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| 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):
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
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):
Isoliquiritigenin Alzheimer’s-Relevant Mechanisms
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| Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases. Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer. Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA. Catalase and Cancer Oxidative Stress and Cancer: Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis. Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells. Expression Levels in Different Cancers: Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior. Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis. Prognostic Implications: Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress. Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched). |
| 7766- | ISL, | Isoliquiritigenin alleviates myocardial ischemia-reperfusion injury by regulating the Nrf2/HO-1/SLC7a11/GPX4 axis in mice |
| - | in-vivo, | Stroke, | NA |
| 7782- | ISL, | BUT, | SCP, | Butein, isoliquiritigenin, and scopoletin attenuate neurodegeneration via antioxidant enzymes and SIRT1/ADAM10 signaling pathway |
| - | in-vitro, | AD, | SH-SY5Y |
| 7758- | ISL, | Targeting the JAK/STAT pathway with isoliquiritigenin in ovarian cancer: molecular mechanisms and therapeutic implications |
| - | Review, | Ovarian, | NA |
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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