Component Of Licorice Research Articles

Isoliquiritigenin prevents the progression of psoriasis-like symptoms by inhibiting NF-κB and proinflammatory cytokines

Isoliquiritigenin (ISL) is an important flavonoid component of licorice and has been reported to possess anti-inflammatory and antioxidant properties, but its exact mechanism of action remains poorly understood. Previously, we demonstrated that ISL could suppress IL-6 expression in multiple myeloma. Here, we further characterized the anti-inflammatory effects of ISL in several psoriasis models, including the keratin 14/vascular endothelial growth factor (VEGF) transgenic mouse, the imiquimod (IMQ)-induced psoriasis-like mouse, and the human keratinocytes HaCaT and NHEK in vitro. We found that ISL ameliorated the inflammatory process in psoriasis models but not in their respective controls. Moreover, the anti-inflammatory effects of ISL were attributed to the suppression of nuclear factor-κB (NF-κB) activity, which consequently resulted in the reduction of pro-inflammation cytokines IL-6 and IL-8 expression. In conclusion, ISL exhibited anti-inflammatory effects in psoriasis models, by downregulating IL-6 and IL-8 via suppression of NF-κB activity, suggesting that ISL might serve as a potential candidate for treatment of psoriasis and other autoimmune inflammatory diseases. ISL could ameliorate the inflammatory process of psoriasis. ISL could suppress NF-κB and subsequent production of a series of pro-inflammatory cytokines. Dual-inhibitory activity against IL-6 and IL-8 of ISL is implemented via inhibiting NF-κB. ISL exerts no inhibitory effects on normal human keratinocytes or wild-type Balb/c mice, implying its low toxicity and safety.

Pseudoaldosteronism induced by Yokukansan in an elderly Japanese type 2 diabetic patient with Alzheimer's disease.

The number of patients with Alzheimer's disease (AD), and/or behavioral and psychological symptoms of dementia (BPSD) has been markedly increasing all over the world, and has become a social and health problem. Furthermore, it has been recently established that the diabetic condition is a major risk factor for the development of dementia1. Second-generation antipsychotics have been used, but some cases are refractory2. Yokukansan is a licorice-containing Chinese medicine, and has been very often used for the treatment of such disease3. A previous report showed that Yokukansan exerts beneficial effects and can be used very safely3. It is known that a large amount of licorice could induce pseudoaldosteronism, but Yokukansan contains only a small amount of licorice. Therefore, it has been thought that the use of Yokukansan does not lead to the onset of pseudoaldosteronism. However, here we report a case of pseudaldosteronism that developed after starting Yokukansan in an elderly Japanese diabetic patient with AD and BPSD. In February 2013, a 77-year-old Japanese man with type 2 diabetes was admitted to the Kawasaki Medical School, Kurashiki, Japan, because of hypokalemia and weight gain. He had been taking Yokukansan for 5 months (7.5 g/day containing 1.5 g of licorice). He frequently felt general fatigue, and his bodyweight was increased by 7 kg. On admission, his bodyweight was 64.3 kg and height 160.5 cm. He did not have vomiting or diarrhea and did not use any diuretics. Physical examination revealed mild systolic hypertension. Marked pretibial pitting edema was observed in the bilateral lower extremities. Table​Table11 shows the laboratory findings on admission. Serum potassium was 3.0 mEq/L with mild renal dysfunction. The low-renin and low-aldosterone state was observed with concomitant metabolic alkalosis. In addition, the transtubular potassium gradient (TTKG) was very high (11.0). Given these findings, we made the diagnosis of Yokukansan-induced pseudoaldsteronism, and stopped this drug. After commencement of oral potassium replacement, potassium level was increased (3.8 mEq/L at day 10) and TTKG was decreased to 3.5. Pitting edema disappeared with 6-kg weight reduction. On day 20, he was discharged from the hospital. Table 1 Laboratory findings on admission Recently, Yokukansan has been very often used for dementia, and its sales amount has been drastically increasing. It has been thought that Yokukansan can be used very safely3. To the best of our knowledge, this is the first report showing that Yokukansan induced pseudoaldosteronism in diabetic patients. The mechanism of how licorice causes pseudoaldosteronism is likely through the inhibition of renal enzyme 11-hydroxysteroid dehydrogenase type 2. Cortisol, as well as aldosterone, can bind to the mineralocorticoid receptor (MR), but, 11-hydroxysteroid dehydrogenase type 2 converts cortisol to cortisone that does not work on MR. As a result, aldosterone dominantly binds to MR4. However, licorice inactivates 11-hydroxysteroid dehydrogenase type 2 and increases the cortisol binding to MR, which explains the mechanism for licorice-induced pseudoaldosteronism. It is known that the onset of pseudoaldosteronism depends on the dose of licorice, but the present case developed pseudoaldosteronism with a very low dose of licorice (1.5 g/day). In fact, a similar frail and elderly female case of Yokukansan-induced pseudoaldosteronism with severe hypokalemia was reported by Nishiya et al.5 Thereby, we should pay careful attention when using Yokukansan, even with a low-dose component of licorice. Taken together, we should consider the possibility of pseudoaldosteronism when we use Yokukansan for dementia, and careful monitoring of electrolytes, especially potassium, is necessary.

Rapid screening for novel antioxidants in Glycyrrhiza inflata using high-resolution peak fractionation

Licorice is often consumed as a flavoring agent in food products, and a commonly used herb with several bioactivities, including antioxidation. The bioactive components in licorice against oxidative stress have not been fully elucidated. Nuclear-factor-E2 related factor 2/antioxidant responsible element (Nrf2/ARE) is a major pathway protecting cells from oxidative damage. In this study, an ARE-luciferase/β-galactosidase enzyme dual reporter gene assay was used in conjunction with high-resolution peak fractionation to rapidly identify antioxidants in Glycyrrhiza inflata. The structures of potential antioxidants were identified by high-performance liquid chromatography (HPLC) coupled with quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Ultimately, eight active antioxidants were identified and confirmed by real-time polymerase chain reaction (RT-PCR). Five novel Nrf2 activators are reported. This study presents potential Nrf2 activating compounds in licorice and provides further evidence for the antioxidant properties of G. inflata, which is important for elucidating the ingredients partially responsible for the antioxidant properties of licorice.

Chemopreventive Effects of Licorice and Its Components.

Cancer is still a major health issue worldwide and identifying novel but safe compounds for prevention and treatment is a high priority. Licorice (Glycyrrhiza) is a perennial plant that is cultivated in many countries and has been reported to exert antioxidant, anti-inflammatory and anticancer effects. However, some components of licorice exert unwanted side effects and therefore identifying safer licorice components would be ideal. The anticancer activities of many of the licorice components appear to include cycle arrest, apoptosis induction, and general antioxidant effects. Commonly reported indirect protein targets important in tumorigenesis include many cell cycle-related proteins, apoptosis-associated proteins, MMP proteins, COX-2, GSK-β, Akt, NF-κB, and MAP kinases. Importantly, several licorice components were reported to directly bind to and inhibit the activities of PI3-K, MKK4, MKK7, JNK1, mTOR, and Cdk2, resulting in decreased carcinogenesis in several cell and mouse models with no obvious toxicity. This review focuses on specific components of licorice for which a direct protein target has been identified.

Protective Effects of Glycyrrhizic Acid and 18β-Glycyrrhetinic Acid against Cisplatin-Induced Nephrotoxicity in BALB/c Mice.

The clinical use of antineoplastic drug cisplatin (CP) is commonly complicated by nephrotoxic side effects that limit its application and therapeutic efficiency. This study used a model of CP-induced renal injury in male BALB/c mice to investigate the protective effects of the active components of licorice, glycyrrhizic acid (GA), and 18β-glycyrrhetinic acid (18βGA) against CP-induced nephrotoxicity, and the chemoprotectant, amifostine, was used as a control. Oral administration of GA or 18βGA significantly reduced CP-induced increases in the levels of blood urea nitrogen, creatinine, and lactate dehydrogenase. Hematoxylin and eosin staining revealed that GA and 18βGA delayed the progression of renal injury, including tubular necrosis, hyaline casts, and tubular degeneration in response to CP exposure. Oxidative status and inflammatory responses in CP-treated mice were restored to near-normal levels by treatment with GA or 18βGA. These protective effects might be associated with upregulation of nuclear factor E2-related protein (Nrf2) and downregulation of nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) in the kidney. Notably, we demonstrated that GA and 18βGA rendered renal cells resistant to CP-induced HMGB1 cytoplasmic translocation and release. These findings suggest that GA and 18βGA might be act as the chemoprotectants against CP-induced nephrotoxicity.

18β-Glycyrrhetinic Acid Suppresses Cell Proliferation through Inhibiting Thromboxane Synthase in Non-Small Cell Lung Cancer

18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice. The anti-cancer activity of 18β-GA has been studied in many cancer types, whereas its effects in lung cancer remain largely unknown. We first showed that 18β-GA effectively suppressed cell proliferation and inhibited expression as well as activity of thromboxane synthase (TxAS) in non-small cell lung cancer (NSCLC) cells A549 and NCI-H460. In addition, the administration of 18β-GA did not have any additional inhibitory effect on the decrease of cell proliferation induced by transfection with TxAS small interference RNA (siRNA). Moreover, 18β-GA failed to inhibit cell proliferation in the immortalized human bronchial epithelial cells 16HBE-T and another NSCLC cell line NCI-H23, both of which expressed minimal level of TxAS as compared to A549 and NCI-H460. However, 18β-GA abolished the enhancement of cell proliferation induced by transfection of NCI-H23 with pCMV6-TxAS plasmid. Further study found that the activation of both extracellular signal-regulated kinase (ERK)1/2 and cyclic adenosine monophosphate response element binding protein (CREB) induced by TxAS cDNA transfection could be totally blocked by 18β-GA. Altogether, we have delineated that, through inhibiting TxAS and its initiated ERK/CREB signaling, 18β-GA suppresses NSCLC cell proliferation. Our study has highlighted the significance of 18β-GA with respect to prevention and treatment of NSCLC.

Interaction Analysis of Glycyrrhizin on Licorice Extract-induced Apoptosis of Human Leukemia Cells by Knockout Extract

Licorice is the most frequently prescribed herb in traditional Chinese medicine (TCM) and Japanese Kampo medicine. Although glycyrrhizin (GC) is one of the major active components of licorice, the other components are also known to possess biological activities. We had previously prepared GC-knockout (GC-KO) extract, which contained all components of licorice extract (LE) except GC using a immunoaffinity column conjugated with anti-GC monoclonal antibodies (MAb). In this study, we used the GC-KO extract to investigate the potential role of GC in LE-induced apoptotic cell death. LE markedly induced apoptotic cell death in human leukemia HL-60 cells. Although treatment with GC alone had no influence on cell viability, induction of cell death by the GC-KO extract was weaker than that by LE. Interestingly, the addition of GC to the GC-KO extract significantly rescued cell growth inhibition and activated caspase-3. These data suggest that GC may synergistically enhance the induction of apoptosis in the presence of other components of LE. Moreover, these pharmacological analyses indicate the utility of KO extracts in determining new functions of target compounds and the interactions between target compounds and other constituents of medicinal plant extracts.

Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root.

BACKGROUND/OBJECTIVELicorice has been shown to possess cancer chemopreventive effects. However, glycyrrhizin, a major component in licorice, was found to interfere with steroid metabolism and cause edema and hypertension. The roasting process of licorice modifies the chemical composition and converts glycyrrhizin to glycyrrhetinic acid. The purpose of this study was to examine the anti-carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to identify the active compound in EERL.MATERIALS/METHODSEthanol and aqueous extracts of roasted and un-roasted licorice were prepared. The active fraction was separated from the methylene chloride (MC)-soluble fraction of EERL and the structure of the purified compound was determined by nuclear magnetic resonance spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage skin carcinogenesis model.RESULTSEERL was determined to be more potent and efficacious than the ethanol extract of un-roasted licorice in inhibiting the growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer cells. The aqueous extracts of un-roasted and roasted licorice showed minimal effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231 breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction and identified as the active compound of EERL. Both EERL and licochalcone A induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin papilloma formation in mice.CONCLUSIONSNon-polar compounds in EERL exert potent anti-carcinogenic effects, and that roasted rather than un-roasted licorice should be favored as a cancer preventive agent, whether being used as an additive to food or medicine preparations.

THE INHIBITORY EFFECT OF SHAKUYAKUKANZOTO ON K+ CURRENT IN H9c2 CELLS

Shakuyakukanzoto (shao-yao-gan-cao-tang) is a commonly used Chinese traditional herbal medicine for the treatment of acute pain with muscle cramp. However, its mechanism of action is unclear. We previously reported that a low concentration of Kanzo (licorice) and isoliquiritigenin, a component of licorice, inhibited the potassium (K(+)) current in H9c2 cells. Therefore, in the present study, we examined the effects of Shakuyakukanzoto, Shakuyaku or Kanzo on the K(+) current (IKur) in H9c2 cells. Shakuyakukanzoto inhibited IKur in a concentration-dependent manner. The half-maximal concentration of Shakuyakukanzoto was approximately 1.3 mg/mL and the Hill coefficient was 1.2. The order of potency of inhibiting IKur was Kanzo>Shakuyakukanzoto>Shakuyaku. Glycyrrhizin, a major component of licorice, had no inhibitory effect on IKur. A small interfering RNA experiment indicated that IKur was most likely to be Kv2.1 in H9c2 cells. Our results suggest that Shakuyakukanzoto may normalize intracellular and extracellular K(+) balance by inhibiting IKur and reducing K(+) efflux, while the Na(+)-K(+) pump promotes K(+) influx into myofibers. Consequently, excess K(+) may be reduced from external space of myofibers. This may be a part of the Shakuyakukanzoto mechanism for improving muscle pain.

Hypertension Unusual Cause

We expose a case of a woman with hypertension and hypokalemia. The differential diagnosis should include primary hyperaldosteronism, diuretics or lazantes intake, secondary hyperaldosteronism. In this patient, additional tests performed show no cause of hormonal disruption and the whole picture is due to a high intake of licorice. Glycyrrhetinic acid, the active component of licorice, inhibits renal IIbeta-hydroxisteroid dehydrogenase. This allows cortisol to stimulate mineralocorticoid receptors. Licorice ingestion should be considered in the differential diagnosis of hypertension with hypokalemia.

Glycyrrhetinic Acid Reverses the Lipopolysaccharide-Induced Hypocontractility to Noradrenaline in Rat Aorta: Implications to Septic Shock

Septic shock and associated vascular hyporeactivity to vasoconstrictor agonists remain a major problem of critical care medicine. Here we report that glycyrrhetinic acid (GA), the active component of licorice, effectively restores vascular contractility in the model of lipopolysaccharide (LPS)-treated rat aorta. GA was as effective as the NO synthase inhibitor N(G)-nitroarginine methylester. GA did not affect the vascular NO levels (measured by EPR spin trapping) and relaxations to L-arginine in LPS-treated rings as well as relaxation to S-nitroso-N-acetylpenicillamine in control rings. Thus, GA may represent an interesting alternative to NO synthase inhibitors in sepsis-associated vascular dysfunction.

Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling

Licorice has been shown to affect the activities of several cytochrome P450 enzymes. This study aims to identify the key constituents in licorice which may affect these activities. Bioactivity assay was combined with metabolic profiling to identify these compounds in several complex licorice extracts. Firstly, the inhibition potencies of 40 pure licorice compounds were tested using an liquid chromatography/tandem mass spectrometry cocktail method. Significant inhibitors of human P450 isozymes 1A2, 2C9, 2C19, 2D6, and 3A4 were then selected for examination of their structural features by molecular docking to determine their molecular interaction with several P450 isozymes. Based on the present in vitro inhibition findings, along with our previous in vivo metabolic studies and the prevalence of individual compounds in licorice extract, we identified several licorice constituents, viz., liquiritigenin, isoliquiritigenin, together with seven isoprenylated flavonoids and arylcoumarins, which could be key components responsible for the herb-drug interaction between cytochrome P450 and licorice. In addition, hydrophilic flavonoid glycosides and saponins may be converted into these P450 inhibitors in vivo. These studies represent a comprehensive examination of the potential effects of licorice components on the metabolic activities of P450 enzymes.

Correlation analysis between the rate of respiration in the root and the active components in licorice (Glycyrrhiza uralensis)

The aim of this study was to investigate the correlation between root respiration and the percentage of active components in licorice (Glycyrrhiza uralensis Fisch.), in order to provide a foundation for the regulation and modulation of the quality of G. uralensis. Respiration efflux of annual and biennial G. uralensis was determined using a Li-7000 CO2/H2O analyzer. The root systems were scanned at a resolution of 3,000 dpi using an Epson Expression 10000XL scanner. Root growth was determined by analyzing the scanned images using WinRHIZO version Pro2007d software and the rate of respiration in the root was subsequently calculated. In addition, the percentages of the five major active components in licorice, glycyrrhizic acid, glycyrrhizin, isoliquiritin, liquiritigenin and isoliquiritigenin, were detected using high-performance liquid chromatography (HPLC). The correlation between the root respiration and the percentage of the active components was investigated. Significant seasonal changes were observed in the rates of respiration of first and zero-class roots. In annual and biennial G. uralensis, the maximum and minimum values for rate of respiration were present in July (P<0.05) and November (P<0.05), respectively. The correlation coefficients between the five major active components and the rate of respiration were −0.304 (glycyrrhizin), −0.129 (liquiritigenin), −0.441 (glycyrrhizic acid; P<0.05), −0.471 (isoliquiritin; P<0.05) and 0.148 (isoliquiritigenin). The percentages of glycyrrhizic acid and isoliquiritin were significantly negatively correlated with the rate of respiration in annual and biennial G. uralensis. Understanding the correlation between the root rate of respiration and the active components in G. uralensis may be beneficial to ensuring the quality of cultivated G. uralensis.

Inhibitory Effect of a Combined Treatment of Glycyrrhizin and Caffeine on Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate in Two-Stage Carcinogenesis in Mouse Skin

Cancer prevention is an important problem in the field of public health. Glycyrrhizin, a natural sweetening agent, is one of the components of licorice and caffeine in coffee and tea. Glycyrrhizin and caffeine were found to inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in two-stage carcinogenesis in mouse skin. Furthermore, the combined treatment of glycyrrhizin and caffeine is more effective than their single treatment on tumor promotion by TPA in mice following initiation with 7,12-dimethylbenz[a]anthracene.

Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-κB pathway activation in human umbilical vein endothelial cells

Ethnopharmacological relevanceLicorice (Glycyrrhiza uralensis roots) is used as a traditional medicine for the treatment of diabetes mellitus and its vascular complications. Glycyrrhizic acid (GA, also known as Glycyrrhizin), a triterpenoid saponin glycoside, is considered to be a bioactive component in Licorice and is beneficial to diabetic vascular complications. Aim of studyThe present study was conducted to evaluate the potential protective activities on AGEs-induced endothelial dysfunction, including anti-apoptosis, antioxidant stress and anti-proinflammatory responses, and explore the underlying mechanism. Materials and methodsHuman umbilical vein endothelial cells (HUVECs) were incubated and pre-treated with GA (10−9–10−6M) or RAGE-Ab (5μg/ml) in the presence or absence of 200μg/ml AGEs. AO/EB fluorescence staining assay was performed to evaluate anti-apoptosis activity. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in cell supernatant were detected by kits while the intracellular reactive oxygen species (ROS) generation was determined by 2,7-dichlorodihydrofluorescin diacetate (DCFH-DA) kit. Immunocytochemistry analysis was designed to determine transforming growth factor beta1(TGF-β1) protein expression while immunofluorescence analysis for RAGE and NF-kB. The protein expressions of TGF-β1, RAGE and NF-kB were analyzed by Western blot analysis. ResultsPretreatment with GA at a concentration of 10−8–10−6M significantly reduced the AGEs-induced apoptosis in HUVECs. GA significantly increased antioxidant enzyme SOD activity and decreased peroxide degradation product MDA level in a dose-dependent manner. Furthermore, GA also remarkably inhibited the overgeneration of AGEs-induced ROS. Both immunocytochemistry analysis and western blot analysis showed that GA significantly decreased the protein expression of poinflammatory cytokine TGF-β1 in a similar manner which RAGE-Ab did. Additionally, AGEs-induced RAGE and NF-kB protein expressions were down-regulated significantly by the pretreatment with GA or RAGE-Ab. ConclusionThese findings provide evidences that GA possesses protective activity on AGEs-induced endothelial dysfunction, including anti-apoptosis, anti-inflammation and antioxidant stress, via inhibiting RAGE/NF-kB pathway. GA might be an alternative for the prevention and treatment of diabetic vascular complications in an appropriate dosage.

Liquiritigenin prevents Staphylococcus aureus-mediated lung cell injury via inhibiting the production of α-hemolysin

Staphylococcus aureus is a significant Gram-positive bacterium that is associated with a broad spectrum of diseases ranging from minor skin infections to lethal pneumonia, endocarditis, and toxinoses. α-Hemolysin is one of the most important exotoxins that contribute to the pathogenesis of S. aureus infections. Liquiritigenin is one of the most significant active components in licorice. In this study, hemolysis, western blot, and real-time reverse transcription-PCR assays were performed to investigate the impact of liquiritigenin on the production of S. aureus α-hemolysin. The results showed that low concentrations of liquiritigenin remarkably decreased S. aureus α-hemolysin production in a dose-dependent manner. Using live/dead cell staining and lactate dehydrogenase assays, we found that liquiritigenin could protect human lung cells (A549) from α-hemolysin-mediated injury. The data indicated that this compound could potentially be useful in developing drugs aiming at staphylococcal α-hemolysin.

Dehydroglyasperin C, a component of liquorice, attenuates proliferation and migration induced by platelet-derived growth factor in human arterial smooth muscle cells

Liquorice is one of the botanicals used frequently as a traditional medicine in the West and in the East. Platelet-derived growth factor (PDGF)-BB is involved in the development of CVD by inducing abnormal proliferation and migration of vascular smooth muscle cells. In our preliminary study, dehydroglyasperin C (DGC), an active compound of liquorice, showed strong antioxidant activity. Since phytochemicals with antioxidant activities showed beneficial effects on chronic inflammatory diseases, the present study aimed to investigate the effects of DGC on PDGF-induced proliferation and migration of human aortic smooth muscle cells (HASMC). Treatment of HASMC with DGC for 24 h significantly decreased PDGF-induced cell number and DNA synthesis in a dose-dependent manner without any cytotoxicity, as demonstrated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide test and thymidine incorporation. Upon cell cycle analysis, DGC blocked the PDGF-induced progression through the G0/G1 to S phase of the cell cycle, and down-regulated the expression of cyclin-dependent kinase (CDK); 2, cyclin E, CDK4 and cyclin D1. Furthermore, DGC significantly attenuated PDGF-stimulated phosphorylation of PDGF receptor-b, phospholipase C-g1, AKT and extracellular-regulated kinase 1/2, and DGC inhibited cell migration and the dissociation of actin filaments by PDGF. In a rat vascular balloon injury model, DGC suppressed an excessive reduction in luminal diameters and neointimal formation compared with the control group. These results demonstrate the mechanistic basis for the prevention of CVD and the potential therapeutic properties of DGC.

English

Medicinal plants play a vital role in covering the basic health needs. They may offer a new source of antibacterial agents. The aim of this study&nbsp;was&nbsp;to screen&nbsp;in-vitro&nbsp;theantimicrobial activity of some Egyptian medicinal plants against clinical methicillin-resistant Staphylococcus aureus&nbsp;(MRSA)&nbsp;strains isolated from different hospitals in Egypt followed by studying the MIC and cytotoxicty of the most active one. Screening of antimicrobial activities of 70% ethanolic extracts obtained from 19 plants against 59 MRSA clinical isolates were tested by agar well diffusion method. Licorice showed the highest antimicrobial effect against all 59 MRSA isolates (leaves were more active than roots).Minimum inhibitory&nbsp;concentrations (MICs)&nbsp;of licorice leaves were 8&nbsp;&mu;g/ml, whereas that of Flucloxacillin range between 32&nbsp; to&nbsp;&lt;128 ug/ml&nbsp;when tested against five MRSA strains. Colorimetric cytotoxicity assay of licorice leaves extract was done on HEPG2 and HCTI16 cell lines and revealed that the IC50&nbsp;were 19.5 and 15 &micro;g/ml respectively. Separation of the components in licorice leaves using&nbsp;thin layer chromatography (TLC)&nbsp;results in two active fractions identified with the help of spectroscopic analysis as inflacoumarin A and Licochalcone A.&nbsp;Our results reveal&nbsp;that the Egyptian licorice leaves extract represent a new candidate for antimicrobial agent against MRSA more than that achieved by root. This is the first report which highlights the antimicrobial activity of licorice leaves. &nbsp; Key words:&nbsp;Plant extracts,&nbsp;licorice, MRSA,&nbsp;antimicrobial.

Licorice-related rhabdomyolysis: a big price for a sweet tooth

A 50-year-old lady on hydrochlorothiazide (HCTZ) presented to the hospital after 4 days of generalized muscle aches and dark urine. She admitted to consuming one and a half bags of black licorice bites containing 2% natural licorice during the past 3 weeks. Examination showed high blood pressure, while labs revealed elevated creatine kinase, hypokalemia, hypocalcemia and hypophosphatemia with low aldosterone and plasma renin levels and high intact PTH. The active component of licorice is glycyrrhizic acid, which inhibits an enzyme required to convert cortisol to a less active metabolite, cortisone. This causes excess cortisol, simulating syndrome of apparent mineralocorticoid excess (AME), thus resulting in hypertension, hypokalemia and metabolic alkalosis. In our patient, licorice induced hypokalemia resulted in rhabdomyolysis. The rhabdomyolysis along with the effect of licorice led to secondary hypocalcaemia, which in turn triggered secondary hyperparathyroidism. This might have had a phosphaturic effect that caused hypophosphatemia, further worsening rhabdomyolysis. This case illustrates the complex relationship of various electrolytes, which can lead to self perpetuation of the disease, hence demanding more vigilance.

Separation of Liquiritin by Two-Dimensional Liquid Chromatography

Two-dimensional liquid chromatography (2DLC) is an important technology for the separation and analysis of complex samples. Liquiritin, an important active component in licorice, was chosen as the target compound and it was separated by three kinds of off-line 2DLC, i.e. size exclusion chromatography × reversed phase chromatography, normal phase × reversed phase chromatography and reversed phase chromatography × reversed phase chromatography (SEC×RP, NP×RP and RP×RP). The chromatographic conditions were selected and the 2D systems were combined. The results show that it is feasible to separate Liquiritin from licorice extract using 2DLC. Among the 2D modes mentioned above, the highest purity of Liquiritin was obtained in the RP×RP mode, and the concentration of Liquiritin was increased most significantly in the NP×RP mode.