Isoliquiritigenin

Last updated
Isoliquiritigenin
Isoliquiritigenin.svg
Names
Preferred IUPAC name
2′,4,4′-Trihydroxychalcone
Other names
  • 6'-Deoxychalcone
  • 4,2',4'-Trihydroxychalcone
  • 2',4',4-Trihydroxychalcone
Identifiers
3D model (JSmol)
AbbreviationsILTG
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.202.617 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 237-316-5
KEGG
PubChem CID
UNII
  • InChI=1S/C15H12O4/c16-11-4-1-10(2-5-11)3-8-14(18)13-7-6-12(17)9-15(13)19/h1-9,16-17,19H/b8-3+ X mark.svgN
    Key: DXDRHHKMWQZJHT-FPYGCLRLSA-N X mark.svgN
  • InChI=1/C15H12O4/c16-11-4-1-10(2-5-11)3-8-14(18)13-7-6-12(17)9-15(13)19/h1-9,16-17,19H/b8-3+
    Key: DXDRHHKMWQZJHT-FPYGCLRLBB
  • C1=CC(=CC=C1C=CC(=O)C2=C(C=C(C=C2)O)O)O
Properties
C15H12O4
Molar mass 256.257 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Isoliquiritigenin is a phenolic chemical compound found in licorice. [1]

Contents

Occurrence

Liquorice roots Market Aix-en-Provence 20100828 Liquorice.jpg
Liquorice roots

Isoliquiritigenin occurs in some species of the genus Glycyrrhiza glabra (licorice). [2]

Pharmacological properties

Isoliquiritigenin has various pharmacological properties and is also responsible for the corresponding properties of the plants it contains. In various studies, its effects included anti-inflammatory, antimicrobial agent, and antioxidant activities, and it also demonstrated targeted cancer therapy effects. [2] In in vitro studies and some in vivo studies, isoliquiritigenin showed effects against breast cancer, colorectal carcinoma, ovarian carcinoma, bronchial carcinoma, and leukemia, among others. [3] It also interferes with several cellular signaling pathways and has an anti-inflammatory effect, which may have applications in the treatment of inflammatory diseases. [4]

Metabolism

The enzyme 6'-deoxychalcone synthase uses malonyl-CoA, 4-coumaroyl-CoA, NADPH, and H+ to produce CoA, isoliquiritigenin, CO2, NADP+, and H2O.

The enzyme isoliquiritigenin 2'-O-methyltransferase further transforms isoliquiritigenin into 2'-O-methylisoliquiritigenin.

Mechanism of action

Isoliquiritigenin has been found to be a potent (65 times higher affinity than diazepam) GABA-A benzodiapine receptor positive allosteric modulator. [5] It can target miR-301b/LRIG1 signaling pathways, resulting in the inhibition of melanoma growth in vitro . [6]

Related Research Articles

<span class="mw-page-title-main">Allosteric regulation</span> Regulation of enzyme activity

In the fields of biochemistry and pharmacology an allosteric regulator is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the protein's activity, either enhancing or inhibiting its function. In contrast, substances that bind directly to an enzyme's active site or the binding site of the endogenous ligand of a receptor are called orthosteric regulators or modulators.

<span class="mw-page-title-main">Metabotropic glutamate receptor</span> Type of glutamate receptor

The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter.

The epoxyeicosatrienoic acids or EETs are signaling molecules formed within various types of cells by the metabolism of arachidonic acid by a specific subset of cytochrome P450 enzymes termed cytochrome P450 epoxygenases. These nonclassic eicosanoids are generally short-lived, being rapidly converted from epoxides to less active or inactive dihydroxy-eicosatrienoic acids (diHETrEs) by a widely distributed cellular enzyme, soluble epoxide hydrolase (sEH), also termed epoxide hydrolase 2. The EETs consequently function as transiently acting, short-range hormones; that is, they work locally to regulate the function of the cells that produce them or of nearby cells. The EETs have been most studied in animal models where they show the ability to lower blood pressure possibly by a) stimulating arterial vasorelaxation and b) inhibiting the kidney's retention of salts and water to decrease intravascular blood volume. In these models, EETs prevent arterial occlusive diseases such as heart attacks and brain strokes not only by their anti-hypertension action but possibly also by their anti-inflammatory effects on blood vessels, their inhibition of platelet activation and thereby blood clotting, and/or their promotion of pro-fibrinolytic removal of blood clots. With respect to their effects on the heart, the EETs are often termed cardio-protective. Beyond these cardiovascular actions that may prevent various cardiovascular diseases, studies have implicated the EETs in the pathological growth of certain types of cancer and in the physiological and possibly pathological perception of neuropathic pain. While studies to date imply that the EETs, EET-forming epoxygenases, and EET-inactivating sEH can be manipulated to control a wide range of human diseases, clinical studies have yet to prove this. Determination of the role of the EETS in human diseases is made particularly difficult because of the large number of EET-forming epoxygenases, large number of epoxygenase substrates other than arachidonic acid, and the large number of activities, some of which may be pathological or injurious, that the EETs possess.

<span class="mw-page-title-main">Cordycepin</span> Chemical compound

Cordycepin, or 3'-deoxyadenosine, is a derivative of the nucleoside adenosine, differing from the latter by the replacement of the hydroxy group in the 3' position with a hydrogen. It was initially extracted from the fungus Cordyceps militaris, but can now be produced synthetically. It is also found in other Cordyceps species as well as Ophiocordyceps sinensis.

<span class="mw-page-title-main">Betulinic acid</span> Chemical compound

Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It is found in the bark of several species of plants, principally the white birch from which it gets its name, but also the ber tree, selfheal, the tropical carnivorous plants Triphyophyllum peltatum and Ancistrocladus heyneanus, Diospyros leucomelas, a member of the persimmon family, Tetracera boiviniana, the jambul, flowering quince, rosemary, and Pulsatilla chinensis.

<span class="mw-page-title-main">Honokiol</span> Chemical compound

Honokiol is a lignan isolated from the bark, seed cones, and leaves of trees belonging to the genus Magnolia. It has been identified as one of the chemical compounds in some traditional eastern herbal medicines along with magnolol, 4-O-methylhonokiol, and obovatol.

<span class="mw-page-title-main">GPER</span> Protein-coding gene in the species Homo sapiens

G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the GPER gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible for some of the rapid effects that estradiol has on cells.

<span class="mw-page-title-main">NFE2L2</span> Human protein and coding gene

Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.

Leukotriene B<sub>4</sub> receptor 2 Protein-coding gene in humans

Leukotriene B4 receptor 2, also known as BLT2, BLT2 receptor, and BLTR2, is an Integral membrane protein that is encoded by the LTB4R2 gene in humans and the Ltbr2 gene in mice.

<span class="mw-page-title-main">Metabotropic glutamate receptor 2</span> Mammalian protein found in humans

Metabotropic glutamate receptor 2 (mGluR2) is a protein that, in humans, is encoded by the GRM2 gene. mGluR2 is a G protein-coupled receptor (GPCR) that couples with the Gi alpha subunit. The receptor functions as an autoreceptor for glutamate, that upon activation, inhibits the emptying of vesicular contents at the presynaptic terminal of glutamatergic neurons.

<span class="mw-page-title-main">Free fatty acid receptor 4</span> Protein-coding gene in the species Homo sapiens

Free Fatty acid receptor 4 (FFAR4), also termed G-protein coupled receptor 120 (GPR120), is a protein that in humans is encoded by the FFAR4 gene. This gene is located on the long arm of chromosome 10 at position 23.33. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR4 is a rhodopsin-like GPR in the broad family of GPRs which in humans are encoded by more than 800 different genes. It is also a member of a small family of structurally and functionally related GPRs that include at least three other free fatty acid receptors (FFARs) viz., FFAR1, FFAR2, and FFAR3. These four FFARs bind and thereby are activated by certain fatty acids.

<span class="mw-page-title-main">Alpha-7 nicotinic receptor</span> Type of cell receptor found in humans

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].

<span class="mw-page-title-main">TREM2</span> Protein-coding gene in the species Homo sapiens

Triggering receptor expressed on myeloid cells 2(TREM2) is a protein that in humans is encoded by the TREM2 gene. TREM2 is expressed on macrophages, immature monocyte-derived dendritic cells, osteoclasts, and microglia, which are immune cells in the central nervous system. In the liver, TREM2 is expressed by several cell types, including macrophages, that respond to injury. In the intestine, TREM2 is expressed by myeloid-derived dendritic cells and macrophage. TREM2 is overexpressed in many tumor types and has anti-inflammatory activities. It might therefore be a good therapeutic target.

<span class="mw-page-title-main">Glaucine</span> Chemical compound

Glaucine(1,2,9,10-TetraMethoxyAporphine, Bromcholitin, Glauvent, Tusidil, Tussiglaucin) is an aporphine alkaloid found in several different plant species in the family Papaveraceae such as Glaucium flavum, Glaucium oxylobum and Corydalis yanhusuo, and in other plants like Croton lechleri in the family Euphorbiaceae.

<span class="mw-page-title-main">Selective glucocorticoid receptor modulator</span> Class of experimental drugs

Selective glucocorticoid receptor modulators (SEGRMs) and selective glucocorticoid receptor agonists (SEGRAs) formerly known as dissociated glucocorticoid receptor agonists (DIGRAs) are a class of experimental drugs designed to share many of the desirable anti-inflammatory, immunosuppressive, or anticancer properties of classical glucocorticoid drugs but with fewer side effects such as skin atrophy. Although preclinical evidence on SEGRAMs’ anti-inflammatory effects are culminating, currently, the efficacy of these SEGRAMs on cancer are largely unknown.

In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that an allosteric modulator binds to is not the same one to which an endogenous agonist of the receptor would bind. Modulators and agonists can both be called receptor ligands.

<span class="mw-page-title-main">MMPIP</span> Chemical compound

MMPIP is a drug used in scientific research that acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR7. This receptor subtype appears to be involved in the downstream response to cocaine in the brain.

<span class="mw-page-title-main">Wogonin</span> Chemical compound

Wogonin is an O-methylated flavone, a flavonoid-like chemical compound which is found in Scutellaria baicalensis.

<span class="mw-page-title-main">Amentoflavone</span> Chemical compound

Amentoflavone is a biflavonoid constituent of a number of plants including Ginkgo biloba, Chamaecyparis obtusa (hinoki), Biophytum sensitivum, Selaginella tamariscina, Hypericum perforatum and Xerophyta plicata.

<span class="mw-page-title-main">NS-11394</span> Chemical compound

NS-11394 is a drug which acts as a subtype-selective positive allosteric modulator at GABAA receptors, with selectivity for the α3 and α5 subtypes. It has been researched as an analgesic for use in chronic or neuropathic pain.

References

  1. Nerya, Ohad; Vaya, Jacob; Musa, Ramadan; Izrael, Sarit; Ben-Arie, Ruth; Tamir, Snait (2003). "Glabrene and Isoliquiritigenin as Tyrosinase Inhibitors from Licorice Roots". Journal of Agricultural and Food Chemistry. 51 (5): 1201–1207. doi:10.1021/jf020935u. PMID   12590456.
  2. 1 2 Fu Peng, Qiaohui Du, Cheng Peng, Neng Wang, Hailin Tang, Xiaoming Xie, Jiangang Shen, Jianping Chen (July 2015), "A Review: The Pharmacology of Isoliquiritigenin", Phytotherapy Research, vol. 29, no. 7, pp. 969–977, doi:10.1002/ptr.5348 {{citation}}: CS1 maint: multiple names: authors list (link)
  3. Kai-Lee Wang, Ying-Chun Yu, Shih-Min Hsia (2021-01-01), "Perspectives on the Role of Isoliquiritigenin in Cancer", Cancers, vol. 13, no. 1, p. 115, doi:10.3390/cancers13010115, PMC   7795842 , PMID   33401375 {{citation}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  4. Ziyi Chen, Wenwen Ding, Xiaoxue Yang, Tiangong Lu, Ying Liu (January 2024), "Isoliquiritigenin, a potential therapeutic agent for treatment of inflammation-associated diseases", Journal of Ethnopharmacology, vol. 318, p. 117059, doi:10.1016/j.jep.2023.117059 {{citation}}: CS1 maint: multiple names: authors list (link)
  5. Cho, S; Kim, S; Jin, Z; Yang, H; Han, D; Baek, N. I.; Jo, J; Cho, C. W.; Park, J. H.; Shimizu, M; Jin, Y. H. (2011). "Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of GABAA receptors and shows hypnotic effects". Biochemical and Biophysical Research Communications. 413 (4): 637–42. doi:10.1016/j.bbrc.2011.09.026. PMID   21945440.
  6. Xiang, Shijian; Chen, Huoji; Luo, Xiaojun; An, Baichao; Wu, Wenfeng; Cao, Siwei; Ruan, Shifa; Wang, Zhuxian; Weng, Lidong; Zhu, Hongxia; Liu, Qiang (2018). "Isoliquiritigenin suppresses human melanoma growth by targeting miR-301b/LRIG1 signaling". Journal of Experimental & Clinical Cancer Research . 37 (1): 184. doi: 10.1186/s13046-018-0844-x . PMC   6091185 . PMID   30081934.