GSH Cancer Research Results

GSH, Glutathione: Click to Expand ⟱
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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.
Scientific Papers found: Click to Expand⟱
3972- ACNs,    Recent Research on the Health Benefits of Blueberries and Their Anthocyanins
- Review, AD, NA - Review, Park, NA
*cardioP↑, Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection.
*neuroP↑,
*Inflam↓, Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function
*antiOx↓,
*GutMicro↑, Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health
*Half-Life↑, However, >50% of the 13C still remained in the body after 48 h
*LDL↓, controlled study of 58 diabetic patients, blueberry intake led to a decline in LDL cholesterol, triglycerides, and adiponectin and an increase in HDL cholesterol
*adiP↓,
*HDL↑,
*CRP↓, reduction was documented in inflammatory markers, including serum high-sensitivity C-reactive protein, soluble vascular adhesion molecule-1, and plasma IL-1β
*IL1β↓,
*Risk↓, lower Parkinson disease risk was associated with the highest quintile of anthocyanin (RR: 0.76) and berry (RR: 0.77) intake
*Risk↓, Nurse's Health Study, greater intake of blueberries and strawberries was associated with slower rates of cognitive decline in older adults, with an estimated delay in decline of about 2.5 y
*cognitive↑, Cognitive performance in elderly adults improved after 12 wk of daily intake of blueberry (94) or Concord grape (95) juice.
*memory↑, Better task switching and reduced interference in memory was found in healthy older adults after 90 d of blueberry supplementation
*other↑, After 12 wk of blueberry consumption, greater brain activity was detected using magnetic resonance imaging in healthy older adults during a cognitive challenge.
*BOLD↑, Similarly, during a memory test, regional blood oxygen level-dependent activity detected by MRI (99) was enhanced in the subjects taking blueberry, but not in those taking placebo.
*NO↓, 50–200 mg/d bilberry showed a dose-dependent decrease in neurotoxic NO and malondialdehyde, combined with an increase in neuroprotective antioxidant capacity due to glutathione, vitamin C, superoxide dismutase, and glutathione peroxidase
*MDA↓,
*GSH↑,
*VitC↑,
*SOD↑,
*GPx↑,
*eff↓, The percentage loss of blueberry anthocyanins during −18°C storage was 12% after 10 mo of storage
*eff↓, Freeze-dried blueberry powder loses anthocyanins in a temperature-dependent manner with a half-life of 139, 39, and 12 d when stored at 25, 42, and 60°C, respectively
*eff↓, Blueberries are low in ascorbic acid and high in anthocyanins (187), and notably anthocyanins are readily degraded by ascorbic acid
*eff↝, Shelf-stable blueberry products like jam (196), juice (197), and extracts (198) can lose polyphenolic compounds when stored at ambient temperature whereas refrigeration mitigates losses.
*Risk↓, It can be safely stated that daily moderate intake (50 mg anthocyanins, one-third cup of blueberries) can mitigate the risk of diseases and conditions of major socioeconomic importance in the Western world.

4447- AgNPs,    Anti-inflammatory action of silver nanoparticles in vivo: systematic review and meta-analysis
- Review, Nor, NA
*Inflam↓, Qualitative analysis showed a reduction in pro-inflammatory proteins and in the COX-2 pathway.
*COX2↓,
*ROS↓, Its in vitro mechanism of action shows potential to eliminate free radicals
*Dose↝, The method of synthesizing nanoparticles (NPs) influences parameters such as size, shape, topography, stability, concentration, purity and release of Ag + ions, which in turn influences their anti-inflammatory activity
*eff↑, In vitro studies have compared the ingestion of AgNPs at low concentrations (0.012 % per kg) with gold standard drugs (glucocorticoids; 0.1 % per kg) and observed higher efficacy of NPs in promoting therapeutic effect
*toxicity↓, another study has shown that chronic in vivo application of AgNPs at the minimum concentration necessary to promote therapeutic effect does not cause toxic effects
*IL4↑, AgNPs and mitoxantrone increased levels of anti-inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and decreased pro-inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY and TNFα).
*IL5↑,
*IL10↑,
*IL1↓,
*IL6↓,
*TNF-α↓,
*NF-kB↓, AgNPs selectively inhibit COX-2 and the NF-kB pathway.
*MDA↓, AgNPs reduce biomarkers of oxidative stress [55], such as malondialdehyde (MDA) and cell membrane peroxidation [19,31] and increase intracellular GSH
*GSH↑,

2207- AgNPs,  TQ,    Protective effects of Nigella sativa L. seeds aqueous extract-based silver nanoparticles on sepsis-induced damages in rats
- in-vivo, Nor, NA
*eff↑, Treatment with AgNPs led to a notable reduction in damages of liver, kidney, lung, stomach and duodenum.
*RenoP↑,
*hepatoP↑,
*MDA↓, AgNPs treated groups reduced the levels of tissues MDA and increased the levels of tissues SOD and GSH.
*SOD↑,
*GSH↑,
*TNF-α↓, The expression levels of TNF-α mRNA and IL-1β mRNA were reduced in the rats treated by silver nanoparticles.
*IL1β↓,

2205- AgNPs,    Potential protective efficacy of biogenic silver nanoparticles synthesised from earthworm extract in a septic mice model
- in-vivo, Nor, NA
*Dose↝, The treated group received a single oral dose of 5.5 mg/kg of Ag NPs. 5 to 12 nm
*eff↑, Ag NPs treatment in septic mice significantly decreased liver enzyme activities, total protein, and serum albumin.
*RenoP↑, Ag NPs significantly enhanced kidney function, as indicated by a significant decrease in the levels of creatinine, urea, and uric acid.
*antiOx↑, Ag NPs showed a powerful antioxidant effect via the considerable reduction of malondialdehyde and nitric oxide levels and the increase in antioxidant content.
*MDA↓,
*NO↓,
*hepatoP↑, hepatoprotective effect of Ag NPs may be attributed to their antioxidant properties
*toxicity↝, The Ag NPs dose is 1/10 of LD50, which is 5.5 mg/kg.
*GSH↑, GSH, SOD, GST, and CAT of the septic group. Meanwhile, the Ag NPs-treated mice showed a significant (p < 0.05) increase in all four parameters.
*SOD↑,
*GSTs↑,
*Catalase↑,

5344- Ajoene,    Ajoene, a Stable Garlic By-Product, Has an Antioxidant Effect through Nrf2-Mediated Glutamate-Cysteine Ligase Induction in HepG2 Cells and Primary Hepatocytes
- in-vitro, Nor, HepG2
*Nrf1↑, Ajoene treatment activated Nrf2, as indicated by increased phosphorylation and nuclear accumulation of Nrf2
*PKCδ↑, Ajoene activated protein kinase C-δ (PKCδ).
*GSH↑, Our results demonstrate that ajoene increases PKCd-dependent Nrf2 activation, GCL induction, and the cellular GSH concentration, which may contribute to protecting cells from oxidative stress.
*antiOx↑,

5354- AL,    Therapeutic Potential of Allicin-Rich Garlic Preparations: Emphasis on Clinical Evidence toward Upcoming Drugs Formulation
- Review, Var, NA
*LDL↓, Indeed, clinical studies on healthy subjects have evidenced that standardized garlic treatment (900 mg/day) significantly reduces total cholesterol (TC) and low-density lipoprotein cholesterol (c-LDL).
*antiOx↑, Multiple studies have focused on allicin therapeutic potential as an antioxidant (inducing antioxidant product production),
AntiCan↑, anticancer (triggering cancer cells apoptosis and inhibiting tumor growth),
*cardioP↑, cardioprotective (decreasing angiogenesis and inducing vasorelaxation)
*BP↓, Conversely, aged garlic extract supplementation was shown to be more effective than the placebo in lowering systolic blood pressure
*Weight↓, Garlic powder supplementation (800 mg/daily) resulted in a significant decrease in body weight and body fat mass (
NK cell↑, Actually, aged garlic administration in patients with advanced cancer of the digestive system led to an improvement of natural killer (NK) cell activity but did not cause improvement in QoL
*AntiDiabetic↑, Actually, daily garlic allicin supplementation (0.05–1.5 g) displayed a positive and sustained role in blood glucose, total cholesterol (TC), and high/low density lipoprotein (HDL-c/LDL-c) regulation in type 2 diabetes mellitus (T2DM) management
*GSH↑, 2-month application of coated garlic powder tablets (900 mg with alliin and allicin contents of 1.3% and 0.6%, respectively), the glutathione (GSH) concentration significantly increased in circulating human erythrocytes

2558- AL,    Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment
- Review, AD, NA
*AntiCan↑, Allicin has shown anticancer, antimicrobial, antioxidant properties and also serves as an efficient therapeutic agent against cardiovascular diseases
*antiOx↑,
*cardioP↑,
*neuroP↑, present review describes allicin as an antioxidant, and neuroprotective molecule
cognitive↑, that can ameliorate the cognitive abilities in case of neurodegenerative and neuropsychological disorders.
*ROS↓, As an antioxidant, allicin fights the reactive oxygen species (ROS) by downregulation of NOX (NADPH oxidizing) enzymes, it can directly interact to reduce the cellular levels of different types of ROS produced by a variety of peroxidases.
*NOX↓,
*TLR4↓, inhibition of TLR4/MyD88/NF-κB, P38 and JNK pathways.
*NF-kB↓,
*JNK↓,
*AntiAg↑, A low concentration of allicin (0.4 mM) can inhibit the platelet aggregation up to 90%, the impact is significantly higher than of similar concentration of aspirin.
*H2S↑, Allicin decomposes rapidly and undergoes a series of reactions with glutathione resulting in the production of hydrogen sulphide (H2S).
*BP↓, H2S is a gaseous signalling molecule involved in the regulation of blood pressure.
Telomerase↓, Allicin inhibits the activity of telomerase in a dose dependent manner subsequently inhibiting the proliferation in the cancer cells
*Insulin↑, Studies have shown a significant increase in the blood insulin levels after treatment with allicin
BioAv↝, optimum temperature for the activity of alliinase is 33 °C, it operates best at pH 6.5, the enzyme is sensitive to acids [42,43] (Figure 3), enteric-coated formulations of garlic supplements are therefore recommended
*GSH↑, It helps to lower the hyperglycaemic conditions and improves the glutathione and catalase biosynthesis [37,38]
*Catalase↑,

2657- AL,    Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases
- Review, CardioV, NA - Review, AD, NA
*Inflam↓, allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others).
*antiOx↑, improving the antioxidant system
*neuroP↑,
*cardioP↑,
*AntiTum↑,
*mtDam↑, Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes.
*HSP70/HSPA5↑, llicin improves mitochondrial function by enhancing the expression of HSP70 and decreasing RAAS activation
*NRF2↑,
*RAAS↓,
*cognitive↑, Allicin enhances the cognitive function of APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice by decreasing the expression levels of Aβ, oxidative stress, and improving mitochondrial function.
*SOD↑, positive effects on cognition in an AD mouse model by administrating a preventive dose of allicin. These effects might be mediated by an increase of SOD and reduction of ROS
*ROS↓,
*NRF2↑, Chronic treatment with allicin increased the expression of NRF2 and targeted downstream of NRF2, such as NADPH, quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (γ-GCS), in the hippocampus of aged mice
*ER Stress↓, protective effects of 16 weeks of allicin treatment in a rat model of endoplasmic reticulum stress-related cognitive deficits.
*neuroP↑, allicin was able to ameliorate depressive-like behaviors by decreasing neuroinflammation, oxidative stress iron aberrant accumulation,
*memory↑, allicin improved lead acetate-caused learning and memory deficits and decreased the ROS level
*TBARS↓, Oral administration of allicin was able to reduce thiobarbituric reactive substances (TBARS) and myeloperoxidase (MPO) levels, and concurrently increased (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in a rat model of
*MPO↓,
*SOD↑,
*GSH↑,
*iNOS↓, decreasing the expression of iNOS and increased the phosphorylation of endothelial NOS (eNOS)
*p‑eNOS↑,
*HO-1↑, OSCs upregulate the endogenous antioxidant NRF2 and heme oxygenase-1 (HO-1)

2660- AL,    Allicin: A review of its important pharmacological activities
- Review, AD, NA - Review, Var, NA - Review, Park, NA - Review, Stroke, NA
*Inflam↓, It showed neuroprotective effects, exhibited anti-inflammatory properties, demonstrated anticancer activity, acted as an antioxidant, provided cardioprotection, exerted antidiabetic effects, and offered hepatoprotection.
AntiCan↑,
*antiOx↑,
*cardioP↑, This vasodilatory effect helps protect against cardiovascular diseases by reducing the risk of hypertension and atherosclerosis.
*hepatoP↑,
*BBB↑, This allows allicin to easily traverse phospholipid bilayers and the blood-brain barrier
*Half-Life↝, biological half-life of allicin is estimated to be approximately one year at 4°C. However, it should be noted that its half-life may differ when it is dissolved in different solvents, such as vegetable oil
*H2S↑, allicin undergoes metabolism in the body, leading to the release of hydrogen sulfide (H2S)
*BP↓, H2S acts as a vasodilator, meaning it relaxes and widens blood vessels, promoting blood flow and reducing blood pressure.
*neuroP↑, It acts as a neuromodulator, regulating synaptic transmission and neuronal excitability.
*cognitive↑, Studies have suggested that H2S may enhance cognitive function and protect against neurodegenerative diseases like Alzheimer's and Parkinson's by promoting neuronal survival and reducing oxidative stress.
*neuroP↑, various research studies suggest that the neuroprotective mechanisms of allicin can be attributed to its antioxidant and anti-inflammatory properties
*ROS↓,
*GutMicro↑, may contribute to the overall health of the gut microbiota.
*LDH↓, Liu et al. found that allicin treatment led to a significant decrease in the release of lactate dehydrogenase (LDH),
*ROS↓, allicin's capacity to lower the production of reactive oxygen species (ROS), decrease lipid peroxidation, and maintain the activities of antioxidant enzymes
*lipid-P↓,
*antiOx↑,
*other↑, allicin was found to enhance the expression of sphingosine kinases 2 (Sphk2), which is considered a neuroprotective mechanism in ischemic stroke
*PI3K↓, allicin downregulated the PI3K/Akt/nuclear factor-kappa B (NF-κB) pathway, inhibiting the overproduction of NO, iNOS, prostaglandin E2, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha induced by interleukin-1 (IL-1)
*Akt↓,
*NF-kB↓,
*NO↓,
*iNOS↓,
*PGE2↓,
*COX2↓,
*IL6↓,
*TNF-α↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
*MPO↓, Furthermore, allicin significantly decreased tumor necrosis factor-alpha (TNF-α) levels and myeloperoxidase (MPO) activity, indicating its neuroprotective effect against brain ischemia via an anti-inflammatory pathway
*eff↑, Allicin, in combination with melatonin, demonstrated a marked reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and NF-κB genes in rats with brain damage induced by acryl
*NRF2↑, Allicin treatment decreased oxidative stress by upregulating Nrf2 protein and downregulating Keap-1 expression.
*Keap1↓,
*TBARS↓, It significantly reduced myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) levels,
*creat↓, and decreased blood urea nitrogen (BUN), creatinine, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels.
*LDH↓,
*AST↓,
*ALAT↓,
*MDA↓,
*SOD↑, Allicin also increased the activity of superoxide dismutase (SOD) as well as the levels of glutathione S-transferase (GST) and glutathione (GSH) in the liver, kidneys, and brain
*GSH↑,
*GSTs↑,
*memory↑, Allicin has demonstrated its ability to improve learning and memory deficits caused by lead acetate injury by promoting hippocampal astrocyte differentiation.
chemoP↑, Allicin safeguards mitochondria from damage, prevents the release of cytochrome c, and decreases the expression of pro-apoptotic factors (Bax, cleaved caspase-9, cleaved caspase-3, and p53) typically activated by cisplatin
IL8↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
Cyt‑c↑, In addition, allicin was reported to induce cytochrome c, increase expression of caspase 3 [86], caspase 8, 9 [82,87], caspase 12 [80] along with enhanced p38 protein expression levels [81], Fas expression levels [82].
Casp3↑,
Casp8↑,
Casp9↑,
Casp12↑,
p38↑,
Fas↑,
P53↑, Also, significantly increased p53, p21, and CHK1 expression levels decreased cyclin B after allicin treatment.
P21↑,
CHK1↓,
CycB/CCNB1↓,
GSH↓, Depletion of GSH and alterations in intracellular redox status have been found to trigger activation of the mitochondrial apoptotic pathway was the antiproliferative function of allicin
ROS↑, Hepatocellular carcinoma (HCC) cells were sensitised by allicin to the mitochondrial ROS-mediated apoptosis induced by 5-fluorouracil
TumCCA↑, According to research findings, allicin has been shown to decrease the percentage of cells in the G0/G1 and S phases [87], while causing cell cycle arrest at the G2/M phase
Hif1a↓, Allicin treatment was found to effectively reduce HIF-1α protein levels, leading to decreased expression of Bcl-2 and VEGF, and suppressing the colony formation capacity and cell migration rate of cancer cells
Bcl-2↓,
VEGF↓,
TumCMig↓,
STAT3↓, antitumor properties of allicin have been attributed to various mechanisms, including promotion of apoptosis, inhibition of STAT3 signaling
VEGFR2↓, suppression of VEGFR2 and FAK phosphorylation
p‑FAK↓,

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↓,

3270- ALA,    Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis
- Trial, AD, NA
*cognitive↑, led to a stabilization of cognitive functions in the study group
*other↝, In patients with mild dementia (ADAScog < 15), the disease progressed extremely slowly (ADAScog: +1.2 points/year, MMSE: -0.6 points/year), in patients with moderate dementia at approximately twice the rate.
*neuroP↑, alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD
*IronCh↑, a-Lipoic acid chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione
*ROS↓,
*GSH↑,

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

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

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
*antiOx↑, naturally occurring enzyme cofactor with antioxidant and iron chelator properties and has many known effects. ALA has neuroprotective effects on PD.
*IronCh↑,
*neuroP↑,
*ROS↓, decreasing the levels of intracellular reactive oxygen species and iron.
*Iron↓,
*BBB↑, ALA also provides neuroprotection against PD because it can penetrate the blood–brain barrier.
*motorD↑, ALA ameliorates motor behavior and prevents DA neuron loss in the SN of PD rat models.
*GSH↑, ALA Inhibits the Decrease in the Activity of SOD and GSH in the SN of a Rat Model of PD Induced by 6-OHDA

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?,

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↑,

3448- ALA,    Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line
*Inflam↓, inflammatory and oxidant effects of hypoxia were increased by activation of TRPA1, but its action on the values was decreased by the ALA treatment.
*ROS↓,
*GSH↑, through upregulation thiol redox system members [glutathione (GSH) and glutathione peroxidase (GSH-Px)] and down-regulation of mitochondrial ROS and extracellular productions.
*GPx↑,
*Casp3↓, HYPOX-induced caspase 3 and 9 activities were decreased by the ALA treatment
*Casp9↓,
*MMP↑, ALA treatment decreased HYPOX-induced mitochondrial membrane depolarization (JC-1) and intracellular ROS production levels

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

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
*hepatoP↑, Curc and Lip acid can be considered as promising natural therapies against liver injury, induced by NHPA, through their antioxidant and antifibrotic actions.
*α-SMA↓, Curc and Lip acid reduced the expression of alpha-smooth muscle actin and collagen III, upregulated by NHPA intoxication
*COL3A1↓,
*ROS↓, scavenging activity to ROS and a capacity to regenerate endogenous antioxidants such as GSH, and vitamins C and E.
*GSH↑,
*ALAT↓, ALT, AST, and ALP activity levels compared to those of the control group. The use of NACS, Curc, and/or Lip acid significantly reduced the toxic effects of NHPA on those enzymes,
*AST↓,
*ALP↓,
*MDA↓, The combination therapy showed an apparent reduction in MDA level more than other treatments

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

3541- ALA,    Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology
- Review, Var, NA
*antiOx↑, α-LA has been widely used as an antioxidant compound in many multivitamin formulations, food supplements, anti-aging formulas, and even in human and pet food recipes
*IronCh↑, potential role in the chelation of metals and in restoring normal levels of intracellular glutathione (GSH) after depletion caused by toxicants,
*GSH↑,
*BBB↑, ALA, which can pass through the blood-brain barrier (BBB
Apoptosis↑, increased level of apoptosis, mitochondrial membrane depolarization, ROS production, lipid peroxidation, poly-(ADP)-ribose polymerase 1 (PARP1), caspase 3 and 9 expression levels in simultaneous ALA (0.05 mM) and cisplatin(0.025 mM)-treated MCF7
MMP↓,
ROS↑,
lipid-P↑,
PARP1↑,
Casp3↑,
Casp9↑,
*NRF2↑, ALA's ability to activate Nfr2 in GSH production
*GSH↑,
*ROS↓, administration of ALA has been shown to reduce oxidative stress
RenoP↑, ALA also reduced lipid peroxidation in the kidneys caused by the anticancer drug cisplatin,
ChemoSen↑, ALA enhances the functions of various anticancer drugs such as 5-fluorouracil in CRC [146] and cisplatin in MCF-7 cells
*BG↓, ALA was shown to lower the blood glucose levels in patients with type 2 diabetes

3542- ALA,    Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review
- Review, Var, NA
*antiOx↑, powerful antioxidant that regenerates other antioxidants (e.g., vitamins E and C, and reduced glutathione) and has metal-chelating activity.
*VitE↑,
*VitC↑,
*GSH↑,
*IronCh↑,
*BioAv↑, Both fat and water soluble, it is readily absorbed from the gut and crosses cellular and blood-brain membrane barriers
*BBB↑,

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↑,

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↓, Suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α) followed inhibition of cleaved caspase-3
*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

3544- ALA,    Alpha lipoic acid for dementia
- Review, AD, NA
*antiOx↑, ALA is a low molecular weight antioxidant, readily absorbed from the diet or an oral dose, and crosses the blood brain barrier
*BBB↑,
*VitC↑, DHLA regenerates through redox cycling other antioxidants like vitamin C and E and raises levels of intracellular glutathione, an important thiol antioxidant
*VitE↑,
*GSH↑,
*IronCh↑, ALA al- so chelates certain metals, forming stable complexes with copper, manganese and zinc (Sigel 1978)
*neuroP↑, ALA would seem an ideal candidate as an antioxidant agent in neurodegenerative diseases.
*NO↓, ALA also modulates nitric oxide levels in brain and neural tissue, which may have effects in neurodegeneration, learning, cognition, and aging (Gross 1995)
*cognitive↑, elderly patients with dementia were given ALA. Findings suggested a stabilization of cognitive functions in the study group,
*AntiAge↑,
*memory↑, ALA has gained considerable attention following studies demonstrating partial reversal of memory loss in aged rats.
*ROS↓, scavenging hy- droxyl or superoxide radicals (Suzuki 1991) and by scavenging per- oxyl radicals (

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↑,

5319- ALC,    l-carnitine and cancer cachexia: Clinical and experimental aspects
- Review, Var, NA
fatigue↓, carnitine supplementation has been tested in preliminary studies concerning human cachexia, resulting in improved fatigue and quality of life.
QoL↑,
*GSH↑, l-carnitine treatment improved the tumor-induced decrease in muscular glutamate and glutathione levels and the increased plasma glutamate levels in tumor-bearing rodents
Dose↝, Significant improvements in fatigue were also observed in a randomized phase III clinical trial, in which l-carnitine (4 g/day) was orally given to patients with advanced cancer

2317- Api,    Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress
- in-vivo, Nor, NA
*hepatoP↑, promoting the recovery of liver function in mice with liver fibrosis.
*PKM2↓, API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer
*Hif1a↓, blocking PKM2-HIF-1α access
*MDA↓, leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of mice
*Catalase↓,
*GSH↑,
*SOD↑,
*GPx↑,
*TAC↑,
*α-SMA↓, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis
*Vim↓,
*ROS↓, API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress,

3676- Ash,    Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats
- in-vivo, Arthritis, NA
*CRP↓, WSAq resulted in a dose-dependent reduction in arthritic index, autoantibodies and CRP
*ROS↓, oxidative stress in CIA rats was ameliorated by treatment with different doses of WSAq, as evidenced by a decrease in lipid peroxidation and glutathione-S-transferase activity and an increase in the glutathione
*lipid-P↓,
*GSTs↓,
*GSH↑,
*antiOx↑, WSAq exhibited antioxidant and anti-arthritic activity and reduced inflammation in CIA rats
*Inflam↓,

3156- Ash,    Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug
- Review, Var, NA
MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 ± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2–related factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway

3164- Ash,    Withaferin A alleviates fulminant hepatitis by targeting macrophage and NLRP3
*hepatoP↑, Withania Somnifera, is a hepatoprotective agent
*IKKα↓, WA also inhibits inflammation by directly inhibiting IκκB activity46,47 or NLRP3 inflammasome activation in vitro in immune cells
*NLRP3↓,
*NRF2↑, WA probably protects against FH by targeting the macrophage and/or hepatocyte stress via activating NRF2, AMPKα
*AMPK↑,
*Inflam↓, Thus, WA potently protects against GalN/LPS-induced hepatotoxicity and inflammation
*Apoptosis↓, WA suppressed hepatic apoptosis in vivo
*cl‑Casp3↓, attenuate the increase of cleaved CASP3 and cleaved PARP1
*cl‑PARP1↓,
*NLRP3↓, WA prevented GalN/LPS-induced FH partially by inhibiting activation of the NLRP3 inflammasome
*ROS↓, fig 7
*ALAT↓,
*AST↓,
*GSH↑, (GSH) levels were significantly depleted by ~50% 6 h after GalN/LPS administration and were recovered to levels comparable with that of control mice by WA treatment

4303- Ash,    Ashwagandha (Withania somnifera)—Current Research on the Health-Promoting Activities: A Narrative Review
- Review, AD, NA
*neuroP↑, neuroprotective, sedative and adaptogenic effects and effects on sleep.
*Sleep↑,
*Inflam↓, anti-inflammatory, antimicrobial, cardioprotective and anti-diabetic properties
*cardioP↑,
*cognitive↑, Significant improvements in cognitive function were observed as a result of the inhibition of amyloid β-42, and a reduction in pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and MCP-1, nitric oxide, and lipid peroxidation was also observed.
*Aβ↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*MCP1↓,
*lipid-P↓,
*tau↓, reducing β-amyloid aggregation and inhibiting τ protein accumulation.
*ROS↓, withaferin A is responsible for inhibiting oxidative and pro-inflammatory chemicals and regulating heat shock proteins (HSPs), the expression of which increases when cells are exposed to stressors.
*BBB↑, ability of withanolide A to penetrate the blood-brain barrier (BBB) was demonstrated.
*AChE↓, potentially inhibiting acetylcholinesterase activity, which may have benefits in the treatment of canine cognitive dysfunction and Alzheimer’s disease
*GSH↑, increased glutathione concentration, increased glutathione S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase activities,
*GSTs↑,
*GSR↑,
*GPx↑,
*SOD↑,
*Catalase↑,
ChemoSen↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin
*Strength↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin

5384- AsP,  MEL,    Synergistic Anticancer Effect of Melatonin and Ascorbyl Palmitate Nanoformulation: A Promising Combination for Cancer Therapy
- in-vivo, Var, NA
AntiCan↑, assess the anticancer effect of melatonin (MEL) and ascorbyl palmitate-loaded pluronic nanoparticles (APnp) combination on Ehrlich ascites carcinoma (EAC)-bearing mice.
TumCG↓, MEL alone showed a decrease in tumor growth by 48%, while in the case of using MEL combined with APnp, it displayed inhibition of tumor growth by 62%
Apoptosis↑, It also induced apoptosis and DNA damage.
DNAdam↑,
TumCCA↑, Besides, mediated cell cycle arrest.
IL6↓, IL-6/STAT3 pathway was inactivated to a greater extent after our combination treatment.
STAT3↓,
TumCP↓, antiproliferative effect of MEL and APnp via decreased expression of Ki-67
Ki-67↓,
TumCI↓, Our combination of MEL and APnp was able to inhibit cancer cell invasion and metastasis by decreasing the protein expression of MMP-9.
TumMeta↓,
MMP9↓,
eff↑, The synergy score was 21.06 ( > 10 indicates synergistic effect)
*Catalase↑, Administration of MEL alone or MEL+ APnp treated mice showed a significant and highly significant increase, respectively (P<0.05, P<0.01) in the antioxidant enzyme activities of CAT and SOD, and GSH.
*SOD↑,
*GSH↑,
*MDA↓, Figure 2 demonstrated a highly significant and extremely significant reduction, respectively (P<0.01, P<0.001) in the MDA and NO levels compared to the EAC control group.
*NO↓,
*antiOx↑, Figure 2 demonstrated a highly significant and extremely significant reduction, respectively (P<0.01, P<0.001) in the MDA and NO levels compared to the EAC control group.
*hepatoP↑, combined MEL and APnp- treated animals displayed a noteworthy amelioration for all examined organs when compared to the control EAC inoculated group, Figure 3.
*RenoP↑,

2605- Ba,  BA,    Potential therapeutic effects of baicalin and baicalein
- Review, Var, NA - Review, Stroke, NA - Review, IBD, NA - Review, Arthritis, NA - Review, AD, NA - Review, Park, NA
cardioP↑, cardioprotective activities.
Inflam↓, Decreasing the accumulation of inflammatory mediators and improving cognitive function
cognitive↑,
*hepatoP↑, Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms
*ROS?, Reducing oxidative stress and protecting the mitochondria to inhibit apoptosis are proposed as hepatoprotective mechanisms of baicalin in NAFLD
*SOD↑, Baicalin could reduce the levels of ROS and fatty acid-induced MDA, and increase superoxide dismutase (SOD) and glutathione amounts compared to the control.
*GSH↑,
*MMP↑, Moreover, baicalin could partially restore mitochondrial morphology and increase ATP5A expression and mitochondrial membrane potential (Gao et al., 2022).
*GutMicro↑, After baicalein treatment, a remodelling in the overall structure of the gut microbiota was observed
ChemoSen↑, Besides, a combination of baicalin and doxorubicin could elevate the chemosensitivity of MCF-7 and MDA-MB-231 breast cancer cells
*TNF-α↓, Baicalin can protect cardiomyocytes from hypoxia/reoxygenation injury by elevating the SOD activity and anti-inflammatory responses through reducing TNF-α, enhancing IL-10 levels, decreasing IL-6, and inhibiting the translocation of NF-κB to the nucl
*IL10↑,
*IL6↓,
*eff↑, Studies show that baicalin and baicalein may be effective against IBD by suppressing oxidative stress and inflammation, and regulating the immune system.
*ROS↓,
*COX2↓, baicalein can improve the symptoms of ulcerative colitis by lowering the expression of pregnane X receptor (PXR), (iNOS), (COX-2), and caudal-type homeobox 2 (Cdx2), as well as the NF-κβ and STAT3
*NF-kB↓,
*STAT3↓,
*PGE2↓, Administration of baicalin (30-90 mg/kg) could decrease the levels of prostaglandin E2 (PEG2), myeloperoxidase (MPO), IL-1β, TNF-α, and the apoptosis-related genes including Bcl-2 and caspase-9
*MPO↓,
*IL1β↓,
*MMP2↓, Rheumatoid arthritis RA mouse model by supressing relevant proinflammatory cytokines such as IL-1b, IL-6, MMP-2, MMP-9, TNF-α, iNOS, and COX-2)
*MMP9↓,
*β-Amyloid↓, Alzheimer’s disease (AD) : reduce β-amyloid and trigger non-amyloidogenic amyloid precursor proteins.
*neuroP↑, For instance, administration of baicalin orally for 14 days (100 mg/kg body weight) exhibited neuroprotective effects on pathological changes and behavioral deficits of Aβ 1–42 protein-induced AD in vivo.
*Dose↝, administration of baicalin (500 mg/day, orally for 12 weeks) could improve the levels of total cholesterol, TGs, LDLC and apolipoproteins (APOs), and high-sensitivity C-reactive protein (hs-CRP) in patients with rheumatoid arthritis and coronary arte
*BioAv↝, the total absorption of baicalin depends on the activity of intestinal bacteria to convert baicalin to baicalein as the first step.
*BioAv↝, Kidneys, liver, and lungs are the main organs in which baicalin accumulates the most.
*BBB↑, Baicalin and baicalein can pass through the blood brain barrier (BBB)
*BDNF↑, mechanism of action for baicalein is illustrated in Figure 3. Activation of the BDNF/TrkB/CREB pathway, inhibition of NLRP3/Caspase-1/GSDMD pathway,

2613- Ba,    Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice
- in-vivo, Nor, NA
*hepatoP↑, baicalein significantly ameliorated APAP-exposed liver damage and histological hepatocyte changes
*MDA↓, baicalein (50 or 100 mg/kg) pretreatment significantly inhibited liver MDA level (p < 0.05; Figure 4), increased SOD, CAT and GSH activity.
*SOD↑,
*Catalase↑,
*GSH↑,
*MAPK↓, Baicalein Prevented the MAPK Pathway Activation
*p‑JAK2↓, BAI Suppressed the Expression of p-JAK2 and p-STAT3 Proteins in APAP Liver Injury
*p‑STAT3↓,
*ALAT↓, our experimental results suggested that serum ALT and AST levels were obviously alleviated by Baicalein in a dose-dependent manner
*AST↓,
*ROS↓, hepatoprotective role of BAI via attenuating oxidative stress
*antiOx↑, hepatoprotective activity of Baicalein might be associated with its antioxidative capacity.

2689- BBR,    Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells
- in-vitro, Nor, PC12 - in-vitro, AD, NA - in-vitro, Stroke, NA
*ROS↓, In both cell lines, pretreatment with berberine (especially at low concentrations) significantly decreased ROS generation, lipid peroxidation, and DNA fragmentation, while improving glutathione content and SOD activity in glutamate-injured cells.
*lipid-P↓,
*DNAdam↓, Berberine significantly diminished glutamate-induced DNA fragmentation
*GSH↑,
*SOD↑,
*eff↑, This is relevant to berberine treatment in neurodegenerative disorders, such as dementia (Alzheimer’s disease), seizures, and stroke.
*cl‑Casp3↓, Berberine significantly decreased cleaved caspase-3 and bax/bcl-2 expressions in the glutamate-injured cells
*BAX↓,
*neuroP↑, the current study demonstrated that berberine exerts neuroprotective effects against glutamate-induced N2a and PC12 cytotoxicity via antioxidant and anti-apoptotic mechanisms
*Dose↝, the protective effect of berberine was more significant at lower concentrations and decreased with increasing concentration.
*Ca+2↓, Nadjafi et al demonstrated that berberine protects OLN-93 oligodendrocytes against ischemic-induced cell death by attenuating the intracellular Ca2+ overload similar to the NMDA or the AMPA/kainate receptors antagonists

3684- BBR,    Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies
- Review, AD, NA
*Inflam↓, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects.
*antiOx↓,
*AChE↓,
*BChE↓, berberine exerts inhibitory effects on the four key enzymes in the pathogenesis of AD: acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A, and monoamine oxidase B
*MAOA↓,
*MAOB↓,
*lipid-P↓, Fig3
*GSH↑,
*ROS↓,
*APP↓,
*BACE↓,
*p‑tau↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*MAPK↓,
*PI3K↓,
*Akt↓,
*neuroP↑, neuroprotective effects of berberine have been extensively studied
*memory↑, berberine displayed significant effects in preventing memory impairment in these mechanistically different animal models, suggesting an over-all improvement of memory function by berberine

4299- BBR,    Berberine attenuates cognitive impairment and ameliorates tau hyperphosphorylation by limiting the self-perpetuating pathogenic cycle between NF-κB signaling, oxidative stress and neuroinflammation
- in-vivo, AD, NA
*memory↑, BBR improved learning and memory in APP/PS1 mice.
*p‑tau↓, BBR decreased the hyperphosphorylated tau protein in the hippocampus of APP/PS1 mice.
*NF-kB↓, BBR lowered the activity of NF-κB signaling in the hippocampus of AD mice.
*GSH↑, BBR-administration promoted the activity of glutathione (GSH) and inhibited lipid peroxidation in the hippocampus of AD mice.
*lipid-P↓,
*cognitive↑, BBR attenuated cognitive deficits and limited hyperphosphorylation of tau via inhibiting the activation of NF-κB
*ROS↓, by retarding oxidative stress and neuro-inflammation.
*Inflam↓,

2725- BetA,    Betulinic acid protects against renal damage by attenuation of oxidative stress and inflammation via Nrf2 signaling pathway in T-2 toxin-induced mice
- in-vivo, Nor, NA
*RenoP↑, BA pretreatment alleviated excessive glomerular hemorrhage and inflammatory cell infiltration in kidneys caused by T-2 toxin.
*SOD?, Moreover, pretreatment with BA mitigated T-2 toxin-induced renal oxidative damage by up-regulating the activities of SOD and CAT, and the content of GSH, while down-regulating the accumulation of ROS and MDA
*Catalase↑,
*GSH↑,
*ROS↓,
*MDA↓,
*IL1β↓, decreasing the mRNA expression of IL-1β, TNF-α and IL-10, and increasing IL-6 mRNA expression
*TNF-α↓,
*IL10↓,
*IL6↑,
*NRF2↑, pretreatment with BA could activate Nrf2 signaling pathway.

2731- BetA,    Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives
- Review, GBM, NA - Review, Park, NA - Review, AD, NA
BBB↑, Notably, its ability to cross the blood–brain barrier addresses a significant challenge in treating neurological pathologies.
*GSH↑, BA can also dramatically reduce catalepsy and stride length, while increasing the brain’s dopamine content, glutathione activity, and catalase activity in hemiparkinsonian rats
*Catalase↑,
*motorD↑,
*neuroP↑, in Alzheimer’s disease rat models, it can improve neurobehavioral impairments . BA has exhibited great neuroprotective properties.
*cognitive↑, BA improves cognitive ability and neurotransmitter levels, and protects from brain damage by lowering reactive oxygen species (ROS) levels
*ROS↓,
*antiOx↑, enhancing brain tissue’s antioxidant capacity, and preventing the release of inflammatory cytokines
*Inflam↓,
MMP↓, BA can decrease the mitochondrial outer membrane potential (MOMP)
STAT3↓, The compound can inhibit the signal transducer and activator of transcription (STAT) 3 signaling pathways, involved in differentiation, proliferation, apoptosis, metastasis formation, angiogenesis, and metabolism, and the NF-kB signaling pathway,
NF-kB↓,
Sp1/3/4↓, BA has shown an ability to control cancer growth through the modulation of Sp transcription factors, inhibit DNA topoisomerase
TOP1↓,
EMT↓, inhibit the epithelial-to-mesenchymal transition (EMT)
Hif1a↓, BA has also been associated with an antiangiogenic response under hypoxia conditions, through the STAT3/hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) signaling pathway
VEGF↓,
ChemoSen↑, BA has shown great potential as an adjuvant to therapy since its use combined with standard treatment of chemotherapy and irradiation can enhance their cytotoxic effect on cancer cells
RadioS↑,
BioAv↓, Despite having great potential as a therapeutic agent, it is hard for BA to fulfill the requirements for adequate water solubility, maintaining both significant cytotoxicity and selectivity for tumor cells.

2758- BetA,    Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway
- in-vivo, Nor, NA
*ROS↓, protective effects and mechanisms of BA in blocking oxidative stress caused by acute exposure to T-2 toxin in the thymus of mice was studied.
*MDA↓, BA pretreatment reduced ROS production, decreased the MDA content, and increased the content of IgG in serum and the levels of SOD and GSH in the thymus.
*SOD↑,
*GSH↑,
*p‑p38↓, BA downregulated the phosphorylation of the p38, JNK, and ERK proteins, while it upregulated the expression of the Nrf2 and HO-1 proteins in thymus tissues.
*p‑JNK↓,
*p‑ERK↓,
*NRF2↑,
*HO-1↑,
*MAPK↓, suppressing the MAPK signaling pathway.
*heparanase↑, BA also showed protective activities against alcohol-induced liver damage and dexamethasone-induced spleen and thymus oxidative damage, and these protective effects were related to the antioxidant capacity of BA
*antiOx↑, BA Increased T-2 Toxin-Induced Thymus Antioxidative Capacity

2760- BetA,    A Review on Preparation of Betulinic Acid and Its Biological Activities
- Review, Var, NA - Review, Stroke, NA
AntiTum↑, BA is considered a future promising antitumor compound
Cyt‑c↑, BA stimulated mitochondria to release cytochrome c and Smac and cause further apoptosis reactions
Smad1↑,
Sepsis↓, Administration of 10 and 30 mg/kg of BA significantly improved survival against sepsis and attenuated lung injury.
NF-kB↓, BA inhibited nuclear factor-kappa B (NF-κB) expression in the lung and decreased levels of cytokine, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9)
ICAM-1↓,
MCP1↓,
MMP9↓,
COX2↓, In hPBMCs, BA suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PEG2) production by inhibiting extracellular regulated kinase (ERK) and Akt phosphorylation and thereby modulated the NF-κB signaling pathway
PGE2↓,
ERK↓,
p‑Akt↓,
*ROS↓, BA significantly decreased the mortality of mice against endotoxin shock and inhibited the production of PEG2 in two of the most susceptible organs, lungs and livers [80]. Moreover, BA reduced reactive oxygen species (ROS) formation
*LDH↓, and the release of lactate dehydrogenase
*hepatoP↑, hepatoprotective effect of BA from Tecomella undulata.
*SOD↑, Pretreatment of BA prevented the depletion of hepatic antioxidants superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) and ascorbic acid (AA) and decreased the CCl4-induced LPO level
*Catalase↑,
*GSH↑,
*AST↓, A also attenuated the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) plasma level,
*ALAT↓,
*RenoP↑, BA also exhibits renal-protective effects. Renal fibrosis is an end-stage renal disease symptom that develops from chronic kidney disease (CKD).
*ROS↓, BA protected against this ischemia-reperfusion injury in a mice model by enhancing blood flow and reducing oxidative stress and nitrosative stress
*α-SMA↓, Moreover, BA reduced the expression of α-smooth muscle actin (α-SMA) and collagen-I

2761- BetA,    Betulinic acid increases lifespan and stress resistance via insulin/IGF-1 signaling pathway in Caenorhabditis elegans
- in-vivo, Nor, NA
Insulin↓, BA improves insulin sensitivity in metabolic syndrome rats (51), but inhibits insulin/IGF-1 receptor signaling to suppress de novo lipogenesis in HepG2 cells
IGF-1↓,
*SOD↑, figure 4
*Catalase↑,
*GSH↑,
*MDA↓,
*antiOx?, Betulinic acid has robust antioxidant activity in vivo.

3517- Bor,  Se,    The protective effects of selenium and boron on cyclophosphamide-induced hepatic oxidative stress, inflammation, and apoptosis in rats
- in-vivo, Nor, NA
*hepatoP↑, However, it was found that Se protects the liver slightly better against CP damage than B
*ALAT↓, statistically significant difference was observed in the serum levels of ALT, AST, ALP, TAS, TOS and OSI.
*AST↓,
*ALP↓,
*NF-kB↓, A statistically significant difference was observed in serum levels of NF-kB, TNF-α, IL -1β, IL -6 and IL -10 when the Se + CP and B + CP-treated groups were compared with the CP-treated group
*TNF-α↓, fig 9
*IL1β↓,
*IL6↓,
*IL10↑,
*SOD↑, A statistically remarkable change in serum levels of SOD, CAT, GPx, MDA and GSH was observed in the group receiving only CP compared to groups Se, B and the control.
*Catalase↑,
*MDA↓, Fig 10
*GSH↑,
*GPx↑,
*antiOx↑, suggests that B and Se increase intracellular antioxidant status.
*NRF2↑, Se and B treatment can protect rat liver tissue from CP-induced oxidative stress, inflammation, and apoptosis by regulating Bax/Bcl-2 and Nrf2-Keap-1 signaling pathways.
*Keap1↓,

3516- Bor,    Boron in wound healing: a comprehensive investigation of its diverse mechanisms
- Review, Wounds, NA
*Inflam↓, anti-inflammatory, antimicrobial, antioxidant, and pro-proliferative effects.
*antiOx↑,
*ROS↓, The antioxidant properties of boron help protect cells from oxidative stress, a common feature of chronic wounds that can impair healing
*angioG↑, Boron compounds exhibit diverse therapeutic actions in wound healing, including antimicrobial effects, inflammation modulation, oxidative stress reduction, angiogenesis induction, and anti-fibrotic properties.
*COL1↑, Boron has been shown to increase the expression of proteins involved in wound contraction and matrix remodeling, such as collagen, alpha-smooth muscle actin, and transforming growth factor-beta1.
*α-SMA↑,
*TGF-β↑,
*BMD↑, Animals treated with boron showed favorable changes in bone density, wound healing, embryonic development, and liver metabolism
*hepatoP↑,
*TNF-α↑, BA elevates TNF-α and heat-shock proteins 70 that are related to wound healing.
*HSP70/HSPA5↑,
*SOD↑, antioxidant properties of BA showed that boron protects renal tissue from I/R injury via increasing SOD, CAT, and GSH and decreasing MDA and total oxidant status (TOS)
*Catalase↑,
*GSH↑,
*MDA↓,
*TOS↓,
*IL6↓, Boron supports gastric tissue by alleviating ROS, MDA, IL-6, TNF-α, and JAK2/STAT3 action, as well as improving AMPK activity
*JAK2↓,
*STAT3↓,
*AMPK↑,
*lipid-P↓, boron may improve wound healing by hindering lipid peroxidation and increasing the level of VEGF
*VEGF↑,
*Half-Life↝, Boron is a trace element, usually found at a concentration of 0–0.2 mg/dL in plasma with a half-life of 5–10 h, and 1–2 mg of it is needed in the daily diet

760- Bor,    Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats with Experimental Alzheimer’s Disease
- in-vivo, AD, NA
*memory↑, BA reduced damage to learning and memory functions and significantly lowered oxidative stress markers in the AD model.
*ROS↓, been reported that BA also reduces oxidative stress by increasing glutathione reserves,
*GSH↑,
*Aβ↓, and strongly inhibits Aβ aggregation via hydroxyl group
*Inflam↓, BA can act as a protective agent in apoptotic processes by regulating oxidative and inflammatory processes as well as mitochondrial membrane potential
*MMP↑,
*lipid-P↓, BA added to the diet prevented lipid peroxidation by supporting and strengthening the antioxidant defense system.
*Ca+2↓, Boron is thought to prevent apoptosis and strengthen antioxidant defense by reducing intracellular oxygen radicals and calcium levels.
*cognitive↑, Our hypothesis is that boric acid can improve cognitive function and histopathological outcomes by reducing oxidative stress in rats with STZ-induced Alzheimer’s Disease
*TOS↓, After BA administration, it increased TAS by increasing the antioxidant effect, and as a result, TOS and OSI decreased.

4272- Bor,    Neuroprotective properties of borax against aluminum hydroxide-induced neurotoxicity: Possible role of Nrf-2/BDNF/AChE pathways in fish brain
*NRF2↑, BX clearly activating the Nrf-2/ROS signaling pathway.
*ROS↓,
*antiOx↑, BX supported antioxidant capacity without leading apoptosis, lipid peroxidation, inflammatory response and DNA damage.
*lipid-P↑,
*Inflam↓,
*DNAdam↓,
*BDNF↑, BX also increased the BDNF levels and AChE activity.
*neuroP↑, BX exerted a neuroprotective effect against AH-induced neurotoxicity via down-regulating cytokine-related pathways, minimising DNA damage, apoptosis
*GSH↑, as well as up-regulating GSH, AChE, BDNF and antioxidant enzyme levels.

2775- Bos,    The journey of boswellic acids from synthesis to pharmacological activities
- Review, Var, NA - Review, AD, NA - Review, PSA, NA
ROS↑, modulation of reactive oxygen species (ROS) formation and the resulting endoplasmic reticulum stress is central to BA’s molecular and cellular anticancer activities
ER Stress↑,
TumCG↓, Cell cycle arrest, growth inhibition, apoptosis induction, and control of inflammation are all the effects of BA’s altered gene expression
Apoptosis↑,
Inflam↓,
ChemoSen↑, BA has additional synergistic effects, increasing both the sensitivity and cytotoxicity of doxorubicin and cisplatin
Casp↑, BA decreases viability and induces apoptosis by activat- ing the caspase-dependent pathway in human pancreatic cancer (PC) cell lines
ERK↓, BA might inhibit the activation of Ak strain transforming (Akt) and extracellular signal–regulated kinase (ERK)1/2,
cl‑PARP↑, initiation of cleavage of PARP were prompted by the treatment with AKBA
AR↓, AKBA affects the androgen receptor by reducing its expression,
cycD1/CCND1↓, decrease in cyclin D1, which inhibits cellular proliferation
VEGFR2↓, In prostate cancer, the downregulation of vascular endothelial growth factor receptor 2–mediated angiogenesis caused by BA
CXCR4↓, Figure 6
radioP↑,
NF-kB↓,
VEGF↓,
P21↑,
Wnt↓,
β-catenin/ZEB1↓,
Cyt‑c↑,
MMP2↓,
MMP1↓,
MMP9↓,
PI3K↓,
MAPK↓,
JNK↑,
*5LO↓, Table 1 (non cancer)
*NRF2↑,
*HO-1↑,
*MDA↓,
*SOD↑,
*hepatoP↑, Preclinical studies demonstrated hepatoprotective impact for BA against different models of hepatotoxicity via tackling oxidative stress, and inflammatory and apoptotic indices
*ALAT↓,
*AST↓,
*LDH↑,
*CRP↓,
*COX2↓,
*GSH↑,
*ROS↓,
*Imm↑, oral administration of biopolymeric fraction (BOS 200) from B. serrata in mice led to immunostimulatory effects
*Dose↝, BA at low concentration tend to stimulate an immune response, as those utilized in the study of Beghelli et al. (2017) however, utilizing higher concentration suppressed the immune response
*eff↑, Useful actions on skin and psoriasis
*neuroP↑, AKBA has substantially diminished the levels of inflammatory markers such as 5-LOX, TNF-, IL-6, and meliorated cognition in lipopolysaccharide-induced neuroinflammation rodent models
*cognitive↑,
*IL6↓,
*TNF-α↓,

5740- Buty,    A Review of Nutritional Regulation of Intestinal Butyrate Synthesis: Interactions Between Dietary Polysaccharides and Proteins
- Review, RCC, NA
*eff↓, excessive protein fermentation produces branched-chain fatty acid (BCFA), ammonia, phenols, and other metabolites that inhibit butyrate production
Dose↝, Several studies have found that the ratio of acetate to propionate to butyrate in the colon of healthy individuals (regardless of region) has been found to be approximately 60:20:20 [2,3].
eff↑, An appropriate polysaccharide-to-protein ratio appears crucial for maintaining gut microbial homeostasis and facilitating butyrate generation.
HDAC↓, butyrate is a classic HDAC inhibitor that increases the acetylation level of histone H3 and H4,
ac‑H3↓,
ac‑H4↓,
*HCAR2↑, butyrate is produced by the gut microbiota at high concentrations (10–20 mM) and acts as an endogenous agonist of GPR109A.
*Inflam↓, When butyrate activates GPR109A on colonocytes, it triggers intracellular signaling cascades, promotes the secretion of the anti-inflammatory cytokine IL-18,
*ROS↓, Moreover, butyrate reduces the level of reactive oxygen species by activating the Nrf2 antioxidant pathway and enhancing glutathione (GSH) synthesis, and alleviate stress damage to the to intestinal barrier and immune cells.
*NRF2↑,
*GSH↑,
*CLDN1↑, Butyrate also enhances epithelial barrier function by upregulating the expression of tight junction proteins such as Claudin-1, Occludin, and ZO-1 in intestinal epithelial cells.
*ZO-1↑,
IL1β↓, rucial role in repairing and strengthening the intestinal barrier by downregulating the transcription of pro-inflammatory genes, including IL-1β, IL-6, and COX-2,
IL6↓,
COX2↓,
eff↝, Different types of monosaccharides significantly influence the efficiency of butyrate production due to their distinct chemical properties and microbial utilization mechanisms.
eff↑, After entering the colon, polysaccharides serve as fermentation substrates for gut microbiota and are broken down into butyrate.
other↝, A central challenge in current research on gut microbiota and butyrate production lies in determining the optimal dietary ratio of polysaccharides to proteins.


Showing Research Papers: 1 to 50 of 252
Page 1 of 6 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 252

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 1,   HO-1↑, 1,   Iron↑, 1,   lipid-P↑, 1,   OXPHOS↓, 1,   ROS↑, 5,  

Mitochondria & Bioenergetics ⓘ

Insulin↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   FDG↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   PDH↑, 1,   TCA↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 5,   BAX↑, 1,   Bcl-2↓, 1,   BIM↑, 1,   Casp↑, 1,   Casp12↑, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 3,   DR5↑, 1,   Fas↑, 1,   Ferroptosis↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   p38↑, 2,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

RET↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↓, 1,   ac‑H4↓, 1,   other↝, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   eIF2α↓, 1,   ER Stress↑, 1,   HSP90↓, 1,  

DNA Damage & Repair ⓘ

CHK1↓, 1,   DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 1,   PARP1↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   P21↑, 2,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CD44↓, 1,   cMET↓, 1,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 2,   HDAC↓, 1,   IGF-1↓, 1,   mTOR↓, 1,   Nanog↓, 1,   NOTCH1↓, 1,   PI3K↓, 2,   SOX2↓, 1,   STAT3↓, 4,   TOP1↓, 1,   TumCG↓, 3,   Wnt↓, 2,  

Migration ⓘ

AP-1↓, 1,   p‑FAK↓, 1,   Ki-67↓, 1,   MMP1↓, 1,   MMP2↓, 1,   MMP9↓, 3,   Smad1↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 1,   uPA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   EGR4↓, 1,   Hif1a↓, 2,   VEGF↓, 3,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCR4↓, 1,   ICAM-1↓, 1,   IL1β↓, 1,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 2,   MCP1↓, 1,   NF-kB↓, 5,   NK cell↑, 1,   PGE2↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 3,   ChemoSen↑, 5,   Dose↝, 2,   eff↑, 3,   eff↝, 1,   Half-Life↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 1,   IL6↓, 2,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   AntiTum↑, 1,   cardioP↑, 1,   chemoP↑, 1,   cognitive↑, 2,   fatigue↓, 1,   QoL↑, 1,   radioP↑, 1,   RenoP↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 126

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx?, 1,   antiOx↓, 2,   antiOx↑, 28,   Catalase↓, 1,   Catalase↑, 14,   GPx↑, 7,   GSH↑, 51,   GSR↑, 2,   GSTs↓, 1,   GSTs↑, 4,   H2O2∅, 1,   HDL↑, 1,   HO-1↑, 5,   Iron↓, 1,   Keap1↓, 2,   lipid-P↓, 14,   lipid-P↑, 1,   MDA↓, 15,   MPO↓, 3,   NQO1↑, 2,   Nrf1↑, 1,   NRF2↑, 17,   ROS?, 1,   ROS↓, 38,   ROS↑, 1,   SOD?, 1,   SOD↑, 20,   TAC↑, 1,   TBARS↓, 2,   TOS↓, 2,   VitC↑, 5,   VitE↑, 4,  

Metal & Cofactor Biology ⓘ

IronCh↑, 13,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 2,   Insulin↑, 1,   MMP↑, 4,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   Acetyl-CoA↑, 2,   adiP↓, 1,   ALAT↓, 7,   AMPK↑, 4,   AMPK⇅, 1,   FAO↑, 1,   glucose↑, 1,   GlucoseCon↑, 9,   H2S↑, 2,   LDH↓, 3,   LDH↑, 1,   LDL↓, 2,   NADPH↑, 1,   PDH↑, 1,   PDKs↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt?, 1,   Akt↓, 2,   Akt↑, 2,   Apoptosis↓, 1,   BAX↓, 1,   Casp3↓, 1,   cl‑Casp3↓, 2,   Casp9↓, 1,   iNOS↓, 3,   JNK↓, 1,   p‑JNK↓, 1,   MAPK↓, 3,   MAPK↑, 2,   p38↑, 1,   p‑p38↓, 1,  

Kinase & Signal Transduction ⓘ

HCAR2↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 6,   other↓, 1,   other↑, 2,   other↝, 2,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,   HSP70/HSPA5↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↓, 2,   cl‑PARP1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 2,   p‑ERK↓, 1,   IGF-1↑, 1,   PI3K↓, 2,   PI3K↑, 3,   PTEN↓, 2,   STAT3↓, 2,   p‑STAT3↓, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↑, 1,   APP↓, 1,   Ca+2↓, 3,   CLDN1↑, 1,   COL1↑, 1,   COL3A1↓, 1,   heparanase↑, 1,   MMP2↓, 1,   MMP9↓, 3,   PKCδ↑, 3,   TGF-β↑, 1,   VCAM-1↓, 5,   Vim↓, 1,   ZO-1↑, 1,   α-SMA↓, 3,   α-SMA↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   eNOS↑, 1,   p‑eNOS↑, 1,   Hif1a↓, 1,   Hif1a↑, 1,   NO↓, 5,   VEGF↑, 2,  

Barriers & Transport ⓘ

BBB↑, 11,   GLUT1↑, 1,   GLUT3↑, 2,   GLUT4↑, 4,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   CRP↓, 3,   HCAR2↑, 1,   ICAM-1↓, 1,   IKKα↓, 1,   IL1↓, 1,   IL10↓, 1,   IL10↑, 3,   IL1β↓, 9,   IL4↑, 1,   IL5↑, 1,   IL6↓, 8,   IL6↑, 1,   Imm↑, 1,   Inflam↓, 24,   JAK2↓, 1,   p‑JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 12,   PGE2↓, 2,   TLR4↓, 1,   TNF-α↓, 10,   TNF-α↑, 1,  

Cellular Microenvironment ⓘ

NOX↓, 1,  

Synaptic & Neurotransmission ⓘ

5HT↑, 2,   AChE↓, 4,   BChE↓, 1,   BDNF↑, 2,   ChAT↑, 5,   MAOA↓, 1,   tau↓, 1,   p‑tau↓, 3,  

Protein Aggregation ⓘ

Aβ↓, 6,   BACE↓, 1,   MAOB↓, 1,   NLRP3↓, 2,   β-Amyloid↓, 1,  

Hormonal & Nuclear Receptors ⓘ

RAAS↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 3,   BioAv↝, 6,   Dose↝, 6,   eff↓, 5,   eff↑, 8,   eff↝, 1,   Half-Life↓, 2,   Half-Life↑, 1,   Half-Life↝, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 7,   ALP↓, 2,   AST↓, 7,   BG↓, 1,   BMD↑, 1,   BP↓, 3,   BP↝, 1,   creat↓, 1,   CRP↓, 3,   GutMicro↑, 3,   IL6↓, 8,   IL6↑, 1,   LDH↓, 3,   LDH↑, 1,  

Functional Outcomes ⓘ

AntiAge↑, 2,   AntiCan↑, 2,   AntiDiabetic↑, 1,   AntiTum↑, 1,   BOLD↑, 1,   cardioP↑, 8,   cognitive↑, 19,   hepatoP↑, 15,   memory↑, 13,   motorD↑, 3,   neuroP↑, 24,   RenoP↑, 5,   Risk↓, 3,   Sleep↑, 1,   Strength↑, 1,   toxicity↓, 1,   toxicity↝, 1,   Weight↓, 2,  
Total Targets: 193

Scientific Paper Hit Count for: GSH, Glutathione
26 Thymoquinone
18 Alpha-Lipoic-Acid
16 Silymarin (Milk Thistle) silibinin
12 Curcumin
10 Resveratrol
10 Quercetin
9 Rosmarinic acid
8 Lycopene
8 Sulforaphane (mainly Broccoli)
7 Selenium
6 Chemotherapy
6 Propolis -bee glue
6 Selenium NanoParticles
6 Shikonin
5 Silver-NanoParticles
5 Betulinic acid
5 Chlorogenic acid
5 Luteolin
4 Allicin (mainly Garlic)
4 Ashwagandha(Withaferin A)
4 Melatonin
4 Boron
4 Carnosic acid
4 Carvacrol
4 Honokiol
3 Berberine
3 Chrysin
3 Radiotherapy/Radiation
3 doxorubicin
3 Piperine
3 Pterostilbene
3 Rutin
2 Baicalein
2 Caffeic Acid Phenethyl Ester (CAPE)
2 Thymol-Thymus vulgaris
2 Chocolate
2 diet Methionine-Restricted Diet
2 EGCG (Epigallocatechin Gallate)
2 Fisetin
2 Magnetic Fields
2 Methylsulfonylmethane
2 Piperlongumine
2 chitosan
2 Selenite (Sodium)
1 Anthocyanins
1 Ajoene (compound of Garlic)
1 Acetyl-l-carnitine
1 Apigenin (mainly Parsley)
1 Ascorbyl Palmitate
1 Baicalin
1 Boswellia (frankincense)
1 Butyrate
1 Caffeic acid
1 Crocetin
1 Galantamine
1 Cysteamine
1 Ellagic acid
1 Exercise
1 Ferulic acid
1 Shilajit/Fulvic Acid
1 Gallic acid
1 Ginkgo biloba
1 γ-linolenic acid (Borage Oil)
1 Hydrogen Gas
1 Hydroxycinnamic-acid
1 Magnetic Field Rotating
1 Moringa oleifera
1 Mushroom Lion’s Mane
1 N-Acetyl-Cysteine
1 Oleuropein
1 HydroxyTyrosol
1 Phenylbutyrate
1 Parthenolide
1 Orlistat
1 salinomycin
1 polyethylene glycol
1 Anti-oxidants
1 Date Fruit Extract
1 Sesame seeds and Oil
1 Shankhpushpi
1 Squalene
1 Taurine
1 methotrexate
1 Ursolic acid
1 Urolithin
1 Vitamin B12
1 Folic Acid, Vit B9
1 Vitamin C (Ascorbic Acid)
1 immunotherapy
1 Vitamin K2
1 probiotics
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#:%  Target#:137  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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