| 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 → ROS ↑ (cancer cells; high dose / stressed mitochondria) ALA → ROS ↓ (normal cells; low–moderate dose) same pattern seen with: Vitamin C, Menadione, Quercetin, EGCG, Resveratrol- 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↓">GSH↓ Catalase↓ HO1↓ GPx↓ - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑">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 Cancer-Relevant Pathways
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| Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress. Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system. cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment. While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied. Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy. Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death. Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion. Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS). "...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..." "Cancer cells have a high level of GSH compared to normal cells." "...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy." The loss of GSH is broadly known to be directly related to the apoptosis progression. |
| 3437- | ALA, | Revisiting the molecular mechanisms of Alpha Lipoic Acid (ALA) actions on metabolism |
| - | Review, | Var, | NA |
| 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 |
| 3446- | ALA, | CUR, | The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression |
| - | in-vivo, | Nor, | NA |
| 3438- | ALA, | The Potent Antioxidant Alpha Lipoic Acid |
| - | Review, | NA, | NA | - | Review, | AD, | NA |
| 3448- | ALA, | Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line |
| 3284- | ALA, | Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA |
| - | vitro+vivo, | Park, | NA |
| 3272- | ALA, | Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential |
| - | Review, | AD, | NA |
| 3271- | ALA, | Decrypting the potential role of α-lipoic acid in Alzheimer's disease |
| - | Review, | AD, | NA |
| 3270- | ALA, | Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis |
| - | Trial, | AD, | NA |
| 3269- | ALA, | Sulfur-containing therapeutics in the treatment of Alzheimer’s disease |
| - | NA, | AD, | NA |
| 3543- | ALA, | The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease |
| - | Study, | AD, | NA |
| 3547- | ALA, | Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3545- | ALA, | Potential therapeutic effects of alpha lipoic acid in memory disorders |
| - | Review, | AD, | NA |
| 3544- | ALA, | Alpha lipoic acid for dementia |
| - | Review, | AD, | NA |
| 3542- | ALA, | Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review |
| - | Review, | Var, | NA |
| 3541- | ALA, | Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology |
| - | Review, | Var, | NA |
| 3539- | ALA, | Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential |
| - | Review, | AD, | NA |
| 297- | ALA, | Insights on the Use of α-Lipoic Acid for Therapeutic Purposes |
| - | Review, | BC, | SkBr3 | - | Review, | neuroblastoma, | SK-N-SH | - | Review, | 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#:29 Target#:137 State#:% Dir#:2
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