Lemongrass Extract/Citral / CompStab Cancer Research Results

LGE, Lemongrass Extract/Citral: Click to Expand ⟱
Features:
lemongrass extract/ Cymbopogon citratus / lemongrass essential oil

Promising in vitro and limited animal anticancer evidence, especially via ROS-mediated apoptosis and mitochondrial/cell-cycle effects. Citral likely is main active ingredient.

Lemongrass Extract/Citral — Lemongrass preparations are derived principally from the leaves of Cymbopogon citratus and may be prepared as aqueous or ethanolic extracts or as volatile essential oil. Citral (CIT) is an acyclic monoterpene aldehyde and is usually the dominant constituent of lemongrass essential oil; chemically, citral is a mixture of the geometric isomers geranial (citral A) and neral (citral B). The database abbreviation LGE is appropriate for lemongrass extract, while CIT is preferable when the isolated compound is specifically studied. Essential-oil preparations can contain roughly 60–80% citral, but composition varies substantially with cultivar, plant tissue, extraction method, and geographic origin. Whole aqueous or ethanolic lemongrass extracts are not pharmacologically equivalent to purified citral because they contain additional terpenes and nonvolatile phytochemicals.

Primary mechanisms (ranked):

  1. ROS accumulation and oxidative stress in cancer cells, producing DNA damage and triggering mitochondrial apoptosis.
  2. Mitochondrial apoptotic signaling through ↓ mitochondrial membrane potential, ↑ Bax, ↓ Bcl-2/Bcl-xL, and ↑ caspase-3 activation; p53-dependent signaling is important in several models.
  3. ALDH1A3 inhibition, potentially suppressing cancer stem-cell phenotype, clonogenicity, retinoic-acid-linked transcription, and chemotherapy resistance.
  4. Microtubule disruption through inhibition of tubulin polymerization together with MARK4 inhibition, producing antiproliferative and cell-cycle effects.
  5. Suppression of proliferative and survival signaling including AKT, ERK1/2, and NF-κB in selected cancer models.
  6. Cell-cycle arrest, commonly G0/G1 or G1/S depending on model and preparation.
  7. Endoplasmic-reticulum stress and stress-associated autophagy in some p53-deficient cancer cells.
  8. Chemosensitization, including enhanced effects of doxorubicin, docetaxel, FOLFOX-associated drugs, paclitaxel, and other cytotoxics in preclinical models; transporter effects including MDR1/MRP1/BCRP suppression have been reported.

Bioavailability / PK relevance: Citral is lipophilic, volatile, chemically unstable, and rapidly metabolized. Animal disposition studies indicate extensive gastrointestinal absorption but rapid conversion to oxidized, reduced, and conjugated metabolites, with little persistence of unchanged citral in circulation and predominantly urinary elimination of metabolites. Thus, good absorption does not imply high systemic exposure to intact citral. Encapsulation with polymers, cyclodextrins, lipid systems, or nanoparticles has been investigated to improve stability and effective exposure. Human pharmacokinetic data defining circulating intact citral after therapeutic oral dosing remain limited.
-citral is chemically unstable, especially in acidic aqueous systems, and that its stability can be improved by partitioning it into an oil phase, micelles, emulsions, cyclodextrins, or related delivery systems.

In-vitro vs systemic exposure relevance: Many anticancer experiments use citral concentrations in the tens to hundreds of micromolar range, commonly about 20–200 µM, or relatively concentrated lemongrass extracts. These exposures cannot presently be assumed to be attainable as sustained concentrations of intact citral in human plasma after tea, food, or conventional oral supplementation because parent citral undergoes very rapid metabolism. Whole-extract studies also cannot be quantitatively translated into equivalent systemic citral exposure. Consequently, the strongest mechanistic findings should be considered preclinical and concentration-dependent.

Clinical evidence status: Preclinical. Anticancer activity is supported by numerous cancer-cell studies and several animal xenograft experiments using citral or lemongrass extracts. Chemosensitization is also preclinical. Human studies of lemongrass tea and topical essential oil provide limited tolerability and non-oncology clinical information, but there is no established human anticancer efficacy and no approved oncology indication for citral or lemongrass extract. Citral is permitted as a food flavoring agent and is listed by the FDA under food-use regulations; this regulatory status does not establish therapeutic anticancer efficacy. Safety is concentration- and formulation-dependent: concentrated citral and essential oils can be cytotoxic or genotoxic in cultured normal cells, while some cancer models demonstrate relative tumor-cell selectivity.

Mechanistic Effects of Lemongrass Extract and Citral

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS and oxidative stress ↑ ROS, ↓ GSH ↔ or ↑ ROS (dose-dependent) R Oxidative damage and apoptosis One of the best-supported anticancer mechanisms of citral and lemongrass preparations. ROS elevation precedes mitochondrial dysfunction in several cancer models; antioxidant effects can occur in non-cancer systems, making modulation context-dependent.
2 Mitochondrial apoptosis ↓ membrane potential, ↑ Bax, ↓ Bcl-2, ↓ Bcl-xL, ↑ caspase-3 ↔ or weaker effect (model-dependent) R/G Intrinsic apoptosis Demonstrated in colorectal, leukemia, breast, ovarian, and other cancer models. ROS frequently acts upstream of mitochondrial depolarization.
3 ALDH1A3 and cancer stem cells ↓ ALDH1A3 activity Not established R/G ↓ clonogenicity and stem-cell-associated tumor growth Citral directly inhibits ALDH1A3-associated activity and reduced growth of ALDH1A3-driven breast tumor models. Potential relevance to cancer stem cells and drug resistance.
4 Tubulin and microtubules ↓ tubulin polymerization, ↑ microtubule depolymerization ↓ (high concentration or exposure-dependent) P/R Microtubule disruption and proliferation inhibition Citral can directly disrupt microtubules and inhibit polymerization. This is not inherently cancer-selective and is therefore an efficacy and toxicity mechanism.
5 MARK4 ↓ MARK4 Not established R Antiproliferative signaling and microtubule regulation Biochemical binding and kinase inhibition studies support MARK4 as a direct citral target associated with its microtubule-related activity.
6 p53 apoptotic signaling ↑ p53 phosphorylation and activity Not established R/G ↑ Bax, PUMA, NOXA and apoptosis ROS-dependent p53 activation contributes strongly to apoptosis in p53-competent cells. p53-deficient cells may instead depend more heavily on ER-stress mechanisms.
7 AKT and PI3K survival signaling ↓ AKT, ↓ PI3K signaling Not established R/G Reduced survival and proliferation Reported particularly in melanoma and other cancer-cell systems; importance varies by cancer type.
8 ERK signaling ↓ ERK1/2 Not established R/G Reduced proliferative signaling Observed alongside AKT suppression and oxidative stress in melanoma models.
9 NF-κB survival signaling ↓ NF-κB Context-dependent R/G Reduced prosurvival and inflammatory signaling NF-κB suppression has been reported in melanoma and leukemia models and may contribute to apoptosis.
10 Cell cycle ↑ G0/G1 or G1/S arrest ↔ or less affected (model-dependent) G ↓ proliferation Phase of arrest varies with cell type, citral concentration, and whether purified citral or whole lemongrass extract is used.
11 Endoplasmic reticulum stress ↑ CHOP, ↑ ATF4, ↑ phospho-eIF2α, ↑ GADD45 Not established R/G Stress-associated growth inhibition and apoptosis Especially relevant in p53-deficient models where ER stress may compensate for reduced p53-mediated apoptotic signaling.
12 Autophagy ↑ (context-dependent) Not established G Stress response contributing to cytotoxicity Autophagy-associated proteins including ATG5 have been altered after citral treatment; whether autophagy is lethal or adaptive is model-dependent.
13 Chemosensitization ↑ Potential toxicity sparing in selected models G Enhanced chemotherapy response Lemongrass extract or citral has enhanced responses to FOLFOX-associated drugs, paclitaxel, docetaxel, doxorubicin, and other agents in preclinical studies. Clinical confirmation is absent.
14 Drug efflux and multidrug resistance ↓ MDR1, ↓ MRP1, ↓ BCRP, ↑ intracellular doxorubicin Not established G Reduced multidrug resistance Lemongrass oil and citral increased doxorubicin accumulation in resistant cancer-cell models. Whole oil and purified citral are not necessarily equivalent.
15 Drug metabolism signaling ↓ PXR, ↓ CYP3A4, ↓ GST (model-dependent) Drug-metabolizing enzymes can also be altered G Potential alteration of chemotherapy disposition Potentially contributes to chemosensitization but also raises a possible drug-interaction concern. Rat studies demonstrate modulation of hepatic xenobiotic-metabolizing enzymes at high citral or lemongrass-oil doses.
16 Clinical Translation Constraint Preclinical activity Limited selectivity at sufficiently high exposure G Low parent-drug exposure and uncertain therapeutic window Citral is rapidly metabolized, volatile, and chemically unstable. Many effective in-vitro concentrations likely exceed sustained systemic concentrations of intact citral achievable through ordinary oral intake. Nanoparticle and other delivery systems improve experimental exposure but are not established cancer treatments.

TSF: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
CompStab, Compound Stability: Click to Expand ⟱
Source:
Type:

Compound Stability

Alternative Names: Chemical stability, physicochemical stability, storage stability, formulation stability

Type: Physicochemical property / formulation outcome / compound preservation measure

Function: Compound stability describes the ability of a chemical or bioactive substance to retain its chemical identity, concentration, structure, and biological activity over time under defined environmental, storage, formulation, or physiological conditions.

Measured By: Remaining parent compound concentration, degradation rate, half-life, oxidation products, hydrolysis products, photodegradation, thermal degradation, or retention of biological activity.

Favorable Direction: ↑ Stability is favorable and indicates reduced degradation and greater preservation of the active compound. ↓ Stability indicates increased degradation or loss of active compound.

Interpretation Note: Stability should be interpreted according to the condition measured, such as storage stability, oxidative stability, thermal stability, photostability, gastrointestinal stability, or plasma stability.



Natural Compound Stability - Practical Source/Formulation Perspective

Interpretation: Chemical instability of an isolated compound does not necessarily mean that the natural food, botanical product, or supplement used to deliver it is unstable. Some compounds are stored naturally as more stable precursors and generated shortly before or after consumption. Others are protected within dry plant material, oils, glycosides, or formulated delivery systems.

Compound Isolated Compound Stability Common Natural / Supplement Source Practical Stability in Usual Source Why the Source May Be More Stable Main Limitation Best Practical Approach
Allicin Very Low Fresh garlic; garlic powder standardized for allicin potential Moderate-Good as precursor system Intact garlic primarily stores stable alliin separately from alliinase. Crushing or wetting activates alliinase and rapidly generates allicin shortly before use. Allicin itself rapidly decomposes after formation. Heating can destroy alliinase, and stomach acid can inhibit alliinase in some supplements. Use fresh crushed garlic shortly after preparation, or a validated garlic powder/enteric-coated supplement with measured alliinase activity and allicin yield.
Sulforaphane Very Low Broccoli sprouts, broccoli seeds, glucoraphanin-rich extracts, stabilized sulforaphane supplements Good when stored as glucoraphanin precursor Broccoli stores the relatively stable glucosinolate glucoraphanin. Myrosinase converts it to reactive sulforaphane after plant tissue disruption. Cooking can destroy myrosinase. Gut conversion of glucoraphanin without active myrosinase is variable. Broccoli sprouts/seeds with active myrosinase, or glucoraphanin + active myrosinase formulation. Stabilized direct sulforaphane preparations are another option.
EGCG Very Low in neutral aqueous solution Green tea, matcha, green-tea extract capsules Moderate-Good in dry tea/powder Low moisture and the intact dry tea matrix greatly reduce oxidation compared with dissolved purified EGCG. Heat, oxygen, alkaline pH, and prolonged storage after brewing accelerate degradation. Store matcha/tea cool, dry, airtight, and dark. Consume brewed tea relatively soon after preparation. Acidic beverages improve catechin stability.
Anthocyanins Low Berries, berry powders, purple/blue fruits, extracts Moderate in acidic whole-food matrices Natural fruit acidity and copigmentation with other polyphenols can stabilize anthocyanins. Neutral/alkaline pH, heat, oxygen, light, and long storage. Whole fruit, freeze-dried berry powder, refrigerated acidic extracts, or encapsulated preparations.
Curcumin Low in neutral/alkaline aqueous solution Turmeric powder, turmeric extracts, phospholipid/lipid formulations Moderate-Good as dry turmeric/powder Dry plant material protects curcuminoids from the rapid hydrolysis and autoxidation seen after dissolution. Poor water solubility and rapid degradation after dissolution, especially near physiological pH. Dry turmeric/extract, lipid/oil formulation, lecithin/phospholipid complex, or encapsulated curcumin.
Thymoquinone Low-Moderate Black seed oil / Nigella sativa oil; standardized TQ preparations Moderate in protected oil The lipid matrix limits direct aqueous exposure and can reduce some degradation pathways. Light, oxygen, prolonged heat, and oxidation of both TQ and the oil. Fresh high-quality black seed oil in dark, airtight containers; cool storage; standardized encapsulated oil where dose consistency matters.
Kaempferol Moderate Foods and botanicals mainly as kaempferol glycosides, including saffron, tea, leafy vegetables, capers and others Moderate-Good as glycosides in dry plant material Plant glycosides can be more water-compatible and sometimes more chemically stable than free aglycone kaempferol. Actual kaempferol exposure depends on glycoside hydrolysis, intestinal metabolism, and source. Whole-food or standardized botanical source can be more practical than free kaempferol powder; formulated aglycone can be used where precise dosing is needed.
Quercetin Low-Moderate as free aglycone Onions, apples, capers, tea and many botanicals; often present as glycosides Moderate-Good in plant glycosides Glycosylation and dry plant matrices generally protect quercetin better than aqueous free aglycone. Different glycosides have different absorption and conversion to quercetin metabolites. Whole-food/glycoside sources or stabilized phospholipid/lipid formulations.
Rutin Moderate-Good Buckwheat, buckwheat sprouts, citrus and other plants Good Rutin is itself a quercetin glycoside and is generally more stable than free quercetin. Bioavailability is lower and conversion depends on intestinal metabolism. Whole buckwheat/sprout source or standardized rutin extract where a defined dose is needed.
Resveratrol Low-Moderate Grape skins, red grapes, Polygonum cuspidatum extracts, supplements Moderate as dry extract Dry botanical extracts protect trans-resveratrol better than dilute aqueous solutions. UV/light causes trans-to-cis isomerization; oxidation also occurs. Opaque capsules/containers, dry standardized extract, cool storage.
Astaxanthin Very Low when freely exposed Haematococcus pluvialis algal oleoresin, krill oil, lipid softgels Moderate-Good in lipid/oleoresin formulations Natural algal oleoresin and oil matrices physically protect the conjugated carotenoid and limit exposure to oxygen/water. Light, heat, oxygen, and prolonged storage still cause oxidation/isomerization. Oil-based softgel/oleoresin, antioxidants, dark airtight packaging, cool storage.
Lycopene Very Low when purified/exposed Tomatoes, tomato paste, tomato oleoresin, oil-based supplements Moderate-Good in food/oil matrix Food matrices and oils reduce direct oxygen exposure; processed tomato products can also improve bioaccessibility. Heat plus oxygen/light can still cause oxidation, although controlled cooking can improve bioavailability by matrix disruption and cis-isomer formation. Tomato products with dietary fat or protected oleoresin/oil formulations.
Beta-Carotene Low Carrots, sweet potato, leafy vegetables, oil dispersions Moderate-Good in plant/lipid matrix Plant chromoplasts and lipid formulations partly protect carotenoids from oxygen/light. Oxidative loss during prolonged processing/storage. Whole-food source with dietary fat or stabilized oil/softgel formulation.
DHA / EPA Very Low to oxidation Fish oil, krill oil, algal oil, phospholipid formulations Moderate when properly packaged Oil softgels, antioxidants and oxygen-limited packaging can greatly slow oxidation. Once an oil is opened and repeatedly exposed to air, oxidation accelerates. Fresh antioxidant-protected oil/softgels, opaque airtight packaging, refrigeration after opening where appropriate.
Vitamin C Low in solution Fresh fruits/vegetables; dry tablets/powders Good as dry formulation; moderate in intact produce Dry state greatly slows oxidation, and intact plant tissue limits oxygen exposure before cutting. Cutting, heating, storage, oxygen, metals and neutral/alkaline pH accelerate loss. Fresh produce or dry supplement; avoid prolonged aqueous storage and excessive heat.
Pterostilbene Good Blueberries, Pterocarpus species, purified supplements Good Methoxy groups make pterostilbene more lipophilic and generally more chemically robust than resveratrol. Strong light/oxidative conditions can still degrade it. Standard dry supplement or protected botanical extract.

Important Database Distinction:

Concept Example Interpretation
Isolated compound stability Sulforaphane itself How rapidly the purified active compound degrades.
Precursor stability Glucoraphanin in broccoli A more stable precursor can preserve potential activity until conversion occurs.
Matrix stability EGCG in dry matcha The food/botanical matrix protects the compound compared with an aqueous purified solution.
Generated-at-use active Alliin + alliinase → allicin The unstable compound does not need to survive long-term storage because it is produced shortly before or after consumption.
Formulation stability Astaxanthin in an antioxidant-protected oil softgel The delivery formulation reduces oxygen, water or light exposure.
Bioavailability Glucoraphanin → sulforaphane conversion Distinct from stability. A highly stable precursor may still give poor active-compound exposure if conversion is inefficient.


Scientific Papers found: Click to Expand⟱
8205- LGE,    Citral: Bioactivity, Metabolism, Delivery Systems, and Food Preservation Applications
- Review, Nor, NA
*CompStab↓, *Bacteria↓, *antiOx↑, *Inflam↓, *AntiDiabetic↑, *AntiCan↑,
8202- LGE,    Application of microencapsulation technology to improve the stability of citral in rodent diets
- in-vivo, Nor, NA
*CompStab↓, *Dose↝, *CompStab↑,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

CompStab↓, 2,   CompStab↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,  
Total Targets: 8

Scientific Paper Hit Count for: CompStab, Compound Stability
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#:398  Target#:1778  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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