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| Garlic (Allium sativum L.) (active ingredient- Allicin, an active sulfer compound). Allicin — a reactive organosulfur thiosulfinate generated in situ when garlic (Allium sativum) tissue is crushed (alliin → allicin via alliinase). Functionally, it behaves as a short-lived electrophilic “reactive sulfur species” that rapidly modifies cellular thiols (e.g., glutathione and cysteine residues on proteins), producing broad redox and stress-signaling effects. Classification: small-molecule phytochemical (organosulfur thiosulfinate). Standard abbreviation(s): AL (common in Nestronics), “allicin”. Source/origin: freshly crushed raw garlic; allicin is not present in intact cloves and is chemically unstable, converting to other organosulfur metabolites after formation. Primary mechanisms (ranked):
Bioavailability / PK relevance: “Allicin exposure” is dominated by formation conditions and rapid chemical/biologic turnover. Many oral preparations deliver alliin/alliinase that may generate allicin after ingestion; measured systemic allicin is typically transient, while downstream allyl-sulfur metabolites (e.g., allyl methyl sulfide–related products) are more detectable. Cooking/processing and GI conditions substantially change allicin bioequivalence versus crushed raw garlic. In-vitro vs systemic exposure relevance: Many anticancer cell studies use ~50–300 µM allicin; whether such free allicin concentrations are achievable at tumor sites after dietary/supplement intake is uncertain because of rapid thiol quenching and conversion to other sulfur species. Reported biological effects at lower concentrations may still occur locally (GI lumen/mucosa) or via metabolites, but direct extrapolation from high-µM in-vitro dosing is high-risk. Clinical evidence status: Predominantly preclinical (cell/animal) for anticancer mechanisms; human data are mixed and often evaluate garlic preparations rather than purified allicin, with outcomes confounded by formulation-dependent “allicin bioequivalence” and co-occurring organosulfur compounds (e.g., DADS/DATS/SAMC). Cancer-therapeutic evidence remains inconclusive. DADS (diallyl disulfide is a sulfur-based anticancer drug generated from garlic)Summary: - Four main organic sulfides in garlic, diallyl disulfide (DADS), diallyl trisulfide (DATS), S-allylmercaptocysteine (SAMC) and allicin. - Reversible inhibitor of ACSS2. - may inhibit NF-κB signaling - induce oxidative stress in cancer cells by generating ROS - might downregulate STAT3 activation - Inconclusive evidence for cancer treatment. - may inhibit platelet aggregation 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. -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. "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." -Allicin is not present in intact garlic. -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) -Allicin is unstable, degrading within hours into other sulfur compounds (like diallyl disulfide). -Note half-life reports vary 2.5-90hrs?. -moderately water-soluble but rapidly degrades/quenched (especially with thiols), so aqueous solutions have limited practical stability : BioAv Pathways: - induce ROS production - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓ - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓ - Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK. - inhibit Growth/Metastases : EMT↓, MMP2↓, MMP9↓, VEGF↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓(not commonly listed as inhibitor), DNMT1↓, P53↑, HSP↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, FAK↓, ERK↓, - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, - inhibits Cancer Stem Cells : CSC↓, - Others: PI3K↓, AKT↓, STAT3, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells Allicin has been reported to exhibit a range of effects, including: Antimicrobial activity: 10-50 μM Antioxidant activity: 10-100 μM Anti-inflammatory activity: 20-50 μM Anticancer activity: 50-100 μM or (50–300uM) (2–5 mg allicin per kilogram of body weight per day) Cardiovascular health: 20-50 μM Approximate μM concentrations of allicin that can be achieved: 1 clove of garlic (3g): approximately 10-50 μM of allicin single clove of garlic may yield about 5–9 mg of allicin, 1 tablespoon of minced garlic (15g): approximately 50-150 μM of allicin 1 cup of chopped garlic (100g): approximately 200-500 μM of allicin 1 tablespoon of chopped garlic chives (15g): approximately 5-20 μM of allicin 1 cup of chopped garlic chives (100g): approximately 20-50 μM of allicin 1 ounce (28g) of garlic microgreens: approximately 50-200 μM of allicin 1 cup of garlic microgreens (100g): approximately 200-500 μM of allicin 1 ounce (28g) of garlic chive microgreens: approximately 20-50 μM of allicin 1 cup of garlic chive microgreens (100g): approximately 50-100 μM of allicin 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. Available in supplement tablet/capsule form for example at 2000mg (fresh bulb equilvalent) IC50 of normal cells it >160mg/mL (large selectivity). IC50 might be about 12-30ug/ml (approximately 62-185 µM) (which is about 30-90 grams of garlic consumption). This makes it difficult to consume enough supplements to achieve that level. Pathways: ROS Generation and Oxidative Stress (inducing) • ROS generation is often considered a primary trigger that feeds into downstream pathways (e.g., MAPK activation, mitochondrial membrane permeabilization). Mitochondrial (Intrinsic) Apoptotic Pathway • ROS-induced mitochondrial damage can lead to the release of cytochrome c and subsequent activation of caspases (e.g., caspase-9 and caspase-3). NF-κB Signaling Inhibition (block) Modulation of MAPK Pathways (e.g., p38 MAPK and JNK) • ROS generation by allicin can activate stress-responsive kinases such as p38 MAPK and c-Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt Pathway ROS levels and PI3K/Akt signaling, with increased oxidative stress often correlating with reduced Akt phosphorylation and activity. 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 Allicin (Garlic) — mechanistic axes relevant to oncology
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| JNK acts synergistically with NF-κB, JAK/STAT, and other signaling molecules to exert a survival function. Janus signaling promotes cancer cell survival. JNK, or c-Jun N-terminal kinase, is a member of the mitogen-activated protein kinase (MAPK) family. It plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis (programmed cell death). JNK is activated in response to various stress signals, such as UV radiation, oxidative stress, and inflammatory cytokines. JNK activation can promote apoptosis in cancer cells, acting as a tumor suppressor. However, in other contexts, it can promote cell survival and proliferation, contributing to tumor progression. JNK is often unregulated in cancers, leading to increased cancer cell proliferation, survival, and resistance to apoptosis. This activation is typically associated with poor prognosis and aggressive tumor behavior. |
| 2655- | AL, | Allicin and Digestive System Cancers: From Chemical Structure to Its Therapeutic Opportunities |
| - | Review, | GC, | NA |
| 2558- | AL, | Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment |
| - | Review, | AD, | NA |
| 2669- | AL, | Rad, | Inhibition of ICAM-1 expression by garlic component, allicin, in gamma-irradiated human vascular endothelial cells via downregulation of the JNK signaling pathway |
| - | in-vitro, | Nor, | HUVECs |
| 2666- | AL, | Targeting the Interplay of Autophagy and ROS for Cancer Therapy: An Updated Overview on Phytochemicals |
| - | Review, | Var, | NA |
| 248- | AL, | Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway |
| - | in-vitro, | GBM, | U87MG |
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
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