disease
- Review, AD, NA
*antiOx↑, Alpha-lipoic acid (α-LA), a natural antioxidant
*memory↑, multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects
*neuroP↑, α-LA could be considered neuroprotective
*Inflam↓, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies.
*IronCh↑, α-LA leads to a marked downregulation in iron absorption and active iron reserve inside the neuron
*NRF2↑, α-LA induces the activity of the nuclear factor erythroid-2-related factor (Nrf2), a transcription factor.
*BBB↑, capable of penetrating the BBB
*GlucoseCon↑, Fig 2, α-LA mediated regulation of glucose uptake
*Ach↑, α-LA may show its action on the activity of the ChAT enzyme, which is an essential enzyme in acetylcholine metabolism
*ROS↓,
*p‑tau↓, decreased degree of tau phosphorylation following treatment with α-LA
*Aβ↓, α-LA possibly induce the solubilization of Aß plaques in the frontal cortex
*cognitive↑, cognitive reservation of α-LA served AD model was markedly upgraded in additional review
*Hif1a↑, α-LA treatment efficaciously induces the translocation and activity of hypoxia-inducible factor-1α (HIF-1α),
*Ca+2↓, research found that α-LA therapy remarkably declines Ca2+ concentration and calpain signaling
*GLUT3↑, inducing the downstream target genes expression, such as GLUT3, GLUT4, HO-1, and VEGF.
*GLUT4↑,
*HO-1↑,
*VEGF↑,
*PDKs↓, α-LA also ameliorates survival in mutant mice of Huntington's disease [150–151], possibly due to the inhibition of the activity of pyruvate dehydrogenase kinase
*PDH↑, α-LA administration enhances PDH expression in mitochondrial hepatocytes by inhibiting the pyruvate dehydrogenase kinase (PDK),
*VCAM-1↓, α-LA inhibits the expression of cell-cell adhesion molecule-1 and VCAM-1 in spinal cords and TNF-α induced neuronal endothelial cells injury
*GSH↑, α-LA may enhance glutathione production in old-aged models
*NRF2↑, activation of the Nrf2 signaling by α-LA
*hepatoP↑, α-LA also protected the liver against oxidative stress-mediated hepatotoxicity
*ChAT↑, α-LA in mice models may prevent neuronal injury possibly due to an increase in ChAT in the hippocampus of animal models

3269- ALA,    Sulfur-containing therapeutics in the treatment of Alzheimer’s disease
- NA, AD, NA
*AChE↓, ALA activated AChE and increased glucose uptake, thus providing more acetyl-CoA to generate acetylcholine (ACh). (note activated AChE in this review likely should say inhibited!!!)
*GlucoseCon↑,
*ACC↑,
*GSH↑, ALA increased intracellular GSH levels by chelating redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and Aβ aggregation.
*Aβ↓,
*Catalase↑, Levels of several antioxidant enzymes including catalase, GR, glutathione-S-transferase (GST), NADPH, and quinone oxidoreductase-1 (NQO1) were enhanced by ALA
*GSR↑,
*GSTs↑,
*NADPH↑,
*NQO1↑,
*iNOS↓, LA prevented the induction of iNOS, inhibited TNFα-induced activation of NF-κB [42], levels of which are increased in AD.
*NF-kB↓,
*lipid-P↓, ALA reduced the levels of lipid peroxidation products
*BBB↑, ALA could easily cross the blood–brain barrier (BBB)
*memory↑, ALA treatment significantly improved the spatial memory and cognition capacity of the mice in the Morris water maze and novel object recognition test.
*cognitive↑,
*antiOx↑, antioxidant and anti-inflammatory activities of ALA
*Inflam↓,

3547- ALA,    Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration
- Review, AD, NA - Review, Park, NA
*memory↑, a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect
*neuroP↑,
*motorD↑, Improved motor dysfunction
*VitC↑, elevates the activities of antioxidants such as ascorbate (vitamin C), α-tocoferol (vitamin E) (Arivazhagan and Panneerselvam, 2000), glutathione (GSH)
*VitE↑,
*GSH↑,
*SOD↑, superoxide dismutase (SOD) activity (Arivazhagan et al., 2002; Cui et al., 2006; Militao et al., 2010), catalase (CAT) (Arivazhagan et al., 2002; Militao et al., 2010), glutathione peroxidase (GSH-Px)
*Catalase↑,
*GPx↑,
*5HT↑, ↑levels of neurotransmitters (dopamine, serotonin and norepinephrine) in various brain regions
*lipid-P↓, ↓ level of lipid peroxidation,
*IronCh↑, ↓cerebral iron levels,
*AChE↓, ↓ AChE activity, ↓ inflammation
*Inflam↓,
*GlucoseCon↑, ↑brain glucose uptake; ↑ in the total GLUT3 and GLUT4 in the old mice;
*GLUT3↑,
*GLUT4↑,
NF-kB↓, authors showed that LA inhibited the stimulation of nuclear factor-κB (NF-κB)
*IGF-1↑, LA restored the parameters of total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Mahboob et al. (2016), analyzed the effects of LA in AlCl3- model of neurodegeneration,
*IL1β↑,
*TNF-α↑,
*cognitive↑, demonstrating its capacity in ameliorating cognitive functions and enhancing cholinergic system functions
*ChAT↑, LA treatment increased the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) relative to AlCl3-treated group.
*HO-1↑, R-LA and S-LA also enhanced expression of genes related to anti-oxidative response such as heme oxygenase-1 (HO-1) and phase II detoxification enzymes such as NAD(P)H:Quinone Oxidoreductase 1 (NQO1).
*NQO1↑,

3543- ALA,    The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease
- Study, AD, NA
*cognitive↑, Our study suggests that ALA therapy could be effective in slowing cognitive decline in patients with AD and IR.
*antiOx↑, Alpha-lipoic acid (ALA) is a naturally occurring disulfide molecule with antioxidant and anti-inflammatory properties.
*Inflam↓,
*neuroP↑, ALA plays many different roles in pathogenic pathways of dementia, acting as a neuroprotective agent.
*Ach↑, It increases acetylcholine production, inhibits hydroxyl radical production, and increases the process of getting rid of reactive oxygen species.
*ROS↓,
*GlucoseCon↑, (ii) increased glucose uptake, supplying more acetyl-CoA for the production of Ach;
*lipid-P↓, (v) scavenging lipid peroxidation products;
*GSH↑, (vi) inducing enzymes of glutathione synthesis
*Acetyl-CoA↑,

3539- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*ROS↓, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age.
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑,
*antiOx↑, LA has long been touted as an antioxidant
*NRF2↑, activate Phase II detoxification via the transcription factor Nrf2
*MMP9↓, lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*VCAM-1↓,
*NF-kB↓,
*cognitive↑, it has been used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits, and has been implicated as a modulator of various inflammatory signaling pathways
*Inflam↓,
*BioAv↝, LA bioavailability may be dependent on multiple carrier proteins.
*BioAv↝, observed that approximately 20-40% was absorbed [
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies
*H2O2∅, Neither species is active against hydrogen peroxide
*neuroP↑, chelation of iron and copper in the brain had a positive effect in the pathobiology of Alzheimer’s Disease by lowering free radical damage
*PKCδ↑, In addition to PKCδ, LA activates Erk1/2 [92, 93], p38 MAPK [94], PI3 kinase [94], and Akt [94-97].
*ERK↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, In skeletal muscle, LA is proposed to recruit GLUT4 from its storage site in the Golgi to the sarcolemma, so that glucose uptake is stimulated by the local increase in transporter abundance.
*GlucoseCon↑,
*BP↝, Feeding LA to hypertensive rats normalized systolic blood pressure and cytosolic free Ca2+
*eff↑, Clinically, LA administration (in combination with acetyl-L-carnitine) showed some promise as an antihypertensive therapy by decreasing systolic pressure in high blood pressure patients and subjects with the metabolic syndrome
*ICAM-1↓, decreased demyelination and spinal cord expression of adhesion molecules (ICAM-1 and VCAM-1)
*VCAM-1↓,
*Dose↝, Considering the transient cellular accumulation of LA following an oral dose, which does not exceed low micromolar levels, it is entirely possible that some of the cellular effects of LA when given at supraphysiological concentrations may be not be c

3454- ALA,    Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
TumCG↑, Lipoic acid inhibits breast cancer cell growth via accumulation of autophagosomes.
Glycolysis↓, Lipoic acid inhibits glycolysis in breast cancer cells.
ROS↑, Lipoic acid induces ROS production in breast cancer cells/BCSC.
CSCs↓, Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs
selectivity↑, In contrast, LA at similar doses. had no significant effect on the cell viability of the human embryonic kidney cell line (HEK-293)
LC3B-II↑, LA treatment (0.5 mM and 1.0 mM) increased the expression level of LC3B-I to LC3B-II in both MCF-7 and MDA-MB231cells at 48 h
MMP↓, LA induced mitochondrial ROS levels, decreased mitochondria complex I activity, and MMP in both MCF-7 and MDA-MB231 cells
mitResp↓, In MCF-7 cells, we found a substantial reduction in maximal respiration and ATP production at 0.5 mM and 1 mM of LA treatment after 48 h
ATP↓,
OCR↓, LA at 2.5 mM decreased OCR
NAD↓, we found that LA (0.5 mM and 1 mM) significantly reduced ATP production and NAD levels in MCF-7 and MDA-MB231 cells
p‑AMPK↑, LA treatment (0.5 mM and 1.0 mM) increased p-AMPK levels;
GlucoseCon↓, LA (0.5 mM and 1 mM) significantly decreased glucose uptake and lactate production in MCF-7, whereas LA at 1 mM significantly reduced glucose uptake and lactate production in MDA-MB231 cells but it had no effect at 0.5 mM
lactateProd↓,
HK2↓, LA reduced hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) expression in MCF-7 and MDA-MB231 cells
PFK↓,
LDHA↓,
eff↓, Moreover, we found that LA-mediated inhibition of cellular bioenergetics including OCR (maximal respiration and ATP production) and glycolysis were restored by NAC treatment (Fig. 6E and F) which indicates that LA-induced ROS production is responsibl
mTOR↓, LA inhibits mTOR signaling and thereby decreased the p-TFEB levels in breast cancer cells
ECAR↓, LA also inhibits glycolysis as evidenced by decreased glucose uptake, lactate production, and ECAR.
ALDH↓, LA decreased ALDH1 activity, CD44+/CD24-subpopulation, and increased accumulation of autophagosomes possibly due to inhibition of autophagic flux of breast cancer.
CD44↓,
CD24↓,

297- ALA,    Insights on the Use of α-Lipoic Acid for Therapeutic Purposes
- Review, BC, SkBr3 - Review, neuroblastoma, SK-N-SH - Review, AD, NA
PDH↑, ALA is capable of activating pyruvate dehydrogenase in tumor cells.
TumCG↓, ALA also significantly inhibited tumor growth in mouse xenograft model using BCPAP and FTC-133 cells
ROS↑, ALA is able to generate ROS, which promote ALA-dependent cell death in lung cancer [75], breast cancer [76] and colon cancer
AMPK↑,
EGR4↓,
Half-Life↓, Data suggests that ALA has a short half-life and bioavailability (about 30%)
BioAv↝,
*GSH↑, Moreover, it is able to increase the glutathione levels inside the cells, that chelate and excrete a wide variety of toxins, especially toxic metals from the body
*IronCh↑, The existence of thiol groups in ALA is responsible for its metal chelating abilities [14,35].
*ROS↓, ALA exerts a direct impact in oxidative stress reduction
*antiOx↑, ALA is being referred as the universal antioxidant
*neuroP↑, ALA has neuroprotective effects on Aβ-mediated cytotoxicity
*Ach↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*lipid-P↓, ALA has multiple and complex effects in this way, namely scavenging ROS, transition metal ions, increasing the levels of reduced glutathione [59,63], scavenging of lipid peroxidation products
*IL1β↓, ALA downregulated the levels of the inflammatory cytokines IL-1B and IL-6 in SK-N-BE human neuroblastoma cells
*IL6↓,
TumCP↓, ALA inhibited cell proliferation, [18F]-FDG uptake and lactate formation and increased apoptosis in neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and in the breast cancer cell line SkBr3.
FDG↓,
Apoptosis↑,
AMPK↑, ALA suppressed thyroid cancer cell proliferation and growth through activation of AMPK and subsequent down-regulation of mTOR-S6 signaling pathway in BCPAP, HTH-83, CAL-62 and FTC-133 cells lines.
mTOR↓,
EGFR↓, ALA inhibited cell proliferation through Grb2-mediated EGFR down-regulation
TumCI↓, ALA inhibited metastatic breast cancer cells migration and invasion, partly through ERK1/2 and AKT signaling
TumCMig↓,
*memory↑, Alzheimer’s Disease: ALA led to a marked improvement in learning and memory retention
*BioAv↑, Since ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
*BioAv↝, ALA were found to be considerably higher in adults with mean age greater than 75 years as compared to young adults between the ages of 18 and 45 years.
*other↓, ALA treatment has been recently studied by some clinical trials to explain its efficacy in preventing miscarriage
*other↝, 1800 mg of ALA or placebo were administrated orally every day, except during the period 2 days before to 4 days after administration of each dose of platinum to avoid potential interference with platinum’s antitumor effects
*Half-Life↓, Data shows a short half-life and bioavailability of about 30% of ALA due to mechanisms involving hepatic degradation, reduced ALA solubility as well as instability in the stomach.
*BioAv↑, ALA bioavailability is greatly reduced after food intake and it has been recommended that ALA should be admitted at least 2 h after eating or if taken before; meal should be taken at least 30 min after ALA administration
*ChAT↑, ALA show anti-dementia or anti-AD properties by increasing acetylcholine (ACh) production through activation of choline acetyltransferase, which increases glucose absorption
*GlucoseCon↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   p‑Akt↓,1,   ALDH↓,1,   AMPK↑,2,   p‑AMPK↑,1,   Apoptosis↑,1,   ATP↓,3,   BioAv↝,1,   CD24↓,1,   CD44↓,1,   ChemoSen↑,2,   CSCs↓,2,   ECAR↓,1,   eff↓,1,   EGFR↓,1,   EGR4↓,1,   FDG↓,1,   Furin↓,1,   GlucoseCon↓,3,   Glycolysis↓,3,   Half-Life↓,1,   HK2↓,1,   IGF-1R↓,1,   lactateProd↓,1,   LC3B-II↑,1,   LDHA↓,2,   mitResp↓,1,   MMP↓,1,   mTOR↓,3,   NAD↓,1,   NF-kB↓,1,   OCR↓,1,   OXPHOS↓,1,   p‑P70S6K↓,1,   PDH↑,1,   PFK↓,1,   PI3K↓,2,   PKM2↓,2,   RadioS↑,1,   ROS↑,4,   selectivity↑,1,   TumCG↓,1,   TumCG↑,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,   tumCV↓,1,  
Total Targets: 47

Results for Effect on Normal Cells:
5HT↑,1,   ACC↑,1,   Acetyl-CoA↑,2,   Ach↑,5,   AChE↓,2,   Akt?,1,   Akt↑,1,   AMPK↑,1,   AMPK⇅,1,   AntiAge↑,1,   AntiCan↑,1,   antiOx↑,8,   ATP↑,1,   Aβ↓,3,   BBB↑,3,   BioAv↑,2,   BioAv↝,3,   BP↝,1,   Ca+2↓,1,   cardioP↑,1,   Catalase↑,3,   ChAT↑,4,   cognitive↑,7,   Dose↝,1,   eff↑,2,   ERK↑,1,   FAO↑,1,   GlucoseCon↑,11,   GLUT3↑,3,   GLUT4↑,4,   Glycolysis↑,1,   GPx↑,2,   GSH↑,9,   GSR↑,1,   GSTs↑,1,   H2O2∅,1,   Half-Life↓,1,   hepatoP↑,1,   Hif1a↑,2,   HK1↑,1,   HO-1↑,3,   ICAM-1↓,1,   IGF-1↑,1,   IL1β↓,1,   IL1β↑,1,   IL6↓,1,   Inflam↓,7,   iNOS↓,1,   IronCh↑,6,   lipid-P↓,5,   MAPK↑,1,   memory↑,5,   MMP↑,1,   MMP9↓,1,   motorD↑,1,   NADPH↑,1,   neuroP↑,8,   NF-kB↓,3,   NQO1↑,2,   NRF2↑,4,   other↓,1,   other↝,1,   PDH↑,1,   PDKs↓,1,   PGC-1α↑,1,   PI3K↑,2,   PKCδ↑,1,   PTEN↓,1,   ROS↓,8,   ROS↑,1,   SOD↑,2,   TAC↑,1,   tau↓,1,   p‑tau↓,1,   TNF-α↑,1,   VCAM-1↓,3,   VEGF↑,2,   VitC↑,1,   VitE↑,1,   Weight↓,1,  
Total Targets: 80

Scientific Paper Hit Count for: GlucoseCon, Glucose Consumption
14 Alpha-Lipoic-Acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:29  Target#:623  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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