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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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| Glutathione S-transferases (GSTs) are a family of phase II detoxification enzymes that play key roles in catalyzing the conjugation of glutathione (GSH) to a wide range of electrophilic compounds. This family includes multiple isoenzymes (e.g., GST-α, GST-μ, GST-π) with tissue-specific expression patterns and overlapping as well as distinct substrate specificities. -GSTs are important for detoxifying potentially harmful compounds, including products of oxidative stress, environmental toxins, and chemotherapeutic agents. -They contribute to the cellular defense mechanism against oxidative damage and help maintain cellular redox balance. -Beyond detoxification, GSTs can modulate cell signaling pathways, potentially affecting cell proliferation, apoptosis, and drug resistance. -GST-π is commonly upregulated in several cancers such as breast, lung, colorectal, and hematologic malignancies. -Elevated expression of specific GST isoenzymes—most notably GST-π—has been associated with a poorer prognosis in several cancer types. This is often linked to resistance to chemo- or radiotherapy, as higher GST activity can lead to more efficient detoxification of these agents, reducing their cytotoxic effects. -In contrast, reduced GST expression in some contexts might indicate a less robust detoxification system, which can correlate with increased sensitivity to oxidative stress and possibly a less aggressive tumor phenotype. |
| 7789- | ISL, | Cancer Chemopreventive Activity and Metabolism of Isoliquiritigenin, a Compound Found in Licorice |
| - | Review, | Nor, | 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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