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glycyrrhizin attenuates HMGB1-induced hepatocyte apoptosis by inhibiting the p38-dependent mitochondrial pathway

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World Journal of Gastroenterology 2012年第7期18卷 679-684页

作者： Geum-Youn Gwak Tae Gun Moon Dong Ho Lee Byung Chul Yoo Department of Medicine Samsung Medical CenterSugnkyunkwan University School of Medicine50 Irwon-DongGangnam-Gu135-710 SeoulSouth Korea

AIM： To examine how High-mobility group box I （HMGB1） regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin （GL）, a known HMGB1 inhibitor, prevents HMGBl-induced hepatocyte apoptosis.

关键词： High-mobility group box 1 Hepatocyte Apoptosis glycyrrhizin p38 Mitochondria

Uptake of albumin nanoparticle surface modified with glycyrrhizin by primary cultured rat hepatocytes

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World Journal of Gastroenterology 2005年第20期11卷 3075-3079页

作者： Sheng-JunMao Shi-XiangHou RuHe Liang-KeZhang Da-PengWei Yue-QiBi HuiJin WestChinaSchoolofPharmacy SichuanUniversityChengdu610041SichuanProvinceChina

AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane. METHODS: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NPGL and Cal-BSA-NP by rat hepatocytes was determinedby fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL. RESULTS: Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of CalBSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P＜0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by ***: A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a

关键词： glycyrrhizin Surface modified Bovine serum albumin Nanoparticles Hepatocytes

Immobilization of β-glucuronidase:biocatalysis of glycyrrhizin to 18β-glycyrrhetinic acid and in-silico lead finding

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Journal of Chinese Pharmaceutical Sciences 2020年第5期29卷 333-340页

作者： Makhmur Ahmad Mohammad Rashid Babar Ali Shamshir Khan Naseem Akhtar Mohd Faiyaz Khan Bibhu Prasad Panda Department of Pharmaceutics College of Dentistry and PharmacyBuraydahAl-Qassim 31717Kingdom of Saudi Arabia Department of Pharmacognosy and Medicinal Chemistry College of Dentistry and PharmacyBuraydahAl-Qassim 31717Kingdom of Saudi Arabia Department of Clinical Pharmacy Prince Sattam bin Abdul Azeez UniversityAl-KharjKingdom of Saudi Arabia Microbial and Pharmaceutical Biotechnology L aboratory School of Pharmaceutical Education and ResearchCenter for Advanced Research in Pharmaceutical SciencesJamia HamdardNew Delhi-110062India

The non-covalent immobilization ofβ-glucuronidase enzyme obtained from Rhizopus oryzae was carried out by entrapment in natural fiber(papaya and coconut).The bioconversion capability of immobilized enzyme was analyzed based on conversion of glycyrrhizin to 18β-glycyrrhetinic acid under different *** hydrolytic activity of theβ-glucuronidase enzyme was highly depended on the microbial source and matrix,in which enzyme was ***β-glucuronidase immobilized in papaya fibers produced the highest GA content(13.170μg/mL)at 10 h of *** ***β-glucuronidase immobilized in coconut fibers produced the highest GA content(21.425μg/mL)at 15 h of *** Molinspiration software was used to predict drug like molecular properties of the 18β-glycyrrhetinic acid,and software suggested that the compounds had potential of becoming the orally active ***,in silico studies were conducted on proposed 18β-glycyrrhetinic acid to select the best possible drug candidates based on drug properties and bioactivity score of the compounds.

关键词： 18β-Glycyrrhetinic acid glycyrrhizin β-Glucuronidase Natural fiber In-silico study

N-acetylcysteine and glycyrrhizin combination:Benefit outcome in a murine model of acetaminophen-induced liver failure

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World Journal of Hepatology 2020年第9期12卷 596-618页

作者： Charlotte Minsart Sandrine Rorive Arnaud Lemmers Eric Quertinmont Thierry Gustot Laboratory of Experimental Gastroenterology Erasme HospitalUniversitéLibre de BruxellesBrussels 1070Belgium Department of Pathology Erasme HospitalUniversitéLibre de BruxellesBrussels 1070Belgium DIAPATH-Center for Microscopy and Molecular Imaging UniversitéLibre de BruxellesGosselies 6041Belgium Department of Gastroenterology Hepato Pancreatology and Digestive OncologyErasme HospitalUniversitéLibre de BruxellesBrussels 1070Belgium Inserm Unité1149 Centre de Recherche sur l’inflammationParis 75006France UMR S_1149 UniversitéParis DiderotParis 75006France

BACKGROUND Acetaminophen overdose is the most frequent cause of drug-induced liver failure in developed *** progress has been made in understanding the mechanism of hepatocellular injury,but N-acetylcysteine remains the only effective treatment despite its short therapeutic ***,other hepatoprotective drugs are needed for the delayed treatment of acetaminopheninduced *** interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1(HMGB1)protein,a member of the family of damage-associated molecular pattern,known to play an important pathological role in various *** To investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver *** Eight-week-old C57BL/6J wild-type female mice were used for all our *** fasted for 15 h were treated with acetaminophen(500 mg/kg)or vehicle(phosphate-buffered saline)by intraperitoneal injection and separated into the following groups:glycyrrhizin(200 mg/kg);N-acetylcysteine(150 mg/kg);and N-acetylcysteine/*** all groups,mice were sacrificed 12 h following acetaminophen *** assessment of hepatotoxicity was performed by measuring plasma levels of alanine aminotransferase,aspartate aminotransferase and lactate *** was also evaluated by histological examination of hematoxylin and eosin-stained tissues *** rates were compared between various groups using Kaplan-Meier *** Consistent with data published in the literature,we confirmed that intraperitoneal administration of acetaminophen(500 mg/kg)in mice induced severe liver injury as evidenced by increases in alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase but also by liver necrosis *** administration was shown to reduce the release of HMGB1 and significantly decreased the severity of liver injury.

关键词： Acetaminophen Acute liver injury glycyrrhizin N-acetylcysteine Nacetylcysteine/glycyrrhizin combination Murine model High mobility group box 1

Effects of Dietary β-Glucan and glycyrrhizin on Non-Specific Immunity and Disease Resistance of the Sea Cucumber (Apostichopus japonicus Selenka) Challenged with Vibrio splendidus

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Journal of Ocean University of China 2010年第4期9卷 389-394页

作者： CHANG Jie ZHANG Wenbing MAI Kangsen MA Hongming XU Wei The Key Laboratory of Mariculture Ministry of Education of China Ocean University of China Qingdao 266003 P. R. China School of Animal Science and Technology Inner Mongolia University for the Nationalities Tongliao 028000 P.R. China

Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged with Vibrio splendidus by injection at 1.0×108 cfu/sea cucumber for 15 *** capacity (PC), intracellular superoxide anion production (ISAP), ly-sozyme (LSZ) activity and superoxide dismutase (SOD) activity in the coelomic fluid were analyzed on the 0th, 5th, 10th and 15th days after *** showed that after the 45-day feeding period, PC, ISAP, LSZ activity and SOD activity in sea cucumbers fed with dietary β-glucan or glycyrrhizin were significantly higher than in those fed with the basal *** the 5th day after infection, all the immune parameters examined in the sea cucumbers injected with *** decreased in value *** the 15th day, PC, ISAP and LSZ activity returned to levels similar to those on the 0th *** the sea cucumbers injected with saline, there were no significant differences in all the immune parameters examined and in the cumulative morbidity during the 15-day challenging *** injecting with ***, the cumulative morbidity of sea cucumbers fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin when challenged with *** challenged sea cucumber fed with the basal diet was significantly higher than those fed with dietary β-glucan or *** was no significant difference in cumulative morbidity between the dietary β-glucan and glycyrrhizin treatments over time.

关键词： β-Glucan glycyrrhizin Apostichopus japonicus Selenka Immunity Vibrio splendidus

Efficacy of glycyrrhizin combined with cyclosporine in the treatment of non-severe aplastic anemia

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Chinese Medical Journal 2013年第11期126卷 2083-2086页

作者： REN Cui-ai LI Yan-xiang CUI Jing-ying SHENG Zhi-xin RAN Xue-hong WANG Bao-hong ZHANG Mao-hong Department of Hematology Weifang People's Hospital WeifangShandong 261041 China Shandong University School of Medicine Jinan Shandong 250012China Department of Hematology Qilu Hospital of Shandong UniversityJinan Shandong 250012 China

Background Cyclosporine A （CsA） has been widely used in the treatment of aplastic anemia （AA）, but the application of CsA was limited in patients who had liver diseases or abnormal liver function due to its liver toxicity. glycyrrhizin has long been used in China in the treatment of various liver diseases to lower transaminases. In this study, we observed the efficacy and safety of glycyrrhizic acid combined with CsA in the treatment of newly diagnosed patients with non-severe AA （NSAA）. Methods A total number of 76 patients with newly diagnosed NSAA were enrolled into the study at our hospital between July 2005 and June 2010. The patients were divided randomly into two groups： the glycyrrhizin-treatment group （group A） and the control group （group B） with 38 patients in each group. All patients received 3-5 mg·kg^-1·d^-1 CsA for at least 4 months and were treated either with or without glycyrrhizin for 4 months. Results sixty-eight patients were eligible for evaluation. In the control group, 9.09% patients （n=3） achieved a complete response while 51.52% （n=17） attained a partial response. The overall response rate was 60.61% （n=20）. The remaining 13 patients （39：39%） did not have any response. In the glycyrrhizin-treatment group, complete response rate was 20% （n=7） and partial response rate was 62.86% （n=22）. The overall response rate was 82.86% （n=29） and the non-response rate was 17.14% （n=6）. Response rate was significantly increased with the addition of glycyrrhizin to CsA compared with CsA alone （P〈0.05）. Conclusion The combination of glycyrrhizin and cyclosporine regimen was an effective treatment for NSAA in terms of improvement of response rate, reduction in CsA-related liver injury, and attenuation of severity of nausea and other adverse events in the treatment of patients with NSAA.

关键词： glycyrrhizin anemia, aplastic cyclosporine

Neuroprotection of glycyrrhizin against Ischemic Vascular Dementia in Vivo and Glutamate-induced Damage in Vitro

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Chinese Herbal Medicines 2010年第2期2卷 125-131页

作者： HOU Yuan-yuan1,YANG Yang1,2,YAO Yang2,BAI Gang1,2 1.College of Pharmacy,Nankai University,Tianjin 300071,China 2.College of Life Sciences,Nankai University,Tianjin 300071,China College of Pharmacy Nankai UniversityTianjin 300071China College of Pharmacy Nankai UniversityTianjin 300071China College of Life Sciences Nankai UniversityTianjin 300071China College of Life Sciences Nankai UniversityTianjin 300071China

Objective To evaluate the neuroprotective effects of glycyrrhizin(GL) on vascular dementia(VaD) in vivo and Glutamate-induced damage in *** Male Wistar rats were subjected to permanent occlusion of the bilateral common carotid *** d 15 postsurgery,rat cognition was assessed using the Morris water *** activity of superoxide dismutase and the content of malondialdehyde of brains were also *** damage was evaluated histologically using HE *** vitro cell viability was examined in PC12 cells exposed to Glutamate,and mRNA levels of Bcl-2 and Bax were *** GL(20 mg/kg for 12 d) improved the performance of learning and memory of VaD rats,decreased the level of lipid peroxidation,and attenuated the pathological alterations in the hippocampal CA1 and CA3 ***,GL(0.6 mmol/L) could protect PC12 cell lines from injury induced by Glutamate(10 mmol/L) and inhibit apoptosis of neuronal *** The present findings suggest that GL may have therapeutic potential in treating VaD.

关键词： glycyrrhizin neuroprotection vascular dementia

Determination of bioactive marker glycyrrhizin in Glycyrrhiza glabra root and commercial formulation by validated HPTLC-densitometric method

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Journal of Coastal Life Medicine 2014年第11期 882-887页

作者： Perwez Alam Mohamed Fahd Alajmi Nasir Ali Siddiqui Adnan J Al-Rehaily Omar Ahmed Basudan Department of Pharmacognosy College of PharmacyKing Saud UniversityRiyadhKingdom of Saudi Arabia

Objective:To develop a simple sensitive high performance thin layer chromatography(HPTLC)-densitometric method for quantification of glycyrrhizin in the Glycyrrhiza glabra root methanol extract and licorice root capsule methanol ***:Chromatography was performed on glass-backed silica gel 60 F254 HPTLC plates with the green solvents ethyl acetate:glacial acetic acid:methanol:water in proportion of 6:2:1:0.5,v/v/v/v as mobile *** and quantification of developed plate was done densitometrically at 254 *** method was validated for detection and quantification limits,precision,recovery and robustness according to International Conference on Harmonization ***:The system gave compact spot for glycyrrhizin(R_(f)=0.280±0.001).The regression curve of standard was found to be Y=4.213x+*** limit of detection(15.7 ng per band),limit of quantification(47.1 ng per band),recovery(99.4%-99.8%)and precision(≤1.62%and≤1.84%;intraday and interday)were satisfactory for *** range for glycyrrhizin was 20-200 ng(r^(2)=0.996).The content of glycyrrhizin was estimated as 5.9%and 11.2%w/w in glycyrrhizin in the Glycyrrhiza glabra root methanol extract and licorice root capsule methanol extract,***:This estimation technique is very much useful for the estimation of glycyrrhizin present in various formulations as well as for quality control of crude drugs containing glycyrrhizin.

关键词： Licorice root capsule Glycyrrhiza root Validation HPTLC glycyrrhizin

Effect of Discontinuous Administration of β -glucan and glycyrrhizin on the Growth and Immunity of Pacific White Shrimp Litopenaeus Vannamei

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Feed & Livestock 2010年第3期3卷 5-6页

作者： Nan Bai Kangsen Mai Wenbing Zhang Hongming Ma Qinghui Ai Xiaojie Wang Key Laboratory of Mariculture （Ministry of Education） Ocean Universily of China Clingdao 266003 PR China

A six-week growth trial was conducted to compare the effects of different feeding strate- gies of dietary immunostimulants on the growth and immunity of white shrimp Litopenaeus vannamei （4.70 ±0.20g）. Shrimps were fed with diet containing glycyrrhizin continuously, containing β -glucan continuously, discontinuously （seven days with diet containing β -gluseven days with diet without -glucan; two days with diet containing β-glucan following five days with diet without -glucan）,

关键词： Pacific white shrimp β -glucan glycyrrhizin immunity immunity fatigue