Significance of fermented rice beverage on management of antibiotic associated diarrhea (AAD) on Wistar rats

Antibiotic associated diarrhoea (AAD) is caused mostly by disruption of the physiological gut microflora. One potential strategy to prevent this is the concurrent use of probiotic bacteria or yeast. Tribal populations of West Garo Hill region of Meghalaya use locally available unique microflora to prepare fermented food products whichserve as a potential source of novel probiotic organisms and bioactive compounds. In this context, here, we have evaluated the potentiality of laboratory made functional fermented rice beverage in mitigating AAD on animal models viz. Wistar rats. The animal models were administered with fermented rice beverage (test group A1), combination of indigenous Lactobacillus isolates (test group A2), a yeast isolate (test group A3), loperamide (test group STD), normal control (test group NC) and disease control (test group DC). Furthermore, various diarrhea assessment parameters were checked from each group followed by analysis of fecal microbiome, haematological parameters, histopathology of colon, liver and cecal short chain fatty acids (SCFAs) determination. NC and A1 was least affected by AAD induction with a faecal consistency score of 1 on the final day of the study. After day 10, a significant reduction (P <0.05) in the faecal water content was observed in A1, A2 and STD till day 15. Compared to the NC, a slight decrease in body weight was found in the rest of five test groups at day 5, 10 and 15. Except NC, the remaining five test groups showed a significant decrease of lactobacilli and yeast counts in faecal microbiota at 5th day. An increase in the enterococci and coliform counts indicated severe diarrheal condition but A1 reported with significant increase (P <0.05) in the population of Lactobacillus at day 15. An increase in red blood corpuscles, haemoglobin, packed cell volume, mean cell haemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration was observed. During the histopathology analysis of colon and liver, normal layers of mucosa, submucosa, muscularis and serous with absence of any abnormal changes or lesions was seen in A1. The cecal concentrations of lactate, acetate and propionate were significantly higher in A1 as compared to the other test groups. Therefore, fermented rice beverage possesses potential to be used in inhibition of antibiotic associated diarrhea with further clinical investigations.

Intoxication à la réglisse révélée par une hypokaliémie sévère associée à une HTA Labile: à propos d'une observation et revue de la littérature / Licorice intoxication revealed by severe hypokalemia and labile hypertension: a case report with review of the literature

Cette observation illustre un tableau de pseudo-hyperaldostéronisme primaire par intoxication à la réglisse révélé par une hypokaliémie sévère chez un monsieur de 56 ans dans un contexte d'HTA de découverte récente. L'interrogatoire a retrouvé une notion de consommation régulière quotidienne de pastis sans alcool d'environ un litre et le bilan endocrinien a trouvé une activité rénine plasmatique effondrée et une hypoaldostéronémie. L'hypokaliémie et l'HTA ont régressé au bout de trois mois avec l'arrêt de la consommation du pastis et à distance de tout traitement antihypertenseur. Les abus de la réglisse sont rarement mentionnés spontanément par les patients ou sont ignorés d'eux, d'où l'intérêt d'une anamnèse minutieuse

This patient illustrates a case of primary pseudo-hyperaldosteronism due to licorice intoxication revealed by severe hypokalemia in a 56-year-old man with newly discovered hypertension. Past medical history revealed a notion of regular consumption of pastis without alcohol (about one liter per day) and hormonal assessment showed a collapsed plasma renin activity and hypoaldosteronemia. Hypokalaemia and hypertension resolved three months after cessation of pastis consumption, without any antihypertensive treatment. The abuse of licorice is rarely mentioned spontaneously by patients or is ignored by them, hence the interest of a careful medical history.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Regulatory Effect of Polygala tenuifolia and Licorice-simmered P. tenuifolia on Learning and Memory， HPA Axis Function and Neurotransmitters in Rats with Heart-kidney Imbalance Insomnia / 中国实验方剂学杂志

Objective:To compare the regulatory effects of <italic>Polygala tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> on learning and memory， hypothalamus-pituitary-adrenal axis （HPA axis） function and neurotransmitters in rats with heart-kidney imbalance insomnia. Method:The rat model of insomnia induced by multi-factor stimulation was established. After the model being made， the administration groups were given the extracts of <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> by gavage （dose of 8 g·kg^-1·d^-1）， while the normal group and model group were given the same volume of normal saline for 7 days. Morris water maze was used to detect the changes of learning and memory ability of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH） and cortisol （CORT） in serum of rats from each group. The contents of 5-hydroxytryptamine （5-HT）， dopamine （DA）， <italic>γ</italic>-aminobutyric acid （GABA） and glutamic acid （Glu） in the hypothalamus of rats were determined simultaneously by ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS）. Result:Compared with the normal group， the spatial learning and memory ability of rats in the model group<italic> </italic>was decreased， the times and time of staying in target quadrant were significantly reduced （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the levels of CORT， CRH and ACTH in serum were significantly increased （<italic>P<</italic>0.01）， the contents of GABA， DA， 5-HT in hypothalamus tissue were significantly decreased （<italic>P<</italic>0.01）， and the content of Glu was significantly increased （<italic>P<</italic>0.01）. Compared with the model group， the spatial learning and memory ability of rats in the <italic>P. tenuifolia</italic> group and licorice-simmered <italic>P. tenuifolia </italic>group<italic> </italic>were increased， the times and time of staying in the target quadrant were significantly increased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the levels of CORT， CRH and ACTH in serum were significantly decreased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the contents of GABA， DA and 5-HT in hypothalamus tissue were significantly increased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and the content of Glu was significantly decreased （<italic>P<</italic>0.05）. The recovery degree of each index in the licorice-simmered <italic>P. tenuifolia</italic> group was better than that in the <italic>P. tenuifolia</italic> group. Conclusion:Both <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> can improve the learning and memory ability， improve the function of HPA axis， regulate the level of central neurotransmitters， and have the effect of calming the mind and improving the intelligence of rats with heart-kidney imbalance insomnia. The effect of licorice-simmered <italic>P. tenuifolia</italic> is better than that of <italic>P. tenuifolia.</italic>

Ferulate 5-hydroxylase gene (F5H) regulation of glycyrrhizic acid biosynthesis determined by gene overexpression and knockout / 药学学报

Ferulate 5-hydroxylase (F5H) is a key enzyme involved in the phenylpropane metabolism pathway. Based on our previous transcriptome sequencing study, F5H played a negative regulatory role in glycyrrhizic acid (GA) biosynthesis. Therefore, in this study we cloned the F5H gene and investigated its regulatory effect on GA accumulation through gene overexpression and knockout. F5H was cloned from Glycyrrhiza glabra L. (GenBank Accession No. MK882511). A plant binary expression vector pCA-F5H was constructed by inserting F5H into pCAMBIA1305.1 at Spe I and Bgl II sites. The sgRNA sequences were designed based on the first exon of F5H. The CRISPR/Cas9 gene editing vector pHSE-F5H was constructed by inserting F5H sgRNA into pHSE401 at two Bsa Ⅰ sites. PCA-F5H and pHSE-F5H were transfected into Agrobacterium tumefaciens ATCC15834, which was used to induce hairy root overexpressing or knocking out F5H with licorice hypocotyl as explants. At the same time, wild type and negative control hairy roots were also generated. UPLC was used to assay the GA content in different hairy root lines, and results showed that the GA content in hairy root lines knocking out F5H was significantly higher, whereas in hairy root lines overexpressing F5H GA content was lower than that in the wild-type and negative control. In this work, through a reverse genetics strategy, the negative regulatory effect of F5H on GA biosynthesis was confirmed through gene overexpression and knockout. This work will lay a foundation for further elucidation of the molecular regulatory network of GA biosynthesis.

Analysis on international trade competitiveness of licorice extract / 中草药

Licorice extract has the efficacy of anti-inflammatory, anti-viral, anti-oxidation and anti-aging. It is widely used in the pharmaceutical, food and cosmetic industries. This paper analyzes the status of licorice extract’s global trade and its international competitiveness. The main purpose is to clarify the status of our country’s licorice extract in the international market and provide reference for improving the international competitive advantage of licorice extract of China. Germany, the United States, Netherlands, France, Japan, Israel and China were the main import and export countries for licorice extract. The international market share (IMS), trade competitiveness index (TC Index), revealed comparative advantage index (RCA Index) and competitive advantage index (CA Index) were used to compare the licorice extract’s international competitiveness of these countries. It showed that Israel has the strongest international competitiveness and followed by France. The United States has the maximum IMS, but its competitiveness was on sagging tendency. Germany and the Netherlands are the major importers of licorice extract. Although they are lack of international competitiveness, its international competitiveness is on the rise, especially in Germany. China’s licorice extract has a high IMS, but its international trade competitiveness is weak, far lower than the United States and France. Japan was the basic export country of China’s licorice extract. The TC index and CA index of licorice extract in Japan are less than zero, which means Japan’s licorice extract is not competitive.

Analysis of volatile organic compounds (VOCs) fingerprint of raw and honey-fried licorice based on headspace-gas-chromatography ion-mobility spectrometry (HS-GC-IMS) / 中国中药杂志

Licorice is one of the most commonly used traditional Chinese medicine. In clinic, raw licorice and honey-fried licorice are used in medicines, with the main effects in clearing away heat and detoxifying, moistening lungs and removing phlegm. Honey-fried licorice has effects in nourishing the spleen and stomach and replenishing Qi and pulse. Because traditional Chinese medicine exerts the effects through multiple components and multiple targets, the index components used in the quality evaluation of licorice are often difficult to reflect their real quality. In addition, most of studies for the quality standards have shown that honey-fried licorice are the same as licorice, with a lack of quality evaluation standards that can demonstrate their processing characteristics. The quality of medicine is directly related to its clinical efficacy, so it is necessary to establish a more effective quality control method. Licorice has a beany smell, which is one of the main quality identification characteristics. In this study, by taking advantage of the odor characteristics, a headspace-gas chromatography-ion migration mass spectrometry technology was used to establish a quality evaluation method. A total of 76 volatile components were identified. Through the dynamic principal component analysis, 7 kinds of volatile substances in raw licorice and 13 kinds of volatile substances in honey-fried licorice were statistically obtained, and could be taken as index components for the quality evaluation of raw and honey-fried licorice, respectively. This study could help realize the combination and unification of modern detection and traditional quality evaluation methods, and make a more realistic evaluation for the quality of licorice.

Fingerprint analysis and Q-marker prediction of processed liquorice products / 中国中药杂志

Licorice has long been regarded as one of the most popular herbs, with a very wide clinical application range. Whether being used alone or as an ingredient in prescription, it has an important role which cannot be ignored. However, the efficacy and chemical constituents of licorice will change after honey-processing. Therefore, it is necessary to find quality markers before and after honey-processing to lay the foundation for a comprehensive evaluation of the differences between raw and processed licorice pieces. HPLC-DAD was employed to establish fingerprints of raw and processed licorice. Multivariate statistical analysis methods including principal component analysis(PCA) and orthogonal partial least squares discrimination analysis(OPLS-DA) were applied to screen out the differential components before and after processing of licorice. Based on network pharmacology, the targets and pathways corresponding to the differential components were analyzed with databases such as Swiss Target Prediction and Metascape, and the "component-target-pathway" diagram was constructed with Cytoscape 3.6.0 software to predict the potential quality markers. A total of 17 common peaks were successfully identified in the established fingerprint, and seven differential components were selected as potential quality markers(licoricesaponin G2, glycyrrhizic acid, liquiritigenin, liquiritin, isoliquiritin, liquiritin apioside and isoliquiritigenin). The HPLC fingerprint method proposed in this study was efficient and feasible. The above seven differential chemical components screened out as potential quality markers of licorice can help to improve and promote the overall quality. These researches offer more sufficient theoretical basis for scientific application of licorice and its corresponding products.

Preparation and quality evaluation of licorice flavonoids self-microemulsifying drug delivery system / 中草药

Objective: To study the prescription and preparation technology of licorice flavonoids self-microemulsifying drug delivery system (LF-SMEDDS) and evaluate its quality. Methods: The optimal formulation of LF-SMEDDS was screened by test of solubility, compatibility of oil and emulsifier, and pseudo-ternary phase diagram. Simplex lattice method was applied to optimize formulation with average particle size, polydispersity index and drug loading as evaluation indexes, the physicochemical characteristics, in vitro dissolution and stability were also determined. Results: The optimal prescription composition of LF-SMEDDS was 10% of Cinnamomi Cortex oil, 55% of RH-40, and 35% of 1,2-propanediol. The LF-SMEDDS exhibited uniform and transparent appearance, with the average particle size of (16.30 ± 0.22) nm, polydispersity index of 0.155 ± 0.008, Zeta pontential of (-20.11 ± 0.50) mV and drug loading of (86.03 ± 0.37) mg/g. The results of in vitro dissolution test indicated that the accumulative dissolution of LF was 90.65% at 30 min. The stability experiment showed that LF-SMEDDS was affected by high temperature and illumination, indicating that it should be stored at low temperature and protected from light. Conclusion: The LF-SMEDDS is simple in preparation and stable in quality, significantly increasing the solubility of LF and improving its oral bioavailability, which can provide reference for further research and development about the related preparations of the active fraction.

Comprehensive evaluation of quality of licorice (Glycyrrhiza uralensis) in different growing regions of Gansu Province based on multi-index components combined with chemometrics methods / 中草药

Objective: In this study, the wild and cultivated licorice of Gansu representative regions (Hexi, Longzhong and Longdong) were measured and analyzed by multi-index components combined with chemometrics methods, which will provide scientific basis for the evaluation of the quality of licorice and the suitable producing areas in Gansu Province. Methods: Seven main bioactive components (glycyrrhizin, liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, liquiritigenin and isoliquiritigenin) in 25 batches of licorice samples were simultaneously determined by HPLC-DAD to comprehensively evaluate the quality of licorice combined with factor analysis and cluster analysis. Results: Factor analysis showed that there was a strong correlation between the first common factor and glycyrrhizin, liquiritin and isoliquiritin; and between the second common factor and liquiritigenin, isoliquiritigenin. The variance contribution rate of two common factors was 84.28%, which reflected licorice quality overall. And cluster analysis showed that the quality of 3-year-old licorice (Glycyrrhizae Radix) cultivated in Hangjinqi of Inner Mongolia was the best, followed by that cultivated in Hexi and Longxi of Gansu Province. The quality of licorice in Longzhong of Gansu Province was worse. Conclusion: These results showed that it was more suitable to develop licorice planting in Longxi and Hexi area in Gansu Province. The overall evaluation of multi-index components and chemometrics has reference value for quality control of licorice and optimization its suitable planting areas.

The in vitro antioxidative activity of the compound astragalus, glycyrrhiza and schisandra extract and the determination of bioactive component contents / 国际药学研究杂志

Objective: To investigate the antioxidative activity of compound Astragalus, Glycyrrhiza and Schisandra extract(CAGSE)and determine the content of related bioactive components. Methods: The CAGSE was prepared by the extraction of the Astragalus, Glycyrrhiza and Schisandra raw materials with ethanol. Experimental groups for the antioxidative activity test were set as the control group, vitamin C group(VC group, positive control)and the CAGSE 0.1, 0.2 and 0.5 g/ml groups. The antioxidant effect of CAGSE was evaluated by the assay for the inhibition of linoleic acid autooxidation, the reducing power assay(the method of Oyaizu)and the assay for the 1, 1-diphenyl-2-picryl hydrazine(DPPH)free radical scavenging activity. The content of schisandrae b was determined by the HPLC method, the total phenol content(TPC)was determined by the folin-ciocalteu method using gallic acid as the standard, and the total flavonoid content(TFC)was determined by the ultraviolet spectrophotometry with rutin as the standard. Results :Com- pared with the VC group, the inhibition rate on the linoleic acid autooxidation was significantly increased in all of the CAGSE 0.1, 0.2, and 0.5 g/ml groups(P<0.05)and the reducing power was also significantly enhanced in all the CAGSE groups(P<0.05). The DPPH free radical scavenging activity was significantly higher in the CAGSE 0.1, 0.2 and 0.5 g/ml groups than in the VC group(P<0.05). The TFC in the 0.1 g/ml concentration CAGSE was 54.39 mg/g, the TPC was 38.65 mg/g, and the content of schisandrin b was 0.76 mg/g. Conclusions: The CAGSE showed a significant antioxidant activity, and the content of total flavonoids, total phenolics and schisandrin b were 54.39, 38.65 and 0.76 mg/g, respectively.

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change / 药物分析学报

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate com-bination 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 sphin-ganine 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 in-compatibility 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".

Simultaneous Determination of 9 Components in Huoxiang Zhengqi Oral Liquid by HPLC / 中国药房

OBJECTIVE： To establish a method for simultaneous determination of nine components in Huoxiang zhengqi oral liquid， and to improve and perfect the quality standard of Huoxiang zhengqi oral liquid. METHODS： The contents of nine components in 10 batches of Huoxiang zhengqi oral liquid were determined by HPLC， such as licorice coumarin， isorlicin， liquiritinapioside， narirutin， liquiritin， saponins， hesperidin， magnolol and honokiol. The determination was performed on Kromasil Eternity XT-5-C18 column with mobile phase consisted of acetonitrile-0.05％ phosphoric acid solution （gradient elution） at the flow rate of 1 mL/min. The detection wavelength was set at 220 nm， and column temperature was 25 ℃. The sample size was 10 μL. RESULTS： The linear range of licorice coumarin， isorlicin， liquiritinapioside， narirutin， liquiritin， saponins， hesperidin， magnolol and honokiolin were 0.000 5-0.007 5， 0.000 8-0.025 0， 0.006 1-0.976 0， 0.001 6-0.250 0， 0.007 8-0.025 0， 0.000 4- 0.062 7， 0.008 6-0.276 0， 0.010 0-0.500 0， 0.010 0-0.500 0 mg/mL （r＝0.999 2-1.000 0）. The detection limits were 0.001 3， 0.000 1， 0.004 7， 0.005 0， 0.012 0， 0.001 3， 0.007 8， 0.007 7 0， 0.005 8 μg/mL， and the quantitative limits were 0.013 0， 0.000 8， 0.047 0， 0.050 0， 0.120 0， 0.013 0， 0.078 0， 0.070 0， 0.058 0 μg/mL， respectively； RSD of precision， stability and repeatability tests were less than 3.0％ （n＝6）. Average recovery rates were 98.67％， 101.85％， 98.97％， 103.05％， 100.00％， 97.78％， 97.91％， 100.13％， 101.95％； RSDs were 1.14％， 2.18％， 0.40％， 0.17％， 1.38％， 0.85％， 1.38％， 0.10％， 1.35％ （n＝6）. CONCLUSIONS： The established method is accurate and reliable， which can provide reference for the establishment of the overall quality control evaluation system and the improvement of quality standard for Huoxiang zhengqi oral liquid.

Study on Anti-synovial Angiogenesis Mechanism of Licorice and Aconite Decoction in the Treatment of Adjuvant Arthritis Model Mice / 中国药房

OBJECTIVE： To investigate the therapeutic effect of Licorice and aconite decoction in the treatment of adjuvant arthritis （AA） model mice through anti-synovial angiogenesis pathway. METHODS： Totally 48 male Balb/c mice were randomly divided into normal group， model group， Licorice and aconite decoction group and tripterygium glycosides group （positive drug group）， with 12 mice in each group. Except for normal group， AA model was established by intradermal injection of Freund’s complete adjuvant into the left hind toe of mice. 12 d after modeling， normal group and model group were given same volume of water intragastrically； Licorice and aconite decoction group （7.8 g/kg，by total amount of crude drug） and tripterygium glycosides group （0.01 g/kg） were given relevant medicine 20 mL/kg intragastrically， once a day， for consecutive 18 d. The joint lesions of mice were observed and recorded， and the foot swelling degree of mice was measured by water volume method. HE staining was used to observe the pathological change of ankle joint in mice. The protein levels of platelet endothelial cell adhesion molecule-1 （CD31） and vascular endothelial growth factor （VEGF） were determined by immunofluorescence assay. The protein expressions of nuclear factor κB（NF-κB） and zinc finger transcription factor GATA4 （GATA4） were detected by Western blotting assay. RESULTS： Compared with normal group， ankle joint of model group mice was markedly reddened and swollen， and foot swelling degree increased significantly （P＜0.05）. Synovial tissue of ankle joint proliferated， pannus increased significantly， and a large number of inflammatory cells and joint erosion were observed. The protein expression of CD31， VEGF， NF-κB and GATA4 in synovial tissue of mice were increased significantly （P＜0.05）. Compared with model group， the redness and swelling of ankle joint in mice were alleviated， and the foot swelling degree was significantly reduced in Licorice and aconite decoction group （P＜0.05）. Pannus in synovial tissue decreased and other pathological symptoms were improved. The protein expression of CD31， VEGF， NF-κB and GATA4 were decreased significantly in synovial tissue （P＜0.05）. CONCLUSIONS： Licorice and aconite decoction can decrease the protein expression of VEGF，NF-κB and GATA4 in synovial tissue， reduce the generation of pannus in synovial tissue and effectively inhibit the angiogenesis in synovial tissue so as to prevent bone destruction and protect joint of AA model mice.

Dose-toxicity-effect relationship between licorice combined with rhubarb in purgation / 中国中药杂志

The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.

Electrical storm induced by hypokalemia associated with herbal medicines containing licorice

A 60-year-old woman presented with polymorphic ventricular tachycardia secondary to hypokalemia, which necessitated dozens of DC cardioversions. She was not taking any other medication and denied any vomiting or diarrhea. Further investigation for hypokalemia suggested a hypermineralocorticoid state. Repeated inquiry prompted the patient to admit to taking herbal medicine containing licorice. She was treated with magnesium sulfate, potassium infusion, and intravenous lidocaine. A potassium-sparing diuretic was also prescribed. On the seventh day, the patient was discharged from the hospital with advice to discontinue taking herbal medicines containing licorice. She has been followed up at our outpatient clinic without further symptoms for 3 years. This case highlights the potential for cardiovascular complications associated with consumption of herbal medicines such as licorice. Clinicians should be aware that patients presenting to the emergency department with ventricular arrhythmia and uncertain hypokalemia should be questioned about licorice intake. Obtaining a detailed history from patients admitted to the hospital for electrical storm is essential.

Licorice Ameliorates imbalance between reactive oxygen species and antioxidant enzymes in the brain of sleep deprived rats

@#Sleep deprivation can be described as inadequate quantity or quality of sleep characterized by insufficient sleep duration, delayed sleep onset, and occurrence of napping episodes during the day. Sleep deprivation in animals and obstructive sleep apnea syndrome in human was reported to be associated with increased oxidative stress. Glycyrrizha glabra (licorice) is a medicinal plant known to be a highly efficacious medicinal herb with several pharmacological effects. Hence, the aim of this study was to demonstrate whether or not licorice root extract will regulate the imbalance between the reactive oxygen species and production of antioxidant enzymes in the brain of sleep deprived rats. Twenty - five 6-week-old male Wistar rats were randomly divided into five groups to undergo sleep deprivation and recovery for 5 days each. Group I (Control): Group II: sleep deprivation (SD); Group III: sleep deprivation and recovery (SD+SR) all received distill water (10ml/kg) orally; Group IV: sleep deprivation and licorice (SD+Lic), Group V: sleep deprivation, recovery with licorice (SD+SR+Lic) both received licorice (150mg/kg) orally once daily. MDA concentration among rats in Groups II (51%), III (46.7%) and IV (31.3%) were significantly higher when compared with control. Rats in Group III (20.5%), Group IV (24.6%) and Group V (30.8%) showed increased significant change in GSH concentration when compared with Group II. The concentration of CAT among rats in Group II was significantly lower than those rats in Group III (43.8%), Group IV (53.8%) and Group V (72.9%). These results clearly show that sleep deprivation significantly affects the oxidative status of rats. In conclusion, licorice root extract has ameliorative effect on the imbalance between the reactive oxygen species and production of antioxidant enzymes in the brain of sleep deprived rats.

Anti-inflammatory and immunomodulatory effects of Tripterygium wilfordii processed with licorice on mice model of ulcerative colitis / 中国中药杂志

The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.

Toxicity-reducing effect of compatibility of Tripterygium and licorice in animals: systematic review / 中国中药杂志

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.

Therapeutic effect of Rhubarb licorice root decoction on liver and kidney injury in rats exposed to cadmium / 中国职业医学

OBJECTIVE: To investigate the protective effects of rhubarb and licorice( Rhubarb licorice root decoction) on liver and kidney injury in rats exposed to cadmium. METHODS: Healthy male specific pathogen-free grade SD rats were randomly divided into control group,model group,licorice group and Rhubarb licorice root decoction group by random number table. Except the control group,the other 3 groups were intraperitoneally injected with 1. 00 g/L cadmium chloride solution at the dose of 1 mg/kg body mass,once every other day for 6 times. After 7 days,the rats in the licorice group and the Rhubarb licorice root decoction were given licorice soup and Rhubarb licorice root decoction,respectively. The dose was 50 mg/kg body mass,once per day for 30 days. At 24 hours after the last gavage,rats were secrificed and the liver and kidney were isolated. Liver and kidney organ coefficients were calculated and the pathologic changes in liver and kidney tissues were observed. The fully automatic biochemical analyser was conducted to detect the activity of aspartate aminotransferase( AST) and alanine aminotransferase( ALT) in liver tissue and the activity of superoxide dismutase( SOD) and level of malondialdehyde( MDA) in liver and kidney tissues. RESULTS: Large area of necrosis were found in the liver and kidney in the model group. In the ticorice group and Rhubarb licorice root decoction group,the necrosis in the liver and kidney decreased,and Rhubarb licorice root decoction group improved more obviously than ticorice group.The coefficient of liver and kidney,the activity of AST and ALT in liver tissue,and MDA level in liver and kidney tissues of the model group increased( P < 0. 05),meanwhile the activity of SOD in liver and kidney tissues decreased( P < 0. 05)when compared with the control group. The above indexes in licorice group and Rhubarb licorice root decoction group had improvement than that of model group( P < 0. 05). The improvement of above indexes in the Rhubarb licorice root decoction group was better than that in the licorice group( P < 0. 05). CONCLUSION: Rhubarb licorice root decoction has protective effect on liver and kidney damage caused by cadmium exposure.