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↓">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


NF-kB, Nuclear factor kappa B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
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?,

3283- ALA,    Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells
- in-vitro, Nor, NA
*TNF-α↓, LA also strongly inhibited TNF-alpha-induced mRNA expression of monocyte chemoattractant protein-1
*NF-kB↓, LA dose-dependently inhibited TNF-alpha-induced IkappaB kinase activation, subsequent degradation of IkappaB, the cytoplasmic NF-kappaB inhibitor, and nuclear translocation of NF-kappaB.
*antiOx↑, LA in its free, non-protein-bound form has potent antioxidant and metal-chelating properties
*IronCh↑,
*GSSG↓, DHLA/LA couple may chemically reduce glutathione disulfide (GSSG) to GSH
*VCAM-1↓, E-selectin, VCAM-1, ICAM-1, and MCP-1 message levels decreased by 93%, 77%, 67%, and 100%, respectively, when HAEC were pretreated with 0.5mmol/l LA
*E-sel↓,
*ICAM-1↓,
*MCP1↓,
*NF-kB↓, Lipoic acid inhibits TNF-a-induced activation of NF-kB and degradation of IkBs
IKKα↓,

3272- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*antiOx↑, LA has long been touted as an antioxidant,
*glucose↑, improve glucose and ascorbate handling,
*eNOS↑, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*NRF2↑,
*MMP9↓,
*VCAM-1↓,
*NF-kB↓,
*cardioP↑, used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits,
*cognitive↑,
*eff↓, The efficiency of LA uptake was also lowered by its administration in food,
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies;
*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↑, LA markedly increases intracellular glutathione (GSH),
*PKCδ↑, PKCδ, LA activates Erk1/2 [92,93], p38 MAPK [94], PI3 kinase [94], and Akt
*ERK↑,
*p38↑,
*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 [95],
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, stimulate GLUT4 translocation
*GLUT1↑, LA-stimulated translocation of GLUT1 and GLUT4.
*Inflam↓, LA as an anti-inflammatory agent

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↓,

3549- ALA,    Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia
- Review, AD, NA
*Inflam↓, LA and ALA attenuate neuroinflammation by modulating inflammatory signaling.
*other↝, ratio of LA to ALA in typical Western diets is reportedly 8–10:1 or higher, which is rather higher than the ideal ratio of LA to ALA (1–2:1) required to reach the maximal conversion of ALA to its longer chain PUFAs
*other↝, LA and ALA are essential PUFAs that must be obtained from dietary intake because they cannot be synthesized de novo
*neuroP↑, several studies have also suggested that lower dietary intake of LA influences AA metabolism in brain and subsequently causes progressive neurodegenerative disorders
*BioAv↝, LA cannot be synthesized in the human body
*adiP↑, study suggested that LA-rich oil consumption leads to the high levels of adiponectin in the blood [114], which could stimulate mitochondrial function in the liver and skeletal muscles for energy thermogenesis
*BBB↑, Although LA can penetrate the BBB, most of the LA that enters the brain cannot be changed into AA [48,49], and 59 % of the LA that enters the brain is broken down by fatty acid β-oxidation
*Casp6↓, In neurons, LA and ALA attenuate the activation of cleaved caspase-3/-9, p-NF-Kb and the production of TNF-a, IL-6, IL-1b, and ROS by binding GPR40 and GPR120.
*Casp9↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*ROS↓,
*NO↓, LA reduces NO production and inducible nitric oxide synthases (iNOS) protein expression in BV-2 microglia
*iNOS↓,
*COX2↓, ALA increases antioxidant enzyme activities in the brain [182] and inhibits the activation of COX-2 in AD models
*JNK↓, ALA has also been shown to suppress the activation of c-Jun N-terminal kinases (JNKs) and p-NF-kB p65 (Ser536), which is involved in inflammatory signaling
*p‑NF-kB↓,
*Aβ↓, and to inhibit Aβ aggregation and neuronal cell necrosis
*BP↓, LA also improves blood pressure, blood triglyceride and cholesterol levels, and vascular inflammation
*memory↑, One study suggested that long-term intake of ALA enhances memory function by increasing hippocampal neuronal function through activation of cAMP response element-binding protein (CREB) [192], extracellular signal-regulated kinase (ERK), and Akt signa
*cAMP↑,
*ERK↑,
*Akt↑,
cognitive?, Furthermore, ALA administration inhibits Aβ induced neuroinflammation in the cortex and hippocampus and enhances cognitive function

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↑,

3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, potential therapeutic effects for the prevention or treatment of neurodegenerative disease
*Inflam↓, ALA is able to regulate inflammatory cell infiltration into the central nervous system and to down-regulate VCAM-1 and human monocyte adhesion to epithelial cells
*VCAM-1↓, down-regulate vascular cell adhesion molecule-1 (VCAM-1) and the human monocyte adhesion to epithelial cells
*5HT↑, ALA is able to improve the function of the dopamine, serotonin and norepinephrine neurotransmitters
*memory↑, scientific evidence shows that ALA possesses the ability to improve memory capacity in a number of experimental neurodegenerative disease models and in age-related cognitive decline in rodents
*BioAv↝, Between 27 and 34% of the oral intake is available for tissue absorption; the liver is one of the main clearance organs on account of its high absorption and storage capacity
*Half-Life↓, The plasma half-life of ALA is approximately 30 minutes. Peak urinary excretion occurs 3-6 hours after intake.
*NF-kB↓, As an inhibitor of NF-κβ, ALA has been studied in cytokine-mediated inflammation
*antiOx↑, In addition to the direct antioxidant properties of ALA, some studies have shown that both ALA and DHLA and a great capacity to chelate redox-active metals, such as copper, free iron, zinc and magnesium, albeit in different ways (
*IronCh↑, ALA is able to chelate transition metal ions and, therefore, modulate the iron- and copper-mediated oxidative stress in Alzheimer’s plaques
*ROS↓, iron and copper chelation with DHLA may explain the low level of free radical damage in the brain and the improvement in the pathobiology of Alzheimer’s Disease
*ATP↑, ALA may increase the mitochondrial synthesis of ATP in the brain of elderly rats, thereby increasing the activity of the mitochondrial enzymes
*ChAT↑, ALA may also play a role in the activation of the choline acetyltransferase enzyme (ChAT), which is essential in the anabolism of acetylcholine
*Ach↑,
*cognitive↑, One experimental study has shown that in rats that had been administered ALA there was an inversion in the cognitive dysfunction with an increase in ChAT activity in the hippocampus
*lipid-P↓, administration of ALA reduces lipid peroxidation in different areas of the brain and increases the activity of antioxidants such as ascorbate (vitamin C), α-tocopherol (vitamin E), glutathione,
*VitC↑,
*VitE↑,
*GSH↑,
*SOD↑, and also the activity of superoxide dismutase, catalase, glutathione-peroxidase, glutathione-reductase, glucose-6-P-dehydrogenase
*Catalase↑,
*GPx↑,
*Aβ↓, Both ALA and DHLA have been seen to inhibit the formation of Aβ fibrils

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

3456- ALA,    Renal-Protective Roles of Lipoic Acid in Kidney Disease
- Review, NA, NA
*RenoP↑, We focus on various animal models of kidney injury by which the underlying renoprotective mechanisms of ALA have been unraveled
*ROS↓, ALA’s renal protective actions that include decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating renal fibrosis, and attenuating nephron cell death.
*antiOx↑,
*Inflam↓,
*Sepsis↓, figure 1
*IronCh↑, ALA can also chelate metals such as zinc, iron, and copper and regenerate endogenous antioxidants—such as glutathione—and exogenous vitamin antioxidants—such as vitamins C and E—with minimal side effects
*BUN↓, ALA can decrease acute kidney injury by lowering serum blood urea nitrogen, creatinine levels, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), thereby decreasing endothelin-1 vasoconstriction, neutrophil dif
*creat↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*MDA↓, pretreatment with ALA decreased MDA content and ameliorated renal oxidative stress
*NRF2↑, activate the Nrf2 signaling pathway, leading to upregulation of the second-phase cytoprotective proteins such as heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1)
*HO-1↑,
*NQO1↑,
*chemoP↑, ALA has also been shown to lower plasma creatinine levels and urine output, increase creatinine clearance and urine osmolality, and normalize sodium excretion in cisplatin kidney injury
*eff↑, ALA can also minimize renal toxicity induced by gold nanoparticles, which are often used as drug carriers
*NF-kB↓, Enhancing autophagy, inhibiting NF-KB, attenuating mitochondrial oxidative stress

3451- ALA,    Alpha-lipoic acid ameliorates H2O2-induced human vein endothelial cells injury via suppression of inflammation and oxidative stress
- in-vitro, Nor, HUVECs
*LDH↓, ALA reduces LDH release from H2O2-induced cells
*NOX4↓, ALA downregulates the expression of Nox4
*NF-kB↓, ALA inhibits H2O2-induced activation of the NF-κB signaling pathway
*iNOS↓, ALA suppresses the upregulation of iNOS, VCAM-1 and ICAM-1 in H2O2-induced HUVECs
*VCAM-1↓,
*ICAM-1↓,
*ROS↓, ALA protected HUVECs against oxidative damage induced by H2O2, as assessed by cell viability and LDH activity.
*cardioP↑, regulating Nox4 protein expression and play a protective role in cardiovascular disease.

3450- ALA,    α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells
- in-vitro, NA, AGS
*IL8↓, α-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-κB in H. pylori-infected gastric epithelial cells
*MAPK↓,
*JAK↓,
*STAT↓,
*NF-kB↓,

3449- ALA,    Alpha-Lipoic Acid Downregulates IL-1β and IL-6 by DNA Hypermethylation in SK-N-BE Neuroblastoma Cells
- in-vitro, AD, SK-N-BE
*antiOx↑, ability to maintain its antioxidant properties both in its oxidised and reduced form
*NRF2↑, Antioxidant action of ALA is mediated by two essential nuclear factors: nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) [5,6,7,8,9,10]
*NF-kB↓,
*IL1β↓, ALA-dependent down-regulation of IL-1β and IL-6 in neuronal cells.
*IL6↓,
neuroP↑, ALA was already indicated as a potential therapeutic agent in aging-associated neurodegenerative disorders

272- ALA,    Evidence that α-lipoic acid inhibits NF-κB activation independent of its antioxidant function
- in-vitro, NA, HUVECs
NF-kB↓,

278- ALA,    The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment
- Review, NA, NA
ROS↑, direct anticancer effect of the antioxidant ALA is manifested as an increase in intracellular ROS levels in cancer cells
NRF2↑, enhance the activity of the anti-inflammatory protein nuclear factor erythroid 2–related factor 2 (Nrf2), thereby reducing tissue damage
Inflam↓,
frataxin↑,
*BioAv↓, Oral ALA has a bioavailability of approximately 30% due to issues such as poor stability in the stomach, low solubility, and hepatic degradation.
ChemoSen↑, ALA can enhance the functionality of various other anticancer drugs, including 5-fluorouracil in colon cancer cells and cisplatin in MCF-7 breast cancer cells
Hif1a↓, it is inferred that lipoic acid may inhibit the expression of HIF-1α
eff↑, act as a synergistic agent with natural polyphenolic substances such as apigenin and genistein
FAK↓, ALA inhibits FAK activation by downregulating β1-integrin expression and reduces the levels of MMP-9 and MMP-2
ITGB1↓,
MMP2↓,
MMP9↓,
EMT↓, ALA inhibits the expression of EMT markers, including Snail, vimentin, and Zeb1
Snail↓,
Vim↓,
Zeb1↓,
P53↑, ALA also stimulates the mutant p53 protein and depletes MGMT
MGMT↓, depletes MGMT by inhibiting NF-κB signalling, thereby inducing apoptosis
Mcl-1↓,
Bcl-xL↓,
Bcl-2↓,
survivin↓,
Casp3↑,
Casp9↑,
BAX↑,
p‑Akt↓, ALA inhibits the activation of tumour stem cells by reducing Akt phosphorylation.
GSK‐3β↓, phosphorylation and inactivation of GSK3β
*antiOx↑, indirect antioxidant protection through metal chelation (ALA primarily binds Cu2+ and Zn2+, while DHLA can bind Cu2+, Zn2+, Pb2+, Hg2+, and Fe3+) and the regeneration of certain endogenous antioxidants, such as vitamin E, vitamin C, and glutathione
*ROS↓, ALA can directly quench various reactive species, including ROS, reactive nitrogen species, hydroxyl radicals (HO•), hypochlorous acid (HclO), and singlet oxygen (1O2);
selectivity↑, In normal cells, ALA acts as an antioxidant by clearing ROS. However, in cancer cells, it can exert pro-oxidative effects, inducing pathways that restrict cancer progression.
angioG↓, Combining these two hypotheses, it can be hypothesized that ALA may regulate copper and HIF-2α to limit tumor angiogenesis.
MMPs↓, ALA was shown to inhibit invasion by decreasing the mRNA levels of key matrix metalloproteinases (MMPs), specifically MMP2 and MMP9, which are crucial for the metastatic process
NF-kB↓, ALA has been shown to enhance the efficacy of the chemotherapeutic drug paclitaxel in breast and lung cancer cells by inhibiting the NF-κB signalling pathway and the functions of integrin β1/β3 [138,139]
ITGB3↓,
NADPH↓, ALA has been shown to inhibit NADPH oxidase, a key enzyme closely associated with NP, including NOX4

298- ALA,  Rad,    Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1
- in-vitro, BC, MDA-MB-231
Apoptosis↑,
P53↑,
p38↑,
NF-kB↑, NF-κB were significantly increased in the ALA+RT group compared to the control
TumCCA↑, G2/M cell cycle arrest.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Results for Effect on Cancer/Diseased Cells:
p‑Akt↓,1,   angioG↓,1,   Apoptosis↑,1,   BAX↑,1,   Bcl-2↓,1,   Bcl-xL↓,1,   Casp3↑,1,   Casp9↑,1,   ChemoSen↑,1,   cognitive?,1,   eff↑,1,   EMT↓,1,   FAK↓,1,   frataxin↑,1,   GSK‐3β↓,1,   Hif1a↓,1,   IKKα↓,1,   Inflam↓,1,   ITGB1↓,1,   ITGB3↓,1,   Mcl-1↓,1,   MGMT↓,1,   MMP2↓,1,   MMP9↓,1,   MMPs↓,1,   NADPH↓,1,   neuroP↑,1,   NF-kB↓,3,   NF-kB↑,1,   NRF2↑,1,   p38↑,1,   P53↑,2,   ROS↑,1,   selectivity↑,1,   Snail↓,1,   survivin↓,1,   TumCCA↑,1,   Vim↓,1,   Zeb1↓,1,  
Total Targets: 39

Results for Effect on Normal Cells:
5HT↑,2,   ACC↑,1,   Ach↑,1,   AChE↓,2,   adiP↑,1,   Akt?,1,   Akt↑,3,   AMPK↑,2,   AMPK⇅,1,   antiOx↑,9,   ATP↑,1,   Aβ↓,3,   BBB↑,4,   BioAv↓,1,   BioAv↝,4,   BP↓,1,   BP↝,1,   BUN↓,1,   cAMP↑,1,   cardioP↑,2,   Casp6↓,1,   Casp9↓,1,   Catalase↑,3,   ChAT↑,2,   chemoP↑,1,   cognitive↑,5,   COX2↓,1,   creat↓,1,   Dose↝,1,   E-sel↓,1,   eff↓,1,   eff↑,2,   eNOS↑,1,   ERK↑,3,   FAO↑,1,   glucose↑,1,   GlucoseCon↑,4,   GLUT1↑,1,   GLUT3↑,1,   GLUT4↑,3,   GPx↑,2,   GSH↑,6,   GSR↑,1,   GSSG↓,1,   GSTs↑,1,   H2O2∅,1,   Half-Life↓,1,   HO-1↑,2,   ICAM-1↓,3,   IGF-1↑,1,   IL1β↓,3,   IL1β↑,1,   IL6↓,3,   IL8↓,1,   Inflam↓,7,   iNOS↓,3,   IronCh↑,7,   JAK↓,1,   JNK↓,1,   LDH↓,1,   lipid-P↓,3,   MAPK↓,1,   MAPK↑,2,   MCP1↓,1,   MDA↓,1,   memory↑,4,   MMP9↓,2,   motorD↑,1,   NADPH↑,1,   neuroP↑,4,   NF-kB↓,11,   p‑NF-kB↓,1,   NO↓,1,   NOX4↓,1,   NQO1↑,3,   NRF2↑,4,   other↝,2,   p38↑,1,   PI3K↑,3,   PKCδ↑,2,   PTEN↓,2,   RenoP↑,1,   ROS↓,7,   Sepsis↓,1,   SOD↑,2,   STAT↓,1,   TNF-α↓,3,   TNF-α↑,1,   VCAM-1↓,6,   VitC↑,2,   VitE↑,2,  
Total Targets: 91

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B
15 Alpha-Lipoic-Acid
1 Radiotherapy/Radiation
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:29  Target#:214  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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