Glycyrrhizin Research Articles

Food-grade emulsion gels and oleogels prepared by all-natural dual nanofibril system from citrus fiber and glycyrrhizic acid

The natural dual nanofibril system consisting of the rigid semicrystalline nanofibrils disintegrated from citrus fiber (CF) and soft semiflexible nanofibrils self-assembled from glycyrrhizic acid (GA) has been recently shown to be effective structural building blocks for fabrication of emulsion gels. In this work, the effect of the CF nanofibrils prepared by different mechanical disintegration approaches (i.e., high-pressure microfluidization and hydrodynamic cavitation) on the interfibrillar CF-GA interactions and the subsequent formation and properties of emulsion gels were investigated, with the aim of evaluating the potential of the dual nanofibril-stabilized emulsion gels as templates for synthesizing all-natural edible oleogels. The obtained results demonstrate that compared to the cavitation, the high-pressure microfluidization is more capable of generating CF nanofibrils with a higher degree of nanofibrillation and individualization, thus forming a denser CF-GA gel network with higher viscoelasticity and structural stability due to the stronger multiple intrafibrillar and interfibrillar interactions. The emulsion gels stabilized by the dual nanofibril system are demonstrated to be an efficient template to fabricate solid-like oleogels, and the structural properties of the oleogels can be well tuned by the mechanical disintegration of CF and the GA nanofibril concentration. The prepared oleogels possess high oil loading capacity, dense network microstructure, superior rheological and large deformation compression performances, and satisfactory thermal stability, which is attributed to the compact and ordered CF-GA dual nanofibrillar network via multiple hydrogen-bonding interactions in the continuous phase as well as at the droplet surface. This study highlights the unique use of all-natural dual nanofibrils to develop oil structured soft materials for sustainable applications.

Elucidation of anti-pneumonia pharmacodynamic material basis and potential mechanisms of Xiebai San by combining spectrum–efficacy relationship and surface plasmon resonance

Ethnopharmacological relevanceXiebai San (XBS), a classic Chinese prescription, has been used for the clinical treatment of pneumonia-related diseases for thousands of years. However, the anti-pneumonia pharmacodynamic material basis of XBS and its underlying mechanisms remain unclear. Aim of the studyThis study aimed to comprehensively investigate and verify the anti-pneumonia pharmacodynamic material basis and mechanisms of XBS. Materials and methodsThis study explored the anti-pneumonia activity and key pneumonia targets of XBS in lipopolysaccharide (LPS)-induced zebrafish and RAW264.7 cells in vivo and in vitro through transcriptomics, western blotting, and reverse transcription–quantitative polymerase chain reaction (RT–qPCR). The chemical fingerprint of XBS was established using high-performance liquid chromatography, and the similarities and areas of characteristic peaks of 15 batches of XBS were analyzed. Based on the spectrum–efficacy relationship, the potential anti-inflammatory components were screened according to their peak areas and efficacy using principal component analysis (PCA), bivariate correlation, and partial least squares regression analysis. Active components that bind to core targets were further screened based on surface plasmon resonance (SPR). The binding mode of proteins and components was simulated via molecular docking, which enabled the identification of the primary active components of XBS, thereby elucidating its anti-pneumonia properties. Finally, the anti-inflammatory activities of these components were verified in vitro. ResultsXBS decreased neutrophil aggregation in zebrafish and nitric oxide (NO) secretion in RAW264.7 cells as well as suppressed the release of downstream inflammatory cytokines such as iNOS, TNF-α, IL-1β, IL-18, and CXCL10 related to TNF and JAK–STAT signaling pathways. The phosphorylation of IκBα, Akt, and Stat3 was alleviated after XBS in cells. The fingerprint similarities of 15 batches of XBS ranged from 0.381 to 0.994, with a large difference. A total of 15 characteristic peaks were identified, and the relative standard deviation of their peak areas ranged from 24.1% to 70.7%. The results of in vitro anti-inflammatory activities of 15 batches of XBS showed that all samples inhibited the expression levels of NO and nine inflammatory markers. The anti-inflammatory index of 15 batches of XBS was determined to be 0.69–0.96 based on transformation of the anti-inflammatory rate and composite index method via PCA. The spectrum–efficacy relationship model of 15 characteristic peak areas and the anti-inflammatory index showed that 7 main potential active components were related to the anti-inflammatory activity of XBS. Moreover, four components (mulberroside A, isoquercitrin, liquiritigenin, and glycyrrhizic acid) screened based on SPR had different affinities toward TNFR1, Akt1, and Stat3 proteins, and the binding modes were elucidated via molecular docking. Finally, in LPS-induced RAW264.7 cells, all four active components (at a concentration of 60 μM) significantly inhibited the expression levels of NO and inflammatory markers. ConclusionsBased on the comprehensive strategy of spectrum–efficacy relationship and SPR, mulberroside A, isoquercitrin, liquiritigenin, and glycyrrhizic acid were identified as the primary pharmacodynamic active components involved in the anti-pneumonia activity of XBS and were found to intervene in TNF and JAK–STAT signaling pathways.

Comprehensive identification of key quality markers of Buzhong Yiqi Oral Liquid based on multi-dimensional characteristic networks

Traditional Chinese Medicine (TCM) formulations often contain a complex mixture of compounds, making it challenging to evaluate their quality. Buzhong Yiqi Oral Liquid (BYOL), a well-known TCM formulation, has been used to treat gastrointestinal diseases and fatigue for a long time. However, the effective substances for its therapeutic effects remain unclear. This study aimed to establish a novel quality control approach for BYOL using a multidimensional feature network to identify quality markers (Q-markers). The multidimensional characteristic network was constructed by a “Spider-Web” model, including the compatibility of ingredients, traceability of compounds from raw materials to the final product, effectiveness, measurability, and stability. Multivariate statistical analysis was applied to quantify the individual dimensions of the feature network, and candidate compounds were identified based on regression regions within the network. Using the multidimensional characteristic network, 12 components were identified as key Q-markers for BYOL, consisting of calycosin-7-O-β-D-glucoside, formononetin, astragaloside IV, liquiritin, quercetin, hesperidin, glycyrrhizic acid, isorhamnetin, liquiritin apioside, hesperidin, luteolin, and nobiletin. The identified Q-markers offered valuable insights for future research on medicinal substances and quality control of BYOL.

Glycyrrhizic acid ameliorates hepatic fibrosis by inhibiting oxidative stress via AKR7A2

BackgroundHepatic fibrosis is a reversible pathological phenomenon caused by the abnormal proliferation of connective tissues in the liver for self-repair after persistent liver injury. Among these tissues, the activation status of hepatic stellate cells (HSCs) is crucial. Glycyrrhizic acid (GA) agents have been proven to have excellent anti-fibrosis effects, but their targets are unclear. PurposeTo investigate the anti-hepatic fibrosis effect of GA and its target in activated HSCs. MethodsA mouse model of hepatic fibrosis was prepared with 20 % carbon tetrachloride (CCl4) and GA was administered continuously for 4 weeks. Subsequently, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅲ procollagen peptide (P III P), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (Col Ⅳ) were measured. Liver tissues were subjected to hematoxylin and eosin (HE), Masson, and Sirius red staining and proteome sequencing analysis. Based on LX-2 cells, activity-based protein profiling (ABPP) was used to investigate the potential targets of GA, which was further validated by the cellular thermal shift assay (CETSA), immunofluorescence co-localization, molecular docking, small interfering RNA (siRNA) and western blot (WB) assays. ResultsIn vivo, GA significantly reduced serum ALT, AST, HA, P III P, Col IV, and LN levels. HE, Masson, and Sirius red staining showed that GA significantly ameliorated hepatic inflammatory response and collagen deposition in CCl4-treated mice. Proteome sequencing results showed that GA mainly regulated glutathione S-transferase family members involved in glutathione metabolism. In vitro, GA significantly inhibited LX-2 cell proliferation and reduced reactive oxygen species accumulation. ABPP suggested that aldo-keto reductase family 7 member A2 (AKR7A2) was the major binding protein of GA in LX-2 cells. CETSA, fluorescence co-localization, molecular docking, and surface plasmon resonance further validated GA binding to AKR7A2. The WB results showed that GA up-regulated AKR7A2 expression both in vitro and in vivo and was corroborated by siRNA experiments. ConclusionGA targeted AKR7A2 in LX-2 cells to defend against sustained oxidative stress injury, thereby inhibiting the proliferation of activated HSCs and reversing hepatic fibrosis.

Self-assembled nanoparticles of costunolide and glycyrrhizic acid for enhanced ulcerative colitis treatment

Ulcerative colitis (UC) is a persistent inflammatory condition that specifically targets the colon and rectum. Existing therapies fail to adequately address the clinical requirements of people suffering from this ailment. Despite the acknowledged potential of nanomedicines in the field of anti-inflammatory treatment, their widespread use in clinical settings is impeded by their expensive nature and the uncertainty surrounding their safety profiles. This study illustrates that two naturally occurring phytochemicals, Costunolide (COS) and Glycyrrhizic acid (GA), form carrier-free, multifunctional spherical nanoparticles (NPs) through noncovalent interactions, such as π–π stacking and hydrogen bonding. The COS-GA NPs displayed a synergistic anti-inflammatory effect, providing much more evidently improved therapeutic benefits for dextran sodium sulfate (DSS)-induced UC mice due to more effective reduction in inflammation and oxidative stress than did equal dosages of COS or GA used alone. In addition, COS-GA NPs have biocompatibility and biosafety properties unique to them. This study will serve as affirmation of the potential of COS-GA NPs as innovative natural anti-inflammatory and antioxidant activities and also such agents as drug discovery in UC, leading possibly to better outcomes in people living with this disabling condition.

Characterization and Dissolution Mechanism of Low-Molecular-Weight Organic Acids or Inorganic Mesoporous Particle-Based Piperine Amorphous Solid Dispersions.

The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance (1H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.

Glycerin as an alternative solvent for the extraction of glycyrrhizic acid from the roots of Glycyrrhiza glabra

Licorice root extracts are one of the most common and widely used plant extracts. Due to the high content of biologically active substances and pronounced properties, they are used in various industries – in medicine, pharmacology, cosmetics and food industries. The underground part of Licorice contains more than 100 different chemical substances, the most biologically active of which are flavonoids and triterpene saponins. The most significant saponin is glycyrrhizic acid. Science knows many ways to obtain licorice extract, and the research is still being actively carried out to find even more effective, inexpensive and accessible methods.The purpose of the research was to investigate the feasibility and potential of glycerol as a solvent for the extraction of glycyrrhizic acid from the roots of Glycyrrhiza glabra.The methods. Isolation of glycyrrhizic acid from the roots of Glycyrrhiza glabra was carried out using the maceration method. Glycerrin and the classic extractant ethanol were tested as an extractant for comparative analysis. Determination of glycyrrhizic acid content in licorice glabra roots was carried out using differential spectrophotometry.The Results. Optimal conditions for the extraction of glycyrrhizic acid from the roots of Glycyrrhiza glabra were selected. The maximum content of glycyrrhizic acid was observed in the sample prepared at a water-glycerol ratio of 3:2.The scientific novelty of the work lies in the study of the possibility of using glycerol as a solvent for extraction and the selection of optimal conditions for the extraction of glycyrrhizic acid from the roots of Glycyrrhiza glabra in order to increase the level of extraction of the target substance.

Natural Products of Licorice for Uranium Decorporation with Low Toxicity and High Efficiency.

The development and exploration of uranium decorporation agents with straightforward synthesis, high removal ability, and low toxicity are crucial guarantees for the safety of workers in the nuclear industry and the public. Herein, we report the use of traditional Chinese medicine licorice for uranium decorporation. Licorice has good adsorption performance and excellent selectivity for uranium in the simulated human environment. Glycyrrhizic acid (GL) has a high affinity for uranium (p(UO2) = 13.67) and will complex with uranium at the carbonyl site. Both licorice and GL exhibit lower cytotoxicity compared to the commercial clinical decorporation agent diethylenetriamine pentaacetate sodium salts (CaNa3-DTPA). Notably, at the cellular level, the uranium removal efficiency of GL is eight times higher than that of CaNa3-DTPA. Administration of GL by prophylactic intraperitoneal injection demonstrates that its uranium removal efficiency from kidneys and bones is 55.2 and 23.9%, while CaNa3-DTPA shows an insignificant effect. The density functional theory calculation of the bonding energy between GL and uranium demonstrates that GL exhibits a higher binding affinity (-2.01 vs -1.15 eV) to uranium compared to DTPA. These findings support the potential of licorice and its active ingredient, GL, as promising candidates for uranium decorporation agents.

The effect of matrine and glycyrrhizic acid on porcine reproductive and respiratory syndrome virus in Vitro and in vivo

Porcine reproductive and respiratory syndrome (PRRS) is endemic worldwide, seriously affecting the development of the pig industry, but vaccines have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated based on the mass ratio of glycyrrhizic acid to matrine and calculated their inhibition rates against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. The compound with the strongest anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group for the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the virus challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can actually accelerate the death of infected pigs. Next, we further analyzed the pigs that exhibited semiprotective effects following vaccination with the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality rates and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1β, IFN-γ, and TNF-α) were significantly greater in the compound-treated pigs than in the positive control-treated pigs (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive levels of inflammatory cytokines and caused body damage, preventing a therapeutic effect. In conclusion, the present study revealed that the in vitro effectiveness of these agents does not indicate that they are effective in vivo or useful for developing anti-PRRSV drugs. Our findings also showed that, to identify effective anti-PRRSV drugs, comprehensive drug screening is needed, for compounds with solid anti-inflammatory effects both in vitro and in vivo. Our study may aid in the development of new anti-PRRSV drugs.

Vapor/Vapor‐Solid Interfacial Growth of Covalent Organic Framework Membranes on Alumina Hollow Fiber for Advanced Molecular Separation

AbstractCovalent organic frameworks (COFs), known for their chemical stability and porous crystalline structure, hold promises as advanced separation membranes. However, fabricating high‐quality COF membranes, particularly on industrial‐preferred hollow fiber substrates, remains challenging. This study introduces a novel vapor/vapor‐solid (V/V−S) method for growing ultrathin crystalline TpPa‐1 COF membranes on the inner lumen surface of alumina hollow fibers (TpPa‐1/Alumina). Through vapor‐phase monomer introduction onto polydopamine‐modified alumina at 170 °C and 1 atm, efficient polymerization and crystallization occur at the confined V−S interface. This enables one‐step growth within 8 h, producing 100 nm thick COF membranes with strong substrate adhesion. TpPa‐1/Alumina exhibits exceptional stability and performance over 80 h in continuous cross‐flow organic solvent nanofiltration (OSN), with methanol permeance of about 200 L m−2 h−1 bar−1 and dye rejection with molecular weight cutoff (MWCO) of approximately 700 Da. Moreover, the versatile V/V−S method synthesizes two additional COF membranes (TpPa2Cl/Alumina and TpHz/Alumina) with different pore sizes and chemical environments. Adjusting the COF membrane thickness between 100–500 nm is achievable easily by varying the growth cycle numbers. Notably, TpPa2Cl/Alumina demonstrates excellent OSN performance in separating the model active pharmaceutical ingredient glycyrrhizic acid (GA) from dimethyl sulfoxide (DMSO), highlighting the method's potential for large‐scale industrial applications.

Vapor/Vapor-Solid Interfacial Growth of Covalent Organic Framework Membranes on Alumina Hollow Fiber for Advanced Molecular Separation.

Covalent organic frameworks (COFs), known for their chemical stability and porous crystalline structure, hold promises as advanced separation membranes. However, fabricating high-quality COF membranes, particularly on industrial-preferred hollow fiber substrates, remains challenging. This study introduces a novel vapor/vapor-solid (V/V-S) method for growing ultrathin crystalline TpPa-1 COF membranes on the inner lumen surface of alumina hollow fibers (TpPa-1/Alumina). Through vapor-phase monomer introduction onto polydopamine-modified alumina at 170 °C and 1 atm, efficient polymerization and crystallization occur at the confined V-S interface. This enables one-step growth within 8 h, producing 100 nm thick COF membranes with strong substrate adhesion. TpPa-1/Alumina exhibits exceptional stability and performance over 80 h in continuous cross-flow organic solvent nanofiltration (OSN), with methanol permeance of about 200 L m-2 h-1 bar-1 and dye rejection with molecular weight cutoff (MWCO) of approximately 700 Da. Moreover, the versatile V/V-S method synthesizes two additional COF membranes (TpPa2Cl/Alumina and TpHz/Alumina) with different pore sizes and chemical environments. Adjusting the COF membrane thickness between 100-500 nm is achievable easily by varying the growth cycle numbers. Notably, TpPa2Cl/Alumina demonstrates excellent OSN performance in separating the model active pharmaceutical ingredient glycyrrhizic acid (GA) from dimethyl sulfoxide (DMSO), highlighting the method's potential for large-scale industrial applications.

An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer

BackgroundIrinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.ObjectiveThis study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.MethodsThe orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.ResultsIn vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.ConclusionThe optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

Glycyrrhetinic acid triggers a protective autophagy by inhibiting the JAK2/STAT3 pathway in cerebral ischemia/reperfusion injury

Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18β-GA) in ameliorates CIRI. Our results showed that 18β-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18β-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18β-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18β-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18β-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18β-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18β-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.

Paeonol and glycyrrhizic acid in combination ameliorate the recurrent nitroglycerin-induced migraine-like phenotype in rats by regulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway

Ethnopharmacological relevancePaeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine. Aim of the studyThis research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats. Materials and methodsUsing a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques. ResultsFollowing treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1β and TNF-α. ConclusionsOur findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

Alleviation of Salt Stress and Changes in Glycyrrhizic Acid Accumulation by Dark Septate Endophytes in Glycyrrhiza glabra Grown under Salt Stress.

This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice. First, the salt stress tolerance and resynthesis with the plant effect of isolated DSE from wild licorice were tested. Second, the performance of licorice inoculated with DSE, which had the best salt-tolerant and growth-promoting effects, was examined under salt stress. All isolated DSE showed salt tolerance and promoted plant growth, withCurvularia lunata D43 being the most effective. Under salt stress, C. lunata D43 could promote growth, increase antioxidant enzyme activities, enhance glycyrrhizic acid accumulation, improve key enzyme activities in the glycyrrhizic acid synthesis pathway, and induce the expression of the key enzyme gene and salt tolerance gene of licorice. The structural equation model demonstrated that DSE alleviate the negative effects of salt stress through direct and indirect pathways. Variations in key enzyme activities, gene expression, and bioactive constituent concentration can be attributed to the effects of DSE. These results contribute to revealing the value of DSE for cultivating medicinal plants in saline soils.

High sensitivity determination of sweetener glycyrrhizic acid by triple-wavelength overlapping resonance Rayleigh scattering method and its analytical application

Under suitable acidic conditions, the triphenylmethane cationic dyes ethyl violet (EV) and crystal violet (CV) can form hydrogen-bonded cationic supramolecular aggregates with water molecules, respectively. Upon the addition of glycyrrhizic acid (GZA), these hydrogen-bonded cationic supramolecular aggregates undergo ionic association reactions with GZA, leading to the forming of new ion-associated hydrogen-bonded supramolecular aggregates. By optimizing the reaction conditions, two novel systems for the determination of GZA were developed using the triple-wavelength overlapping resonance Rayleigh scattering (TWO-RRS) technique. The enhancement observed in these systems was proportional to the concentration of GZA within a specific range. The linear ranges for these systems were 0.05–0.55 μg/mL, with limits of detection (LOD) at 0.016 μg/mL and 0.011 μg/mL, respectively. The standard addition method was employed to determine the content of GZA in actual samples. This study presents a new and valuable method for the determination of GZA, a sweetener.

Glycyrrhizin alleviates BoAHV-1-induced lung injury in guinea pigs by inhibiting the NF-κB/NLRP3 Signaling pathway and activating the Nrf2/HO-1 Signaling pathway.

Varicellovirus bovinealpha 1 (BoAHV-1) is a significant pathogen responsible for respiratory disease in cattle, capable of inducing lung damage independently or co-infection with bacteria. The widespread spread of BoAHV-1 in cattle herds has caused substantial economic losses to the cattle industry. The pathogenic mechanisms of BoAHV-1 are often relevant to robust inflammatory responses, increased oxidative burden, and the initiation of apoptosis. Glycyrrhizin (GLY) is a small-molecule triterpenoid saponin compound obtained from the herb liquorice, which has a broad spectrum of pharmacological properties such as antiviral, anti-inflammatory, and antioxidant effects. Furthermore, GLY regulates lung physiology by modulating oxidative stress, inflammatory response, and cell apoptosis through interference with the NF-κB/NLRP3 and Nrf2/HO-1 Signaling pathways. However, the potential of GLY to mitigate lung injury induced by BoAHV-1 and its underlying mechanism remains unclear. Therefore, in this study, we investigated the protective effect of GLY against pulmonary injury induced by BoAHV-1 in a guinea pig model by reducing viral load and suppressing the inflammatory response, oxidative stress, and apoptosis. The results of this study demonstrated that GLY exerted a protective effect against BoAHV-1-induced lung injury in guinea pigs. Specifically, GLY reduced the levels of pro-inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interleukin (IL)-8 in guinea pig tissues while suppressing the expression of Caspase-1. Additionally, GLY reduced BoAHV-1 load and the number of TUNEL-positive lung cells in guinea pig lungs while inhibiting Caspase 3 protein expression. Furthermore, GLY significantly enhanced lung antioxidant capacity by increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity while simultaneously reducing malondialdehyde (MDA) levels. Lung histological observation and score further validated the protective effect of GLY on BoAHV-1-induced lung injury. Furthermore, we observed that the expression of phosphorylated NF-κB p65 (p-NF-κB p65) and NLRP3 proteins in the lung tissue of BoAHV-1-infected guinea pigs decreased after GLY treatment while the expression of Nrf2 and HO-1 proteins increased. These results indicated that GLY inhibited the NF-κB/NLRP3 Signaling pathway and activated the Nrf2/HO-1 Signaling pathway during BoAHV-1 infection. Ultimately, our findings demonstrated that GLY alleviates BoAHV-1-induced inflammation response, oxidative stress, and cell apoptosis by inhibiting the NF-κB/NLRP3 Signaling pathway and activating the Nrf2/HO-1 Signaling pathway to protect guinea pigs from lung injury caused by BoAHV-1. Ultimately, our findings demonstrated that GLY alleviates BoAHV-1-induced inflammation response, oxidative stress, and cell apoptosis by inhibiting the NF-κB/NLRP3 Signaling pathway and activating the Nrf2/HO-1 Signaling pathway to protect guinea pigs from lung injury caused by BoAHV-1. Importantly, this study provides a compelling argument for the GLY in combating respiratory disease in cattle caused by BoAHV-1.

Constructing a hydrogel based on self-assembly properties of glycyrrhizic acid: A drug delivery system with digestive tract responsive

Glycyrrhizic acid (GA), an amphiphilic compound, is known for its natural sweetness and excellent self-assembly properties. Based on its self-assembled formulation forming ability, GA has been used as drug carriers and absorption enhancers, thereby altering the in vivo absorption kinetic processes of loaded drugs. This study mainly focuses on the influence of the GA self-assembled drug delivery system on the solubility, stability, and in vitro release of various active ingredients in traditional Chinese medicine, especially simulating the physiological rhythms and environment of in vivo absorption. Our findings indicate that GA has a significant solubilizing effect on poorly water-soluble components. The inclusion of GA improves the stability of the majority of the measured components to different extents in the digestive tract. Furthermore, in vitro release studies have demonstrated that the GA hydrogel system effectively slows drug release and is also enterosoluble, indicating responsiveness to the digestive tract, which contributes to stable concentrations of the drug in the blood. To sum up, the GA self-assembled drug delivery system can enhance solubility and stability to varying degrees by altering the in vivo absorption kinetics of representative active ingredients, exhibiting drug sustained release and self-assembly system enteric-like characteristics in different physiological environments. This indicates that the drug delivery system formed by GA through self-assembly can interact with the digestive tract environment, thus enhancing the in vivo bioavailability of drugs by influencing their biopharmaceutical properties.

Preparation and characterization of self-assembling nanoparticles in Gancao Ganjiang decoction

Gancao Ganjiang decoction (GGD) is one of the classic formulas in China known for its effective therapeutic effects in treating various diseases. Component research before and after the compatibility of Gancao and Ganjiang revealed that 6-gingerol content considerably changed. Compared with the decoction of Ganjiang, 6-gingerol in GGD demonstrated improved solubility. It was assumed that the partially hydrophilic glycyrrhizic acid and 6-gingerol self-assembled into nanoparticles, which then improved the solubility of 6-gingerol. The self-assembled nanoparticles in GGD were separated and characterized. Subsequently, 6-gingerol–glycyrrhizic acid nanoparticles (6-Gin-Gly NPs) were further prepared and characterized via dynamic light scattering (DLS) and transmission electron microscope (TEM). The formation mechanism of the self-assembled nanoparticles was examined using ultraviolet–visible spectroscopy (UV–vis), Fourier transform infrared spectroscopy (FTIR), electrospray ionization–mass spectrometry (ESI-MS), and molecular docking. The in vitro antioxidant activity of the 6-Gin-Gly NPs was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino bis(3-ethylbenzothiazoline-6- sulfonic acid)+ (ABTS+) free radical scavenging assays, which confirmed that the nanoparticles considerably enhanced their in vitro antioxidant capacity. In this study, the solubility of insoluble components was improved by the formation of self-assembled nanoparticles, which provided substantial reference data for the study of complicated multi-component interaction in herbal medicine decoction.

Local delivery of methotrexate/glycyrrhizin-loaded hyaluronic acid nanofiber for the management of oral cancer

The challenges in treating oral cancer include the limited effectiveness and systemic side effects of conventional chemotherapy and radiation therapy. Hyaluronic acid (HA) based Glycyrrhizin (GL) and Methotrexate (MT) loaded localized delivery systems, specifically nanofiber (NF) based platforms, were developed to address these challenges. The electrospinning method was used for the successful fabrication of a homogenous NF membrane and characterized for morphology, drug entrapment efficiency, tensile strength, and ex-vivo mucoadhesive study. Also, it was evaluated for in-vitro drug release profile, ex-vivo drug permeability, in-vitro anti-inflammatory, apoptosis assay by MTT and flow, and against specific cell lines in order to determine their potential for therapeutic use. Superior tensile breaking force (50 g), mucoadhesive strength of 153 gm/cm2, drug permeability, and releasing properties of designed NF, making them perfect requirements for oral cavity delivery. The anticancer potential of MT in the MTT assay and flow cytometry analysis was significantly increased in oral epidermal carcinoma cell (KB cell) for drug-loaded NF with 63.97 ± 1.99 % apoptosis, at 24 h. With these incorporated, GL with MT in NF had an anti-inflammatory potential, also demonstrated in-vitro and in-vivo. In the Ehrlich Ascites Carcinoma (EAC) induced mice model, the optimal formulation’s shows better potential for tumor regression when comparing the developed NF formulation to the drugs. Experimental results show that by lowering mucositis-related inflammation and enhancing the effectiveness of oral cancer treatment, a developed nanofiber-based local drug delivery system offers a feasible strategy for managing oral cancer.