Licorice:comprehensive review of its chemical composition,pharmacodynamics,and medicinal value

Licorice,a perennial herb of Leguminosa,is one of the oldest and most widely used herbal medicines worldwide.Its distinct sweet flavor and rich medicinal value make it an integral component of traditional Chinese medicine(TCM)formulations,which continue to be widely employed.The main chemical constituents of licorice include triterpenoid saponins,flavonoids,and polysaccharides.Experimental and clinical studies have demonstrated that various extracts and pure compounds derived from licorice exhibit a wide range of pharmacological properties including anti-inflammatory,antioxidant,antimicrobial,antiviral,antitumor,immune-regulatory,and neuroprotective activities.The bioactive constituents of licorice offer therapeutic benefits for cardiovascular and cerebrovascular diseases,diabetes mellitus,and liver disorders.This comprehensive review discusses the primary chemical constituents of licorice and their pharmacological activities,describes in vivo and in vitro models employed for studying licorice,and its potential targets and mechanisms of action.Furthermore,we discuss the toxicological profile,side effects,dosage recommendations,and clinical applications of licorice.This review aims to establish a foundation for further research on the safe and effective utilization of licorice while facilitating an in-depth exploration of its properties and fostering the development of novel therapeutic agents.

Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

Effect of Mongolian Vinegar Soaked Licorice on Liver Fibrosis Induced by Carbon Tetrachloride Combined with High-fat Diet in Rats

[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4)olive oil solution(0.3 mL/100 g)combined with a high-fat diet was used for 5 weeks to establish the rat model with liver fibrosis.After the modeling,the rats were divided into a low dose(0.8 g/kg),a medium dose(2.5 g/kg),a high dose(5 g/kg)group,a colchicine(1.5 mg/kg)positive group,and a vinegar group(2 mL/kg).The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in the rats were measured automatically.The serum hyaluronic acid(HA)was detected by radioimmunoassay,and the serum laminin(LN)and procollagen type III peptide(PIIIP)levels were measured by enzyme-linked immunoassay.Liver histopathological morphological changes were observed by HE and Masson staining,and expressions of cytochrome CYP2E1 and transcription factor Nrf2 were detected by immunohistochemistry.[Results]The rat liver fibrosis model was established successfully at the 6~(th)week.Compared with the model group,the levels of ALT,AST,HA,LA,PIIIP,CYP2E1 and Nrf2 of all the examined indexes in the dosing group were decreased(P<0.05).As shown in the pictures of liver pathological tissue sections,the liver fibrosis was significantly alleviated in the positive group and the 3 administration groups.[Conclusions]Vinegar soaked licorice can significantly improve the liver fibrosis induced by carbon tetrachloride combined with high-fat diet in rats,and the effect of the high-dose group was similar to that of the positive group.

MICROWAVE-ASSISTED EXTRACTION OF GLYCYRRHIZIC ACID FROM LICORICE ROOT-EFFECT OF THE PROPERTY OF SOLUTION ON EXTRACTION OF GA

The property of extraction solution is an important factor influencing the extraction efficiency. In the present work, the effect of the property of solution on extraction of GA was studied, which including the concentration of ethanol, ammonia and cation (M+), pH of extraction solution, different kinds of organic solvent etc. The results show that 50%-60%(v/v) ethanol can reach high percentage extraction of GA. If 1% (v/v) ammonia solution was added into 60%(v/v) ethanol, the percentage extraction can be increased from 2.0% to 2.31%. Without ammonia, 50mmol/L [M+] (M+ = K+, NH4+) was added into 60%(v/v) ethanol, percentage extraction of GA can reach about 2.26%. If pH of solution (60% ethanol) was adjust to pH=4.0, it can reach high percentage extraction. If pH of solution (60% ethanol + 50mmol [M+], pH=6.1) was adjust tO PH=4.0, especially M+ is K+ or NH4+, it can reach almost same extraction efficiency as that of 1% ammonia solution + 60% ethanol, and the operation environment can be greatly improved.

Licorice Extracts Attenuate Nephrotoxicity Induced by Brucine Through Suppression of Mitochondria Apoptotic Pathway and STAT3 Activation

Licorice,one of the most widely used medicinal herbs in East Asia,has effects such as anti-inflammation,antioxidant,and detoxifying.This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity.Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice.The content of blood urea nitrogen and creatinine in serum,the activities of superoxide dismutase and content of glutathione,malonaldehyde in kidney tissue were detected.Hematoxylin-eosin staining was employed to observe the histopathological changes of kidney.The expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical analysis.The results illustrated that treatment with licorice extracts(LE)significantly protected against the brucineinduced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine,attenuating pathologic damage.The unbalance of oxidative stress was repaired by LE via increasing the level of glutathione,promoting the activities of superoxide dismutase and decreasing the content of malonaldehyde.In addition,LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3(STAT3)activation.Taken together,these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis pathway.More importantly,the renoprotective effects may be mediated,at least partly,by preventing the activation of STAT3 protein.

Improving the Antibacterial Property of Chitosan Hydrogel Wound Dressing with Licorice Polysaccharide

A series of hydrogels with different ratios of chitosan and licorice polysaccharide(LP)were prepared by crosslinking to different concentrations of genipin(gp).They were characterized by FTIR(Fourier transform infrared spectroscopy),SEM(Scanning electron microscope),swelling ratio,rheological measurements,degradation with time,cytotoxicity,and antibacterial efficacy.Results show that the hydrogels have porous structures.With an increase in LP content,the swelling rate grows in the early stage of immersion in buffer and drops later.The swelling ratio ranged from 986%to 1677%,and stiffness varied from 777 Pa to 1792 Pa.The addition of LP reduced the mechanical strength and delayed gelation and degradation of the hydrogels.However,the most important discovery was that gp increases the viability of NIH 3T3 cells from 94%to 137%,and LP raises the bacteriostatic efficacy from 51%to 78%.Hydrogels synthesized from 1%genipin,3%chitosan,and 4%licorice polysaccharide showed the best antibacterial and fibroblast proliferation promoting activities.They exhibited moderate swelling and degradation rates over time,while being more suitable to affect healing of chronic wound infections.These results provide a new strategy to improve the antibacterial effectiveness and cyto-compatibility of chitosan hydrogels with water soluble active LPs from Glycyrrhiza that derive from traditional Chinese medicine.

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate combination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM “Eighteen Incompatible Medicaments”, are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphinganine were screened out as the principal alternative biomarkers of compatibility group;sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of incompatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM “Eighteen Incompatible Medicaments”.

Performance, Immune, and Carcass Characteristics of Broiler Chickens as Affected by Thyme and Licorice or Enzyme Supplemented Diets

Numbers of 300 day-old broiler chickens through a CRD design with 5 treatments, 3 replicates and 20 chicks in each pen were used to evaluate the effect of thyme (T), licorice (L), thyme + licorice (TL), and enzyme supplemented (E) diets on performance, immune and carcass characteristics. According to the results, performance traits, immune indices, and carcass traits in herbal medicine and enzyme supplemented diets were improved significantly than control diet (P < 0.05). Weight gain and FCR in T and E groups were significantly higher and lower than other groups respectively (P < 0.05). Internal organs such as abdominal fat and liver weight as indicators of lipogenesis rate were decreased in T, L, and TL diets than control or E diet significantly (P < 0.05). Immune organs such as burse and spleen weight as indicators of immune situation were increased in TL diet than other treatments significantly (P < 0.05). These findings indicated that thyme and licorice singly or in combination as organic herbal medicine can affect performance, carcass and immune characteristics. Also an improved immune organ such as burse or spleen in this study indicates that this herbal medicine can promote the immune situation and efficacy of health and livability.

Molecular Cloning and Expression Analysis of an Actin Gene from Chinese Licorice(Glycyrrhiza uralensis Fisch)

A PCR-based homologous cloning strategy was used to identify an actin gene from the roots of Chinese licorice（Glycyrrhiza uralensis Fisch）. Results of sequence analysis indicate that a 1137 bp cDNA with an open reading frame encoding 377 amino acids, actin ortholog, GuActin, was successfully cloned and characterized（GenBank accession No. EU190972）. Thus far, GuActin is the first actin of Chinese licorice that has been identified at a molecular level. Analysis by Northern blot shows that GuActin was expressed strongly in the roots, particularly in radicles than in stems and leaves. These results suggest that GuActin may be a member of the vegetative subfamily of the actin family.

Licorice and its main components on the treatment of diabetes and its complications:A review of in vivo and in vitro studies

Licorice is one of the oldest herbal medicines for its various ethno pharmacological uses.In both Asian and European countries,it has been recorded for treatment of inflammatory diseases.A large number of ingredients have been isolated from licorice,including triterpene saponins and flavonoids,which are normally being considered to be the main biologically active components.In the last decade,licorice has been proved exert anti-diabetic effect in various in vivo and in vitro models of diabetes mellitus.Furthermore,licorice can also antagonize all sorts of diabetes complications,including diabetic nephropathy,atherosclerosis,diabetic retinopathy and neuropathy.Except anti-inflammation,licorice and its active components show anti-diabetic effects by improving insulin resistance and increasing insulin secretion,regulating lipid metabolism,and anti-oxidation.The useful effects of licorice and its active components are due to regulating different pathways and proteins,including NF-κB,AMPK,insulin signaling pathway,MAPK,etc.In this review,we provide an overview of the beneficial effects and related molecular mechanism of licorice and its effective components on improving diabetes and its complications.

Black licorice ingestion:Yet another confounding agent in patients with melena

We describe an 80-year-old woman with atrial fibrillation,anti-coagulated with warfarin,who on two separate occasions developed black tarry stools and an elevated international normalized ratio(INR) after eating a pound of Black Licorice.During her most recent episode,her hematocrit was 14(baseline 34) and her INR was 5.5(baseline 2.1).She was advised to restrict licorice consumption,and a follow-up INR two weeks later was 1.2.Black Licorice is derived from the root of the plant,Glycyrrhiza glabra.The components of its extract inhibit the P450 system enzymes that metabolize Warfarin,inhibit thrombin,and prolong fibrinogen clotting times.Hence,the anti-thrombotic activity and inhibition of warfarin metabolism might synergistically amplify anticoagulation.The presence of Black Licorice in the stool can also mimic melena and confound its clinical presentation.Health care providers should caution patients who are at risk for bleeding or on warfarin to avoid black licorice due to an elevated risk of gastroint estinal bleeding.

THE EFFECT OF VIOLENT DIGGING OF LICORICE RESOURCES ON THE ENVIRONMENT OF ARID AREA

Licorice (Glycyrrhira) is one of the important medical resources in arid area. It is dis-tributed between 30 and 55 degrees north latitude, especially in arid area 40 degrees northlatitude. There are about nine or ten species of licorice in our country. Not only it has ahigh economical value, but also it is an important sand-control plant for

Promoting effect of licorice extract on induction of β-glucuronidase in Penicillium purpurogenum Li-3

PeniciUium purpurogenum Li-3, a fungus producing β-glucuronidase （PGUS）, can con- vert glycyrrhizin （GL） to glycyrrhetinic acid monoglucuronide （GAMG） when grown in medium with GL as the sole carbon source. In order to improve the conversion rate of GL and the yield of GAMG, licorice extract （LE） was added as an inducer to enhance the production of GAMG by the PGUS. In this work, the influence of LE on the conversion rate of GL to GAMG was studied. When the Penicil- lium purpurogenum Li-3 was grown in the medium containing LE and GL （ concentration ratio of LE to GL was 2： 3）, the conversion rate of GL was 84. 12% with 38. 18% increase and the yield of GAMG was 80. 47% with 37. 18% increase, comparing with to the medium only containing GL at 48 h. The enzyme activity of ^-glucuronidase was also enhanced from 22. 4 U/mL to 82.3 U/mL, which in- creased up to about 3. 67 fold. The results showed that LE could significantly improve the induced expression level of PGUS.

Impact of Ion Implantation on Licorice(Glycyrrhiza uralensis Fisch) Growth and Antioxidant Activity Under Drought Stress

Low energy ion beams are known to have stimulation effects on plant generation and to improve plants＇ intrinsic quality. In the present study, the growth and physiological index of licorice implanted with 0, 8, 10; 12 and 14× （2.6× 10^15） ions/cm^2 were investigated under well-watered and drought-stress conditions. The results showed that a proper dose of ion implan- tation was particularly efficient in stimulating the licorice growth and improving the plant biomass significantly in both the well-watered and drought-stress conditions. The physiological results of licorice measured by leaf water potential, lipid oxidation, soluble protein and antioxidant system showed a significant correlation between ion implantation and water regime except for leaf water potential. Therefore, the study indicated that ion implantation can enhance licorice＇s drought tolerance by increasing the activity of superoxide dismutase （SOD）, eatalase （CAT） and DPPH （1,1-diphenyl-2-picrylhydrazyl） radical scavenging ability to lower oxidative damage to lipids in plants. Ion beam implantation, therefore, provides an alternative method to enhance licorice drought tolerance.

Estimation of multivariate detection limits of four quality parameters in licorice using MEMS–NIR spectrometry coupled with two sampling accessories

In this work,multivariate detection limits(MDL)estimator was obtained based on the microelectro-mechanical systems–near infrared(MEMS–NIR)technology coupled with two sampling accessories to assess the detection capability of four quality parameters(glycyrrhizic acid,liquiritin,liquiritigenin and isoliquiritin)in licorice from di®erent geographical regions.112 licorice samples were divided into two parts(calibration set and prediction set)using Kennard–Stone(KS)method.Four quality parameters were measured using high-performance liquid chromatography(HPLC)method according to Chinese pharmacopoeia and previous studies.The MEMS–NIR spectra were acquired from¯ber optic probe(FOP)and integrating sphere,then the partial least squares(PLS)model was obtained using the optimum processing method.Chemometrics indicators have been utilized to assess the PLS model performance.Model assessment using chemometrics indicators is based on relative mean prediction error of all concentration levels,which indicated relatively low sensitivity for low-content analytes(below 1000 parts per million(ppm)).Therefore,MDL estimator was introduced with alpha error and beta error based on good prediction characteristic of low concentration levels.The result suggested that MEMS–NIR technology coupled with fiber optic probe(FOP)and integrating sphere was able to detect minor analytes.The result further demonstrated that integrating sphere mode(i.e.,MDL0:05;0:05,0.22%)was more robust than FOP mode(i.e.,MDL0:05;0:05,0.48%).In conclusion,this research proposed that MDL method was helpful to determine the detection capabilities of low-content analytes using MEMS–NIR technology and successful to compare two sampling accessories.

Optimization of Processing Technology for Roasted Licorice with Water by Orthogonal Method

[Objectives]To optimize the processing technology for roasted licorice with water.[Methods]Through the orthogonal experimental design,taking the water added,moistening time,frying temperature and frying time as the factors,and the content of glycyrrhizin and glycyrrhizic acid as the evaluation index,the processing technology for roasted licorice with water was optimized.[Results]The best processing technology of licorice was as follows:Pure licorice slices were mixed with water and moistened for 3 h,and then fried at 160℃for 6 min.20 kg of water was added to every 100 kg of licorice.[Conclusions]The best processing technology for roasted licorice with water was established,laying a foundation for the research and application of roasted licorice with water and its preparation.

Observation on the effect of licorice flavonoid Chinese herbal medicine spotting cream combined with Awei A capsule in the treatment of psoriasis

Objective: To study the curative effect of licorice flavonoid Chinese herbal frond cream combined with Awei A capsule in the treatment of psoriasis. Methods: During the period from April 2016 to March 2018, a total of 116 patients with psoriasis in our hospital were randomly divided into the experimental group (the treatment of licorice flavonoids and Chinese acupoint cream combined with Awei A capsule) and the control group (single use) Avi A capsule treatment). Comparison of blood lipid metabolism indexes (high-density lipoprotein, apolipoprotein, low-density lipoprotein) and serum biochemical indicators (neutrophil elastase, endogenous inhibitor of NE, placental cadherin) statistical difference in content. The statistical differences between PASI score and DLQI score before and after treatment were compared between the two groups. At the end of treatment, the statistical difference between the clinical efficacy and the incidence of adverse reactions was compared between the two groups. Results:The levels of serum NE, Trappin-2 and P-cad in patients before and after treatment showed a significant downward trend. The content of NE, Trappin-2 and P-cad in the experimental group was significantly lower than that in the control group. The content of HDL-C in lipid metabolism index increased significantly before and after treatment, and the content of APOA and LDL-C decreased significantly. The content of HDL-C in the experimental group was significantly higher than that in the control group. The content of APOA and LDL-C was significantly lower than that of the control group. The PASI score and DLQI score of patients before and after treatment decreased significantly. After treatment, the PASI score and DLQI score of the experimental group were significantly lower than those of the control group. The clinical efficacy of the two groups was significantly different. The efficacy of the experimental group was significantly better than that of the control group. The skin of the experimental group was dry, itchy, and the skin desquamation was significantly less than that of the control group. Conclusion: Licorice Flavonoids and Avi A capsules have the advantages of improving blood lipid metabolism in the treatment of psoriasis, while reducing the recurrence rate and reducing the occurrence of common adverse reactions such as skin itching, dryness and abnormal liver function. It has a good clinical application significance.

Enrichment of flavonoid aglycones in licorice extract enhanced anti-inflammatory potential,but its hypnotic effect was not altered

OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy.According to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investigated the anti-inflammatory ingredients of licorice,but for the potency of flavonoid glycoside and their aglycones on inflammation are not evaluated.This study was designed to assess the contributions of licorice flavonoid glycosides and their aglycons to its anti-inflammatory and hypnotic effects.METHODS For the flavonoid aglycone's enrichment,the extract of licorice(EL)was fermented in submerged culture of the edible fungus Grifola frondosa HB0071 mycelia which can produce β-glucosidase and catalyze the flavonoid glycosides to aglycones.EL and fermented extract of licorice(FEL) were used in this study.The anti-inflammation test was carried out in arachidonic acid(AA)-induced ear edema model and the hypnotic test was performed by using electroencephalogram(EEG) analysis method in normal freely moving SD rats.The chemicals constituents were analyzed by HPLC.RESULTS During fermentation,the falvonoid glycosides of licorice were hydrolyzed by the time process.Along with fermentation time,the concentration of the major flavonoid glycosides,liquiritin and isoliquiritin were decreased obviously,and simultaneously their aglycons,liquiritigenin and isoliquiriti.genin were remarkably increased in FEL.Moreover,the content of another major constituent glycyrrhi.zic acid and glycyrrhetinic acid were not changed after the fermentation.In AA-induced mice ear ede.ma test,after topical application,FEL(effective dose range:5-20 μg·ear-1) showed more potent inhibito.ry activity than EL(effective dose range:25-100 μg·ear-1).On the other hand,oral administration of EL and FEL exhibited the same hypnotic potency and both enhanced the total sleep time including rapid eye movement(REM) sleep and non-REM sleep time.CONCLUSION These results suggested that the enrichment of flavonoid aglycons such as liquiritigenin and isoliquiritigenin enhanced the anti-inflam.matory potency of licorice extract,and this potentiation has nothing to do with glycyrrhizic acid or glycyr.rhetinic acid.In addition,enrichment of flavonoid aglycones did not alter the hypnotic effect of licorice.

不同产地甘草中核苷和碱基类成分分析与评价

为揭示不同产地甘草物质基础不同,本研究采用UPLC-TQ/MS测定153批不同产地甘草样品中12种核苷、碱基类成分含量,并利用主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)进行不同产地质量特征分析。研究结果显示,不同产地总核苷、碱基类成分含量宁夏>甘肃>内蒙古>新疆,产地之间存在显著差异(P<0.05)。甘草核苷类成分以胞苷和鸟苷含量较高,二者占总核苷和碱基含量的26.2%~47.8%;碱基类成分以腺嘌呤和鸟嘌呤较高,二者占总核苷和碱基含量的19.3%~38.7%。基于测定的12种核苷、碱基类成分,PLS-DA判别分析可以将不同产地的甘草分为两组,一组为宁夏和内蒙古产甘草,另外一组为甘肃和新疆产甘草,主要差异成分为鸟嘌呤、腺嘌呤、尿苷、胞苷和鸟苷。进一步采用PLS-DA分别分析两个组内不同产地的甘草质量特征显示,甘肃和新疆产甘草可以明确区分,宁夏和内蒙古产甘草不能准确区分。以上研究结果表明,不同产地甘草中核苷、碱基类成分存在差异,进而影响其质量特征。基于核苷、碱基类成分分析,宁夏和内蒙古产甘草质量一致度较高。本研究为揭示不同产地甘草质量存在差异提供了理论支持,为其合理开发利用奠定了基础。