Description: <b>Garlic</b> (Allium sativum L.) (active ingredient- Allicin, an active sulfer compound).<br>
Summary:<br>
- Four main organic sulfides in garlic, diallyl disulfide (DADS), diallyl trisulfide (DATS), S-allylmercaptocysteine (SAMC) and allicin.<br>
- Reversible inhibitor of ACSS2.<br>
- may inhibit NF-κB signaling<br>
- induce oxidative stress in cancer cells by generating ROS<br>
- might downregulate STAT3 activation<br>
- Inconclusive evidence for cancer treatment.<br>
- may inhibit <a href="tbResEdit.php?rid=2558">platelet aggregation</a><br>
Allicin is a reactive sulfur species (RSS) [23] with oxidizing properties, and it is able to oxidize thiols in cells, e.g., glutathione and cysteine residues in proteins.<br>
-Allicin is not present in intact garlic; rather, it is formed when garlic is chopped or crushed.
-Using crushed or chopped raw garlic or adding garlic at the end of the cooking process (after the heat is reduced) can help preserve its potential allicin content.<br>
<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6073756/"> "Consumption of alliinase-inhibited cooked garlic was found to give higher than expected allicin bioequivalence, with AMS formation being about 30% (roasted garlic) or 16% (boiled garlic) that of crushed raw garlic."</a> <br>
<br>
-Allicin is not present in intact garlic.<br>
-It's formed enzymatically when alliin (a sulfur-containing amino acid) is converted by alliinase when garlic is chopped or crushed.Best consumed raw immediately after crushing (wait 5–10 min before consuming for full conversion)<br>
-Allicin is unstable, degrading within hours into other sulfur compounds (like diallyl disulfide).<br>
<br>
-Note <a href="tbResList.php?qv=27&tsv=1109&wNotes=on&exSp=open">half-life</a> reports vary 2.5-90hrs?.<br>
-low solubility of apigenin in water :
<a href="tbResList.php?qv=27&tsv=792&wNotes=on&exSp=open">BioAv</a>
<br><br>
<br>
Pathways:<br>
<!-- ROS : MMP↓, ER Stress↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, UPR↑, cl-PARP↑-->
- induce
<a href="tbResList.php?qv=27&tsv=275&wNotes=on">ROS</a> production<br>
- ROS↑ related:
<a href="tbResList.php?&qv=27&tsv=197&wNotes=on&word=MMP↓">MMP↓</a>(ΔΨm),
<a href="tbResList.php?&qv=27&tsv=103&wNotes=on">ER Stress↑</a>,
<a href="tbResList.php?&qv=27&tsv=38&wNotes=on&word=Ca+2↑">Ca+2↑</a>,
<a href="tbResList.php?&qv=27&tsv=77&wNotes=on">Cyt‑c↑</a>,
<a href="tbResList.php?&qv=27&wNotes=on&word=Casp">Caspases↑</a>,
<a href="tbResList.php?&qv=27&tsv=82&wNotes=on&word=DNAdam↑">DNA damage↑</a>,
<a href="tbResList.php?&qv=27&tsv=459&wNotes=on">UPR↑</a>,
<a href="tbResList.php?&qv=27&tsv=239&wNotes=on">cl-PARP↑</a>,
<a href="tbResList.php?&qv=27&wNotes=on&word=HSP">HSP↓</a>
<br>
<!-- ANTIOXIDANT : NRF2, SOD, GSH, CAT, HO-1, GPx, GPX4, -->
- Lowers
<a href="tbResList.php?&qv=27&tsv=1103&wNotes=on&word=antiOx↓">AntiOxidant</a> defense in Cancer Cells:
<a href="tbResList.php?&qv=27&tsv=226&wNotes=on&word=NRF2↓">NRF2↓</a>,
<a href="tbResList.php?&qv=27&tsv=137&wNotes=on&word=GSH↓">GSH↓</a>
<br>
- Raises
<a href="tbResList.php?&qv=27&tsv=1103&wNotes=on&word=antiOx↑">AntiOxidant</a>
defense in Normal Cells:
<a href="tbResList.php?&qv=27&tsv=226&wNotes=on&word=NRF2↑">NRF2↑</a>,
<a href="tbResList.php?&qv=27&tsv=298&wNotes=on&word=SOD↑">SOD↑</a>,
<a href="tbResList.php?&qv=27&tsv=137&wNotes=on&word=GSH↑">GSH↑</a>,
<a href="tbResList.php?&qv=27&tsv=46&wNotes=on&word=Catalase↑">Catalase↑</a>,
<br>
<!-- INFLAMMATION : NF-kB↓, COX2↓, COX2↓ PRO-INFL CYTOKINES: IL-1β↓, TNF-α↓, IL-6↓, IL-8↓, -->
- lowers
<a href="tbResList.php?&qv=27&tsv=953&wNotes=on&word=Inflam">Inflammation</a> :
<a href="tbResList.php?&qv=27&tsv=214&wNotes=on&word=NF-kB↓">NF-kB↓</a>,
<a href="tbResList.php?&qv=27&tsv=66&wNotes=on&word=COX2↓">COX2↓</a>,
<a href="tbResList.php?&qv=27&tsv=235&wNotes=on&word=p38↓">p38↓</a>, Pro-Inflammatory Cytokines :
<a href="tbResList.php?&qv=27&tsv=978&wNotes=on&word=IL1β↓">IL-1β↓</a>,
<a href="tbResList.php?&qv=27&tsv=309&wNotes=on&word=TNF-α↓">TNF-α↓</a>,
<a href="tbResList.php?&qv=27&tsv=158&wNotes=on&word=IL6↓">IL-6↓</a>,
<a href="tbResList.php?&qv=27&tsv=368&wNotes=on&word=IL8↓">IL-8↓</a>
<br>
- PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK.<br>
<!-- GROWTH/METASTASES : EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1, uPA↓, VEGF↓, ERK↓-->
- inhibit Growth/Metastases :
<a href="tbResList.php?&qv=27&tsv=96&wNotes=on">EMT↓</a>,
<a href="tbResList.php?&qv=27&tsv=201&wNotes=on">MMP2↓</a>,
<a href="tbResList.php?&qv=27&tsv=203&wNotes=on">MMP9↓</a>,
<a href="tbResList.php?&qv=27&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=27&tsv=105&wNotes=on">ERK↓</a>
<br>
<!-- REACTIVATE GENES : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, -->
- reactivate genes thereby inhibiting cancer cell growth :
<a href="tbResList.php?qv=27&tsv=140&wNotes=on">HDAC↓</a>(not commonly listed as inhibitor),
<a href="tbResList.php?qv=27&tsv=85&wNotes=on">DNMT1↓</a>,
<a href="tbResList.php?qv=27&tsv=236&wNotes=on">P53↑</a>,
<a href="tbResList.php?&qv=27&wNotes=on&word=HSP">HSP↓</a>
<br>
<!-- CELL CYCLE ARREST : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓ -->
- cause Cell cycle arrest :
<a href="tbResList.php?&qv=27&tsv=322&wNotes=on">TumCCA↑</a>,
<a href="tbResList.php?&qv=27&tsv=73&wNotes=on">cyclin D1↓</a>,
<a href="tbResList.php?&qv=27&tsv=378&wNotes=on">cyclin E↓</a>,
<a href="tbResList.php?&qv=27&tsv=467&wNotes=on">CDK2↓</a>,
<a href="tbResList.php?&qv=27&tsv=894&wNotes=on">CDK4↓</a>,
<a href="tbResList.php?&qv=27&tsv=895&wNotes=on">CDK6↓</a>,
<br>
<!-- MIGRATION/INVASION : TumCMig↓, TumCI↓, FAK↓, ERK↓, -->
- inhibits Migration/Invasion :
<a href="tbResList.php?&qv=27&tsv=326&wNotes=on">TumCMig↓</a>,
<a href="tbResList.php?&qv=27&tsv=110&wNotes=on">FAK↓</a>,
<a href="tbResList.php?&qv=27&tsv=105&wNotes=on">ERK↓</a>,
<br>
<!-- ANGIOGENESIS : VEGF↓, VEGFR2↓, HIF-1α↓, NOTCH↓, FGF↓, PDGF↓, EGFR↓ ITG(Integrins↓)-->
- inhibits
<a href="tbResList.php?qv=27&tsv=447&wNotes=on">angiogenesis↓</a> :
<a href="tbResList.php?qv=27&tsv=334&wNotes=on">VEGF↓</a>,
<a href="tbResList.php?&qv=27&tsv=143&wNotes=on">HIF-1α↓</a>,
<a href="tbResList.php?&qv=27&tsv=94&wNotes=on&word=EGFR↓">EGFR↓</a>,
<br>
<!-- CSCs : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, -->
- inhibits Cancer Stem Cells :
<a href="tbResList.php?qv=27&tsv=795&wNotes=on">CSC↓</a>,
<br>
<!-- OTHERS : -->
- Others: <a href="tbResList.php?qv=27&tsv=252&wNotes=on">PI3K↓</a>,
<a href="tbResList.php?qv=27&tsv=4&wNotes=on">AKT↓</a>,
<a href="tbResList.php?qv=27&tsv=373&wNotes=on">STAT3</a>,
<a href="tbResList.php?qv=27&tsv=377&wNotes=on">Wnt↓</a>,
<a href="tbResList.php?qv=27&tsv=342&wNotes=on">β-catenin↓</a>,
<a href="tbResList.php?qv=27&tsv=9&wNotes=on">AMPK↓</a>,
<a href="tbResList.php?qv=27&tsv=105&wNotes=on">ERK↓</a>,
<a href="tbResList.php?qv=27&tsv=168&wNotes=on">JNK</a>,
<br>
<!-- SYNERGIES : -->
- Synergies:
<a href="tbResList.php?qv=27&tsv=1106&wNotes=on&exSp=open">chemo-sensitization</a>,
<a href="tbResList.php?qv=27&tsv=1171&wNotes=on&exSp=open">chemoProtective</a>,
<a href="tbResList.php?qv=27&tsv=1107&wNotes=on&exSp=open">RadioSensitizer</a>,
<a href="tbResList.php?qv=27&tsv=1185&wNotes=on&exSp=open">RadioProtective</a>,
<a href="tbResList.php?qv=27&tsv=961&esv=2&wNotes=on&exSp=open">Others(review target notes)</a>,
<a href="tbResList.php?qv=27&tsv=1105&wNotes=on">Neuroprotective</a>,
<a href="tbResList.php?qv=27&tsv=557&wNotes=on">Cognitive</a>,
<a href="tbResList.php?qv=27&tsv=1175&wNotes=on">Renoprotection</a>,
<a href="tbResList.php?qv=27&tsv=1179&wNotes=on">Hepatoprotective</a>,
<a href="tbResList.php?&qv=27&tsv=1188&wNotes=on">CardioProtective</a>,
<br>
<!-- SELECTIVE: -->
- Selectivity:
<a href="tbResList.php?qv=27&tsv=1110&wNotes=on">Cancer Cells vs Normal Cells</a>
<br>
<br>
Allicin has been reported to exhibit a range of effects, including:<br>
Antimicrobial activity: 10-50 μM<br>
Antioxidant activity: 10-100 μM<br>
Anti-inflammatory activity: 20-50 μM <br>
Anticancer activity: 50-100 μM or (50–300uM) (2–5 mg allicin per kilogram of body weight per day)<br>
Cardiovascular health: 20-50 μM<br>
<br>
Approximate μM concentrations of allicin that can be achieved:<br>
1 clove of garlic (3g): approximately 10-50 μM of allicin<br>
single clove of garlic may yield about 5–9 mg of allicin,<br>
1 tablespoon of minced garlic (15g): approximately 50-150 μM of allicin<br>
1 cup of chopped garlic (100g): approximately 200-500 μM of allicin<br>
1 tablespoon of chopped garlic chives (15g): approximately 5-20 μM of allicin<br>
1 cup of chopped garlic chives (100g): approximately 20-50 μM of allicin<br>
1 ounce (28g) of garlic microgreens: approximately 50-200 μM of allicin<br>
1 cup of garlic microgreens (100g): approximately 200-500 μM of allicin<br>
1 ounce (28g) of garlic chive microgreens: approximately 20-50 μM of allicin<br>
1 cup of garlic chive microgreens (100g): approximately 50-100 μM of allicin<br>
<br>
Allicin is a bioactive compound derived from garlic that has garnered significant interest for its potential anticancer properties through multiple mechanisms, including antioxidant activity, induction of apoptosis, cell cycle arrest, and modulation of key signaling pathways. While regular dietary intake of garlic is associated with cancer prevention benefits, allicin is also being explored as an adjunct to conventional cancer treatments. <br>
<br>
Available in supplement tablet/capsule form for example at 2000mg (fresh bulb equilvalent)<br>
IC50 of normal cells it >160mg/mL (large selectivity).<br>
IC50 might be about 12-30ug/ml (approximately 62-185 µM) (which is about 30-90 grams of garlic consumption).<br>
This makes it difficult to consume enough supplements to achieve that level.<br>
<br>
Pathways:<br>
<br>
ROS Generation and Oxidative Stress (inducing)<br>
• ROS generation is often considered a primary trigger that feeds into downstream pathways (e.g., MAPK activation, mitochondrial membrane permeabilization).<br>
Mitochondrial (Intrinsic) Apoptotic Pathway<br>
• ROS-induced mitochondrial damage can lead to the release of cytochrome c and subsequent activation of caspases (e.g., caspase-9 and caspase-3).<br>
NF-κB Signaling Inhibition (block)<br>
Modulation of MAPK Pathways (e.g., p38 MAPK and JNK)<br>
• ROS generation by allicin can activate stress-responsive kinases such as p38 MAPK and c-Jun N-terminal kinase (JNK).<br>
Inhibition of PI3K/Akt Pathway<br>
ROS levels and PI3K/Akt signaling, with increased oxidative stress often correlating with reduced Akt phosphorylation and activity.<br>
<br>
At lower doses, allicin may lead to a modest increase in ROS levels that the cell’s antioxidant defenses (e.g., glutathione, superoxide dismutase) can manage<br>
<br>
<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>
<tr>
<td>1</td>
<td>Protein thiol modification (S-thioallylation of cysteines)</td>
<td>↑ S-thioallylation / ↓ free protein thiols</td>
<td>Primary chemical mechanism</td>
<td>Direct proteomics evidence that allicin modifies cysteine residues in human cells via S-thioallylation</td>
<td><a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6342545/">(ref)</a></td>
</tr>
<tr>
<td>2</td>
<td>Glutathione pool chemistry (GSH → mixed disulfide)</td>
<td>↑ GSSA formation (S-allylmercaptoglutathione) / functional GSH depletion</td>
<td>Redox buffering impairment</td>
<td>Primary chemistry paper: allicin reacts with reduced glutathione; product (GSSA) identified by HPLC/NMR/MS</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/11118647/">(ref)</a></td>
</tr>
<tr>
<td>3</td>
<td>Thioredoxin reductase (TrxR) as a thiol-enzyme target</td>
<td>↓ TrxR activity (by thiol reaction)</td>
<td>Redox control disruption</td>
<td>Review explicitly describing allicin reacting with thiol groups of enzymes including thioredoxin reductase (allicin named)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/10594976/">(ref)</a></td>
</tr>
<tr>
<td>4</td>
<td>Reactive oxygen species generation (oxidative stress)</td>
<td>↑ ROS</td>
<td>Upstream stress trigger</td>
<td>Experimental work examining allicin-induced oxidative stress and accumulation of reactive species (allicin named; ROS assays described)</td>
<td><a href="https://www.mdpi.com/2076-3921/6/1/1">(ref)</a></td>
</tr>
<tr>
<td>5</td>
<td>Mitochondrial pathway engagement (cytochrome c release)</td>
<td>↑ cytochrome c release</td>
<td>Mitochondria-driven death signaling</td>
<td>Gastric cancer study: allicin induces cytochrome c release from mitochondria (intrinsic pathway)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/21042755/">(ref)</a></td>
</tr>
<tr>
<td>6</td>
<td>Apoptosis execution (caspase-3/8/9)</td>
<td>↑ caspase activation</td>
<td>Programmed cell death</td>
<td>Allicin-induced apoptosis with caspase activation and PARP cleavage reported in cancer cells</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/14757128/">(ref)</a></td>
</tr>
<tr>
<td>7</td>
<td>NF-κB signaling</td>
<td>↓ NF-κB pathway signaling</td>
<td>Reduced pro-survival / inflammatory transcription</td>
<td>Colorectal cancer radiosensitization paper: allicin-associated inhibition of NF-κB signaling components (mRNA/protein assays)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/32418198/">(ref)</a></td>
</tr>
<tr>
<td>8</td>
<td>Cell cycle regulation</td>
<td>↑ cell-cycle arrest</td>
<td>Proliferation blockade</td>
<td>Breast cancer study: allicin induces cell-cycle arrest and apoptosis (allicin named as treatment)</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/34626309/">(ref)</a></td>
</tr>
</table>