Exploring the Pharmacological Potential of Glycyrrhizic Acid: From Therapeutic Applications to Trends in Nanomedicine

Glycyrrhizic acid (GA) is the main active component of the licorice root, which has been known in traditional medicine since the ancient times. It is a molecule composed of a hydrophilic part, two glucuronic acid molecules, and a hydrophobic part, glycyrrhetinic acid. GA, when subjected to acid hydrolysis, releases 18β- and 18α-glycyrrhetinic acids. Glycyrrhetinic acid is most responsible for the pharmacological activities of licorice. GA has been reported to have multiple therapeutic properties: anti-viral, anti-inflammatory, antitumor, antimicrobial and hepatoprotective. Different approaches have revealed similar anti-inflammatory mechanisms of action of GA, such as the inhibition of translocation of nuclear factor-κB (NF-κB) and suppression of Tumour Necrosis Factor alpha (TNF-α) and interleukins. In this sense, several in vitro and in vivo studies have described the use of GA in the prevention and treatment of several complications, especially microbial/viral infection, and as a novel chemo-preventive agent for liver injury. Recent studies postulated that GA nanoparticles (GANPs) can be a promising strategy for the treatment of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infections. This mini-review summarizes the pharmacological activities of GA and its beneficial effects against various health problems and provides perspectives on the development of versatile nanoplatforms to overcome some limiting physicochemical properties and for enhancing the therapeutic benefits of GA.

18 α-Glycyrrhetinic Acid Aggregation-Induced Emission Probes for Visual Fluorescence Detection of Explosive as well Multi-functional Application

With the aggravation of the international situation and the frequency of local wars, a variety of new types of explosives have been put into use and accurate detection of these...

Investigation into the Protective Effects of Hypaconitine and Glycyrrhetinic Acid Against Chronic Heart Failure of the Rats

BackgroundThe 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. 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.ResultsHA + GA treatment 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.ConclusionIn 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.

18β-Glycyrrhetinic Acid Inhibits TGF-β-Induced Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma by Targeting STAT3

18[Formula: see text]-glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor-[Formula: see text] (TGF-[Formula: see text]-induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF-[Formula: see text]-induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF-[Formula: see text]. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF-[Formula: see text]-induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF-[Formula: see text]-induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF-[Formula: see text]-induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC.

Material Basis For Combining Euphrobia Kansui And Licorice Based On Rat Liver Microsomal

Background: The herbal-pair, Kansui and Licorice, belongs to the "eighteen incompatible medicaments" category of traditional Chinese medicine. Kansuiphorin C (KC) is the main toxic component of Kansui. The main component of licorice is glycyrrhizic acid, which is hydrolyzed to glycyrrhetinic acid. Currently, the synergistic mechanism between Kansui and Licorice is unclear. Methods: Rat liver microsomes were used in this experiment, HPLC was used to detect the contents of KC, glycyrrhizic acid, and glycyrrhetinic acid to determine whether these compounds are metabolic substrates of CYP450. A control group with isozyme inhibitors was also employed to reveal the isozyme subtypes involved in compound metabolism. To further explain the induction or inhibitory effect of the above compounds on liver microsomal enzymes, enzyme activity was indirectly revealed based on changes in the contents of known metabolites of CYP2E1, CYP2C9, and CYP3A4. Results: KC and glycyrrhetinic acid were metabolic substrates of CYP450. CYP2E1 and CYP2C9 are mainly involved in the partial metabolism of glycyrrhizic acid in the liver. CYP2E1 and CYP3A4 are mainly involved in the partial metabolism of glycyrrhetinic acid in the liver. CYP2E1, CYP2C9, and CYP3A4 did not play a major role in the metabolism of KC. KC had little effect on the metabolism of glycyrrhizic acid and glycyrrhetinic acid. Glycyrrhizic acid, glycyrrhetinic acid, and KC induced CYP3A4 and inhibit CYP2E1. Both glycyrrhizic acid and glycyrrhetinic acid could inhibit the induction of CYP3A4 after combination with KC. KC with glycyrrhizic acid could synergistically inhibit the activity of CYP2E1, while KC with glycyrrhetinic acid could synergistically induce the activity of CYP2E1 Conclusion: KC and glycyrrhetinic acid were metabolic substrates of CYP450. KC, glycyrrhizic acid and glycyrrhetinic acid have different inducing and inhibiting effects on CYP450 enzyme.

18β-Glycyrrhetinic Acid Protectes Neonatal Rats with Hyperoxia Exposure Through Inhibiting ROS/NF-κB/NLRP3 Inflammasome

Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants. Oxygen supplementation is a lifesaving therapeutic measure used for premature infants with pulmonary insufficiency. However, oxygen toxicity is a significant trigger for BPD, and oxidative stress-induced inflammatory responses, in turn, worsens the oxidative toxicity resulting in lung injury and arresting of lung development. Glycyrrhiza radix is commonly used in the medicine and food industries. 18β-Glycyrrhetinic acid (18β-GA), a primary active ingredient of Glycyrrhiza radix, has a powerful anti-oxidative and anti-inflammatory effects. This study aimed to determine whether 18β-GA has protective effects on neonatal rats with hyperoxia exposure. Newborn Sprague-Dawley rats were kept in either 21% (normoxia) or 80% O2 (hyperoxia) continuously from postnatal day (PN) 1 to 14. 18β-GA was injected intragastrically at 50 or 100 mg/kg body weight once a day from PN 1 to 14. We examined the body weights and alveolar development, and measured ROS level and the markers of pulmonary inflammation. Mature-IL-1β and NF-κB pathway proteins, and the NLRP3 inflammasome, were assessed; concurrently, caspase-1 activity was measured. Our results indicated that hyperoxia resulted in alveolar simplification and decreased bodyweight of neonatal rats. Hyperoxia exposure increased ROS level and pulmonary inflammation, and activated NF-κB and the NLRP3 inflammasome. 18β-GA treatment decreased ROS level, inhibited the activation of NF-κB and the NLRP3 inflammasome, decreased pulmonary inflammation, improved alveolar development, and increased the bodyweight of neonatal rats with hyperoxia exposure. Our study demonstrates that 18β-GA protects neonatal rats with hyperoxia exposure through inhibiting ROS/NF-κB/NLRP3 inflammasome.