Food Enrichment with Glycyrrhiza glabra Extract Suppresses ACE2 mRNA and Protein Expression in Rats-Possible Implications for COVID-19.

Angiotensin converting enzyme 2 (ACE2) is a key entry point of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus known to induce Coronavirus disease 2019 (COVID-19). We have recently outlined a concept to reduce ACE2 expression by the administration of glycyrrhizin, a component of Glycyrrhiza glabra extract, via its inhibitory activity on 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2) and resulting activation of mineralocorticoid receptor (MR). We hypothesized that in organs such as the ileum, which co-express 11betaHSD2, MR and ACE2, the expression of ACE2 would be suppressed. We studied organ tissues from an experiment originally designed to address the effects of Glycyrrhiza glabra extract on stress response. Male Sprague Dawley rats were left undisturbed or exposed to chronic mild stress for five weeks. For the last two weeks, animals continued with a placebo diet or received a diet containing extract of Glycyrrhiza glabra root at a dose of 150 mg/kg of body weight/day. Quantitative PCR measurements showed a significant decrease in gene expression of ACE2 in the small intestine of rats fed with diet containing Glycyrrhiza glabra extract. This effect was independent of the stress condition and failed to be observed in non-target tissues, namely the heart and the brain cortex. In the small intestine we also confirmed the reduction of ACE2 at the protein level. Present findings provide evidence to support the hypothesis that Glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2. Whether this phenomenon, when confirmed in additional studies, is linked to the susceptibility of cells to the virus requires further studies.

Glycyrrhizin: An old weapon against a novel coronavirus.

Currently, over 100 countries are fighting against a common enemy, the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which causes COVID-19. This has created a demand for a substance whose effectiveness has already been demonstrated in a similar scenario. Glycyrrhizin (GZ) is a promising agent against SARS-CoV-2 as its antiviral activity against SARS-CoV has already been confirmed. It is worthwhile to extrapolate from its proven therapeutic effects as there is a high similarity in the structure and genome of SARS-CoV and SARS-CoV-2. There are many possible mechanisms through which GZ acts against viruses: increasing nitrous oxide production in macrophages, affecting transcription factors and cellular signalling pathways, directly altering the viral lipid-bilayer membrane, and binding to the ACE2 receptor. In this review, we discuss the possible use of GZ in the COVID-19 setting, where topical administration appears to be promising, with the nasal and oral cavity notably being the potent location in terms of viral load. The most recently published papers on the distribution of ACE2 in the human body and documented binding of GZ to this receptor, as well as its antiviral activity, suggest that GZ can be used as a therapeutic for COVID-19 and as a preventive agent against SARS-CoV-2.

Compound glycyrrhizin combined with antihistamines for chronic urticaria: A protocol for systematic review and meta analysis.

BACKGROUND: To investigate the efficacy and safety of compound glycyrrhizin (CG) combined with antihistamines in the treatment of chronic urticaria (CU). METHODS: We will use computers to search all databases including Medline, Embase, Pubmed, Web of Science and Cochrane Central Register of Controlled Trials and China's 4 databases: China National Knowledge Infrastructure Database, China Biomedical Literature Database, China Science Journal Database, and Wanfang Database. Find data from creation date to July 2020. In addition, we will manually search the list of medical journals as a supplement. The scope of the search included randomized controlled clinical studies related to CG combined with antihistamines for CU. The primary outcome is the disease activity control. Secondary outcomes include response rate, adverse events, and recurrence rates. The Cochrane RevMan V5.3 Deviation Assessment Tool will be used to assess bias assessment risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). The average difference, standard mean difference, and binary data will be used to represent continuous results. RESULTS: This study will comprehensively review the existing evidence on CG combined with antihistamines for CU. CONCLUSION: This systematic review will provide a basis for judging the effectiveness and safety of CG combined with antihistamines in the treatment of CU. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020156153.

Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism.

Context: Both nobiletin (NBL) and glycyrrhizin (GL) have anti-inflammatory and antitumor properties. These agents may be co-administered in the clinic. However, the drug-drug interaction between them is not clear.Objective: The drug-drug interaction between GL and NBL was investigated, to clarify the effect of GL on the pharmacokinetics of NBL, and its main mechanism.Materials and methods: The pharmacokinetic profiles of oral administration of NBL (50 mg/kg) in Sprague-Dawley rats of two groups with six each, with or without pre-treatment of GL (100 mg/kg/day for 7 days), were investigated. The effects of GL on the metabolic stability and transport of NBL were also investigated through the rat liver microsome and Caco-2 cell transwell models.Results: The results showed that GL significantly decreased the peak plasma concentration (from 1.74 ± 0.15 to 1.12 ± 0.10 µg/mL) and the t1/2 (7.44 ± 0.65 vs. 5.92 ± 0.68) of NBL, and the intrinsic clearance rate of NBL was increased by the pre-treatment with GL (39.49 ± 2.5 vs. 48.29 ± 3.4 µL/min/mg protein). The Caco-2 cell transwell experiments indicated that GL could increase the efflux ratio of NBL from 1.61 to 2.41.Discussion and conclusion: These results indicated that GL could change the pharmacokinetic profile of NBL, via increasing the metabolism and efflux of NBL in rats. It also suggested that the dose of NBL should be adjusted when co-administrated with GL in the clinic.

[Toxicity-reducing effect of compatibility of Tripterygium and licorice in animals: systematic review].

The aim of this paper was to systematically evaluate the toxicity-reducing effect of Tripterygium-licorice in animal experiments,and also to provide evidence for basic research on the toxicity reduction of Tripterygium wilfordii. The PubMed,EMbase,Web of Science,CBM,CNKI and Wan Fang Databases from their establishment to August 31 th,2018 were searched. Two independent reviewers screened the papers,extracted the data,assessed the risk of bias using SYRCLE assessment tool and conducted Meta-analysis with Rev Man 5. 3 software. A total of 10 papers involving 31 studies were finally included,15 studies of which were used for Meta-analysis. Four studies were included for chronic hepatotoxicity animal model. In experimental group( 34 animals),Tripterygium was administered at dose of 0. 09-0. 1 mg·kg-1·d-1,and glycyrrhizic acid was administered at dose of 90-100 mg·kg-1,both for 2 weeks; in control group( 34 animals),glycyrrhizic acid was replaced with equal volume of normal saline. Eleven studies were included for acute hepatotoxicity animal model. In experimental group( 66 animals),glycyrrhizic acid was administered at dose of 75-480 mg·kg-1 for 7 days,then glycyrrhizic acid was stopped,and Tripterygium began to be administered at dose of 0. 6-1. 0 mg·kg-1 per 24 h or 48 h for a total of 1-2 times; in control group( 66 animals),glycyrrhizic acid was replaced with equal volume of normal saline or corresponding solvent. The results of Meta-analysis showed that in both chronic hepatotoxicity animal model and acute hepatotoxicity animal model,the transaminase levels in the experimental group were lower than those in the control group( P < 0. 05). Subgroup analysis of acute hepatotoxicity animal model showed that the transaminase levels in the experimental group were lower than those in the control group for every subgroup except " glycyrrhizic acid 75 mg·kg-1" subgroup. However,in terms of the mean difference( MD) and confidence interval( CI),there was no significant difference in transaminase decline between each subgroup. Low dose of glycyrrhizic acid( 90-100 mg·kg-1) has a toxicity-reduction effect on chronic hepatotoxicity induced by tripterygium( 0. 09-0. 10 mg·kg-1). Middle and high doses of glycyrrhizic acid( 120-480 mg·kg-1) have a toxicity-reduction effect on acute hepatotoxicity induced by tripterygium( 0. 6-1. 0 mg·kg-1),but with no significant dose-effect relationship.

Low-dose methotrexate-induced vulvar edema: A case report.

RATIONALE: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate. PATIENT CONCERNS: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp. DIAGNOSES: The patient was diagnosed based on clinical findings for MTX toxic reactions. INTERVENTIONS: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed. OUTCOMES: The vulvar edema and oral cavity ulceration and scalp ulceration healed. LESSONS: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.

Therapeutic Effect of Glycyrrhizin Arginine Salt on Rat Cholestatic Cirrhosis and its Mechanism.

To investigate the therapeutic effect of glycyrrhizin arginine salt on rat cholestatic cirrhosis, we subjected male Sprague Dawley rats to common bile duct ligation for 14 days and treated them with distilled water (model group), arginine, or a low or high dose of glycyrrhizin arginine salt by gavage. A sham-operated group was used as a control group. Treatment with glycyrrhizin arginine salt substantially improved animal growth rates, reduced the ratio of liver weight to body weight and decreased total bilirubin, aspartate aminotransferase, 8-isoprostane and malondialdehyde compared with the values measured in the model group. The progress of liver fibrosis, as detected by hematoxylin and eosin and Masson's trichrome staining, was slower in the glycyrrhizin arginine salt groups than in the model group or the arginine group. Reductions of bile salt pool size, hepatic hydroxyproline content and fibrosis score were also seen in the glycyrrhizin arginine salt groups compared with the model group. Furthermore, glycyrrhizin arginine salt significantly reduced the expression of transforming growth factor [Formula: see text]1 (TGF-[Formula: see text]1), [Formula: see text]-smooth muscle actin, tumor necrosis factor-[Formula: see text] and matrix metalloproteinases 2 and 9. Glycyrrhizin arginine salt also inhibited the expression of [Formula: see text]-SMA and matrix metalloproteinases 2 and 9 in response to TGF-[Formula: see text]1 in LX-2 cells and primary rat hepatic stellate cells and mitigated the cytotoxicity induced by rat bile in HepG2 cells and primary rat hepatocytes.

The synergy of diammonium glycyrrhizinate remarkably reduces the toxicity of oxymatrine in ICR mice.

Most traditional Chinese medicine prescription dosages are imprecise. This study analyzes the toxicities and adverse effects of a combination the active ingredients of licorice and Kushen medicine: oxymatrine (OMT) and diammonium glycyrrhizinate (DG). The median lethal dose (LD50) and mortality were analyzed in single-dose OMT (or DG) intraperitoneally injected mice with or without combination DG (or OMT). Body weight changes as well as levels of serum sodium and potassium, alanine transaminase (ALT), aspartate transaminase (AST), creatinine, and urea were measured in mice treated with a daily dose of OMT and/or DG for 14days. This study showed that the LD50 of OMT for males and females were 347.44 and 429.15mg/kg, respectively. The LD50 of DG were 525.10 and 997.26mg/kg for males and females, respectively. DG significantly decreased the mice LD50-induced mortality of the OMT, however OMT did not succeed in reducing the LD50-induced mortality rate of DG. The combination of OMT and DG obviously attenuated the changes of the body weight, serum sodium, and potassium induced by DG or OMT alone. These results suggested that toxicity and adverse effects of the OMT was significantly attenuated by DG. The OMT neutralized the adverse effects of the DG, but not the toxicity.

Simultaneous Determination of Twenty-Five Compounds in Rat Plasma Using Ultra-High Performance Liquid Chromatography-Polarity Switching Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study.

An attempt was made to characterize the pharmacokinetic profiles of Qishen Keli (QSKL) that has been widely proved to be effective in clinical practice. A method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of 25 analytes in rat plasma was developed and validated. Satisfactory chromatographic separation was achieved on an ACQUITY UPLC HSS T3 column with gradient elution using mobile phase consisting of 0.02% aqueous formic acid (A) and acetonitrile fortified with 0.02% formic acid (B), and analyte detection was carried out using polarity-switching multiple reaction monitoring mode. Method validation assays in terms of selectivity, linearity, inter- and intra-day variations, matrix effect, and recovery demonstrated the newly developed method to be specific, sensitive, accurate, and precise. Following the oral administration of QSKL at a single dose, the qualified method was successfully applied for pharmacokinetic investigations in sham and model rats. Mild differences occurred for the pharmacokinetic patterns of most components between those two groups, whereas significant differences were observed for glycyrrhizic acid and glycyrrhetic acid. The obtained findings could provide meaningful information for the clarification of the effective material basis of QSKL.

Voluntary liquorice ingestion increases blood pressure via increased volume load, elevated peripheral arterial resistance, and decreased aortic compliance.

We investigated the haemodynamic effects of two-week liquorice exposure (glycyrrhizin dose 290-370 mg/day) in 22 healthy volunteers during orthostatic challenge. Haemodynamics were recorded during passive 10-minute head-up tilt using radial pulse wave analysis, whole-body impedance cardiography, and spectral analysis of heart rate variability. Thirty age-matched healthy subjects served as controls. Liquorice ingestion elevated radial systolic (p < 0.001) and diastolic (p = 0.018) blood pressure and systemic vascular resistance (p = 0.037). During orthostatic challenge, heart rate increased less after the liquorice versus control diet (p = 0.003) and low frequency power of heart rate variability decreased within the liquorice group (p = 0.034). Liquorice intake increased central pulse pressure (p < 0.001) and augmentation index (p = 0.002) supine and upright, but in the upright position the elevation of augmentation index was accentuated (p = 0.007). Liquorice diet also increased extracellular fluid volume (p = 0.024) and aortic to popliteal pulse wave velocity (p = 0.027), and aortic characteristic impedance in the upright position (p = 0.002). To conclude, in addition to increased extracellular fluid volume and large arterial stiffness, two weeks of liquorice ingestion elevated systemic vascular resistance and augmentation index. Measurements performed at rest may underestimate the haemodynamic effects of liquorice ingestion, as enhanced central wave reflection and reduced chronotropic response were especially observed in the upright position.

Comparison of glycyrrhizin content in 25 major kinds of Kampo extracts containing Glycyrrhizae Radix used clinically in Japan.

Glycyrrhizae Radix is the most frequently used crude drug in Japan and is prescribed in Kampo medicine for the treatment of a wide range of diseases. The major active ingredient of Glycyrrhizae Radix, glycyrrhizin (GL), has been shown to possess various pharmacological actions, but is also known to cause adverse effects such as pseudoaldosteronism. To avoid the adverse effects of GL, precautions have been indicated on the package inserts of Glycyrrhizae Radix-containing formulas depending on the amount of Glycyrrhizae Radix they contain. However, it remains unknown whether the extraction efficiency of GL from Glycyrrhizae Radix is constant throughout the different combinations of crude drugs in Glycyrrhizae Radix-containing formulas. To confirm the basis of the safety regulation, in this study we comprehensively determined the GL content of 25 major kinds of Kampo extracts compounding Glycyrrhizae Radix. We found that the GL content per daily dosage in all Kampo extracts are generally proportional to the compounding amount of Glycyrrhizae Radix, except in the case of shoseiryuto (Sho-seiryu-To). We also found that Schisandrae Fructus in Sho-seiryu-To decoction caused a lowered pH condition and drastically decreased the extraction efficacy of GL from Glycyrrhizae Radix. Moreover, we were able to confirm that the extraction efficiency of GL from Glycyrrhizae Radix is dependent on the pH value of the extraction solvent. The extraction efficiency of GL in the 25 kinds of Kampo extracts was not constant but it correlates significantly with the pH value of the decoction. Furthermore, the GL contents are well correlated with pseudoaldosteronism incidence data obtained from the Japanese Adverse Drug Event Report (JADER) database on the 25 kinds of Kampo extracts. This suggests that the GL content is a better index to consider to avoid the adverse effects of Glycyrrhizae Radix-containing Kampo formulas.

Monoammonium glycyrrhizinate protects rifampicin- and isoniazid-induced hepatotoxicity via regulating the expression of transporter Mrp2, Ntcp, and Oatp1a4 in liver.

CONTEXT: Drug-induced liver injury (DILI) is associated with altering expression of hepatobiliary membrane transporters. Monoammonium glycyrrhizin (MAG) is commonly used for hepatic protection and may have a correlation with the inhibition effect of multidrug resistance-associated protein 2 (Mrp2). OBJECTIVE: This study evaluates the dynamic protective effect of MAG on rifampicin (RIF)- and isoniazid (INH)-induced hepatotoxicity in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into four groups of 15 rats. Liver injury was induced by co-treatment with RIF (60 mg/kg) and INH (60 mg/kg) by gavage administration; MAG was orally pretreated at the doses of 45 or 90 mg/kg 3 h before RIF and INH. Rats in each group were sacrificed at 7, 14, and 21 d time points after drug administration. RESULTS: Liver function, histopathological analysis, and oxidative stress factors were significantly altered in each group. The expression of Mrp2 was significantly increased 230, 760, and 990% at 7, 14, and 21 time points, respectively, in RIF- and INH-treated rats. Compared with the RIF and INH groups, Mrp2 was reduced and Ntcp was significantly elevated by 180, 140, and 160% in the MAG high-dose group at the three time points, respectively. The immunoreaction intensity of Oatp1a4 was increased 170, 190, and 370% in the MAG low-dose group and 160, 290, and 420% in the MAG high-dose group at the three time points, respectively, compared with the RIF and INH groups. DISCUSSION AND CONCLUSION: These results indicated that MAG has a protective effects against RIF- and INH-induced hepatotoxicity. The underlying mechanism may have correlation with its effect on regulating the expression of hepatobiliary membrane transporters.

Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics of Ribavirin and Its Major Metabolite in Rats.

The herb-derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (p.o.) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, p.o.), glycyrrhizin (15 mg/kg, intraperitoneal [i.p.]), or oxymatrine (60 mg/kg, p.o.). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration-time curve (AUC0-t ) and the peak plasma concentration (Cmax ) of ribavirin and ribavirin base by 31.2-44.5% and 48.9-50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0-t of both ribavirin and its metabolite by 35.3-37.6% and 38.6-39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax . Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine.

Ocoxin® oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice.

Liver metastatic disease is the main cause of death in colorectal cancer (CRC) patients. During metastatic spread of the disease an imbalance in the oxidative stress and inflammation plays a crucial role in tumor progression. In order to improve the efficacy of current therapies, new complementary therapeutic approaches are being analyzed including biologically active compounds with low side effects. The anti-inflammatory and anti-oxidant properties of Ocoxin® oral solution (OOS) prompt us to analyze its effect on the metastatic development of CRC to the liver. First, in vitro effect of OOS in tumor cell viability and migration was analyzed. Second, in vivo effect of different dosage patterns and concentrations in the development of hepatic metastasis was analyzed by intra-splenic inoculation of C26 colon carcinoma cells in Balb/c mice. Third, the expression of alpha smooth muscle actin, caspase-3 and Ki-67 expression was quantified by immunohistochemistry, then gene expression levels of inflammatory factors were measured by quantitative RT-PCR. According to our results, OOS reduced tumor cell viability and migration in vitro. Moreover, in vivo daily administration of OOS from the 7th day after tumor cell inoculation decreased the total area and size of metastatic foci in the liver. Furthermore, cell proliferation and fibroblast recruitment was decreased in tumor foci while a higher number of apoptotic cells were observed. Finally, RNA levels for the inflammatory mediators COX-2, IFNγ, IL1ß, IL6 and TNFα were reduced in total liver. In conclusion, OOS reduced the metastatic development of colorectal cancer to the liver by increasing apoptosis, and decreasing tumor cell proliferation and fibroblast recruitment in the tumor foci, as well as the expression of inflammatory mediators in total liver. These results point out OOS as a potential supplement to be applied as complementary therapy for the treatment of liver metastasis from colorectal cancer.

The influence of compatibility of processed radix Aconiti Kusnezoffii on the pharmacokinetic of four components in Glycyrrhiza uralensis Fisch.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza uralensis Fisch. and processed radix Aconiti kusnezoffii are the main components in many Chinese traditional patent medicines with the ratio of 1:1, which are used for treatment of rheumatoid arthritis, heart failure and so on. Glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin are the essential bioactive triterpenes and flavones in the extract of G. uralensis, which were analysis by a simple but accurate method. MATERIALS AND METHODS: In the present study, a specific HPLC method was developed and validated for simultaneous determination of pharmacokinetic parameters of glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin in G. uralensis after oral administration of single herb extract and a combination of two herbs extracts respectively. RESULTS: The calibration curves of the four components had good linearity higher than 0.9991 in the measured range. The intra-day and inter-day precisions (RSD) at different levels were both within 9.73%, and the accuracies (RE) were in the range of -7.9-8.0%. Compared with pharmacokinetic parameters of G. uralensis administered orally, values of AUC and Cmax of liquiritigenin and isoliquiritigenin decreased significantly (p<0.05), plasma concentrations of glycyrrhizic acid rose slightly and bimodal phenomenon of concentration-time of isoliquiritigenin and glycyrrhetinic acid disappeared after combined administration. DISCUSSION AND CONCLUSIONS: Some components in the extract of processed radix A. kusnezoffii showed different effects on the pharmacokinetics of the four ingredients in G. uralensis.

Quantification of glycyrrhizin in anti-stress herbal formulations by validate HPTLC method: a rational paradigm towards quality control of herbals.

In the present study an analytical method of high-performance thin-layer chromatography (HPTLC) has been developed for quantification of glycyrrhizin for marketed antistressliquorice root capsules (LRC) and herbal tea (HT). Chromatography was performed by using mobile phase ethyl acetate (EA): glacial acetic acid (GAA): Methanol (MeOH): water (H(2)O) in proportion of 6:2:2:1, v/v/v/v. The developed plate was scanned and quantified densitometrically at absorption maxima 254nm. The method was validated for various analytical parameters viz. precision, accuracy, recovery, robustness, specificity, detection and quantification limits. The developed system was found to give compact spot for glycyrrhizin (R(f)= 0.33± 0.001). The linearity relationship was described by the equation Y=6.841X+ 70.428. The limit of detection (34 ng band(-1)), limit of quantification (101 ng band(-1)), recovery (99.4-99.8%), and precision (<1.84% and <1.62%; intraday and interday, respectively) were found satisfactory for glycyrrhizin. Linearity range for glycyrrhizin was 100-600ng (r(2)=0.998). The amount of glycyrrhizin was estimated by comparing the peak area of standard and the same was present in crude extract. The content of glycyrrhizin was estimated as 11.4% and 4.7% w/w in sample LRC and HT, respectively. The proposed method will be useful to quantify the therapeutic dose of glycyrrhizin in herbal formulations as well as in bulk drug.

Effect of the liquorice root derivatives on salt and water balance in a teleost fish, rainbow trout (Oncorhynchus mykiss).

The effect of liquorice root derivatives (LRDs) glycyrrhizic acid (GL) and glycyrrhetinic acid (18ßGA) on salt and water balance and end points of gill ion transport in a freshwater teleost, (rainbow trout) was examined after feeding fish diets containing GL or 18ßGA (0, 5, 50 or 500 µg/g diet) for a two week period. Serum cortisol levels and gill 11ß-hydroxysteroid dehydrogenase type 2 mRNA abundance decreased in fish fed GL but increased (at select doses) in fish fed 18ßGA. At higher doses of GL, gill Na(+)-K(+)-ATPase and H(+)-ATPase activity increased, while cystic fibrosis transmembrane conductance regulator type II mRNA abundance significantly decreased at the lowest dose of GL. End points of gill transcellular ion transport were not significantly altered in fish fed 18ßGA, except for a reduction in Na(+)-K(+)-ATPase activity at a 50 µg/g dose. In contrast, high doses of GL and 18ßGA increased gill transcript abundance of the tight junction protein claudin-31 (cldn-31). Other end points of gill paracellular transport differed in fishes fed LRDs. Tricellulin mRNA abundance was increased by high dose GL and decreased by high dose 18ßGA, and cldn-23a and cldn-27b mRNA abundance significantly decreased in response to GL irrespective of dose. Despite the above observations, systemic end points of salt and water balance (i.e. serum [Na(+)] and [Cl(-)] as well as muscle moisture) were unaffected by LRDs. Therefore data suggest that LRDs can alter end points of ion transport in fishes but that overall salt and water balance need not be perturbed.

[Studies on effects of Achyranthes bidentata on tongsaimai pellets main active ingredients chlorogenic acid, isoliquiritin, harpagoside and glycyrrhizin in vivo pharmacokinetics].

To study on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients chlorogenic acid, isoliquiritin, harpagoside and glycyrrhizin in rats in vivo pharmacokinetic behaviors, a method for the simultaneous determination of chlorogenic acid, isoliquiritin, harpagoside and liquiritigenin in rat plasma was established by UPLC-MS/MS. The analysis was performed on a waters Acquity BEH C18 column (2.1 mm x 100 mm, 1.7 microm) with the mixture of acetonitrile and 0.1% formic acid/water as mobile phase, and the gradient elution at a flow rate of 0.3 mL x min(-1). The analytes were detected by tandem mass spectrometry with the electrospray ionization (ESI) source and in the multiple reaction monitoring (MRM) mode. It turned out that the analytes of Tongsaimai pellets groups C(max) and AUC(Q-infinity) values were higher than that with A. bidentata group, and the C(max) values of chlorogenic acid had significantly difference (P < 0.05), the AUC(0-infinity) values of chlorogenic acid and glycyrrhizin had significantly difference (P < 0.05); The T(max) and CL values of two groups had no significantly difference. Results showed that the established method was specific, rapid, accurate and sensitive for the studies of Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic, and A. bidentata have varying degrees of effects on Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic behaviors.

Update on the treatment of genital warts.

This review summarizes new treatments from the last seven years employed for the treatment of genital warts caused by human papillomavirus (HPV). Imquimod 3.75% is a new agent with fewer side effects and perhaps a better dosing schedule than imquimod 5%, but is not more effective. Sinecatechins/Polyphenon E 15%, a novel extract from green tea can be effective against genital warts but requires three times a day dosing and is not more effective than existing treatments; the treatment course is 12-16 weeks. Photodynamic therapy combined with other destructive modalities might increase the cure rate for genital warts. The quadrivalent vaccine against HPV 6, 11, 16, 18 is decreasing the incidence of warts in the western world but the evidence does not support vaccination as a treatment for those already infected by HPV. Hyperthermia and immunomodulators might be positive additions to the armamentarium of clinicians. In sum, there are new tools that physicians can use but none is really a great advance over what was available a decade ago.

[Optimization of a compound prescription for treating liver fibrosis].

OBJECTIVE: To optimize a compound prescription for treatment of liver fibrosis with an improved therapeutic effect and low toxicity. METHODS: In rat models of liver fibrosis induced by thioacetamide (TAA), the optimized prescription was screened based on a uniform design with 2-factor 5-level table using Uniform Design 3.0 software and tested using liver content of Hyp as the screening index. To verify the efficacy of the optimized prescription, the rat models of liver fibrosis were randomized into normal control group, model group, colchicine group and optimized prescription group, and the changes of hepatic Hyp content, serum HA, ALT, AST, and ALB levels, and the pathology liver fibrosis were observed after corresponding treatments. RESULTS: The optimized prescription, which contained 70 mg/kg glycyrrhizin and 70 mg/kg matrine, showed a significant therapeutic effect against liver fibrosis in rats (Plt;0.05), and the effect was equivalent to that of colchicine (P>0.05). CONCLUSION: Uniform design is a valuable method in prescription optimization. The optimized compound prescription of matrine and glycyrrhizin has a significant effect in inhibiting liver fibrosis.