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glycyrrhizic acid promotes sciatic nerves recovery in type 1 diabetic rats and protects Schwann cells from high glucose-induced cytotoxicity

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The Journal of Biomedical Research 2022年第3期36卷 181-194,I0003,I0004页

作者： Min Shi Xiangcheng Zhang Ridong Zhang Hong Zhang Dalong Zhu Xiao Han Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingJiangsu 211166China Department of Endocrinology Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingJiangsu 210008China Department of Endocrinology the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical UniversityHuai'anJiangsu 223300China Department of Intensive Care Unit the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical UniversityHuai'anJiangsu 223300China

The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphological abnormality and reduced high-mobility group box-1(HMGB1)expression in the sciatic nerves of diabetic rats independent of blood glucose and body weight.Notably,GA alleviated the increase of HMGB1 and the decrease of cell viability in high glucose-stimulated RSC96 cells.Furthermore,GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells,then restored the decreased expression levels of nerve growth factor(NGF)and neuritin-1,and the increased expression levels of cleaved caspase-3 and neuron-specific enolase.Additionally,GA markedly inhibited receptor for advanced glycation end products(RAGE)expression,p38MAPK phosphorylation,and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells.The promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA treatment.Our findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1,which lead to extenuation of inflammation response,balance of NGF,neuritin-1 and caspase-3,as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.

关键词： diabetic peripheral neuropathy glycyrrhizic acid high-mobility group box-1 inflammation

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glycyrrhizic acid Protects Glomerular Podocytes Induced by High Glucose by Modulating SNARK/AMPK Signaling Pathway

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当代医学科学(英文) 2023年第4期43卷 696-707页

作者： Tian-qi ZHAO Yuan LI Miao ZHANG Meng-chao ZHAO Xue CAO Shao-zhang HOU School of Basic Medicine Ningxia Medical UniversityYinchuan 750004China School of Nursing Ningxia Medical UniversityYinchuan 750004China Department of Pathology People's Hospital of Ningxia Hui Autonomous RegionYinchuan 750004China Department of Pharmacy General Hospital of Ningxia Medical UniversityYinchuan 750004China

Objective:Diabetic nephropathy is one of the most important microvascular complications of diabetes,which mainly refers to glomerular capillary sclerosis.Podocytes are an important part of glomerular capillaries.Previous clinical and basic studies have shown that fibrosis is the main factor of diabetic nephropathy.This study aimed to assess the protective mechanism of glycyrrhizic acid(GA)on glomerular podocytes induced by high glucose as we hypothesized that GA may have antifibrotic and anti-inflammatory effects on podocytes through regulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/sucrose nonfermenting AMPK-related kinase(SNARK)signaling pathway.Methods:SNARK siRNA was used to transfect podocytes.Real-time quantitative polymerase chain reaction and immunofluorescence staining assays were used for molecular and pathological analysis.The expression levels of key pathway proteins(including TGF-β1,α-SMA,SITR1,AMPKα,LKB1,PGC-1α,NF-κB,IL-6,and TNF-α)were verified by Western blotting.The expression of inflammatory factors in podocytes was detected by ELISA.Results:We demonstrated that GA decreased the expression of podocyte fibrosis signaling pathway-related factors by upregulating the AMPK pathway and its related factors.However,after transfection of podocytes with SNARK siRNA,there was an increased expression of fibrosis-related factors and inflammation-related factors.Conclusion:GA can protect podocytes and alleviate fibrosis and inflammation induced by high glucose,which is related to the AMPK signaling pathway.Meanwhile,knockdown of SNARK protein can inhibit the AMPK signaling pathway,aggravate fibrosis,and increase inflammation.

关键词： podocyte glomerular fibrosis glycyrrhizic acid diabetic nephropathy AMPK SNARK

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Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis

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World Journal of Gastrointestinal Surgery 2023年第7期15卷 1317-1330页

作者： Ming-Kun Liu Ying-Jian Chen Fei Chen Zhi-Xiong Lin Zi-Cheng Zhu Yu Lin Yi-Fan Fang Dian-Ming Wu Department of Pediatric Surgery Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Pediatric Surgery Fujian Children’s Hospital(Fujian Branch of Shanghai Children’s Medical Center)College of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhou 350000Fujian ProvinceChina Department of Pediatric Surgery Fujian Children’s HospitalFuzhou 350001Fujian ProvinceChina Department of Clinical Medicine Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina

BACKGROUND The prevention and treatment of Hirschsprung-associated enterocolitis(HAEC)is a serious challenge in pediatric surgery.Exploring the mechanism of HAEC is conducive to the prevention of this disease.AIM To explore the possible mechanism of glycyrrhizic acid(GA)and its therapeutic effect on HAEC.METHODS We developed a model of enteritis induced by trinitrobenzenesulfonic acid(TNBS)in zebrafish,and treated it with different concentrations of GA.We analyzed the effect of GA on the phenotype and inflammation of zebrafish.RESULTS After treatment with TNBS,the area of the intestinal lumen in zebrafish was significantly increased,but the number of goblet cells in the intestinal lumen was significantly reduced,but these did not increase the mortality of zebrafish,indicating that the zebrafish enteritis model was successfully developed.Different concentrations of GA protected zebrafish with enteritis.In particular,high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area,increased the number of goblet cells in the intestinal lumen,and reduced the levels of interleukin(IL)-1βand IL-8.CONCLUSION GA significantly reduced the intestinal luminal area,increased the number of intestinal goblet cells,and decreased IL-1βand IL-8 in zebrafish,and is important for prevention and control of HAEC.

关键词： Hirschsprung-associated enterocolitis High mobility group box 1 protein Toll-like receptor 4 Interleukin-1β Interleukin-8 glycyrrhizic acid

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The Potential Efficacy of glycyrrhizic acid and Its Nanostructure Against Brown Rot of Peach fruits

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Phyton-International Journal of Experimental Botany 2023年第4期92卷 1139-1152页

作者： Tahsin Shoala Basma H.Amin Ismail A.S.Rashid Fayz A.Abdel-Rahman Mohamed E.Khalil Khamis Youssef Environmental Biotechnology Department College of BiotechnologyMisr University for Science and Technology6th of October CityEgypt The Regional Center for Mycology and Biotechnology(RCMB) Al-Azhar UniversityCairo11435Egypt Plant Pathology Research Institute Agricultural Research CenterGiza12619Egypt

Production of peaches(Prunus persica(L.)Batsch)for both local market and export is increasing each year in Egypt.Brown rot disease,caused by Monilinia laxa and Monilinia fructigena,is considered one of the most important postharvest rots affecting peaches in Egypt and economic losses are increasing.Antifungal activity of glycyrrhizic acid nanoparticles(GA-NPs)and glycyrrhizic acid(GA)at 0.2 and 0.4 mmol/L was investigated as a control for both these brown rot pathogens on peach fruits in both in vitro and in vivo studies.In the in vitro studies,GA-NPs were the most effective as shown by the ability to decrease linear growth of both brown rot pathogens in potato dextrose agar(PDA)amended with 0.4 mmol/L GA-NPs.Micrographs of M.fructigena exposed to 0.4 mmol/LGA showed mycelial deformations,nodule formation,detachment of the cell wall,shrinkage and inhomogeneous cytoplasmic materials with large vacuoles.Mycelium of M.laxa exposed to 0.4 mmol/LGA-NPs resulted in thinner and distorted hyphae,nodule formation,cell wall thinning,and swellings.The GANPs and GA treatments improved fruit quality by maintaining firmness and total soluble solids(TSS).GA-NPs were more effective in decreasing decay incidence than their bulk material.The 0.4 mmol/L GA-NPs completely inhibited the disease on naturally infected peach fruits for both seasons of 2018 and 2019.Furthermore,0.4 mmol/L GA-NPs reduced the disease incidence in inoculated fruits by 95(M.laxa)and 88%(M.fructigena)in 2018 season and 96(M.laxa)and 85%(M.fructigena)in 2019 season.In conclusion,GA-NPs could enhance the resistance of peaches against brown rot caused by M.laxa and M.fructigena.

关键词： Prunus persica Monilinia laxa Monilinia fructigena glycyrrhizic acid peach postharvest

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glycyrrhizic acid-Loaded Poly-ɛ-Caprolactone Nanoparticles Decrease PRRSV Infection in MARC-145 Cells

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Open Journal of Veterinary Medicine 2023年第12期13卷 221-236页

作者： Samantha Jardon Oscar Escalona Carlos Gerardo García David Quintanar Carlos Ignacio Soto María Zaida Urbán Susana Elisa Mendoza Multidisciplinary Research Unit L4 (Veterinary Morphology and Cell Biology) UNAM-FESC Campus 4 Cuautitlán Izcalli Mexico Pharmaceutical Technology Research Laboratory UNAM-FESC Campus 1 Cuautitlán Izcalli Mexico Dr. Hideyo Noguchi Regional Research Center UAY Mérida Mexico Laboratory of Virology and Microbiology of Respiratory Diseases of The Pig UNAM-FESC Campus 1 Cuautitlán Izcalli Mexico

Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability with a marked increase in virulence. Vaccines tested to date have been of little use in controlling the problems caused by PRRSV, so the present study was conceived to evaluate the antiviral effect of polymeric nanoparticles (PNPs) made with glycyrrhizic acid (GA). Recent work has proven that this nanoparticle system is stable. These nanoparticles have good GA carrying capacity, a size < 250 nm, a spherical morphology, and a wide safety range. The integrity of cell morphology can be maintained for up to 72 h. The antiviral effect of this nanoparticle system was tested in cultures of MARC-145 cells in pre- and coinfection assays with PRRSV to evaluate changes in cell morphology and effects on cell viability. The use of PNPsGA with the real-time quantitative polymerase chain reaction (RT-qPCR) decreased viral infection by 38% in 3 amplification cycles. These results suggest that this system has an antiviral effect against PRRSV under the study conditions established.

关键词： Cytotoxicity glycyrrhizic acid Cell Morphology Polymeric Nanoparticles PRRS Virus

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glycyrrhizic acid Attenuates Balloon-Induced Vascular Injury Through Inactivation of RAGE Signaling Pathways

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Cardiovascular Innovations and Applications 2020年第2期4卷 239-249页

作者： Zhaowei Zhu Yanan Guo Xuping Li Shuai Teng Xiaofan Peng Pu Zou Shenghua Zhou Department of Cardiovascular Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunanChina

Percutaneous coronary intervention is a well-established technique used to treat coronary artery disease,but the risk of coronary artery in-stent restenosis following percutaneous coronary intervention is still high.Previous studies revealed that high mobility group protein B1(HMGB1)plays a critical role in neointima formation.In this study,we aimed to investigate the role of glycyrrhizic acid(GA),an HMGB1 inhibitor,in the process of neointima formation and the potential mechanisms.We investigated the role of GA in neointima formation through an iliac artery balloon injury model in rabbits.Proliferation,migration,and phenotype transformation of human vascular smooth muscle cells(VSMCs)were observed.Besides,infl ammation and receptor for advanced glycosylation end products(RAGE)signaling pathways were studied.The results indicate that GA attenuated neointima formation and downregulated HMGB1 expression in injured artery in rabbits.HMGB1 promoted proliferation,migration,and phenotype transformation through the activation of RAGE signaling pathways in VSMCs,and blockade of HMGB1 by GA(1,10,and 100μM)could attenuate those processes and reduce proliferation of human VSMCs.In conclusion,the HMGB1 inhibitor GA might be useful to treat proliferative vascular diseases by downregulating RAGE signaling pathways.Our results indicate a new and promising therapeutic agent for restenosis.

关键词： glycyrrhizic acid high mobility group protein B1 infl ammation vascular smooth muscle cell receptor for advanced glycosylation end products

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Effect of glycyrrhizic acid and 18β-glycyrrhetinic acid on the differentiation of human umbilical cord-mesenchymal stem cells into hepatocytes

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World Journal of Stem Cells 2021年第10期13卷 1580-1594页

作者： Abiha Fatima Tuba Shakil Malick Irfan Khan Aisha Ishaque Asmat Salim Stem Cell Laboratory Dr.Panjwani Center for Molecular Medicine and Drug ResearchICCBSUniversity of KarachiKarachi 75270SindhPakistan

BACKGROUND End-stage liver disease is a global health complication with high prevalence and limited treatment options.Cell-based therapies using mesenchymal stem cells(MSCs)emerged as an alternative approach to support hepatic regeneration.In vitro preconditioning strategies have been employed to strengthen the regenerative and differentiation potential of MSCs towards hepatic lineage.Chemical compounds of the triterpene class;glycyrrhizic acid(GA)and 18β-glycyrrhetinic acid(GT)possess diverse therapeutic properties including hepatoprotection and anti-fibrosis characteristics.They are capable of modulating several signaling pathways that are crucial in hepatic regeneration.Preconditioning with hepato-protective triterpenes may stimulate MSC fate transition towards hepatocytes.AIM To explore the effect of GA and GT on hepatic differentiation of human umbilical cord-MSCs(hUC-MSCs).METHODS hUC-MSCs were isolated and characterized phenotypically by flow cytometry and immunocytochemistry for the expression of MSC-associated surface molecules.Isolated cells were treated with GA,GT,and their combination for 24 h and then analyzed at three time points;day 7,14,and 21.qRT-PCR was performed for the expression of hepatic genes.Expression of hepatic proteins was analyzed by immunocytochemistry at day 21.Periodic acid Schiff staining was performed to determine the functional ability of treated cells.RESULTS The fusiform-shaped morphology of MSCs in the treatment groups in comparison with the untreated control,eventually progressed towards the polygonal morphology of hepatocytes with the passage of time.The temporal transcriptional profile of preconditioned MSCs displayed significant expression of hepatic genes with increasing time of differentiation.Preconditioned cells showed positive expression of hepatocyte-specific proteins.The results were further corroborated by positive periodic acid Schiff staining,indicating the presence of glycogen in their cytoplasm.Moreover,bi-nucleated cells,which is the typical feature of hepato

关键词： glycyrrhizic acid 18β-glycyrrhetinic acid Hepatocyte differentiation Human umbilical cord-MSCs Mesenchymal stem cells

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Study on the Preparation and Characterization of glycyrrhizic acid Liposomes

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Pharmacology & Pharmacy 2022年第6期13卷 199-211页

作者： Bing Wang Xiang Luo Jue Wang Yibao Jin Tiejie Wang Xiean Yu Guo Yin NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation Shenzhen Institute for Drug Control Shenzhen China

The purpose of this study was to prepare glycyrrhizic acid nanoliposomes and evaluate the encapsulation efficiency and other properties of glycyrrhizic acid nanoliposomes, which would provide a reference for further research on glycyrrhizic acid in the treatment of liver diseases. Firstly, the preparation conditions of glycyrrhizic acid liposomes were optimized by the orthogonal design method. Then, glycyrrhizic acid liposomes were prepared by ultrasonic-film dispersion method and the encapsulation efficiency was determined by the HPLC method. Finally, the properties of glycyrrhizic acid nanoliposomes were also studied. The results showed that the optimal preparation conditions of liposomes were as follows: the ratio of drug to lipid was 1:30;Lecithin: cholesterol = 1:1;Hydration medium: pure water;Ultrasonic time: 120 s. The encapsulation efficiency of liposomes was about 90%. The final liposomes were round and uniform in distribution, with an average particle size of about 50 nm and absolute zeta potential of −28.9 mV. In this study, glycyrrhizic acid liposomes were prepared and the optimal preparation conditions were optimized. The encapsulation efficiency of the liposomes under the optimized conditions was determined. The evaluation of the morphology, size, particle size and stability of the liposomes was completed.

关键词： glycyrrhizic acid Liposome Orthogonal Design Quality Evaluation

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Simultaneous determination of 12,13-dihydroxyeuparin and glycyrrhizic acid in Yanyanfang mixture by high performance liquid chromatography

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Journal of Pharmaceutical Analysis 2011年第3期1卷 219-222页

作者： Zhi-Sheng Xie Xin-Jun Xu Chun-Yan Xie Jie-Yun Huang Mei Yang Rui-Ming Li Xiao Chen School of Pharmaceutical Sciences Sun Yat-Sen University No. 132 East Waihuan Rd. Guangzhou Higher Education Mega Center Guangzhou 510006 China The First Affiliated Hospital Sun Yat-sen University Guangzhou 510080 China

A reversed phase high performance liquid chromatography （HPLC） method was established for the simultaneous determination of 12, 13-dihydroxyeuparin and glycyrrhizic acid in Yanyanfang mixture. A Grace Apollo Cl8 column （250 mm × 4.6 mm, 5 μm） was used as the stationary phase and the mobile phase was composed of acetonitrile and aqueous phosphoric acid （0.2%, v/v）. Gradient elution was carried out at the flow rate of 1.0 mL/min and the column temperature was 30 ℃. An ultraviolet （UV） detector was used with a selected wavelength of 240 nm. Calibration curves were linear within the concentration range of 4.6-45.75 μg/mL for 12, 13-dihydroxyeuparin （r〉0.9999） and 106.9-1068.9μg/mL for glycyrrhizic acid （r〉0.9999）, respectively. Recoveries were 102.18% for 12, 13-dihydroxyeuparin and 101.17% for glycyrrhizic acid. The method developed could be applied to the simultaneous determination of 12, 13- dihydroxyeuparin and glycyrrhizic acid in Yanyanfang mixture.

关键词： 12, 13-Dihydroxy-euparin glycyrrhizic acid Yanyanfang mixture High performance liquidchromatography

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Cloning and characterization of the gene encoding β-amyrin synthase in the glycyrrhizic acid biosynthetic pathway in Glycyrrhiza uralensis

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Acta Pharmaceutica Sinica B 2013年第6期3卷 416-424页

作者： Honghao Chen Ying Liu Xiaoqin Zhang Xinjie Zhan Chunsheng Liu School of Chinese Pharmacy Beijing University of Chinese MedicineBeijing 100102China

Glycyrrhiza uralensis is considered to be one of the most important herbs in traditional Chinese medicine due to its numerous pharmacological effects particularly its ability to relieve cough and act as a mucolytic.Based on previous research,these effects are mediated by a number of active ingredients,especially glycyrrhizic acid(GA).In the present study,a gene encodingβ-amyrin synthase(β-AS)involved in GA biosynthesis in G.uralensis has been cloned and expressed in Saccharomyces cerevisiae.The cloned enzyme showed similar activity to native enzymes isolated from other Glycyrrhiza species to catalyze the conversion of 2,3-oxidosqualene intoβ-amyrin.In fact theβ-AS gene is particularly important in the GA biosynthetic pathway in G.uralensis.The complete sequence of the enzyme was determined and a phylogenetic tree based on theβ-AS gene of G.uralensis and 20 other species was created.This showed that Glycyrrhiza glabra had the closest kinship with G.uralensis.The results of this work will be useful in determining how to improve the efficacy of G.uralensis by improving its GA content and in exploring the biosynthesis of GA in vitro.

关键词： β-Amyrin synthase Glycyrrhiza uralensis glycyrrhizic acid Molecular cloning Heterologous expression GC–MS

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