Isoliquiritigenin / AntiBio Cancer Research Results

ISL, Isoliquiritigenin: Click to Expand ⟱
Features:

ISL is a distinct natural chalcone, chemically identified as 2′,4′,4-trihydroxychalcone, found particularly in licorice species such as Glycyrrhiza spp.ISL has substantial preclinical evidence involving anticancer, anti-inflammatory, antioxidant, metabolic, and neuroprotective effects. Reported anticancer actions include inhibition of proliferation, angiogenesis, EMT, invasion, and metastasis, with induction of apoptosis, cell-cycle arrest, autophagy, or ferroptosis depending on the model. Frequently reported pathways include PI3K/AKT/mTOR, NF-κB, STAT3, MAPK, Wnt/β-catenin, Nrf2, and Src signalling.

Isoliquiritigenin — isoliquiritigenin (ISL; 2′,4′,4-trihydroxychalcone) is a naturally occurring polyphenolic chalcone found particularly in licorice roots from Glycyrrhiza species. It is formally classified as a flavonoid-family chalcone rather than an isoflavone. ISL is a pleiotropic experimental bioactive compound with anticancer, anti-inflammatory, metabolic, antioxidant/pro-oxidant, and neuroprotective activities. Anticancer effects are strongly model- and concentration-dependent, and clinically relevant systemic exposure to unconjugated ISL is substantially more limited than the micromolar concentrations commonly used in cell culture. ISL also has weak phytoestrogenic activity and can interact with estrogen receptors.

Primary mechanisms (ranked):

  1. Suppression of PI3K/AKT/mTOR survival and growth signalling, with associated apoptosis, autophagy, cell-cycle arrest, and inhibition of metabolic reprogramming.
  2. Mitochondrial apoptosis through ↑ Bax/Bcl-2 ratio, mitochondrial dysfunction, cytochrome-c release, and caspase activation.
  3. Suppression of JAK/STAT signalling, particularly JAK2/STAT3, reducing survival, proliferation, inflammatory signalling, and treatment resistance.
  4. ROS-dependent cytotoxic signalling in several cancer models, including ROS-mediated inhibition of p38/mTOR/STAT3 and activation of mitochondrial apoptosis.
  5. Suppression of NF-κB-mediated inflammatory and prosurvival signalling.
  6. Inhibition of EMT, invasion, and metastasis through pathways including PI3K/AKT, β-catenin, MMPs, Snail-family transcription factors, and restoration of E-cadherin.
  7. Suppression of tumor lipid synthesis and metabolic adaptation through AMPK activation with inhibition of SREBF1/FASN and, in colorectal cancer, FGFR4-associated lipid metabolism.
  8. Modulation of arachidonic-acid/eicosanoid signalling, including inhibition of COX-2, mPGES-1, and CYP4A11 in selected tumor models.
  9. NRF2 modulation is context-dependent: NRF2 activation can provide antioxidant and anti-inflammatory protection in non-malignant/neural models, whereas suppression of NRF2 antioxidant defence has been reported as a mechanism of radiosensitization in some cancer models.
  10. Weak estrogen-receptor agonist/SERM-like activity; low concentrations may stimulate ER-responsive cells under some conditions, making this a relevant mechanistic and safety consideration rather than a uniformly anticancer effect.

Bioavailability / PK relevance: Oral ISL undergoes substantial intestinal absorption barriers and rapid phase-II metabolism, particularly glucuronidation. Animal studies report oral bioavailability of roughly 20–34%, but circulating parent ISL is transient and extensively converted to conjugated metabolites. Human pharmacokinetic studies of licorice-containing Kampo preparations confirm detectable ISL exposure but at levels substantially below many experimental cancer-cell concentrations. Low aqueous solubility and rapid metabolism have driven development of nanoparticles, micelles, SMEDDS, and structural derivatives to improve exposure.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100+ µM ISL, whereas parent-compound concentrations achieved after conventional oral botanical exposure are generally much lower because of rapid intestinal glucuronidation and systemic metabolism. Consequently, direct translation of high-micromolar in-vitro cytotoxicity to oral supplementation is poor. Some lower-concentration receptor, enzyme, inflammatory, and metabolic effects may be more pharmacologically plausible.

Clinical evidence status: Preclinical. Extensive cell-culture and multiple animal xenograft studies support anticancer activity, but ISL itself is not an established cancer treatment and there is no convincing randomized human anticancer efficacy evidence. Human studies primarily provide pharmacokinetic information from multi-component licorice/Kampo preparations rather than therapeutic evaluation of purified ISL. Drug-interaction potential involving CYP and UGT enzymes and weak estrogenic activity warrant caution.

Isoliquiritigenin Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells Primary Effect Notes / Interpretation
1 PI3K / AKT / mTOR ↓ PI3K, ↓ p-AKT, ↓ mTOR signalling ↔ / context-dependent ↓ survival and proliferation; ↑ apoptosis/autophagy One of the most consistently implicated anticancer signalling axes; demonstrated in colorectal, gastric, breast, and other tumor models.
2 Mitochondrial apoptosis ↑ Bax, ↓ Bcl-2, ↑ cytochrome c, ↑ caspase-9/3/7, ↑ PARP cleavage Generally less cytotoxic at comparable lower exposures ↑ intrinsic apoptosis Frequently accompanies ROS accumulation and suppression of survival signalling.
3 JAK2 / STAT3 ↓ JAK2/STAT3 signalling ↔ / context-dependent ↓ proliferation and survival; ↑ apoptosis Supported in multiple tumor contexts and implicated in combination activity with chemotherapy.
4 ROS-mediated cancer stress ↑ ROS (model-dependent) ↓ oxidative stress or ↔ (context-dependent) ↑ mitochondrial injury and apoptosis ISL can function as a pro-oxidant in malignant cells while exerting antioxidant effects in inflammatory or neural models.
5 NF-κB inflammatory survival signalling ↓ NF-κB activation ↓ pathological NF-κB activation ↓ inflammatory survival signalling Contributes to antiproliferative, anti-inflammatory, anti-invasive, and neuroprotective effects.
6 AMPK / SREBF1 lipid synthesis ↑ AMPK, ↓ SREBF1, ↓ lipogenic enzymes Context-dependent ↓ fatty-acid synthesis and tumor growth Directly demonstrated in anaplastic thyroid carcinoma; consistent with metabolic stress induced by reduced ATP.
7 FGFR4 / FASN lipid metabolism ↓ FGFR4, ↓ FASN, ↓ PI3K/AKT Not established ↓ proliferation, migration, and lipid synthesis Recent colorectal-cancer evidence links FGFR4 suppression to inhibition of fatty-acid metabolic reprogramming.
8 EMT and metastatic phenotype ↑ E-cadherin; ↓ N-cadherin, vimentin, Snail-related signalling and MMP activity ↔ / context-dependent ↓ migration, invasion, and metastasis Observed across several tumor models; mechanisms intersect PI3K/AKT, NF-κB, STAT3, and β-catenin.
9 Cell-cycle regulation ↓ cyclins/CDKs; ↑ p21/p27 in selected models Mixed ↑ G1/S or G2/M arrest Exact arrest point varies with cell type and dose.
10 COX-2 / mPGES-1 / CYP4A11 ↓ enzymatic activity and downstream Akt/angiogenic signalling Potential anti-inflammatory activity ↓ eicosanoid-dependent angiogenesis Direct target engagement has been demonstrated in glioma models; reported enzyme inhibition is typically micromolar.
11 Angiogenic signalling ↓ VEGF-associated signalling ↓ stimulated endothelial angiogenic responses ↓ tumor angiogenesis Mechanistically plausible across several studies, although an influential older VEGF/VEGFR2 paper received an Expression of Concern in 2026 and should not be used as sole evidence.
12 NRF2 antioxidant response ↓ NRF2 in some radiosensitization models; otherwise mixed ↑ NRF2 under oxidative/inflammatory stress Context-dependent redox modulation Direction differs substantially by disease context. NRF2 activation is neuroprotective, whereas reduced NRF2 defence may increase cancer-cell oxidative sensitivity.
13 Radiosensitization ↑ radiosensitivity (model-dependent) Not established ↑ radiation-induced tumor damage Reported through modulation of Keap1/NRF2 and antioxidant capacity; remains preclinical.
14 Chemosensitization ↑ response to selected agents (model-dependent) Not established Potential combination therapy Recent lung-cancer work reports enhanced gemcitabine activity associated with suppression of JAK2/STAT3 signalling.
15 Estrogen receptor signalling ↑ ERα and ERβ transcriptional activity at some concentrations ↑ weak estrogenic signalling Mixed proliferative or antiproliferative effects Important caveat: low/intermediate ISL concentrations have stimulated proliferation of ER-positive MCF-7 cells, while higher concentrations become cytotoxic. ISL should not be treated as uniformly anti-estrogenic.
16 Clinical Translation Constraint High-micromolar effects often exceed expected parent-compound systemic exposure Potential CYP and UGT interactions Limits direct clinical translation Poor aqueous solubility, rapid glucuronidation, short parent-compound exposure, phytoestrogenicity, and absence of cancer efficacy trials are major constraints.


Alzheimer’s disease relevance: ISL has meaningful but still preclinical AD relevance. In Aβ42-stimulated microglia, it activates NRF2 while suppressing NF-κB, inflammatory cytokines, nitric oxide, and oxidative injury, indirectly protecting neuronal cells. More recent mouse evidence reports improved cognition together with reduced tau phosphorylation, oxidative stress, mitochondrial dysfunction, neuronal loss, and synaptic impairment. Evidence remains limited to cellular and animal models; there is no established human AD therapeutic evidence.

Primary AD mechanisms (ranked):

  1. Activation of NRF2 antioxidant defence with suppression of Aβ-associated oxidative stress.
  2. Suppression of NF-κB-driven microglial neuroinflammation and inflammatory cytokine production.
  3. Reduction of pathological tau phosphorylation in experimental AD models.
  4. Protection of mitochondrial function and cellular ATP homeostasis.
  5. Preservation of neuronal and synaptic markers with improvement of cognition in a mouse model.

Isoliquiritigenin Alzheimer’s-Relevant Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 NRF2 antioxidant response ↑ NRF2 ↓ oxidative stress Demonstrated in Aβ oligomer-stimulated microglial models.
2 NF-κB neuroinflammation ↓ NF-κB ↓ inflammatory cytokines and nitric oxide Reduces Aβ-induced microglial inflammatory activation.
3 Tau phosphorylation ↓ pathological tau phosphorylation Potential reduction of tau-associated neuronal dysfunction Reported at Ser396 and Thr231 in a streptozotocin-induced mouse model.
4 Mitochondrial homeostasis ↑ mitochondrial functional preservation ↓ mitochondrial dysfunction and oxidative injury Associated with changes in DRP1, Mfn1, Mfn2, ATP, and ROS in experimental AD.
5 Synaptic integrity ↑ PSD95 and SNAP25 preservation ↓ synaptic impairment Preclinical mouse evidence only.
6 Clinical Translation Constraint No established human efficacy Limits therapeutic interpretation Evidence consists primarily of cell and animal studies; CNS exposure of pharmacologically active unconjugated ISL in humans remains insufficiently defined.


AntiBio, Antibiotic/Antimicrobial activity: Click to Expand ⟱
Source:
Type:

Antibiotic / antimicrobial activity: The ability of a substance to suppress or kill microorganisms, especially bacteria, by disrupting microbial survival, growth, biofilm formation, cell-wall integrity, membrane function, protein synthesis, nucleic-acid synthesis, quorum sensing, or virulence.

Natural Products that might have antimicrobial properties

Natural supplement or product Principal constituents Potential antimicrobial activity Evidence assessment Reference
Garlic
Allium sativum		 Allicin, ajoene and diallyl sulfides Antibacterial and antifungal activity, with some antiviral and antiparasitic effects reported in laboratory studies. Extensive laboratory evidence, but insufficient clinical evidence to use garlic as a treatment for established infections. Tesfaye A. Revealing the therapeutic uses of garlic and its potential for drug discovery. Scientific review.
Berberine Berberine isoquinoline alkaloid May damage bacterial membranes, inhibit efflux pumps, interfere with nucleic-acid and protein synthesis, and inhibit biofilm formation. Strong preclinical evidence and limited indication-specific clinical evidence. Poor oral bioavailability and drug interactions limit its use as a general antimicrobial. Berberine as a therapeutic alkaloid against ESKAPE and multidrug-resistant bacteria: a comprehensive review.
Cranberry extract
Vaccinium macrocarpon		 A-type proanthocyanidins Primarily reduces adhesion of uropathogenic bacteria, particularly Escherichia coli, to urinary epithelial cells. May reduce recurrent urinary tract infections in selected populations. It is preventive rather than a reliable treatment for an active UTI. National Center for Complementary and Integrative Health: Cranberry—Usefulness and Safety.
Probiotics
Lactobacillus, Bifidobacterium and Saccharomyces boulardii 		Live microorganisms; effects are strain-specific Competitive exclusion of pathogens, production of bacteriocins, inhibition of pathogen adhesion and restoration of microbiome function. Some human evidence for antibiotic-associated diarrhea and selected gastrointestinal or vaginal indications. Results cannot be generalized from one strain to another. NIH Office of Dietary Supplements: Probiotics—Health Professional Fact Sheet.
Medical-grade honey / Manuka honey Methylglyoxal, hydrogen peroxide, defensin-1, organic acids and high osmolarity Broad topical antibacterial and antibiofilm activity; also supports autolytic debridement and wound healing. Clinically relevant primarily as a standardized, medical-grade topical wound product. Ordinary food honey is not equivalent. Jull AB et al. Honey as a topical treatment for wounds. Cochrane systematic review.
Oregano oil
Origanum vulgare		 Carvacrol and thymol Antibacterial, antifungal and antibiofilm activity, largely through disruption of microbial membranes. Strong laboratory activity, but inadequate human evidence for oral treatment of infections. Concentrated oil can cause irritation. Chemical composition, biological activity and potential uses of oregano and oregano essential oil: a review.
Thyme
Thymus vulgaris		 Thymol and carvacrol Antibacterial, antifungal and antibiofilm activity through membrane damage and altered microbial permeability. Better established as a constituent of topical antiseptic and oral-care formulations than as an oral treatment for systemic infection. PubMed literature: thyme, thymol and antimicrobial activity.
Tea tree oil
Melaleuca alternifolia		 Terpinen-4-ol and related monoterpenes Topical antibacterial and antifungal activity with some antiviral laboratory activity. Some clinical evidence for topical acne and fungal skin conditions. Tea tree oil is toxic when swallowed and may cause contact dermatitis. Carson CF et al. Melaleuca alternifolia oil: a review of antimicrobial and other medicinal properties.
Echinacea
Echinacea species		 Alkamides, caffeic-acid derivatives, polysaccharides and glycoproteins Primarily immunomodulatory; relatively weak and inconsistent direct antimicrobial activity. Evidence for preventing or shortening respiratory infections is inconsistent and preparation-dependent. National Center for Complementary and Integrative Health: Echinacea—Usefulness and Safety.
Elderberry
Sambucus nigra		 Anthocyanins, flavonols and phenolic acids Antiviral effects have been reported in cell-culture and preclinical studies, including interference with viral entry or replication. Small human trials have examined respiratory symptoms, but evidence remains insufficient to establish treatment of influenza or other viral infections. National Center for Complementary and Integrative Health: Elderberry.
Curcumin / turmeric
Curcuma longa		 Curcumin and related curcuminoids Antibacterial, antifungal, antiviral and antibiofilm activity through multiple membrane, enzyme and signalling effects. Predominantly laboratory evidence. Poor aqueous solubility and low systemic bioavailability are major clinical limitations. Moghadamtousi SZ et al. A review on antibacterial, antiviral and antifungal activity of curcumin.
Ginger
Zingiber officinale		 Gingerols, shogaols and zingerone Antibacterial and antifungal activity, including possible inhibition of microbial adhesion and biofilm formation. Primarily laboratory evidence; there is little direct clinical evidence that ginger supplements treat infections. PubMed literature: ginger, gingerols and antimicrobial activity.
Clove
Syzygium aromaticum		 Eugenol and eugenyl acetate Antibacterial, antifungal and local antiseptic activity, principally through membrane and protein disruption. Relevant mainly to topical, food-preservation and dental applications. Evidence for systemic infection treatment is insufficient. PubMed literature: clove, eugenol and antimicrobial activity.
Cinnamon
Cinnamomum species		 Cinnamaldehyde, eugenol and cinnamic acid derivatives Antibacterial, antifungal and antibiofilm activity; may alter microbial membranes and quorum-sensing pathways. Predominantly laboratory evidence. Cassia cinnamon can contribute substantial coumarin exposure when consumed in concentrated amounts. PubMed literature: cinnamon, cinnamaldehyde and antimicrobial activity.
Neem
Azadirachta indica		 Nimbidin, nimbin, nimbolide, azadirachtin and other limonoids Antibacterial, antifungal, antiparasitic and antibiofilm effects have been reported. Some topical and dental research exists, but systemic clinical evidence is inadequate. Oral neem preparations have important safety concerns. PubMed literature: Azadirachta indica and antimicrobial activity.
Black seed
Nigella sativa		 Thymoquinone, thymohydroquinone and related volatile compounds Antibacterial, antifungal, antiparasitic and possible antiviral activity. Considerable laboratory research but limited, heterogeneous clinical evidence for infectious diseases. PubMed literature: Nigella sativa, thymoquinone and antimicrobial activity.
Green tea extract
Camellia sinensis		 Epigallocatechin gallate (EGCG) and other catechins Antibacterial, antiviral and antibiofilm activity; may damage membranes, inhibit microbial enzymes and enhance some antibiotics. Some localized oral-health evidence, but limited evidence for treating systemic infections. Concentrated extracts may cause liver injury in susceptible individuals. PubMed literature: EGCG, green tea and antimicrobial activity.
Licorice root
Glycyrrhiza species		 Glycyrrhizin, glycyrrhetinic acid, liquiritigenin and other flavonoids Antiviral, antibacterial and antifungal effects have been reported in laboratory and preclinical studies. Limited clinical antimicrobial evidence. Glycyrrhizin can cause hypertension, hypokalemia, fluid retention and clinically important drug interactions. National Center for Complementary and Integrative Health: Licorice Root.
Andrographis
Andrographis paniculata		 Andrographolide and related diterpenoid lactones Immunomodulatory, anti-inflammatory and possible antiviral or antibacterial activity. Some evidence for modest symptom reduction in uncomplicated respiratory infections, but this does not establish direct pathogen eradication. PubMed literature: Andrographis and respiratory infections.
Pelargonium sidoides Proanthocyanidins, phenolic acids and oxygenated coumarin derivatives Possible antiviral, antibacterial anti-adhesive and immunomodulatory activity. Some human evidence for modest symptom improvement in acute bronchitis and selected respiratory infections. It is not a substitute for antibiotics when bacterial treatment is indicated. Timmer A et al. Pelargonium sidoides extract for acute respiratory tract infections. Cochrane systematic review.
Monolaurin
Glycerol monolaurate		 Monolaurin, a monoester derived from lauric acid May disrupt lipid membranes and interfere with signalling or virulence in certain bacteria and enveloped viruses. Predominantly laboratory and animal evidence. There is insufficient clinical evidence to recommend oral monolaurin for infections. PubMed literature: glycerol monolaurate and antimicrobial activity.
Caprylic acid Octanoic acid, an eight-carbon medium-chain fatty acid Antifungal and membrane-disrupting activity, particularly against Candida species, has been reported in vitro. Insufficient human evidence for treating candidiasis or systemic fungal infection. Marketing claims commonly exceed the evidence. PubMed literature: caprylic acid and Candida.
Olive leaf extract
Olea europaea		 Oleuropein, hydroxytyrosol and elenolic-acid derivatives Antibacterial, antiviral and antifungal activity has been observed in laboratory studies. Preliminary evidence only; clinical trials have not established it as a treatment for infectious disease. PubMed literature: olive leaf, oleuropein and antimicrobial activity.
Goldenseal
Hydrastis canadensis		 Hydrastine, canadine and berberine Extracts and individual alkaloids show antibacterial activity in laboratory studies. There is no good clinical evidence that goldenseal treats human infections. Product composition, absorption and drug interactions are important limitations. National Center for Complementary and Integrative Health: Goldenseal.
Sweet wormwood / artemisinin
Artemisia annua 		Artemisinin and related sesquiterpene lactones Artemisinin derivatives are potent antimalarial agents. Additional antibacterial, antiviral and antiparasitic effects are being studied. Artemisinin-based combination therapies are established medicines, not ordinary supplements. Herbal preparations should not replace standardized malaria treatment because dose variability can promote treatment failure and resistance. World Health Organization: Guidelines for malaria.

Evidence interpretation

  • Clinical evidence: Effects have been studied in human participants, but usually for a specific preparation, route, dose and indication.
  • Preclinical evidence: Activity has mainly been demonstrated in cell culture, microbial cultures or animal models.
  • Anti-adhesive or probiotic activity: The product may reduce colonization or pathogen attachment without directly killing the microorganism.
  • Topical evidence: Results from topical use cannot be assumed to apply to an orally administered supplement.


Scientific Papers found: Click to Expand⟱
7778- ISL,    Isoliquiritigenin, a potent human monoamine oxidase inhibitor, modulates dopamine D1, D3, and vasopressin V1A receptors
- Study, Park, NA - Study, AD, NA
*neuroP?, TumCP↓, *Inflam↓, *hepatoP↑, angioG↓, *AntiBio↑, *AntiDiabetic↓, *ROS↓, *antiOx↑, *MAOA↓, *MAOB↓,
7782- ISL,  BUT,  SCP,    Butein, isoliquiritigenin, and scopoletin attenuate neurodegeneration via antioxidant enzymes and SIRT1/ADAM10 signaling pathway
- in-vitro, AD, SH-SY5Y
*Inflam↓, *AntiBio↑, *antiOx↑, *Apoptosis↓, *ROS↓, *SIRT1↑, *FOXO3↑, *ADAM10↑, *Bcl-2↝, *Catalase↑, *SOD2↑, *neuroP↑, *GSR↑, *GPx↑, *GSH↑,

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:


Migration(tgid=13) ⓘ

TumCP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,  
Total Targets: 2

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 2,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSR↑, 1,   ROS↓, 2,   SOD2↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 1,   Bcl-2↝, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

FOXO3↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 2,  

Synaptic & Neurotransmission(tgid=18) ⓘ

ADAM10↑, 1,   MAOA↓, 1,  

Protein Aggregation(tgid=19) ⓘ

MAOB↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↓, 1,   hepatoP↑, 1,   neuroP?, 1,   neuroP↑, 1,  
Total Targets: 20

Scientific Paper Hit Count for: AntiBio, Antibiotic/Antimicrobial activity
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#:425  Target#:1483  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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