Glycyrrhiza Uralensis Research Articles

Effect, main targets and molecular mechanisms of glycyrrhiza-derived flavonoids on malignant tumor in comprehensive cancer treatment

Glycyrrhiza flavonoids (GF) are essential antitumor components of Glycyrrhiza uralensis, Glycyrrhiza glabra, and Glycyrrhiza inflata roots and tubers, with antioxidant, anti-inflammatory, antibacterial, immune-enhancing amongst other properties. In recent years, significant progress has been made in understanding the mechanisms and targets of GF in various pharmacological settings. This review summarizes the clinical value, targets and research progress of the molecular mechanisms underlying GF in the treatment of malignant tumors. This will provide as a theoretical foundation for further studies into GF as a therapeutic option in the management of cancerous tumors.

Real-world observations and impacts of Chinese herbal medicine for migraine: results of a registry-based cohort study.

Background: Migraine is a prevalent, recurrent condition with substantial disease burden. Chinese herbal medicine (CHM) has been used frequently for migraine in controlled clinical settings. This study is to summarise the characteristics of patients who seek clinical care in a tertiary Chinese medicine hospital in China; to gather their preferences and values of using CHM; to explore the effect of CHM for migraine and its comorbidities in a real-world setting, and to collect first-hand expertise of clinicians' practice pattern in prescribing CHM for migraine. Methods: This registry-based cohort study was prospectively conducted at Guangdong Provincial Hospital of Chinese Medicine from December 2020 to May 2022. Adult migraine patients seeking their initial anti-migraine clinical care at the hospital were consecutively recruited and followed up for 12weeks. Practitioners specialised in headache management prescribed individualised treatments without research interference. Standardised case report forms were employed to gather information on patients' preferences and perspective of seeking clinical care, as well as to assess participants' migraine severity, comorbidities, and quality of life, at 4-weeks intervals. Various analytical methods were utilised based on the computed data. Results: In this study, we observed 248 participants. Of these, 73 received CHM treatment for 28days or longer. Notably, these participants exhibited a greater disease severity, compared to those treated with CHM for less than 28days. Of the 248 participants, 83.47% of them expected CHM would effectively reduce the severity of their migraine, around 50% expected effects for migraine-associated comorbidities, while 51.61% expressing concerns about potential side effects. CHM appeared to be effective in reducing monthly migraine days and pain intensity, improving patients' quality of life, and potentially reducing comorbid anxiety, with a minimum of 28days CHM treatment. Herbs such as gan cao, gui zhi, chuan xiong, fu ling, bai zhu, yan hu suo, etc. were frequently prescribed for migraine, based on patients' specific symptoms. Conclusion: CHM appeared to be beneficial for migraine and comorbid anxiety in real-world clinical practice when used continuously for 28 days or more. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2000041003.

Mechanism of Guizhi Gancao Decoction against myocardial ischemia-reperfusion injury based on network pharmacology and experimental verification

This study employed network pharmacology to investigate the effect of Guizhi Gancao Decoction(GGD) on myocardial ischemia-reperfusion injury(MI/RI) in rats and decipher the underlying mechanism. Firstly, the chemical components and targets of GGD against MI/RI were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), SwissTargetPrediction, and available articles. STRING and Cytoscape 3.7.2 were used to establish the protein-protein interaction(PPI) network for the common targets, and then Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out for the core targets. The "drug-active component-target-pathway" network was built. Furthermore, molecular docking between key active components and targets was conducted in AutoDock Vina. Finally, the rat model of MI/RI was established, and the myocardial infarction area was measured. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to detect cardiomyocyte pathology and ultrastructural changes. Western blot was employed to determine the expression of related proteins in the myocardial tissue. A total of 75 chemical components of GGD were screened out, corresponding to 318 targets. The PPI network revealed 46 core targets such as tumor protein p53(TP53), serine/threonine kinase 1(AKT1), signal transducer and activator of transcription 3(STAT3), non-receptor tyrosine kinase(SRC), mitogen-activated protein kinase 1(MAPK1), MAPK3, and tumor necrosis factor(TNF). According to GO and KEGG enrichment analyses, the core targets mainly affected the cell proliferation and migration, signal transduction, apoptosis, and transcription, involving advanced glycation end products-receptor(AGE-RAGE), MAPK and other signaling pathways in cancers and diabetes complications. The molecular docking results showed that the core components of GGD, such as licochalcone A,(+)-catechin, and cinnamaldehyde, had strong binding activities with the core target proteins, such as MAPK1 and MAPK3. The results of animal experiments showed that compared with the model group, GGD significantly increase superoxide dismutase, decreased malondialdehyde, lactate dehydrogenase, and creatine kinase-MB, and reduced the area of myocardial infarction. HE staining and TEM results showed that GGD pretreatment restored the structure of cardiomyocytes and alleviated the pathological changes and ultrastructural damage of mitochondria in the model group. In addition, GGD significantly down-regulated the phosphorylation of c-Jun N-terminal kinase and p38 and up-regulate that of extracellular regulated kinases 1/2 in the myocardial tissue. The results suggested that GGD may exert the anti-MI/RI effect by regulating the MAPK signaling pathway via the synergistic effects of Cinnamomi Ramulus and Glycyrrhizae Radix et Rhizoma.

Study of Quality Standards of Xiao’er Qingre Enema Preparation in Hospitals

Objective: To establish the quality standards for the preparation of Xiao’er Qingre enema in hospitals. Method:Thin-layer chromatography (TLC) was used to identify Radix Isatidis and Glycyrrhizae in the prescription. The content of (R,S)-Goitrin was determined by high-performance liquid chromatography (HPLC). Results: In TLC identification, there was no interference between the negative controls of Radix Isatidis and glycyrrhizae, and the spots were well-separated. The HPLC results of (R,S)-Goitrin showed a good linear relationship between the peak area and concentration within the range of 0.476–95.2 μg·mL-1 (r = 0.9999). Conclusion: The TLC and HPLC methods established in this experiment are simple, reproducible, and specific, making them suitable for the quality control Xiao’er Qingre enema preparation in hospitals.

Licorice flavonoid ameliorates ethanol-induced gastric ulcer in rats by suppressing apoptosis via PI3K/AKT signaling pathway

Ethnopharmacological relevanceLicorice is the dry roots and rhizomes of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L. and Glycyrrhiza inflata Bat., which was first recorded in Shengnong's herbal classic. Licorice flavonoid (LF) is the main compound isolated from licorice with an indispensable action in treating gastric ulcer (GU). However, the underlying mechanisms need to be further explored. Aim of the studyThis study aimed to investigate and further elucidate the mechanisms of LF against ethanol-induced GU using an integrated approach. Materials and methodsThe anti-GU effects of LF were evaluated in an ethanol-induced gastric injury rat model. Then, the metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Next, the network pharmacology combined with metabolomics strategy was employed to predict the targets and pathways of LF for GU. Finally, these predictions were validated by molecular docking, RT-qPCR, and western blotting. ResultsLF had a positive impact on gastric injury and regulated the expression of GU-related factors. Upon serum metabolomics analysis, 25 metabolic biomarkers of LF in GU treatment were identified, which were primarily involved in amino acid metabolism, carbohydrate metabolism, and other related processes. Subsequently, a “components-targets-metabolites” network was constructed, revealing six key targets (HSP90AA1, AKT1, MAPK1, EGFR, ESR1, PIK3CA) that may be associated with GU treatment. More importantly, KEGG analysis highlighted the importance of the PI3K/AKT pathway including key targets, as a critical route through which LF exerted its anti-GU effects. Molecular docking analyses confirmed that the core components of LF exhibited a strong affinity for key targets. Furthermore, RT-qPCR and western blotting results indicated that LF could reverse the expression of these targets, activate the PI3K/AKT pathway, and ultimately reduce apoptosis. ConclusionLF exerted a gastroprotective effect against gastric ulcer induced by ethanol, and the therapeutic mechanism may involve improving metabolism and suppressing apoptosis through the PI3K-AKT pathway.

Maternal Effects of Habitats Induce Stronger Salt Tolerance in Early-Stage Offspring of Glycyrrhiza uralensis from Salinized Habitats Compared with Those from Non-Salinized Habitats.

(1) Wild Glycyrrhiza uralensis Fisch (licorice) seeds from different habitats are often mixed for cultivation. However, differences in the responses of seeds from different habitats to salt at the early-stage offspring stage are unclear. (2) Our objective was to evaluate the salt tolerance of G. uralensis germplasms by comparing differences in seed germination and seedling vigor in salinized (abandoned farmland and meadow) and non-salinized (corn farmland edge) soil habitats under different sodium chloride (NaCl) concentrations. (3) The germination rates and germination indexes of seeds from the two salinized habitats with 0-320 mmol·L-1 NaCl were higher and their germination initiation times were earlier. Only seeds from salinized habitats were able to elongate their germs at 240 mmol·L-1 NaCl. Seedlings from salinized habitats had higher fresh weights and relative water contents, while they exhibited lower accumulation of malondialdehyde and less cell electrolyte leakages. Under NaCl treatment, seedlings from the salinized habitats displayed higher superoxide dismutase, catalase, and peroxidase (SOD, CAT, and POD) activities and lower superoxide anion and hydrogen peroxide (O2- and H2O2) contents. Their comprehensive scores showed that the vigor of licorice seeds from salinized habitats was higher. (4) The salt tolerances of different wild G. uralensis seeds were different, and the offspring of licorice from salinized habitats had stronger early-stage salt tolerances.

The SIRT1/Nrf2 signaling pathway mediates the anti-pulmonary fibrosis effect of liquiritigenin

BackgroundAt present, the treatment options available for idiopathic pulmonary fibrosis are both limited and often come with severe side effects, emphasizing the pressing requirement for innovative therapeutic alternatives. Myofibroblasts, which hold a central role in pulmonary fibrosis, have a close association with the Smad signaling pathway induced by transforming growth factor-β1 (TGF-β1) and the transformation of myofibroblasts driven by oxidative stress. Liquiritigenin, an active compound extracted from the traditional Chinese herb licorice, boasts a wide array of biomedical properties, such as anti-fibrosis and anti-oxidation. The primary objective of this study was to examine the impact of liquiritigenin on bleomycin-induced pulmonary fibrosis in mice and the underlying mechanisms.MethodsThe anti-pulmonary fibrosis and anti-oxidant effects of liquiritigenin in vivo were tested by HE staining, Masson staining, DHE staining and bio-chemical methods. In vitro, primary mouse lung fibroblasts were treated with TGF-β1 with or without liquiritigenin, the effects of liquiritigenin in inhibiting differentiation of myofibroblasts and facilitating the translocation of Nrf2 were valued using Quantitative real-time polymerase chain reaction (Q-PCR), western blotting and immunofluorescence. Nrf2 siRNA and SIRT1 siRNA were used to investigate the mechanism underlies liquiritigenin’s effect in inhibiting myofibroblast differentiation.ResultsLiquiritigenin displayed a dose-dependent reduction effect in bleomycin-induced fibrosis. In laboratory experiments, it was evident that liquiritigenin possessed the ability to enhance and activate sirtuin1 (SIRT1), thereby facilitating the nuclear translocation of Nrf2 and mitigating the oxidative stress-induced differentiation of primary mouse myofibroblasts. Moreover, our investigation unveiled that SIRT1 not only regulated myofibroblast differentiation via Nrf2-mediated antioxidant responses against oxidative stress but also revealed liquiritigenin's activation of SIRT1, enabling direct binding to Smad. This led to decreased phosphorylation of the Smad complex, constrained nuclear translocation, and suppressed acetylation of the Smad complex, ultimately curtailing the transcription of fibrotic factors. Validation in live subjects provided substantial evidence for the anti-fibrotic efficacy of liquiritigenin through the SIRT1/Nrf2 signaling pathway.ConclusionsOur findings imply that targeting myofibroblast differentiation via the SIRT1/Nrf2 signaling pathway may constitute a pivotal strategy for liquiritigenin-based therapy against pulmonary fibrosis.

Simultaneous rapid detection of glycyrrhizin and sennoside A in Daiokanzoto samples by lateral flow immunoassay.

Glycyrrhizin (GLY) and sennoside A (SA) are characteristic bioactive marker compounds of the Kampo medicine Daiokanzoto. Their accurate detection in blends of Rhei rhizoma and Glycyrrhizae radix of several species (4:1 or 4:2) is essential for quality control and to ensure therapeutic efficacy. A rapid, efficient assay can significantly facilitate their detection. To establish a rapid qualitative assay for GLY and SA detection, a lateral flow immunoassay (LFA) was developed using specific monoclonal antibody (mAb) nanoparticles. This assay harnesses the competitive binding of mAb nanoparticles to the immobilized analytes on test strips and free analytes in the samples. Two conjugates for detecting GLY and SA, GLY-bovine serum albumin and SA-human serum albumin, were separately immobilized on the test zones of LFA strips. The detection mechanism is reliant on the visual detection of color changes in the test zones. When GLY and SA were present in samples, they contended with the immobilized conjugates on the strip to bind with the mAb nanoparticles and produced distinct color patterns in the test zones. The limits of detection of the assay for GLY and SA were both 3.13 μg/mL. The capability of the LFA was substantiated using plant samples and Daiokanzoto, and its alignment with indirect competitive ELISA results was confirmed. The introduced LFA is a groundbreaking procedure that offers a rapid, straightforward, and sensitive method for simultaneously detecting GLY and SA in Daiokanzoto samples. It is instrumental in ensuring product quality.

Preparation and evaluation of liquorice (Glycyrrhiza uralensis) and ginger (Zingiber officinale) kombucha beverage based on antioxidant capacities, phenolic compounds and sensory qualities

Kombucha is a well-known tea-based fermented drink that contains various bioactive compounds with potential bioactivities. In addition to traditional Camellia sinensis tea, preparation of kombucha using alternative raw material has attracted increasing attention to obtain significant health benefits and good sensory properties. In this study, liquorice and ginger were selected as alternative raw materials for the preparation of kombucha beverages due to their extensive health benefits. Moreover, the effects of fermentation with or without residues on antioxidant activities and phenolic contents of liquorice and ginger kombucha beverages at different fermentation times were examined and compared using the ferric-reducing antioxidant power assay, Trolox equivalent antioxidant capacity assay, Folin-Ciocalteu method, and high-performance liquid chromatography. The results found that kombucha beverages based on liquorice and ginger showed strong antioxidant capacities and high phenolic contents. Fermentation with liquorice residues significantly improved the antioxidant capacities (maximum 2.41 times) and phenolic contents (maximum 3.88 times) of liquorice kombucha without influencing the sensory qualities when compared with fermentation without residues. However, fermentation with ginger residues did not effectively enhance the antioxidant capacities and phenolic contents. Moreover, it could reduce the sensory properties of ginger kombucha. In general, liquorice is well-suited for producing kombucha with residues, while ginger is more suitable for making kombucha without residues. These kombucha beverages might be used for the prevention and management of several oxidative stress-related diseases. This study expands the options of raw materials for producing novel and functional kombucha beverages.

Licochalcone A and B enhance muscle proliferation and differentiation by regulating Myostatin

BackgroundMyostatin (MSTN) inhibition has demonstrated promise for the treatment of diseases associated with muscle loss. In a previous study, we discovered that Glycyrrhiza uralensis (G. uralensis) crude water extract (CWE) inhibits MSTN expression while promoting myogenesis. Furthermore, three specific compounds of G. uralensis, namely liquiritigenin, tetrahydroxymethoxychalcone, and Licochalcone B (Lic B), were found to promote myoblast proliferation and differentiation, as well as accelerate the regeneration of injured muscle tissue. PurposeThe purpose of this study was to build on our previous findings on G. uralensis and demonstrate the potential of its two components, Licochalcone A (Lic A) and Lic B, in muscle mass regulation (by inhibiting MSTN), aging and muscle formation. MethodsG. uralensis, Lic A, and Lic B were evaluated thoroughly using in silico, in vitro and in vivo approaches. In silico analyses included molecular docking, and dynamics simulations of these compounds with MSTN. Protein-protein docking was carried out for MSTN, as well as for the docked complex of MSTN-Lic with its receptor, activin type IIB receptor (ACVRIIB). Subsequent in vitro studies used C2C12 cell lines and primary mouse muscle stem cells to acess the cell proliferation and differentiation of normal and aged cells, levels of MSTN, Atrogin 1, and MuRF1, and plasma MSTN concentrations, employing techniques such as western blotting, immunohistochemistry, immunocytochemistry, cell proliferation and differentiation assays, and real-time RT-PCR. Furthermore, in vivo experiments using mouse models focused on measuring muscle fiber diameters. ResultsCWE of G. uralensis and two of its components, namely Lic A and B, promote myoblast proliferation and differentiation by inhibiting MSTN and reducing Atrogin1 and MuRF1 expressions and MSTN protein concentration in serum. In silico interaction analysis revealed that Lic A (binding energy -6.9 Kcal/mol) and B (binding energy -5.9 Kcal/mol) bind to MSTN and reduce binding between it and ACVRIIB, thereby inhibiting downstream signaling. The experimental analysis, which involved both in vitro and in vivo studies, demonstrated that the levels of MSTN, Atrogin 1, and MuRF1 were decreased when G. uralensis CWE, Lic A, or Lic B were administered into mice or treated in the mouse primary muscle satellite cells (MSCs) and C2C12 myoblasts. The diameters of muscle fibers increased in orally treated mice, and the differentiation and proliferation of C2C12 cells were enhanced. G. uralensis CWE, Lic A, and Lic B also promoted cell proliferation in aged cells, suggesting that they may have anti-muslce aging properties. They also reduced the expression and phosphorylation of SMAD2 and SMAD3 (MSTN downstream effectors), adding to the evidence that MSTN is inhibited. ConclusionThese findings suggest that CWE and its active constituents Lic A and Lic B have anti-mauscle aging potential. They also have the potential to be used as natural inhibitors of MSTN and as therapeutic options for disorders associated with muscle atrophy.

Integrated serum pharmacochemistry and investigation of the anti-influenza A virus pneumonia effect of Qingjin Huatan decoction

Ethnopharmacological relevanceQingjin Huatan Decoction (QJHTT) consists of 11 herbal medicines: Scutellaria baicalensis Georgi, Gardenia jasminoides J. Ellis, Platycodon grandiflorus (Jacq.) A. DC., Ophiopogon japonicus (Thunb.) Ker Gawl., Morus alba L., Fritillaria thunbergii Miq., Anemarrhena asphodeloides Bunge, Trichosanthes kirilowii Maxim., Citrus reticulata Blanco, Poria cocos (Schw.) Wolf, and Glycyrrhiza uralensis Fisch. As a traditional Chinese medicinal formula, QJHTT has been used for more than 400 years in China. It has shown promising results in treating influenza A virus (IAV) pneumonia. Aim of the studyTo elusive the specific pharmacological constituents and mechanisms underlying its anti-IAV pneumonia effects. Materials and methodsThe components in QJHTT were analyzed through the use of a serum pharmacology-based ultra high-performance liquid chromatography Q- Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) method. Simultaneously, the dynamic changes in IAV-infected mouse lung viral load, lung index, and expression of lung inflammation factors were monitored by qRT-PCR. ResultsWe successfully identified 152 chemical components within QJHTT, along with 59 absorbed chemical prototype constituents found in the serum of mice treated with QJHTT. 43.45% of these chemical components and 43.10% of the prototype constituents were derived from the monarch drugs, namely Huangqin and Zhizi, aligning perfectly with traditional Chinese medicine theory. Notably, our analysis led to the discovery of 14 compounds within QJHTT for the first time, three of which were absorbed into the bloodstream. Simultaneously, we observed that QJHTT not only reduced the viral load but also modulated the expression of inflammation factors in the lung tissue including TNF-α, IL-1β, IL-4, IL-6, IFN-γ, and IL17A. A time-effect analysis further revealed that QJHTT intervention effectively suppressed the peak of inflammatory responses, demonstrating a robust anti-IAV pneumonia effect. ConclusionsWe comprehensively analyzed the pharmacological material basis of QJHTT by a highly sensitive and high-resolution UHPLC-Q Exactive Orbitrap-MS method, and demonstrated its efficacy in combating IAV pneumonia by reducing lung viral load and inflammatory factors. This study has significant importance for elucidating the pharmacological basis and pharmacological mechanism of QJHTT in combating IAV pneumonia.

An electrochemiluminescence device for visualized detection of lead in practical samples.

Lead (Pb2+) pollution poses a significant threat to human health due to its potential accumulation through the food chain. In response to this challenge, an array of electrochemiluminescence (ECL) devices has been developed for the accurate and visualized detection of trace Pb2+, achieving an ultra-low limit of detection (LOD) of 9.8 pg L-1. The device utilizes a Pb2+-specific aptamer DNA chain, modified on gold nanoparticles (AuNPs), to create an efficient ECL probe. The integration of this ECL probe into an indium tin oxide (ITO) substrate results in a Pb2+ specific array device. With the assistance of an up-response ECL imaging system, this setup enables the accurate and visualized determination of trace Pb2+, not only in standard solution containing interference ions, but also in practical samples of Lycium ruthenicum Murr., Glycyrrhiza uralensis and lake water. This work advances the visual detection of Pb2+ using ECL-based technology, demonstrating significant potential for enhancing food safety.

Genome-wide identification of Glycyrrhiza uralensis Fisch. MAPK gene family and expression analysis under salt stress relieved by Bacillus subtilis.

Introduction: Research on Glycyrrhiza uralensis, a nonhalophyte that thrives in saline-alkaline soil and a traditional Chinese medicinal component, is focused on improving its ability to tolerate salt stress to increase its productivity and preserve its "Dao-di" characteristics. Furthermore, the inoculation of bioagents such as Bacillus subtilis to increase plant responses to abiotic stressors is currently a mainstream strategy. Mitogen-activated protein kinase (MAPK), a highly conserved protein kinase, plays a significant role in plant responses to various abiotic stress pathways. Methods: This investigation involved the identification of 21 members of the GuMAPK family from the genome of G. uralensis, with an analysis of their protein conserved domains, gene structures, evolutionary relationships, and phosphorylation sites using bioinformatics tools. Results: Systematic evolutionary analysis of the 21 GuMAPKs classified them into four distinct subgroups, revealing significant differences in gene structure and exon numbers. Collinearity analysis highlighted the crucial role of segmental duplication in expanding the GuMAPK gene family, which is particularly evident in G. uralensis and shows a close phylogenetic relationship with Arabidopsis thaliana, tomato, and cucumber. Additionally, the identification of phosphorylation sites suggests a strong correlation between GuMAPK and various physiological processes, including hormonal responses, stress resistance, and growth and development. Protein interaction analysis further supported the role of GuMAPK proteins in regulating essential downstream genes. Through examination of transcriptome expression patterns, GuMAPK16-2 emerged as a prospective pivotal regulatory factor in the context of salt stress and B. subtilis inoculation, a finding supported by its subcellular localization within the nucleus. Discussion: These discoveries offer compelling evidence for the involvement of GuMAPK in the salt stress response and for the exploration of the mechanisms underlying B. subtilis' enhancement of salt tolerance in G. uralensis.

Glycyrrhiza uralensis polysaccharides ameliorates cecal ligation and puncture-induced sepsis by inhibiting the cGAS-STING signaling pathway.

Ethnopharmacological relevance: G. uralensis Fisch. (Glycyrrhiza uralensis) is an ancient and widely used traditional Chinese medicine with good efficacy in clearing heat and detoxifying action. Studies suggest that Glycyrrhiza Uralensis Polysaccharides (GUP), one of the major components of G. uralensis, has anti-inflammatory, anti-cancer and hepatoprotective effects., but its exact molecular mechanism has not been explored in depth. Aim of the study: Objectives of our research are about exploring the anti-inflammatory role of GUP and the mechanisms of its action. Materials and methods: ELISA kits, Western blotting, immunofluorescence, quantitative real-time PCR, immunoprecipitation and DMXAA-mediated STING activation mice models were performed to investigate the role of GUP on the cGAS-STING pathway. To determine the anti-inflammatory effects of GUP, cecal ligation and puncture (CLP) sepsis models were employed. Results: GUP could effectively inhibit the activation of the cGAS-STING signaling pathway accompany by a decrease the expression of type I interferon-related genes and inflammatory factors in BMDMs, THP-1, and human PBMCs. Mechanistically, GUP does not affect the oligomerization of STING, but affects the interaction of STING with TBK1 and TBK1 with IRF3. Significantly, GUP had great therapeutic effects on DMXAA-induced agonist experiments in vivo as well as CLP sepsis in mice. Conclusion: Our studies suggest that GUP is an effective inhibitor of the cGAS-STING pathway, which may be a potential medicine for the treatment of inflammatory diseases mediated by the cGAS-STING pathway.

Generation of a medicine food homology formula and its likely mechanism in treatment of microvascular angina.

Microvascular angina (MVA) is the most common cause of cardiac ischemic chest pain in patients without obstructive coronary artery disease (CAD) and lacks of effective treatment means. Medicine food homology (MFH) involves substances with both nutritional and medicinal qualities that have the potential to improve MVA symptoms as medicines, dietary supplements. However, research on MFH formula (MFHF) for MVA is not available. The study aims to generate a core MFHF for MVA through data mining and offer scientific backing for the utilization of edible medications in the prevention and alleviation of MVA. 11 databases were utilized to construct a database of MFH drugs, and the MFHF was generated through frequency analysis, association rule analysis, and clustering analysis. The composition of the formula is Codonopsis Radix, Astragali Radix, Platycodonis Radix, Persicae Semen, Glycyrrhizae Radix Et Rhizoma, Angelicae Sinensis Radix, and Allii Macrostemonis Bulbus. Through network pharmacology and molecular docking, we identified five major active components of MFHF: Adenosine, Nonanoic Acid, Lauric Acid, Caprylic Acid, and Enanthic Acid, along with nine core targets (NFKB1, ALB, AKT1, ACTB, TNF, IL6, ESR1, CASP3, and PTGS) for the improvement of MVA. These 5 active components have various biological activities, such as reducing oxidative stress, anti-inflammation, analgesia effect, inhibiting platelet aggregation, vasodilatation, vascular endothelial protection, and cardio-protection. GO and KEGG enrichment analyses revealed that MFHF mainly acted on the response to xenobiotic stimulus, integrative component of the plasma membrane, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, pathways in cancer, lipid and atherosclerosis, human cytomegalovirus infection, and the PI3K-Akt signaling pathway, which are the main pathogenesis of MVA.

Qingxuan Runmu Yin alleviates dry eye disease via inhibition of the HMOX1/HIF-1 pathway affecting ferroptosis.

The prevalence of dry eye disease (DED), a multifactorial ocular surface disease characterized by tear film instability, is increasing yearly. Qingxuan Run Mu Yin (QXRMY) is a traditional Chinese medicine (TCM) consisting of Radix Rehmanniae, Radix Scrophulariae, Rhizoma Atractylodis macrocephalae, Herba Dendrobii, Flos Lonicerae, Forsythia suspensa, Ophiopogon japonicus, Saposhnikovia divaricata, Radix Platycodi, and Radix Glycyrrhizae. It has excellent therapeutic effects on dry eye syndrome and a good anti-inflammatory effect on immune-related inflammation. However, the molecular mechanism of Qing Xuan Run Mu Yin in treating dry eye syndrome is largely unknown. The present study used an online database to identify potential target genes of QXRMY for treating DED. The possible mechanisms of these target genes for the treatment of DED were obtained through Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases, Hub genes screened by Cytoscape and intersected with ferroptosis-related genes, and the essential genes were finally obtained based on the results of the analyses. DED cell model and rat model were constructed in this study to validate the critical genes and pathways, and it was confirmed that QXEMY alleviated DED by repressing ferroptosis through inhibiting the HMOX1/HIF-1 pathway. In conclusion, this study integrated network pharmacological analyses and experimental validation to provide an effective method to investigate the molecular mechanism of QXRMY in treating DED.

Improving the geographical origin classification of Radix glycyrrhizae (licorice) through hyperspectral imaging assisted by U-Net fine structure recognition.

Radix glycyrrhizae (licorice) is extensively employed in traditional Chinese medicine, and serves as a crucial raw material in industries such as food and cosmetics. The quality of licorice from different origins varies greatly, so classification of its geographical origin is particularly important. This study proposes a technique for fine structure recognition and segmentation of hyperspectral images of licorice using deep learning U-Net neural networks to segment the tissue structure patterns (phloem, xylem, and pith). Firstly, the three partitions were separately labeled using the Labelme tool, which was utilized to train the U-Net model. Secondly, the obtained optimal U-Net model was applied to predict three partitions of all samples. Lastly, various machine learning models (LDA, SVM, and PLS-DA) were trained based on segmented hyperspectral data. In addition, a threshold method and a circumcircle method were applied to segment licorice hyperspectral images for comparison. The results revealed that compared with the threshold segmentation method (which yielded SVM classifier accuracies of 99.17%, 91.15%, and 92.50% on the training set, validation set, and test set, respectively), the U-Net segmentation method significantly enhanced the accuracy of origin classification (99.06%, 94.72% and 96.07%). Conversely, the circumcircle segmentation method did not effectively improve the accuracy of origin classification (99.65%, 91.16% and 92.13%). By integrating Raman imaging of licorice, it can be inferred that the U-Net model, designed for region segmentation based on the inherent tissue structure of licorice, can effectively improve the accuracy origin classification, which has positive significance in the development of intelligence and information technology of Chinese medicine quality control.

In vivo pharmacokinetics of Glycyrrhiza uralensis polysaccharides.

Glycyrrhiza uralensis polysaccharides (GUPS) are widely applied in biomedicine and functional food due to their multiple pharmacological activities and low toxicity. Despite their widespread use, the in vivo metabolic profile of GUPS remains poorly understood. To address this gap, we developed a quantitative analysis method that involves labeling GUPS with visible fluorescein (5-DTAF) and near-infrared (NIR) fluorescein (Cy7), resulting in stable conjugates with substitution degrees of 0.81% for 5-DTAF and 0.39% for Cy7. The pharmacokinetic studies showed a biphasic elimination pattern in the blood concentration-time curve following both intravenous and oral administration, consistent with a two-compartment model. Using fluorescence quantification and NIR imaging, we observed that GUPS was distributed to various tissues, exhibiting higher concentrations particularly in liver, kidney and lung. Excretion studies indicated that feces were the major excretion pathway of GUPS after oral administration (60.98%), whereas urine was the main pathway after intravenous administration (31.16%). Notably, GUPS could be absorbed rapidly by gut (Tmax 1 ± 0.61h) and showed a biological half-time t1/2 26.4 ± 7.72h after oral administration. Furthermore, the Caco-2 cells uptake studies illustrated that macropinocytosis and clathrin-mediated endocytosis were participated in the transport of GUPS in intestine epithelium. This comprehensive analysis of the in vivo pharmacokinetics of GUPS not only enhances our understanding of its metabolic pathways but also establishes a foundational basis for its clinical application, optimizing its therapeutic potential and safety profile.

Effect of supplementation with Glycyrrhiza uralensis extract and Lactobacillus acidophilus on growth performance and intestinal health in broiler chickens.

Intestinal microbiota community is an important factor affecting the nutritional and health status of poultry, and its balance is crucial for improving the overall health of poultry. The study aimed to investigate the effect of dietary supplementation with Glycyrrhiza uralensis extract (GUE), Lactobacillus acidophilus (Lac) and their combination (GL) on growth performance and intestinal health in broilers in an 84-day feeding experiment. Supplementary 0.1% GUE and 4.5×107 CFU/g Lac significantly increased average daily gain (ADG), and GL (0.1% GUE and 4.5×107 CFU/g Lac) increased ADG and average daily feed intake (ADFI), and decreased feed conversion rate (FCR) in broilers aged 29 to 84 d and 1 to 84 d. Dietary GUE, Lac and GL increased the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity and decreased Malondialdehyde (MDA) content in the jejunum mucosa of broilers, and increased secretory IgA (sIgA) content in broilers at 84 d. Moreover, GUE, Lac and GL increased cecal microbial richness and diversity, and modulated microbial community composition. Both GUE and Lac reduced the harmful bacteria Epsilonbacteraeota, Helicobacter, and H. pullorum at 28 d and Proteobacteria, Escherichia, and E. coli at 84 d, while Lac and GL increased beneficial bacteria Lactobacillus and L. gallinarum at 28 d. Compared with individual supplementation, GL markedly increased the SOD activity and the sIgA content, and reduced Helicobacter and Helicobacter pullorum. In conclusion, GUE and Lactobacillus acidophilus as feed additives benefit growth performance and intestinal health, and their combined use shows an even more positive effect in broilers.

Unveiling key metabolic pathways in Bacillus subtilis-mediated salt tolerance enhancement in Glycyrrhiza uralensis Fisch. through multi-omics analysis

Glycyrrhiza uralensis Fisch. (licorice), an essential medicinal herb, predominantly thrives in arid and semi-arid desert grasslands, where its unique ecological conditions confer upon it a certain degree of salt tolerance. However, the elevated salinity in saline-alkali soil can induce osmotic stress leading to the demise of licorice. Currently, the application of microbial agents stands as a primary strategy to alleviate salt stress. Bacillus subtilis (Bs), known for conferring non-biological stress tolerance in various plants, holds significant promise in mitigating salt stress in licorice. This study investigates the physiological responses, transcriptomic, and metabolomic changes in licorice seedlings inoculated with Bs under different concentrations of salt stress. Under Bs inoculation, the antioxidant enzyme activity, proline content, and malondialdehyde (MDA) levels in licorice seedlings decreased. Concurrently, Bs inoculation stimulated plant growth, photosynthetic capacity, and increased the content of polysaccharides, anthocyanins, and other substances. Metabolomic analysis identified 74 differential metabolites involved in Bs-mediated salt stress responses, including phenylalanine, flavonoids, and amino acid metabolites. Transcriptomic analysis elucidated Bs involvement in salt stress-related secondary metabolism, fatty acid metabolism, amino acid metabolism, cell wall synthesis, and signal transduction pathways, primarily implicating differential genes such as XET, GPX, COMT. Integrated multi-omics analysis revealed that under salt stress, Bs primarily enriches licorice in three crucial metabolic pathways: arginine and proline metabolism, phenylpropane, and flavonoid biosynthesis. In conclusion, the genetic regulatory network uncovered the response mechanisms of Bs in mediating licorice's salt stress.