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Phytotherapy Research : PTR Jun 2008The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional... (Review)
Review
The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components.
Topics: Animals; Chalcones; Flavonoids; Glycyrrhetinic Acid; Glycyrrhiza; Humans; Molecular Structure; Plant Extracts; Saponins; Triterpenes
PubMed: 18446848
DOI: 10.1002/ptr.2362 -
The Netherlands Journal of Medicine Apr 2005Glycyrrhetinic acid, the active constituent of liquorice, inhibits renal IIbeta-hydroxysteroid dehydrogenase. This allows cortisol to stimulate mineralocorticoid...
Glycyrrhetinic acid, the active constituent of liquorice, inhibits renal IIbeta-hydroxysteroid dehydrogenase. This allows cortisol to stimulate mineralocorticoid receptors, which can result in hypertension and hypokalaemia. Treatment options are based on pathophysiological understanding.
Topics: 11-beta-Hydroxysteroid Dehydrogenases; Candy; Glycyrrhetinic Acid; Glycyrrhiza; Humans; Hypertension; Hypokalemia; Receptors, Mineralocorticoid
PubMed: 15869038
DOI: No ID Found -
BMC Complementary Medicine and Therapies Jun 2022The present study aimed to determine the protective effects of hypaconitine (HA) and glycyrrhetinic acid (GA) against chronic heart failure (CHF) in the rats and to...
BACKGROUND
The present study aimed to determine the protective effects of hypaconitine (HA) and glycyrrhetinic acid (GA) against chronic heart failure (CHF) in the rats and to explore the underlying molecular mechanisms.
METHODS
The CHF rat model was established by transverse-aortic constriction (TAC) operation. Transthoracic echocardiography and hematoxylin eosin (HE) staining were used to evaluate the pathophysiological and histopathological changes of CHF model. The total cholesterol (TCHO) and triglyceride (TG) levels were determined by ELISA assay. The protein expression of fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) in the rat ventricular tissues was determined by immunohistochemistry. The serum metabolites were determined by LC-MS/MS assay.
RESULTS
After applied the HA + GA, the cardiac tissue and structure were obviously improved, and the HA + GA treatment also significantly reduced the plasma levels of TCHO and TG in the CHF rats. The expression of FGF2 and VEGFA protein was up-regulated and the expression of eNOS protein was down-regulated in the ventricular tissues of CHF rats, which was significantly restored after HA + GA treatment. HA + GA treatment down-regulated serum isonicotinic acid, phosphatidylcholine, cardiolipin, estrogen glucuronide, and glycocholic acid, up-regulated serum sphingosine and deoxycholic acid in the CHF rats.
CONCLUSIONS
In conclusion, HA + GA showed protective effects on CHF in the rats, and the HA + GA may exert protective effects by reducing lipid levels, up-regulating the expression of FGF2 and VEGFA proteins, attenuating eNOS protein expression, and modulating metabolic pathways. However, the molecular mechanisms underlying HA + GA-mediated effects still require further examination.
Topics: Aconitine; Animals; Chromatography, Liquid; Fibroblast Growth Factor 2; Glycyrrhetinic Acid; Heart Failure; Rats; Tandem Mass Spectrometry; Vascular Endothelial Growth Factor A
PubMed: 35710396
DOI: 10.1186/s12906-022-03632-y -
Molecules (Basel, Switzerland) Mar 2022Liver cancer is one of the most common causes of cancer mortality worldwide. Chemotherapy and radiotherapy are the conventional therapies generally employed in patients... (Review)
Review
Liver cancer is one of the most common causes of cancer mortality worldwide. Chemotherapy and radiotherapy are the conventional therapies generally employed in patients with liver tumors. The major issue associated with the administration of chemotherapeutics is their high toxicity and lack of selectivity, leading to systemic toxicity that can be detrimental to the patient's quality of life. An important approach to the development of original liver-targeted therapeutic products takes advantage of the employment of biologically active ligands able to bind specific receptors on the cytoplasmatic membranes of liver cells. In this perspective, glycyrrhetinic acid (GA), a pentacyclic triterpenoid present in roots and rhizomes of licorice, has been used as a ligand for targeting the liver due to the expression of GA receptors on the sinusoidal surface of mammalian hepatocytes, so it may be employed to modify drug delivery systems (DDSs) and obtain better liver or hepatocyte drug uptake and efficacy. In the current review, we focus on the most recent and interesting research advances in the development of GA-based hybrid compounds and DDSs developed for potential employment as efficacious therapeutic options for the treatment of hepatic cancer.
Topics: Animals; Biocompatible Materials; Glycyrrhetinic Acid; Humans; Liver Neoplasms; Mammals; Quality of Life
PubMed: 35335138
DOI: 10.3390/molecules27061775 -
Molecules (Basel, Switzerland) Jul 2021Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic...
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and -phenylpyrazole-GA derivatives (- and -). We measured their inhibitory activity and enzyme kinetics against PTP1B using -nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or -phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA () exhibited non-competitive inhibition of PTP1B as well as higher potency (IC = 2.5 µM) than that of positive controls ursolic acid (IC = 5.6 µM), claramine (IC = 13.7 µM) and suramin (IC = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.
Topics: Enzyme Inhibitors; Glycyrrhetinic Acid; Humans; Indoles; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Pyrazoles; Structure-Activity Relationship
PubMed: 34299651
DOI: 10.3390/molecules26144375 -
Molecules (Basel, Switzerland) Oct 2022Cantharidin (CTD) is the major component of anticancer drugs obtained from and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC)...
Cantharidin (CTD) is the major component of anticancer drugs obtained from and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75-110 nm with size dispersion (PDI) within the range of 0.19-0.50 and zeta-potential approximately -10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability-their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Glycyrrhetinic Acid; Cantharidin; Folic Acid; Emulsions; Liver Neoplasms; Nanoparticles; Particle Size; Antineoplastic Agents; Drug Carriers
PubMed: 36296377
DOI: 10.3390/molecules27206786 -
British Journal of Pharmacology Feb 2021Coordinated endothelial control of cardiovascular function is proposed to occur by endothelial cell communication via gap junctions and connexins. To study intercellular...
BACKGROUND AND PURPOSE
Coordinated endothelial control of cardiovascular function is proposed to occur by endothelial cell communication via gap junctions and connexins. To study intercellular communication, the pharmacological agents carbenoxolone (CBX) and 18β-glycyrrhetinic acid (18βGA) are used widely as connexin inhibitors and gap junction blockers.
EXPERIMENTAL APPROACH
We investigated the effects of CBX and 18βGA on intercellular Ca waves, evoked by inositol 1,4,5-trisphosphate (IP ) in the endothelium of intact mesenteric resistance arteries.
KEY RESULTS
Acetycholine-evoked IP -mediated Ca release and propagated waves were inhibited by CBX (100 μM) and 18βGA (40 μM). Unexpectedly, the Ca signals were inhibited uniformly in all cells, suggesting that CBX and 18βGA reduced Ca release. Localised photolysis of caged IP (cIP ) was used to provide precise spatiotemporal control of site of cell activation. Local cIP photolysis generated reproducible Ca increases and Ca waves that propagated across cells distant to the photolysis site. CBX and 18βGA each blocked Ca waves in a time-dependent manner by inhibiting the initiating IP -evoked Ca release event rather than block of gap junctions. This effect was reversed on drug washout and was unaffected by small or intermediate K -channel blockers. Furthermore, CBX and 18βGA each rapidly and reversibly collapsed the mitochondrial membrane potential.
CONCLUSION AND IMPLICATIONS
CBX and 18βGA inhibit IP -mediated Ca release and depolarise the mitochondrial membrane potential. These results suggest that CBX and 18βGA may block cell-cell communication by acting at sites that are unrelated to gap junctions.
Topics: Calcium; Calcium Signaling; Carbenoxolone; Endothelial Cells; Gap Junctions; Glycyrrhetinic Acid; Inositol 1,4,5-Trisphosphate; Mitochondria
PubMed: 33269468
DOI: 10.1111/bph.15329 -
Molecules (Basel, Switzerland) May 2020The focus of this work was to prepare Spanish Broom, flax, and hemp dressings impregnated with glycyrrhetinic acid (GA) liposomes or hyalurosomes to promote the healing...
The focus of this work was to prepare Spanish Broom, flax, and hemp dressings impregnated with glycyrrhetinic acid (GA) liposomes or hyalurosomes to promote the healing process and protect the skin wounds. Vesicles were prepared by the film hydration method and characterized in terms of size, particle size distribution, ζ potential, encapsulation efficiency, in vitro release, and biocompatibility on 3T3 fibroblasts. Loaded liposomes and hyalurosomes showed nanometric size (355 ± 19 nm and 424 ± 32 nm, respectively), good size distribution (lower than 0.3), and appropriate encapsulation efficiency (58.62 ± 3.25% and 59.22 ± 8.18%, respectively). Hyalurosomes showed good stability during the storage period, which can be correlated to the negative ζ potential, and allowed a fast and complete release of GA. Preliminary biological studies revealed that both kinds of loaded vesicles were not cytotoxic and that hyalurosomes could exert a slight stimulating effect on fibroblast proliferation. Finally, in vitro release studies from the different dressings impregnated with the loaded vesicles demonstrated that a high amount of GA could be reached at the wound site after 60 min from application. In conclusion, the results suggested that the developed dressings, especially those impregnated with hyalurosomes, can be efficiently used to promote the healing process.
Topics: 3T3 Cells; Animals; Biocompatible Materials; Cannabis; Cell Cycle; Cell Proliferation; Cell Survival; Drug Carriers; Fibroblasts; Flax; Glycyrrhetinic Acid; Hyaluronic Acid; Liposomes; Mice; Particle Size; Skin; Spartium; Wound Healing
PubMed: 32486398
DOI: 10.3390/molecules25112558 -
International Journal of Molecular... Oct 2019In the last 2-3 decades, gene therapy represented a promising option for hepatocellular carcinoma (HCC) treatment. However, the design of safe and efficient gene...
In the last 2-3 decades, gene therapy represented a promising option for hepatocellular carcinoma (HCC) treatment. However, the design of safe and efficient gene delivery systems is still one of the major challenges that require solutions. In this study, we demonstrate a versatile method for covalent conjugation of glycyrrhizin acid (GL) or glycyrrhetinic acid (GA) to increase the transfection efficiency of Polyethyleneimine (PEI, Mw 1.8K) and improve their targeting abilities of hepatoma carcinoma cells. GA and GL targeting ligands were grafted to PEI via N-acylation, and we systematically investigated their biophysical properties, cytotoxicity, liver targeting and transfection efficiency, and endocytosis pathway trafficking. PEI-GA, PEI-GL1 and PEI-GL2 conjugates caused significant increases in gene transfection efficiency and superior selectivity for HepG2 cells, with all three conjugates showing specific recognition of HepG2 cells by the free GA competition assay. The endocytosis inhibition and intracellular trafficking results indicated that PEI-GA and GL1 conjugates behaved similarly to SV40 virus, by proceeding via the caveolae- and clathrin-independent mediated endocytosis pathway and bypassing entry into lysosomes, with an energy independent manner, achieving their high transfection efficiencies. In the HepG2 intraperitoneal tumor model, PEI-GA and PEI-GL1 carrying the luciferase reporter gene gained high gene expression, suggesting potential use for in vivo application.
Topics: Animals; Carcinoma, Hepatocellular; Endocytosis; Female; Gene Transfer Techniques; Genes, Reporter; Genetic Therapy; Glycyrrhetinic Acid; Glycyrrhizic Acid; Hep G2 Cells; Humans; Liver Neoplasms; Mice; Mice, Inbred BALB C; Nanoparticles; Polyethyleneimine
PubMed: 31614879
DOI: 10.3390/ijms20205074 -
Biomolecules Jun 2021The phytotherapeutic properties of (licorice) extract are mainly attributed to glycyrrhizin (GR) and glycyrrhetinic acid (GA). Among their possible pharmacological... (Review)
Review
The phytotherapeutic properties of (licorice) extract are mainly attributed to glycyrrhizin (GR) and glycyrrhetinic acid (GA). Among their possible pharmacological actions, the ability to act against viruses belonging to different families, including SARS coronavirus, is particularly important. With the COVID-19 emergency and the urgent need for compounds to counteract the pandemic, the antiviral properties of GR and GA, as pure substances or as components of licorice extract, attracted attention in the last year and supported the launch of two clinical trials. In silico docking studies reported that GR and GA may directly interact with the key players in viral internalization and replication such as angiotensin-converting enzyme 2 (ACE2), spike protein, the host transmembrane serine protease 2, and 3-chymotrypsin-like cysteine protease. In vitro data indicated that GR can interfere with virus entry by directly interacting with ACE2 and spike, with a nonspecific effect on cell and viral membranes. Additional anti-inflammatory and antioxidant effects of GR cannot be excluded. These multiple activities of GR and licorice extract are critically re-assessed in this review, and their possible role against the spread of the SARS-CoV-2 and the features of COVID-19 disease is discussed.
Topics: Angiotensin-Converting Enzyme 2; Animals; Anti-Inflammatory Agents; Antiviral Agents; COVID-19; Glycyrrhetinic Acid; Glycyrrhiza; Glycyrrhizic Acid; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization; COVID-19 Drug Treatment
PubMed: 34201172
DOI: 10.3390/biom11060855