Glycyrrhizin Research Articles

Optimized ultrasound-assisted extraction of glycyrrhizic acid from Glycyrrhiza glabra followed by one-pot hydrolysis to and nanoemulsified separation of glycyrrhetinic acid for food applications

Optimized ultrasound-assisted extraction of glycyrrhizic acid from Glycyrrhiza glabra followed by one-pot hydrolysis to and nanoemulsified separation of glycyrrhetinic acid for food applications

Supramolecular Self-Assembled Hydrogel for Antiviral Therapy through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects. In this research, a Zn2+-mediated glycyrrhizinic acid (GA)-based hydrogel (ZnGA Gel) was introduced and potentially developed to be a clinically available drug candidate for RSV therapy. ZnGA Gel was fabricated based on the cooperation of two potential RSV inhibiting molecules (Zn2+ and GA), where Zn2+ promoted self-assembly of GA and reduced its gel concentration and GA promoted zinc absorption and distribution in lung tissue in vivo. The facile construction of supramolecular hydrogel by the self-assembled coordination complex made it an injectable, temperature-sensitive, and pH-responsive controlled-release drug delivery for Zn2+. Most importantly, GA was observed to enhance organism absorption and intracellular accumulation of Zn2+ and was identified as a zinc ionophore for the first time. GA can colonize on the cell membrane and disturb cell membrane potential, resulting in an enhanced cell membrane permeability. In the presence of GA, more than 4.7-fold increasing Zn2+ concentrations materialized in the intracellular cytoplasm, compared to Zn2+ alone administration. This intracellular Zn2+ accumulation directly boosted the antiviral activities through improved inhibition of RSV replication-associated proteins and significantly inhibited RSV replication. Oral administration of ZnGA Gel on the RSV-infected mice model achieved an ideal therapeutic effect by effectively lowering viral load in the lungs, alleviating lung injury symptoms, and reducing inflammatory cell infiltration at pathological sites. The mechanism involved the inhibition of RSV replication-related proteins, aligning with our in vitro results. Additionally, ZnGA Gel had demonstrated biocompatibility, and reasonable supplementation of zinc was acceptable and effective for infants and children in clinical practice. Hence, the ZnGA Gel developed by us holds promise as an effective anti-RSV medicine in the future.

Pulmonary delivery of anti-microRNA oligonucleotide and glycyrrhizic acid using ternary peptide micelles for the treatment of acute lung injury

Pulmonary delivery of anti-microRNA oligonucleotide and glycyrrhizic acid using ternary peptide micelles for the treatment of acute lung injury

Targeted Delivery of Celastrol by GA-Modified Liposomal Calcium Carbonate Nanoparticles to Enhance Antitumor Efficacy Against Breast Cancer

Background/Objectives: Breast cancer, a leading health threat affecting millions worldwide, requires effective therapeutic interventions. Celastrol (CEL), despite its antitumor potential, is limited by poor solubility and stability. This study aimed to enhance CEL’s efficacy by encapsulating it within glycyrrhizic acid (GA)-modified lipid calcium carbonate (LCC) nanoparticles for targeted breast cancer therapy. Methods: The 4T1 mouse breast cancer cells were used for the study. GA-LCC-CEL nanoparticles were prepared using a gas diffusion method and a thin-film dispersion method. GA-LCC-CEL were characterized using the zeta-potential, dynamic light scattering and transmission electron microscope (TEM). The in vitro release behavior of nanoparticles was assessed using the in vitro dialysis diffusion method. Cellular uptake was examined using flow cytometry and confocal microscopy. Intracellular ROS and Rhodamine 123 levels were observed under fluorescence microscopy. MTT and colony formation assays assessed cytotoxicity and proliferation, and apoptosis was analyzed by Annexin V-FITC/PI staining. Wound healing and transwell assays evaluated migration, and Western blotting confirmed protein expression changes related to apoptosis and migration. Results: GA-LCC-CEL nanoparticles displayed a well-defined core-shell structure with a uniform size distribution. They showed enhanced anti-proliferative and pro-apoptotic effects against 4T1 cells and significantly reduced breast cancer cell invasion and migration. Additionally, GA-LCC-CEL modulated epithelial-mesenchymal transition (EMT) protein expression, downregulating Snail and ZEB1, and upregulating E-cadherin. Conclusions: GA-LCC-CEL nanoparticles represent a promising targeted drug delivery approach for breast cancer, enhancing CEL’s antitumor efficacy and potentially inhibiting cancer progression by modulating EMT-related proteins.

Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response

As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage response (DDR) in colorectal cancer remains unclear. GL exposure significantly reduced cell colony formation and viability with a concomitant increase in DNA fragmentation in CRC, meanwhile GL induced apoptosis by activating caspase-3. Moreover, GL induced cell cycle arrest in CRC cells at S phase, which was associated with decreased cyclin D1 in vitro. GL treatment significantly ameliorated tumor growth and promoted DDR in vivo. Mechanism analysis revealed that GL significantly downregulated the NHEJ pathway via inhibiting HMGB1. Finally, the expression of HMGB1 was abnormal regulated in CRC tissue than in adjacent normal tissues and associated with TNM stage and overall survival. Our findings indicate that HMGB1 may be a novel therapeutic target in CRC, a result that GL may serve as a promising drug for CRC treatment.

Resatovir Combined with Glycyrrhizic Acid Ameliorates Osteoarthritis and Enhances Autophagy in Chondrocytes

Background Osteoarthritis (OA) is a chronic disease worldwide. With resatovir usually used as an inhibitor, resatovir and glycyrrhizic acid have several pharmacological activities. Purpose We intend to explore the mechanism underlying resatovir combined with glycyrrhizic acid in OA. Methods After the establishment of an animal model of OA through anterior cruciate ligament transection and destabilization of the medial meniscus, the rats were subjected to intramuscular injection of resatovir combined with glycyrrhizic acid (60 mg/kg) or 5% glucose (60 mg/kg) every day for 4 weeks. During the progress, the rat movement and the bend score of knees were observed through behavioral studies. Additionally, the SKP2 gene expression and toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)-related signaling pathways were examined, as apoptosis and autophagy were evaluated by flow cytometry. Results With increased inflammatory cells in the model group, treatment with resatovir combined with glycyrrhizic acid significantly decreased the number of inflammatory cells. Meanwhile, the treatment resulted in decreased SKP2 expression in OA cells when hindering the migration of preosteoclast cells. Interestingly, it was observed that the bend score increased over the treatment with resatovir plus glycyrrhizic acid and TIPPI% declined dramatically. Resatovir treatment enhanced autophagy and apoptosis in OA cells and decreased pP65, P65, and LC3 expression. Conclusion Resatovir combined with glycyrrhizic acid can inhibit the inflammatory response through decreasing SKP2 expression and induce autophagy activation in OA cells through TLR4/NF-κB signaling, thereby attenuating OA progression.

Diammonium glycyrrhizinate ameliorates alcohol-induced liver injury by reducing oxidative stress, steatosis, and inflammation

Alcohol-induced liver injury (ALI) is a serious global health issue. Diammonium glycyrrhizinate (DG), a pharmaceutical form of glycyrrhizic acid, has been reported to have anti-inflammatory and anti-oxidative stress properties. We investigated the potential hepatoprotective effects of DG against ALI and explored the mechanisms of it. In vivo, C57BL/6J mice were used to investigate the protective effect of DG on ALI induced by chronic plus binge alcohol exposure. In vitro, AML-12 cells were applied to evaluate the role of DDX5 in the hepatic protection of DG and explore the possible mechanism of STAT1 activation regulated by DDX5. The results showed that DG significantly alleviated liver injury, inflammation, and lipid deposition in hepatocytes. It also beneficially influenced oxidative stress dysregulation. RNA-seq expression in mouse liver tissue indicated that Dead-box helicase 5 (DDX5) might be a potential target of DG. Compared with the control group, the expression of DDX5 decreased significantly in the ethanol-fed group, while DDX5 was restored in the DG treatment group. In addition, the protective effects of DG against ALI were impaired by DDX5 deficiency. DDX5 inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1) by recruiting the protein inhibitor of activated STAT1 (PIAS1) to STAT1. The protective effect of DG against ALI associated with oxidative stress, steatosis, and inflammation was probably via regulating the DDX5/STAT1 axis.

Summary of legal regulation of additional mandatory particulars for specific types or categories of foods according to the regulation FIC

The paper presents a summary of the legal treatment of additional mandatory particulars for specific types or categories of foods under Regulation (EU) 1169/2011 of the European Parliament and of the Council of 25 October 2011 on the provision of food information to consumers, amending Regulations (EC) No 1924/2006 and (EC) No 1925/2006 of the European Parliament and of the Council, and repealing Commission Directive 87/250/EEC, Council Directive 90/496/EEC, Commission Directive 1999/10/EC, Directive 2000/13/EC of the European Parliament and of the Council, Commission Directives 2002/67/EC and 2008/5/EC and Commission Regulation (EC) No 608/2004. The authors of the paper analyse and interpret the relevant legislation using traditional methods of legal analysis and legal-hermeneutical methods, with an emphasis on the linguistic and systematic interpretation of those provisions that are directly related to the indication of additional mandatory particulars for foods packaged in certain gases, foods containing sweeteners, foods containing glycyrrhizinic acid or its ammonium salt, Beverages with high caffeine content or foods with added caffeine, Foods with added phytosterols, phytosterol esters, phytostanols or phytostanol esters, and frozen meat, frozen meat preparations and frozen unprocessed fishery products. The paper's authors aim to provide the reader with a comprehensive summary of the legislation on the indication of additional mandatory particulars for specific types or categories of food.

Small Molecule Hydrogels Loading Small Molecule Drugs from Chinese Medicine for the Enhanced Treatment of Traumatic Brain Injury.

Self-assembly of hydrogels for mechanical support and drug delivery has been extensively researched in traumatic brain injury (TBI), where treatment options are limited. The chief challenge is that most self-assembled hydrogels rely on high molecular carriers or the incorporation of exogenous inactive substances as mediators. It is difficult for these drug delivery systems to achieve clinical translation due to concerns regarding biological safety. Here we report a small molecule hydrogel (GBR-gel) loading small molecule drugs (glycyrrhizic acid, berberine, and rhein) that originated from popular Chinese medicines without additional drug loading or inactive components under physiological conditions. In the long run, GBR-gel possesses several advantages, including ease of preparation, cost-effectiveness, and high biocompatibility. As a proof-of-concept, GBR-gel allows for prompt administration at the site of brain injury to exert potent pharmacodynamic effects. Further single-cell RNA sequencing and experimental validation indicated that GBR-gel can effectively rescue the suppressed glutamatergic synapse pathway after TBI, thereby attenuating inflammatory responses and neural impairments. Our work provides an alternative strategy for timely intervention of TBI.

Glycyrrhizic Acid Inhibits Hippocampal Neuron Apoptosis by Activating the PI3K/ AKT Signaling Pathway.

Glycyrrhizic acid (GA), one of the main active substances in Glycyrrhiza, has anti-inflammatory, anti-viral, and neuroprotective effects. GA can significantly reduce cerebral infarction size in middle cerebral artery occlusion (MCAO) rats and suppress inflammatory responses. However, the underlying mechanism by which GA protects the neuronal system remains poorly understood. Cell proliferation and viability were tested using CCK-8 and Edu assays. The effects of GA on apoptosis were detected using flow cytometry and Tunel assays. Western blotting was performed to assess protein expression. Behavioral experiments were conducted using the Morris water maze and rotation tests. Infarct size was observed using TTC staining. We report that GA protects neurons by inhibiting apoptosis, mainly through the PI3K/AKT pathway in oxygen-glucose deprivation/reoxygenation (OGD/R) and MCAO rat models. GA increases the viability and proliferation of oxygen- and glucose-deprived hippocampal neurons. Hippocampal neuron apoptosis decreased after GA treatment in vitro and in vivo. Furthermore, we determined that GA treatment increased the active state of PI3K and its downstream protein p-AKT, whereas when using a specific inhibitor of PI3K, Y294002, the levels of p-PI3K and p-AKT decreased. Finally, we showed that GA treatment improved spatial memory and motor coordination in MCAO rats, while TTC staining showed that GA decreased cerebral infarct size in MCAO rats. We reveal that GA protects hippocampal neurons by inhibiting their apoptosis, mainly through the PI3K/AKT signaling pathway.

Coupling effects of irrigation amount and fertilization rate on growth and bioactive components of four-year-old licorice (Glycyrrhiza uralensis Fisch) in arid regions of Xinjiang

Water scarcity, over-fertilization, and improper crop management practices severely limit the sustainable cultivation of licorice (Glycyrrhiza uralensis Fisch) in the arid regions of Xinjiang. To elucidate the impacts of integrated water and fertilizer management on the growth characteristics and bioactive components (glycyrrhizic acid and liquiritin) of four-year-old licorice plants, a comprehensive four-year field experiment was conducted from 2019 to 2022.The experiment included four irrigation levels (W1: 2500 m³/ha, W2: 4000 m³/ha, W3: 5500 m³/ha, W4: 7000 m³/ha) and four fertilization rates (F1: 305 kg/ha, F2: 610 kg/ha, F3: 915 kg/ha, F4: 1220 kg/ha), following a completely randomized design. Results indicated that both irrigation and fertilization significantly influenced plant height, root length, root weight, root diameter, leaf area index, and root-to-shoot ratio. The optimal growth characteristics were observed under the W2F2 treatment. The contents of glycyrrhizic acid and liquiritin varied significantly among different water and fertilizer treatments, with the highest levels observed under the W2F2 treatment. Excessive irrigation (W4) and over-fertilization (F4) led to a decrease in these bioactive components. A comprehensive evaluation of the growth characteristics and bioactive components revealed that the ideal irrigation and fertilization parameters were 4000 m³/ha and 610 kg/ha, respectively. These parameters optimized plant development and bioactive component accumulation while ensuring efficient resource use. This study provides scientific evidence for optimizing irrigation and fertilization strategies to enhance licorice yield in arid regions, thereby supporting sustainable agricultural practices and improving economic benefits.

The interaction effect of water deficit stress and seaweed extract on phytochemical characteristics and antioxidant activity of licorice (Glycyrrhiza glabra L.).

With increasing drought stress due to climate change and water scarcity, the agricultural sector has sought innovative strategies to mitigate the detrimental effects on crop productivity. One approach that has received significant attention is the use of fertilizers and biostimulants as potential means of alleviating drought stress. In this study, five different irrigation levels including 100% (control), 80% (slight stress), 60% (mild stress), 40% (moderate stress), and 20% (severe stress) of field capacity (FC) and seaweed extract (SWE) at three concentrations (0, 5, and 10 g/L) were applied to the pots containing one-year-old licorice (Glycyrrhiza glabra L.) plants in a factorial completely randomized design experiment with three replications for eight weeks. The glycyrrhizic acid content increased with water stress intensity without the application of SWE until severe (20% FC) water stress treatment. The application of 10 g/L SWE under 100% FC led to a significant increase in the glycyrrhizic acid value (32.5±0.889 mg/g DW) compared with non-SWE application (30.0±1.040 mg/g DW). The maximum glabridin content (0.270±0.010 mg/g DW) was obtained under irrigation of 20% field capacity with 10 g/L SWE application. In addition, the activity of the all studied enzymes such as APX (ascorbate peroxidase), CAT (catalase), POD (peroxidase), and SOD (superoxide dismutase) were boosted by increasing the water stress levels. The use of SWE further enhanced the increase of some of these metabolites and enzymes, which, in turn, helped the plant to tolerate stress conditions through the scavenging of more ROS (Reactive oxygen species), wherein for this purpose, the SWE 10 g/L was more effective than other concentration. The plants efficiently eliminated ROS driven from drought stress by both non-enzymatic and enzymatic systems.

Development of phyto-compound-based nanoformulation for skin regeneration and its in vitro evaluation

Skin regeneration is a process that regenerates damaged or aged skin cells, resulting in a healthier and younger appearance. The demand for nano dosage forms containing phyto-compounds in the cosmetics industry is increasing daily to control or prevent this process. Phyto-compounds with cell regenerative properties often show limited effectiveness in conventional use due to their low hydrophilicity and molecular weight, as well as their low absorption from the skin. Glycyrrhizic acid (GA), a phyto-compound obtained from licorice root, has many pharmacological properties, including skin regeneration properties. The aim of this study is to develop a highly stable GA-containing nanoemulsion (GA-NE) formulation for topical application, determine its anti-collagenase activity, and evaluate its safety and effectiveness by in vitro cell culture methods. In this context, GA-NEs were synthesized with sixteen production procedures using independent variables (oil, water percentage, surfactant, and homogenization time). The average droplet size, polydispersity index (PdI), and zeta potential (ZP) of the synthesized GA-NEs were determined by dynamic light scattering (DLS) analysis. The heating-cooling cycle (H-C) test result showed that the F4P3 formulation was the most stable formulation. Therefore, 90-day physicochemical stability tests were performed with the F4P3 formulation. In vitro release results revealed that GA was released from NEs at a rate of 93.15 ± 0.61 % within 24 h. An ex vivo permeation and penetration study was performed, and the permeation and penetration profile of F4P3 was determined. In vitro cell culture studies showed that the F4P3 formulation had higher cell viability and regeneration than GA in the HaCaT cell line. Anti-collagenase activity results also revealed a better activity of the F4P3 formulation compared to GA. Consequently, characterization, efficacy, and safety studies showed that the F4P3 formulation could be an innovative cell regeneration product candidate suitable for topical use with high stability.

La (NO3)3 substantially fortified Glycyrrhiza uralensis’s resilience against salt stress by interconnected pathways

The taproot of Glycyrrhiza uralensis is globally appreciated for its medicinal and commercial value and is one of the most popular medicinal plants. With the decline of wild G. uralensis resources, cultivated G. uralensis has become a key method to ensure supply. However, soil salinization poses challenges to G. uralensis cultivation and affects the yield and quality of it. In this study, the inhibitory effects of NaCl and Na2SO4 on yield and quality of G. uralensis were comprehensively evaluated in a three-year large-scale pot experiment, and the alleviating effects of supplementation with lanthanum nitrate (La (NO3)3) on G. uralensis were further evaluated under salt stress. The findings indicate that La (NO3)3 significantly strengthened the plant's salt tolerance by enhancing photosynthetic capacity, osmolyte accumulation, antioxidant defenses, and cellular balance of ions, which led to a substantial increase in root biomass and accumulation of major medicinal components. In comparison to the NaCl-stress treatment, the 0.75 M La (NO3)3 + NaCl treatment resulted in a 20% and 34% increase in taproot length and biomass, respectively, alongside a 52% and 43% rise in glycyrrhizic acid and glycyrrhizin content, respectively. Similar improvements were observed with 0.75 M La (NO3)3 + Na2SO4 treatment, which increased root length and biomass by 14% and 26%, respectively, and glycyrrhizic acid and glycyrrhizin content by 40% and 38%, respectively. The combined showed that application of La (NO3)3 not only significantly improved the salt resilience of G. uralensis, but also had a more pronounced alleviation of growth inhibition induced by NaCl compared to Na2SO4 stress except in the gas exchange parameters and root growth. This study provides a scientific basis for high-yield and high-quality cultivation of G. uralensis in saline soils and a new approach for other medicinal plants to improve their salt tolerance.Graphical

Pharmacodynamic and pharmacokinetic study of Shaoyao Gancao decoction for repairing intestinal barrier damage in ulcerative colitis

ObjectiveTo study the therapeutic effect and mechanism of Shaoyao Gancao Decoction (SGD) on ulcerative colitis (UC) mice based on the perspective of intestinal barrier, and this study provides a new consultation for the clinical application of SGD. MethodsThe chemical composition of SGD was characterized by HPLC. The UC mouse model was constructed by 3 % dextran sodium sulfate (DSS), which were randomly divided into the model group (DSS), the positive drug group (5-ASA), the Shaoyao group (SYD), Gancao group (GCD), and the Shaoyao Gancao Decoction group (SGD) at low, medium, and high dosages, respectively. The effects of each drug treatment group on UC were evaluated by the rate of body weight loss, disease activity index (DAI), colon length, spleen index, histopathological evaluations, and the levels of serum inflammatory factors (IL-1β, IL-6, IL-10, IL-21, and TNF-α). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining, ELISA was used to detect the content of LPS in serum, and Western blot was used to detect the changes in the expression of tight junction proteins ZO-1, occludin, and the pathway proteins TLR4 and NF-κBp65 in the colonic tissues, to explore the protective effect of SGD on the intestinal barrier of UC mice. The vivo absorption process of the main active ingredients in the SG, SY and GC groups was determined by LC-MS. ResultsThe contents of albiflorin, paeoniflorin, liquiritin apioside, liquiritin and glycyrrhetinic acid were 6.1227 mg/g, 20.8993 mg/g, 4.0054 mg/g, 3.6140 mg/g and 8.2515 mg/g, respectively. Compared with DSS group, SGD reduced weight loss(P<0.01) and DAI scores(P<0.05), prevented colon shortening(P<0.01), and ameliorated histopathological damage of the colon in UC mice(P<0.01). SGD also protected the intestinal barrier to alleviate UC by significantly reducing serum LPS and inflammatory factor levels, altering the number of goblet cells, promoting tight junction proteins (ZO-1 and occludin) and decreasing the expression of TLR4 and NF-κB in colonic tissues. Pharmacokinetic results showed that there was no significant difference in Cmax, AUC0-t (μg/L.h) and Tmax of albiflorin and paeoniflorin between the SY and SG groups, the Tmax was within 1 h; the AUC0-t (μg/L.h) of liquiritin and glycyrrhizic acid were about 1.6 and 1.9 times higher in the SG group compared to the GC group, respectively. The Cmax, Tmax and AUC0-t (μg/L.h) of glycyrrhizinic acid were significantly reduced to 0.73, 0.68 and 0.68 times of that of the GC group. ConclusionSGD may have a therapeutic effect on DSS-induced UC mice by repairing the damaged intestinal barrier through the TLR4/NF-κB pathway. The combination of Shaoyao and Gancao increased the absorption of liquiritin and glycyrrhizic acid in vivo. The combination of Shaoyao and Gancao could promote the absorption of Gancao, and that the pairing of the two herbs could have a synergistic effect.

5074 Licorice Root Supplement As A Cause Of Hypokalemic Hypertension

Abstract Disclosure: G. Gill: None. S.M. Harman: None. L.A. Robles: None. A 67-year-old female Veteran presented to an emergency room with a one-day history of high blood pressure, chest tightness, and exertional dyspnea. Her blood pressure was 162/90 mm Hg, pulse regular at 71 BPM, and pain level 5/10. She had a history of hypertension, stable on hydrochlorothiazide alone, hyperlipidemia, anxiety, and depression. Physical exam was benign. EKG revealed normal sinus rhythm at 60 BPM, normal axis, a prolonged QT interval of 510 ms, and no ST changes. Lab evaluation showed a low potassium of 2.4 mEq/L, sodium 145 mEq/L. Other lab measurements (CBC, liver function tests and cardiac enzymes) were within laboratory reference ranges. Medications included topiramate for migraine and over-the-counter supplements for constipation, “thyroid health,” and a topical “testosterone booster” prescribed by a non-allopathic practitioner. Her hypokalemia was attributed to hydrochlorothiazide and topiramate and both were discontinued. She was started on nifedipine for blood pressure control and 40 mEq/day of potassium for hypokalemia. Within 2 weeks of discharge, she presented again with elevated blood pressure and a plasma potassium of 4.0 mMol/L. Further history revealed that her constipation supplement consisted of licorice root (glycyrrhiza glabra) extract 900 mg per capsule, of which she took 3 to 4 capsules daily. The patient was advised to discontinue all supplements. Thyroid function tests were within normal limits. Due to a suspicion of hyperaldosteronism, the ED physician requested an abdominal CT scan which showed a 1 cm, -17.5 Hounsfield unit, right adrenal nodule. Also consistent with hyperaldosteronism, plasma renin activity (PRA) was suppressed at 0.07 ng/mL/hr. However, a serum aldosterone level was less than 1 ng/dL. Her 24-hour urinary metanephrines were normal and a 24-hour urine free cortisol was 31.6 mcg/dL. Morning plasma cortisol was 5.1 mcg/dL. A tentative diagnosis of licorice-induced hyperaldosteronism was made and the patient was treated with a taper of spironolactone. After discontinuing spironolactone, blood pressure was 116/70mmHg and serum potassium was 4.5 mMol/L with a PRA of 0.66 ng/mL/hr and serum aldosterone of &amp;lt;5.0 ng/dL. The syndrome of factitious hyperaldosteronism due to licorice consumption has been well described. The mechanism, inhibition of renal (type 2) 11-beta-hydroxysteroid dehydrogenase by glycyrrhizic acid, allowing cortisol to exercise its considerable mineralocorticoid action, is well understood. Most prior reports have been in patients habitually consuming licorice candy, usually imported, since conventional licorice sold in the U.S. is artificially flavored. Our report illustrates the importance of obtaining a history of use of over-the-counter supplements and assessing their ingredients and the fact that presence of an adrenal nodule and a low PRA does not always indicate endogenous hyperaldosteronism. Presentation: 6/2/2024

Injectable Hydrogel With Glycyrrhizic Acid and Asiaticoside-Loaded Liposomes for Wound Healing.

Open skin wounds increase the risk of infections and can compromise health. Therefore, applying medications to promote healing at the injury site is crucial. In practice, direct drug delivery is often difficult to maintain for a long time due to rapid absorption or wiping off, which reduces the efficiency of wound healing. Consequently, the development of bioactive materials with both antibacterial and wound-healing properties is highly desirable. This study synthesized liposomes loaded with glycyrrhizic acid (GA) and asiaticoside (AS) by film dispersion-ultrasonication method, which were then incorporated into a GelMA solution and cross-linked by ultraviolet light to form a bioactive composite hydrogel for wound dressings. This hydrogel is conducive to the transport of nutrients and gas exchange. Compared with GelMA hydrogel (swelling rate 69.8% ± 5.7%), the swelling rate of GelMA/Lip@GA@AS is lower, at 52.1% ± 1.0%. GelMA/Lip@GA@AS also has better compression and rheological properties, and the invitro biodegradability is not significantly different from that of the collagenase-treated group. In addition, the hydrogel polymer has a stable drug release rate, good biocompatibility, and an angiogenic promoting effect. Invitro experiments prove that, at concentrations of 0.5, 1, 2, and 3 mg/mL, GelMA/Lip@GA@AS can inhibit the growth of Staphylococcus aureus. We synthesized GelMA/Lip@GA@AS hydrogel and found it possesses advantageous mechanical properties, rheology, and biodegradability. Experimental results invitro showed that the bioactive hydrogel could efficiently release drugs, exhibit biocompatibility, and enhance angiogenesis and antimicrobial effects. These results suggest the promising application of GelMA/Lip@GA@AS hydrogel in wound-dressing materials.

Glycyrrhizic acid promote remyelination after peripheral nerve injury by reducing NF-κB activation

BackgroundPeripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Glycyrrhizic acid (GA) is one of the most widely used in traditional Chinese prescriptions and as a flavoring additive in the food industry; the aims of the study were to investigate the effects of GA during sciatic nerve regeneration in a mouse model of sciatic nerve crush injury. MethodsWe established peripheral nerve crush model and investigated the effects of GA. We further studied the potential mechanism of action of GA by Western blotting, fluorescence immunohistochemistry, and PCR analysis. ResultsGA improves the sensory and motor functions of crushed nerve by preventing Schwann cell loss, axonal loss and promoting remyelination of sciatic nerve. Affected by GA, the inflammatory response in the distal part of the sciatic nerve was reduced. Finally, the neuroprotective properties of GA may be regulated by the nuclear factor (NF)‐κB pathway. ConclusionsOur data suggest that GA can effectively alleviate PNI, and the mechanism involves mediating inflammatory response by suppressing NF-κB pathway activation. Thus, GA may represent a potential therapeutic intervention for nerve crush injury.

Combining virus-based affinity ultrafiltration method with serum pharmacochemistry to identify the antiviral pharmacodynamic substances in licorice

Ethnopharmacological relevanceLiorice (Glycyrrhiza uralensis Fisch.), a widely used Chinese herbal medicine, is frequently employed in clinical practice to treat viral pneumonia. However, the pharmacodynamic substances and mechanisms of action responsible for its antiviral effects against H1N1 and RSV remain unclear. Aim of the studyTo investigate the antiviral effects of licorice against H1N1 and RSV. Building on this, we aimed to more comprehensively and accurately identify the pharmacodynamic substances in licorice responsible for its antiviral activity and mechanisms of action against these two viruses. Materials and methodsFirstly, the antiviral effects of licorice against H1N1 and RSV were confirmed through in vivo and in vitro experiments. Then, a combination of virus-based affinity ultrafiltration method (VAUM) and serum pharmacochemistry were used to screen for pharmacological substances in licorice and identify their molecular targets against H1N1 and RSV. Results: The in vivo experiments showed that licorice effectively alleviates H1N1 and RSV induced weight loss and lung tissue damage in mice, while also reducing viral loads of H1N1 and RSV in the lungs. Subsequent in vitro experiments confirmed the presence of original compounds in licorice that directly inhibit H1N1 and RSV. By combining both methods, glycyrrhizic acid, glycyrrhetinic acid (GA), isoliquiritigenin (ISL), and glyasperin A (targeting the M2 ion channel) were ultimately identified as the pharmacodynamic substances in licorice responsible for anti-H1N1 activity. Additionally, licochalcone A (LCA) and glyasperin A, which target RSV surface proteins, were identified as the pharmacodynamic substances responsible for anti-RSV activity. ConclusionsTraditional Chinese medicine (TCM) exerts its antiviral effects through a 'multi-component, multi-target' mechanism, which poses challenges for single active compound screening methods to adequately address. By integrating VAUM and serum pharmacochemistry for the first time, one approach focused on identifying compounds in TCM that directly bind to viral surface proteins, while the other targeted compounds that enter the bloodstream in their original form and exhibit antiviral activity. This provides a novel approach for studying the pharmacodynamic substances of antiviral effects in TCM.

Targeted photothermal cancer therapy using surface-modified transition metal dichalcogenides

Breast cancer, particularly triple-negative breast cancer (TNBC), is the most impactful cancer affecting women, necessitating continuous evaluation of enhanced treatment methods. In this study, we synthesized a folic acid-modified gold nanoparticle-MoSe2 composite (FAM) by liquid exfoliation using glycyrrhizic acid (GA), spontaneous reduction of AuNP, and linkage between folic acid and AuNP using EDC/NHS coupling. With the assistance of GA, MoSe2 nanosheets can be easily exfoliated in aqueous solutions and exhibit biocompatibility. In addition, the gold nanoparticle deposition on the nanosheet was spontaneously induced due to the electron transfer property of MoSe2. Folic acid was used as a targeting molecule because triple-negative breast cancer (TNBC) lacks the common breast cancer markers. We investigated the effectiveness of photothermal therapy using FAM, which enhances light-heat transfer through the synergistic effect of gold and GA-exfoliated MoSe2 (GM). The nanomaterials exhibited improved photothermal conversion efficiency of 62.2 %, high thermal stability, and increased cellular uptake ratio. Subsequently, when the FAM reached the tumor microenvironment, the materials successfully entered the cells through folate receptor-mediated endocytosis and generated heat to kill cells under an 808 nm laser (0.8 W cm−2) by apoptosis. The biocompatibility and photothermic activity of FAM were determined in vitro by a tetrazolium salt assay, live/dead cell staining, cellular uptake ratio, and flow cytometry with human TNBC cells (MDA-MB-231). In summary, the FAM showed a more advanced therapeutic effect than GM in all outcomes. Our findings indicate that FAM has the potential to be used as a biomaterial for anticancer therapy.