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Publication
Journal: Molecular and Cellular Endocrinology
April/17/2008
Abstract
After the Women's Health Initiative found that the risks of hormone therapy outweighed the benefits, a need for alternative drugs to treat menopausal symptoms has emerged. We explored the possibility that botanical agents used in Traditional Chinese Medicine for menopausal symptoms contain ERbeta-selective estrogens. We previously reported that an extract containing 22 herbs, MF101 has ERbeta-selective properties. In this study we isolated liquiritigenin, the most active estrogenic compound from the root of Glycyrrhizae uralensis Fisch, which is one of the plants found in MF101. Liquiritigenin activated multiple ER regulatory elements and native target genes with ERbeta but not ERalpha. The ERbeta-selectivity of liquiritigenin was due to the selective recruitment of the coactivator steroid receptor coactivator-2 to target genes. In a mouse xenograph model, liquiritigenin did not stimulate uterine size or tumorigenesis of MCF-7 breast cancer cells. Our results demonstrate that some plants contain highly selective estrogens for ERbeta.
Publication
Journal: Journal of Ethnopharmacology
July/1/2010
Abstract
BACKGROUND
Xiaoyaosan, a famous Chinese prescription, composed of Poria (Poria cocos (Schw.) Wolf), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Herba Menthae (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.), has been widely used in the clinic for treating mental disorders. Behavior and biochemical analyses indicate xiaoyaosan has obvious anti-depression activity. However, there is no report on the effects of xiaoyaosan using a metabolomics approach.
OBJECTIVE
A urinary metabolomics method was applied to evaluate the efficacy of xiaoyaosan on rat model of chronic unpredictable mild stress.
METHODS
Rats were divided into 6 groups and drugs were administered during the 21-day model building period. Urine was measured using GC-MS, processed with XCMS and Microsoft Excel and analyzed by SIMCA-P and SPASS software. Variable importance in projection statistics and loading plot were used to find biomarker ions.
RESULTS
Clear separation between model and each drug group was achieved. High dose group of xiaoyaosan was much closer to control group than middle dose group and amitriptyline group. The time-dependent recovery tendency in high dose group was obtained.
CONCLUSIONS
In term of anti-depression effect, high dose xiaoyaosan was the most effective and amitriptyline equaled middle dose xiaoyaosan as shown by metabolomics strategy and behavior tests. Some common and characteristic metabolites on the anti-depression of xiaoyaosan and amitriptyline were obtained. The work showed metabolomics is a valuable tool in studying the efficacy and potential biomarkers of therapeutic effect of complex prescriptions.
Publication
Journal: Journal of Ethnopharmacology
December/27/2011
Abstract
BACKGROUND
Xiaoyaosan (XYS), a famous Chinese prescription, composed of Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.) Wolf), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Herba Menthae (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.), has been widely used in the clinic for treating mental disorders. Behavior and biochemical analyses indicate XYS has obvious anti-depression activity. However, there is no report on the effects of XYS using a metabolomics approach.
OBJECTIVE
Depression is a prevalent complex psychiatric disorder and its pathophysiological mechanism is not yet well understood. This paper was designed to study metabonomic characters of the depression induced by chronic unpredictable mild stress (CUMS) and the therapeutic effects of XYS, classic traditional Chinese medicine (TCM) in treating the depression.
METHODS
A plasma metabonomics method based on gas chromatography/mass spectrometry (GC/MS) was developed. Principal component analysis (PCA) was utilized to classify and reveal the differences between the model group and control group. In turns, the concentration of these differences was analyzed with t-test to determine whether XYS was possible to influence the metabolic pattern induced by CUMS.
RESULTS
The significant difference in metabolic profiling was observed from model group compared with drug-dose group by using the PCA, indicating the recovery effect of XYS on CUMS rats. Some significantly changed metabolites like glycine, glucose and hexadecanoic acid have been identified. These biochemical changes are related to the disturbance in amino acid metabolism, energy metabolism and glycometabolism, which are helpful to further understand the CUMS and the therapeutic mechanism of XYS.
CONCLUSIONS
Metabonomic approach is helpful to further understanding the pathophysiology of depression and assisting in clinical diagnosis of depression and is also a valuable tool for studying the essence of Chinese medicine's syndrome theory and therapeutic effect mechanism of TCM.
Publication
Journal: Journal of Ethnopharmacology
April/1/2014
Abstract
BACKGROUND
Shaoyao-Gancao Decoction (SGD), a well-known traditional Chinese medicine prescription, is a combination of Radix Paeoniae Alba (Paeonia lactiflora Pall, root) and Glycyrrhizae uralensis (Glycyrrhiza uralensis Fisch., root and rhizome, honeyed) for spasmolysis and emergency pain relief. Paeoniflorin (PF) and glycyrrhetinic acid (GA) are two typical active components of SGD for pain relief.
OBJECTIVE
To study comparative pharmacokinetics of ten bioactive compounds in SGDs with two different combinations of RP and GU, and therefore to investigate the herb-herb interaction mechanisms of Shaoyao-Gancao Decoction for better spasmolysis and emergency pain relief in rats.
METHODS
Herbal IR macro-fingerprinting was implemented to provide the full chemical fingerprints of RP, GU and SGD decoctions and to investigate the variation rule of the full chemical profile of SGDs with various combinations of RP and GU. A specifically developed HPLC-MS/MS assay coupled with protein precipitation method was employed to determine the plasma concentrations of the ten analytes. Male Wistar rats were orally administered with SGD1 (RP:GU, 1:1 (w/w)) and SGD2 ((RP:GU, 4:1 (w/w)) equivalent to 9.5 g/kg body weight of GU.
RESULTS
Full chemical fingerprints of RP, GU and SGDs with various combinations of RP and GU were provided in the form of IR macro-fingerprints. Except for liquiritin, there were statistically significant differences (p<0.05 or p<0.01) of these analytes between SGD1 and SGD2 in in vivo pharmacokinetic study. Compared with the results when oral administrated with SGD1, six glycosides (PF, albiflorin, oxypaeoniflorin, isoliquiritin, ononin, and glycyrrhizin) exhibited higher systematic exposure levels (AUC0-t) and slower elimination rates (CL) whereas two glycones (GA and isoliquiritigenin) were the reverse when administrated with SGD2.
CONCLUSIONS
Increasing the amount of RP attenuated the inhibitory effect of GA via competing being consumed by intestinal bacteria (or β-glucosidase) to reduce the conversion amount of glycyrrhizin to GA and subsequently to afford significantly higher bioavailability and longer efficacy of PF, glycyrrhizin, albiflorin, oxypaeoniflorin, isoliquiritin, and ononin, leading to better spasmolysis and emergency pain relief.
Publication
Journal: Journal of Ethnopharmacology
March/14/2016
Abstract
BACKGROUND
Licorice (Glycyrrhizae radix), the root of Glycyrrhiza uralensis Fisch. (Leguminosae), is mainly used to moderate the characteristics of toxic herbs in Traditional Chinese Medicine, which could be partly interpreted as detoxification. However, the underlying mechanism is still not fully elucidated. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the protection against toxic xenobiotics. In our previous research, we have identified that extracts from Glycyrrhiza uralensis induced the expression of Nrf2 nuclear protein and its downstream genes. This research aims to screen the most potent Nrf2 inducer isolated from Glycyrrhiza uralensis and examine its effect on Nrf2 signaling pathway and detoxification system.
METHODS
Four compounds derived from Glycyrrhiza uralensis (glycyrrhetinic acid, liquiritigenin, isoliquiritigenin and liquiritin) were screened by ARE-luciferase reporter. The most potent ARE-luciferase inducer was chosen to further examine its effect on Nrf2 and detoxification genes in HepG2 cells. The role of Nrf2-dependent mechanism was tested by using Nrf2 knockout mice (Nrf2 KO) and Nrf2 wild-type mice (Nrf2 WT).
RESULTS
ARE-luciferase reporter assay showed these four compounds were all potent Nrf2 inducers, and isoliquiritigenin was the most potent inducer. Isoliquiritigenin significantly up-regulated the expression of Nrf2 and its downstream detoxification genes UDP-glucuronosyltransferase 1A1 (UGT1A1), glutamate cysteine ligase (GCL), multidrug resistance protein 2 (MRP2) and bile salt export pump (BSEP) in vitro and in vivo. Additionally, isoliquiritigenin showed Nrf2-dependent transactivation of UGT1A1, GCLC and MRP2.
CONCLUSIONS
Isoliquiritigenin, isolated from Glycyrrhiza uralensis, stimulates detoxification system via Nrf2 activation, which could be a potential protective mechanism of licorice.
Publication
Journal: Journal of Ethnopharmacology
March/5/2014
Abstract
BACKGROUND
Licorice (Glycyrrhiza uralensis Fisch., Leguminosae) has been used in herbal medicine and food supplement worldwide for centuries. Licorice is a common ingredient of several prescriptions of traditional Chinese medicine which have been proved to inhibit infection of human respiratory syncytial virus (HRSV). There are two preparations of licorice, Radix Glycyrrhizae and Radix Glycyrrhizae Preparata. However, it is unknown whether licorice or which preparation of licorice is effective against HRSV, nor is its active constituent.
OBJECTIVE
We tested the hypothesis that Radix Glycyrrhizae can effectively decrease HRSV-induced plaque formation in respiratory mucosal cell lines. We also tried to find out the active constituent.
METHODS
Anti-HRSV activities of hot water extracts of preparations of licorice, glycyrrhizin and 18β-glycyrrhetinic acid (18β-GA), the active constituents of licorice, were examined by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Abilities of crude licorice to inhibit viral replication and to stimulate IFN-β were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.
RESULTS
Radix Glycyrrhizae and Radix Glycyrrhizae Preparata dose-dependently inhibited HRSV-induced plaque formation in both HEp-2 and A549 cell lines (p<0.0001). The effect of Radix Glycyrrhizae was better than that of Radix Glycyrrhizae Preparata on HEp-2 cells. However, there was no difference of their anti-HRSV effects on A549 cells. Besides, glycyrrhizin was ineffective at all. Nevertheless, 18β-GA showed a potent anti-HRSV activity. Radix Glycyrrhizae was more effective when given before viral inoculation (p<0.0001) which may be due to its inhibition of viral attachment on (p<0.0001) and penetration (p<0.0001) into the host cells. The anti-HRSV activity of Radix Glycyrrhizae was further confirmed by RT-PCR and qRT-PCR. 300 μg/ml Radix Glycyrrhizae markedly decreased the viral amounts within the cells and in the suspension. Radix Glycyrrhizae might further stimulate mucosal cells to secrete IFN-β to counteract viral infection.
CONCLUSIONS
Both Radix Glycyrrhizae and Radix Glycyrrhizae Preparata are effective against HRSV infection on airway epithelial cells. Radix Glycyrrhizae inhibited HRSV mainly by preventing viral attachment, internalization, and by stimulating IFN secretion. 18β-GA may be one of its active constituents.
Publication
Journal: Journal of Ethnopharmacology
August/28/2013
Abstract
BACKGROUND
Zhusha Anshen Wan (ZSASW), a traditional Chinese medicine (TCM) prescription, composed of cinnabar (cinnabaris), Coptidis Rhizoma (Coptis chinensis French.), Angelicae Sinensis Radix (Angelica sinensis (oliv.) Diels), uncooked Rehmanniae Radix (Rehmannia glutinosa Libosch.), honey fried Glycyrrhizae Radix Et Rhizoma (Glycyrrhiza uralensis Fisch.), has been widely used for sedative therapy. Cinnabar, the chief component of ZSASW, has been proved to possess the toxicities.
OBJECTIVE
In this study, a metabonomics approach based on high-resolution (1)H nuclear magnetic resonance spectroscopy was applied to investigate the protective effects of ZSASW on the toxic effects induced by cinnabar alone.
METHODS
Male Wistar rats were divided into three groups: control group, ZSASW group and cinnabar group. Partial least squares-discriminant analysis (PLS-DA) was performed to identify different metabolic profiles of urine and serum from rats. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed.
RESULTS
The significant difference in metabolic profiling of urine and serum of the rats was observed between cinnabar treated group, control group, and the changes of endogenous metabolites related to the toxicities were identified. The results were also certified by the liver and kidney histopathology examinations and biochemical analysis of blood.
CONCLUSIONS
Our results suggested that the four combined herbal medicines of ZSASW had the effects of protecting from the toxicity induced by cinnabar alone. This work showed that the NMR-based metabonomics approach might be a promising approach to study detoxification of Chinese medicines and reasonable combination of TCM prescriptions.
Publication
Journal: Journal of Ethnopharmacology
October/14/2009
Abstract
Xia-bai-san (XBS) is a traditional Chinese medicine that has been used clinically for centuries in Asian countries to treat some types of common cold and asthma-like diseases similar to infantile pneumonia and childhood bronchitis. In previous studies, XBS was found to suppress the inflammatory process induced in lungs of mice treated with lipopolysaccharide (LPS).
OBJECTIVE
The present study was undertaken to examine the effects of XBS on LPS-inducible production of inflammatory cytokines, up-regulation of intercellular cell adhesion molecule-1 (ICAM-1), and activation of nuclear factor NF-kappaB in cultured human lung cells.
RESULTS
Extracts of four raw herbs (Cortex mori, Cortex lycii, Radix glycyrrhizae, and Fructus oryzae) were used to prepare the decoction. XBS decreased the histological damage and up-regulation of ICAM-1 observed in lungs of mice treated with lipopolysaccharide (LPS). In cultured human pulmonary epithelial A549 cells, XBS and its components Morus alba and Glycyrrhiza uralensis suppressed the up-regulation of IL-8 and ICAM-1 in response to LPS. Production of TNF-alpha, IL-1beta, IL-6 and IL-8 by LPS-treated human THP-1 monomyelocytes was also suppressed by XBS. A549 cells expressed ICAM-1 in response to medium from LPS-treated THP-1 cells; expression was decreased by XBS. The adhesion of THP-1 cells to LPS-treated A549 cells were inhibited in the presence of XBS. Activation of NF-kappaB by LPS in A549 cells was suppressed by XBS, Morus alba, and Glycyrrhiza uralensis through inhibition of IkappaB phosphorylation; the concentrations at which suppression occurred were identical to those at which production of inflammatory cytokines and up-regulation of ICAM-1 were inhibited.
CONCLUSIONS
These findings support the hypothesis that XBS, Morus alba, and Glycyrrhiza uralensis inhibit the inflammatory process in lung tissue through suppression of the IkappaB signaling pathway. XBS may prove helpful in the management of asthma, various allergic disorders, sepsis, or any other condition associated with pulmonary inflammation.
Publication
Journal: Frontiers in Aging Neuroscience
December/7/2018
Abstract
The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer's disease (AD) and Parkinson's disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of Glycyrrhiza uralensis or G. glabra or G. inflata from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan.
Publication
Journal: Journal of Agricultural and Food Chemistry
August/27/2010
Abstract
Inhibition of alpha-glucosidase is a therapeutic approach for diabetes. In this study, a method based on online liquid chromatography-diode array detection-tandem mass spectrometry and biochemical detection (LC-DAD-MS/MS-BCD) was developed to screen and identify alpha-glucosidase inhibitors from selected beverage extracts, including pu-erh tea ( Camellia sinensis var. assamica), eagle tea ( Litsea coreana Levl.), and radix glycyrrhizae ( Glycyrrhiza uralensis Fisch.). As a result, two components, (-)-epigallocatechingallate (EGCG) and (-)-epicatechingallate (ECG), as potent alpha-glucosidase inhibitors, were found in pu-erh tea. The IC(50) values of EGCG and ECG on alpha-glucosidase (EC 3.2.1.20, from Saccharomyces cerevisiae ) were 175.1 and 246.9 microM, respectively, and both were lower than that of acarbose (IC(50) = 3553.0 microM), a commercial alpha-glucosidase inhibitor. Kinetic studies revealed that both EGCG and ECG inhibited alpha-glucosidase activity in a noncompetitive manner. The study suggests that the developed LC-DAD-MS/MS-BCD system is a powerful tool for rapid screening and identification of alpha-glucosidase inhibitors in complex samples and that EGCG and ECG may be good candidates as alpha-glucosidase inhibitors.
Publication
Journal: Journal of Ethnopharmacology
April/18/2017
Abstract
BACKGROUND
Huangqi decoction (HQD) is a well-known traditional Chinese herbal formulation, It is an effective treatment for consumptive disease and chronic liver diseases. It consists of Radix Astragali (Astragalus membranceus(Fisch.) Bge. Root, Huangqi) and Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch., root and rhizome, Gancao). Total astragalus saponins (AST) is a main component of Radix Astragali and glycyrrhizic acid(GA) is a main component of Radix Glycyrrhizae. Our primary results showed that the combination of AST and GA had an obvious synergistic effect in reducing liver collagen deposition and decreasing serum alanine aminotransferase (ALT) activity in dimethylnitrosamine (DMN)-induced liver fibrosis.
OBJECTIVE
Through in vivo and in vitro experiments, we aimed at investigating the key anti-fibrosis signal pathway TGF-β1/Smads to further explore the synergistic mechanism of AST and GA.
METHODS
Two hepatic fibrosis animal models, bile duct ligation-induced (BDL) and DMN-induced, were utilized. Rats were treated orally with AST, GA or AST/GA, with the effects evaluated via liver histopathology, hydroxyproline (Hyp) levels, and α-SMA expression. In the hepatic stellate cell line JS-1, cells were treated with AST/GA for 24h, followed by a cell viability assessment using Cell Counting Kit-8(CCK-8) and Real-time PCR and Western blot analysis of α-SMA, ColⅠ and TGF-β1/Smads signaling pathway related components.
RESULTS
The AST/GA combination attenuated liver tissue inflammation, collagen deposition, Hyp levels, and α-SMA expression in both BDL-and DMN-stimulated hepatic fibrosis rats. In vitro results showed that the AST/GA combination significantly inhibited JS-1 cell viability, significantly suppressed α-SMA, ColⅠ, TGF-β1, Smad2 and Smad3 mRNA and protein expression, as well reduced p-Smad2/3. Compared with AST or GA treatment alone, the AST/GA combination significantly reduced Smad3 mRNA expression levels and TGF-β1, Smad3, and p-Smad2/3 protein levels.
CONCLUSIONS
AST and GA synergistically alleviated both BDL-and DMN-induced hepatic fibrosis via TGF-β1/Smads signaling pathway inhibition in hepatic stellate cells.
Publication
Journal: Phytotherapy Research
June/19/2014
Abstract
Igongsan (IGS), which is an herbal prescription composed of five different herbs, Ginseng Radix (root of Panax ginseng, Araliaceae), Atractylodis Rhizoma Alba (rhizome of Atractylodes Macrocephala, Compositae), Poria Sclerotium (sclerotium of Poria cocos, Polyporaceae), Glycyrrhizae Radix et Rhizoma (root and rhizome of Glycyrrhiza uralensis, Leguminosae), and Citri Unshius Pericarpium (Peel of Citrus unshiu, Rutaceae), has been traditionally used in Korea to treat a variety of inflammatory diseases. In this study, we investigated to elucidate the mechanism responsible for IGS's antiinflammatory effect in mouse peritoneal macrophages. The findings demonstrate that IGS inhibited the production of inflammatory cytokine and prostaglandins E2 . IGS inhibited the enhanced levels of cyclooxygenase-2 and inducible NO synthase caused by lipopolysaccharide (LPS). Additionally, it was shown that the antiinflammatory effect of IGS is through regulating the activation of nuclear factor-kappa B and caspase-1 in LPS-stimulated mouse peritoneal macrophages. These results provide novel insights into the pharmacological actions of IGS as a potential candidate for development of new drugs to treat inflammatory diseases.
CONCLUSIONS
These results provide novel insights into the pharmacological actions of IGS as a potential candidate for development of new drugs to treat inflammatory diseases.
Publication
Journal: Phytomedicine
March/30/2015
Abstract
Liquorice is the root of Glycyrrhiza uralensis Fisch. or Glycyrrhiza glabra L., Leguminosae. Licorice is described as 'National Venerable Master' in Chinese medicine and plays paradoxical roles, i.e. detoxification/strengthen efficacy and inducing/enhancing toxicity. Therefore, licorice was called "Two-Face" herb in this paper. The aim of this study is to discuss the paradoxical roles and the perspective usage of this "Two-Face" herb using data mining and frequency analysis. More than 96,000 prescriptions from Chinese Formulae Database were selected. The frequency and the prescription patterns were analyzed using Microsoft SQL Server 2000. Data mining methods (frequent itemsets) were used to analyze the regular patterns and compatibility laws of the constituent herbs in the selected prescriptions. The result showed that licorice (Radix glycyrrhizae) was the most frequently used herb in Chinese Formulae Database, other frequently used herbs including Radix Angelicae Sinensis (Dang gui), Radix et rhizoma ginseng (Ren shen), etc. Toxic herbs such as Radix aconiti lateralis praeparata (Fu zi), Rhizoma pinelliae (Ban xia) and Cinnabaris (Zhu sha) are top 3 herbs that most frequently used in combination with licorice. Radix et rhizoma ginseng (Ren shen), Poria (Fu ling), Radix Angelicae Sinensis (Dang gui) are top 3 nontoxic herbs that most frequently used in combination with licorice. Moreover, Licorice was seldom used with sargassum (Hai Zao), Herba Cirsii Japonici (Da Ji), Euphorbia kansui (Gan Sui) and Flos genkwa (Yuan Hua), which proved the description of contradictory effect of Radix glycyrrhizae and these herbs as recorded in Chinese medicine theory. This study showed the principle pattern of Chinese herbal drugs used in combination with licorice or not. The principle patterns and special compatibility laws reported here could be useful and instructive for scientific usage of licorice in clinic application. Further pharmacological and chemical researches are needed to evaluate the efficacy and the combination pattern of these Chinese herbs. The mechanism of the combination pattern of these prescriptions should also be investigated whether additive, synergistic or antagonistic effect exist using in vitro or in vivo models.
Publication
Journal: Biological and Pharmaceutical Bulletin
April/7/2004
Abstract
To clarify the feasibility of medicinal use of the cultivated Glycyrrhiza resources, the equivalency between the G. uralensis roots cultivated in eastern Nei-Meng-Gu of China and medicinal licorice (Glycyrrhizae Radix, Gancao in Chinese and Kanzo in Japanese) was examined. The HPLC fingerprint including glycyrrhizin (GL) of the cultivated roots was similar to that of medicinal Gancao, but different from that of non-medicinal Xinjiang-Gancao (Shinkyo Kanzo in Japanese). Similarity between the cultivated roots and two medicinal Gancao was confirmed quantitatively by hierarchical cluster analysis on the basis of HPLC-7-peak-area data. Moreover, the 4-year-old adventitious roots conformed to the five standards described in the Japanese Pharmacopoeia XIV (JP XIV). The 4-year-old adventitious roots had similar pharmaceutical properties to those of medicinal Dongbei-Gancao (Tohoku Kanzo in Japanese) as determined by examining IgE-mediated triphasic skin reaction in mice and pharmacokinetic profile of glycyrrhetic acid, an anti-allergic metabolite of GL. The present pharmaceutical study suggests that the 4-year-old adventitious roots of G. uralensis cultivated in eastern Nei-Meng-Gu of China are comparable to medicinal Gancao conforming to the JP XIV, and may be a potential medicinal source to compensate for the insufficiency of wild Glycyrrhiza plants caused by collection restriction in China.
Publication
Journal: Journal of Natural Medicines
April/13/2009
Abstract
In order to reveal the chemical characteristics of Glycyrrhiza uralensis growing in Mongolia and to clarify whether it can be the source of Glycyrrhizae Radix used in Japan, eight major bioactive constituents in the underground parts of G. uralensis collected in Mongolia were quantitatively analyzed and compared with Glycyrrhizae Radix produced in China. Most of the 15 samples from eastern, southern and western parts of Mongolia contained 26.95-58.55 mg/g of glycyrrhizin, exceeding the criterion (25 mg/g) assigned in the Japanese Pharmacopoeia. The sample collected in Tamsagiyn hooly, Dornod province, in eastern Mongolia was of the highest content 58.55 mg/g. The contents of three flavanone constituents (liquiritin apioside, liquiritin and liquiritigenin) and three chalcones (isoliquiritin apioside, isoliquiritin and isoliquiritigenin) varied significantly according to collection places; the subtotal of the three flavanones ranged from 3.00 to 26.35 mg/g, and the subtotal of the three chalcones ranged from 1.13 to 10.50 mg/g. The content of glycyrrhizin and subtotal contents of flavanones and chalcones in the underground parts of G. uralensis from Mongolia were obviously lower than wild samples, but higher than cultivated samples derived from the same species produced in China. Glycycoumarin, a species-specific constituent of G. uralensis, was detected in all Mongolian samples. Its contents in samples from eastern Mongolia, Sergelen and Tamsagiyn hooly of Dornod province were very high and were compatible with Tohoku-kanzo derived from wild Chinese G. uralensis. The present study suggested that Mongolian G. uralensis could be a source of Glycyrrhizae Radix, mostly of Japanese Pharmacopoeia grade. However, the producing area should be taken into consideration to ensure relatively high quality. In addition, planned use and promotion of cultivation must be advocated to avoid confronting Mongolian Glycyrrhiza with the same threat as its congener in China. Our study sheds some light on selecting cultivation areas and superior strains, which are important tasks to promote cultivation.
Publication
Journal: Archives of Pharmacal Research
March/28/2013
Abstract
This study investigated an ethanol extract from Glycyrrhizae radix (GR), the root of Glycyrrhiza uralensis (Leguminosae), for possible neuroprotective effects on neurotoxicity induced by amyloid β protein (Aβ) (25-35) in cultured rat cortical neurons. Exposure of cultured cortical neurons to 10 μM Aβ (25-35) for 36 h induced neuronal apoptotic death. GR (10-50 μg/mL) prevented the Aβ (25-35)-induced neuronal apoptotic death, as assessed by a MTT assay and Hoechst 33342 staining. Furthermore, GR decreased the expression of Bax and active caspase-3, proapoptotic proteins, and increased Bcl-2, an antiapoptotic protein. GR also significantly inhibited Aβ (25-35)-induced elevation of the intracellular Ca(2+) concentration ([Ca(2+)](i)) and generation of reactive oxygen species (ROS) measured by fluorescent dyes. Isoliquiritigenin (1-20 μM), isolated from GR as an active component, inhibited Aβ (25-35)-induced neuronal apoptotic death, elevation of [Ca(2+)](i), ROS generation, and the change of apoptosis-associated proteins in cultured cortical neurons, suggesting that the neuroprotective effect of GR may be, at least partly, attributable to this compound. These results suggest that GR and isoliquiritigenin prevent Aβ (25-35)-induced neuronal apoptotic death by interfering with the increases of [Ca(2+)](i) and ROS, and GR may have a possible therapeutic role for preventing the progression of neurodegenerative disease such as Alzheimer's disease.
Publication
Journal: Journal of Ethnopharmacology
April/26/2016
Abstract
BACKGROUND
Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People׳s Welfare Pharmacy in the Song Dynasty (AD1078). It consists of Radix Astragali (Astragalus membranceus (Fisch.) Bge. Root, Huangqi) and Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch., root and rhizome, Gancao), and it is an effective recipe that is usually used to treat consumptive disease and chronic liver diseases. Astragaloside (AS) is a main component of Radix Astragali had an effect similar to the Huangqi decoction on hepatic fibrosis.
OBJECTIVE
Cholestasis is associated with a number of chronic liver diseases and Notch signaling has been demonstrated to be involved in ductular reaction. Previous studies have shown that AS can prevent the progression of cholestatic liver fibrosis, however, whether AS affects the Notch signaling pathway is unclear.
METHODS
Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in rats. At first weekend, the rats were randomly divided into a model group (BDL), an AS group, and a Sorafenib positive control group (SORA) and treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, -4, Jagged 1 (JAG1), Delta-like (DLL)-1, -3, -4, Hes1, Numb and RBP-Jκ. Activation of the Wnt signaling pathway was evaluated by analyzing expressions of Wnt-4, -5a, -5b, Frizzled (Fzd)-2, -3, -6 and β-catenin.
RESULTS
(1) Compared with the BDL group, AS significantly reduced the deposition of collagen and the Hyp content of liver tissue and inhibited the activation of HSCs. In addition, AS significantly decreased the protein and mRNA expressions of TGF-β1 and α-SMA. In contrast, AS significantly enhanced expression of the Smad 7 protein. AS also reduced biliary epithelial cell proliferation, and reduced the mRNA and protein expressions of CK7, CK8, CK18, CK19, OV6, Sox9 and EpCAM. (2) The mRNA and protein expressions of Notch-2, -3, -4 and JAG1 were significantly reduced in the AS compared to the BDL group. In contrast, the mRNA and protein level of Numb was clearly enhanced after AS treatment.
CONCLUSIONS
AS may prevent biliary liver fibrosis via inhibition of the Notch signaling pathway, thereby inhibiting the abnormal proliferation of biliary epithelial cells. Results indicate that AS may be a potential therapeutic drug for cholestatic liver disease.
Publication
Journal: Journal of Ethnopharmacology
March/8/2016
Abstract
BACKGROUND
Ge-Gen-Tang (GGT) is a traditional Chinese medicinal formula composed of Puerariae radix (Pueraria lobata Ohwi), Ephedrae Herba (Ephedra sinica Stapf), Cinnamomi Ramulus (Cinnamomum cassia Blume), Paeoniae Radix (Paeonia lactiflora Pallas), Glycyrrhizae Radix preparata (Glycyrrhiza uralensis Fischer), Zingiberis Rhizoma (Zingiber officinale Roscoe), and Zizyphi Fructus (Ziziphus jujuba Mill. var. inermis Rehder) and is widely used to ameoliorate the symptoms of gastrointestinal (GI) disorders related to diarrhea and intestinal mucosal immunity and for anti-cold, antipyretic and analgesic in Eastern Asia.
OBJECTIVE
Interstitial cells of Cajal (ICCs) are pacemaker cells in the GI tract that generate rhythmic oscillations in membrane potentials known as slow waves. We investigated the effects of GGT on pacemaker potentials in cultured ICCs from the mouse small intestine, and sought to identify the receptors and the action mechanisms involved.
METHODS
Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed on within 12h after culture. A whole-cell patch-clamp configuration was used to record potentials (current clamp) from cultured ICCs. Intracellular Ca(2+) ([Ca(2+)]i) increase was studied in cultured ICCs using fura-2AM. All of the experiments were performed at 30-32°C.
RESULTS
Under the current clamping mode, GGT decreased the amplitude and frequency of pacemaker potentials; however, these effects were blocked by intracellular GDPβS, a G-protein inhibitor, and glibenclamide, a specific ATP-sensitive K(+) channels blocker. Prazosin (α1-adrenoceptor antagonist) and butoxamine (β2-adrenoceptor antagonist) did not block the GGT-induced effects, whereas atenolol (β1-adrenoceptor antagonist) blocked the GGT-induced effects. Also, yohimbine (α2-adrenoceptor antagonist) partially blocked the GGT-induced effects. Pretreatment with SQ-22536, an adenylate cyclase inhibitor, did not block the GGT-induced effects, whereas pretreatment with ODQ, a guanylate cyclase inhibitor, or L-NAME, an inhibitor of nitric oxide (NO) synthase, did. Additionally, [Ca(2+)]i analysis showed that GGT decreased [Ca(2+)]i.
CONCLUSIONS
These results suggest that GGT inhibits pacemaker potentials in ICCs in a G protein-, cGMP- and NO-dependent manner through stimulation of α2 and β1-adrenoceptors.
Publication
Journal: Biochemistry and Biophysics Reports
November/14/2017
Abstract
Licorice (Glycyrrhizae radix) is the roots and stolons of Glycyrrhiza uralensis Fischer or Glycyrrhiza glabra Linnaeus in the Japanese Pharmacopoeia. Glycyrrhizae radix has been widely used as a sweetener and a traditional medicine. A Glycyrrhizae radix extract contains many constituents and has antispasmodic, antitussive, anti-ulcer, and anti-inflammatory effects. However, reports comparing the anti-inflammatory effects of these constituents are very few. Here, we purified several constituents from the roots and stolons of G. uralensis and examined and compared their anti-inflammatory effects by monitoring the levels of the inflammatory mediator, nitric oxide (NO), in interleukin (IL)-1β-treated rat hepatocytes. From the G. uralensis extract, we purified the main constituent glycyrrhizin and the constituents that are characteristic of G. uralensis (chalcones and flavanones). These constituents suppressed NO production in IL-1β-treated rat hepatocytes, and isoliquiritigenin showed the greatest suppression activity. Isoliquiritigenin, isoliquiritin, and liquiritigenin significantly decreased both protein and mRNA for the inducible nitric oxide synthase. These constituents reduced the levels of mRNAs encoding tumor necrosis factor α and IL-6. In contrast, although glycyrrhizin is abundant, it showed a 100-fold lower potency in NO suppression. Therefore, both glycyrrhizin and the minor constituents (isoliquiritigenin, isoliquiritin, and liquiritigenin) may be responsible for the anti-inflammatory effects of G. uralensis. It is also implied that these constituents may have a therapeutic potential for inflammatory hepatic disorders.
Publication
Journal: Journal of Ethnopharmacology
February/2/2019
Abstract
<AbstractText>Xiaoyaosan (XYS), a famous TCM prescription with a long history of clinical use for relieving a wide variety of depression symptoms, consists of Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix PaeoniaeAlba (Paeonia lactiflora Pall.), Rhizoma Atractylodis Macrocepha lae (Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.)Wolf), Radix <em>Glycyrrhizae</em> (Glycyrrhiza <em>uralensis</em> Fisch.), Herba Menthae Haplocalycis (Mentha haplocalyx Briq.), and Rhizoma Zin-giberis Recens (Zingiber officinale Rosc.).</AbstractText><AbstractText>We aimed to characterize the diversity and variation of two kinds metabolites of brain, i.e. aqueous and lipophilic metabolites, gaining comprehensive insights into the metabolic processes of depression-like behavior, and to reveal the mechanisms of antidepressant-like effects of XYS.</AbstractText><p><div><b>MATERIALS AND METHODS</b></div>We first established a CUMS (Chronic Unpredictable Mild Stress)-induced depression-like behavior model. We then extracted both aqueous and lipophilic metabolites of rat brains by a two-phase extraction method, which were subsequently characterized by two differential sequences of <sup>1</sup>H nuclear magnetic resonance (NMR). Multivariate analysis including Principal Components Analysis (PCA) and Orthogonal Partial Least Squares-Discriminate Analysis (OPLS-DA) was applied.</p><AbstractText>Metabolic profiling by PCA indicated that XYS significantly reversed the metabolic perturbation caused by CUMS. OPLS-DA showed a total of 15 metabolites including 6 lipophilic and 9 aqueous metabolites was screened as potential biomarkers involved in CUMS-induced depression-like behavior. On top of this, five pathways including (1)D-glutamine and D-glutamate metabolism, (2) valine, leucine and isoleucine biosynthesis, (3) alanine, aspartate and glutamate metabolism, (4) taurine and hypotaurine metabolism and (5) arginine and proline metabolism were recognized as the most influenced pathways associated with the process of CUMS-induced depression-like behavior. Notably, XYS significantly reversed abnormality of 5 aqueous and 4 lipophilic metabolites to normal, suggesting that XYS synergistically mediated abnormalities of multiple pathways (1), (3), (4) and (5).</AbstractText><AbstractText>It is the first report to investigate the antidepressant-like effects and underlying mechanisms of XYS from the perspective of brain metabolites. In a broad sense, this study brings novel and valuable insights to evaluate the efficacy of traditional Chinese medicine (TCM), to interpret mechanisms, and to provide the theoretical basis for further research on therapeutic mechanisms in clinical practice.</AbstractText>
Publication
Journal: Mini reviews in medicinal chemistry
July/27/2018
Abstract
Licorice root (Radix Glycyrrhizae) is a common perennial plants native to Mediterranean countries, central to southern Russia, Asia, Turkey, Iraq and Iran used in traditional Chinese medicine for centuries and licorice has been described as 'the grandfather of herbs' .The genus name Glycyrrhiza (family Leguminoseae) is derived from the ancient Greek words glycos (meaning sweet) and rhiza (meaning root). It consists of about 30 species, but most common ones are Glycyrrhiza glabra L., Glycyrrhiza uralensis Fisch and Glycyrrhiza Inflata. It is known that licorice root contains various chalcones which are an important class of natural products, precursors of flavonoids. Chemically, chalcones consist of open-chain flavonoids, wherein two aromatic rings are joined by a three-carbon α, β-unsaturated ketone, which represent the fundamental nucleus of the structure. They are classified according to chemical structures in Licochalcone A, B, C, D, E, F and G. This review aims to highlight all the in vitro and in vivo studies that have been conducted on the licochalcones, extracted from Glycyrrhiza species. The most important effects are: anti-inflammatory, antioxidant, anticancer, antimicrobial, antiviral, antiallergic, antidiabetic, hepatotoxic and osteogenic. Natural bioactive compounds are mostly value to implement the introduction of biologically active molecules from the bench (research) to the bedside (clinical practice). However, in a future perspective it is necessary to perform additional studies to confirm these biological effects.
Publication
Journal: International Immunopharmacology
August/18/2005
Abstract
In the present study, we performed to selectively deplete glycyrrhizin from Si-Ni-San, a traditional Chinese prescription that consists of 4 Chinese herbs including Radix Glycyrrhizae Uralensis, and examined its influence on the suppressing activity of Si-Ni-San against contact sensitivity in mice. An immunoaffinity column was made by covalently coupling the polyclonal antibody, obtained by the immunization with glycyrrhizin-BSA conjugate, to CNBr-activated Sepharose 4B. By using this column, glycyrrhizin in Si-Ni-San was selectively and almost completely depleted from the whole extract, which was confirmed by high-performance liquid chromatography (HPLC). Both 200 mg/kg of Si-Ni-San and 10 mg/kg of glycyrrhizin, the dose corresponding to its proportion contained in Si-Ni-San, significantly reduced the ear swelling of picryl chloride (PCl)-induced ear contact sensitivity in mice and the inhibition by Si-Ni-San was stronger than that by glycyrrhizin. The adhesion activity to type IV collagen of the isolated spleen cells from PCl-sensitized mice was significantly decreased by both Si-Ni-San and glycyrrhizin. However, the glycyrrhizin-depleted sample of Si-Ni-San (Si-Ni-San(GL-)) only showed a slight inhibition on the cell adhesion. Furthermore, the spleen cells from PCl-sensitized mice produced more matrix metalloproteinase (MMP)-2 and -9 than naive spleen cells did, and both Si-Ni-San and glycyrrhizin remarkably reduced MMP-2 and MMP-9 production. In contrast, Si-Ni-San(GL-) only showed a slight inhibition. These results suggest that glycyrrhizin may act as one of the active constituents of Si-Ni-San in inhibiting delayed-type hypersensitivity reaction via down-regulating the MMP production and the cell adhesion to extracellular matrix. The present study also provides a new approach to recognize and validate an active constituent in traditional prescription through a selective depletion.
Publication
Journal: Journal of Gastroenterology and Hepatology
January/14/2016
Abstract
OBJECTIVE
The anti-inflammatory effects of liquiritigenin, a major flavonoid isolated from Glycyrrhizae uralensis, have been reported in many inflammation models. However, its protective effects have not been reported in a colitis model. This study investigated the anti-inflammatory effect and mechanism of liquiritigenin for trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice.
METHODS
Male mice imprinting control regions (ICR) were randomly divided into five groups: normal, TNBS-induced colitis, colitis treated with liquiritigenin at low dose (10 mg/kg) and high dose (20 mg/kg), or mesalazine (10 mg/kg). TNBS colitis induction was performed except for in the normal group, and they were treated with liquiritigenin or mesalazine except control group. The treatment effect was measured after three days treatment, by body weight, colon length, macroscopic score, histological score, levels of cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and IL-10) in colon tissue as well as the nuclear factor kappa-light-chain-enhancer pathway of activated B cells (NF-κB) activation.
RESULTS
Mice treated with high-dose liquiritigenin showed significant body weight gain, inhibition of colon shortening, protective effect on histological damages, and myeloperoxidase activity of colon tissue compared with the control group. Furthermore, mice treated with high-dose liquiritigenin experienced significantly suppressed tumor necrosis factor-α, IL-1β, and IL-6 as well as enhanced IL-10 expression (all P < 0.05). High-dose liquiritigenin treatment group showed significant decreases in TNBS-induced phosphorylation of IKKβ, p65, and IκB-α.
CONCLUSIONS
Liquiritigenin may ameliorate TNBS-induced colitis in mice by suppressing expression of pro-inflammatory cytokines through NF-κB pathway.
Publication
Journal: Journal of Pharmaceutical and Biomedical Analysis
October/7/2017
Abstract
In this study, Liquid Chromatography (LC) separation combined with quadrupole-Time-Of-Flight Mass Spectrometry (qTOF-MS) detection was used to analyze the characteristic ions of the flavonoids from Liang-wai Gan Cao (Radix Glycyrrhizae uralensis). First, accurate mass measurement and isotope curve optimization could provide reliable molecular prediction after noise deduction, baseline calibration and "ghost peak recognition". Thus, some spectral features in the LC-MS data could be clearly explained. Secondly, the chemical structure of flavonoids was deduced by MS/MS fragment ions, and the in-silico spectra by MS-FINDER program provided strong support for overcoming the bottleneck of phytochemical identification. For a predicted formula and experimental MS/MS spectrum, the MS-FINDER program could sort the candidate compounds in the public database based on a comprehensive weighted score, and we took the first 20 reliable compounds to seek the target compound in an in-house database. Certainly, those fragmentation pathways could also be deduced and described as Retro-Diels-Alder (RDA) fragmentation reaction, losses of C4H8, C5H8, CH3, CO, CO2 and others. Accordingly, 63 flavonoids were identified, and their in-silico bioactivity were clearly disclosed by some bioinformatics tools. In this experiment, the flavonoids obtained by the four extraction processes were tested by LC-qTOF-MS. We looked for possible Q-markers from these data matrices and then quantified them; their similarities/differences were also described. The results also indicated that the Macroporous Adsorption Resins (MARs) purification is a low cost, environmentally friendly and effective approach.
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