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1.
Animal ; 18(9): 101293, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39216153

ABSTRACT

Methane (CH4) from ruminant production systems produces greenhouse gases that contribute to global warming. Our goal was to determine whether monoammonium glycyrrhizinate could inhibit CH4 emissions over the long term without affecting animal performance and immune indices in Karakul sheep. This study aimed to assess the effects of medium-term (60 days) addition of monoammonium glycyrrhizinate on growth performance, apparent digestibility, CH4 emissions, methanogens, fibre-degrading bacteria and blood characteristics in Karakul sheep. Twelve male Karakul sheep (40.1 ± 3.59 kg) with fistula were randomly divided into two groups (n = 6): the Control group received a basal diet + the same volume of distilled water (30 ml) and the Treatment group received a basal diet + 8.75 g/kg monoammonium glycyrrhizinate injected via fistula. The adaptation stage was 15 days, and the measurement stage was 60 days. The sampling during the measurement stage was divided into two stages, stage I (1 ∼ 30 d) and stage II (31 ∼ 60 d). The results showed that monoammonium glycyrrhizinate significantly reduced the relative abundance of Bacteroides caccae, daily CH4 emission and protozoa population, significantly increased the relative abundance of Lachnospiraceae bacterium AD3010, Lachnospiraceae bacterium FE2018, Lachnospiraceae bacterium NK3A20, Lachnospiraceae bacterium NK4A179 and Lachnospiraceae bacterium V9D3004 in stage I (P < 0.05); significantly increased the relative abundance of Lachnospiraceae bacterium AD3010, but significantly decreased the relative abundance of Lachnospiraceae bacterium NK4A179 and Lachnospiraceae bacterium C6A11 in stage II (P < 0.05). Therefore, monoammonium glycyrrhizinate could be used as a CH4 inhibitor to limit the rumen CH4 emissions of Karakul sheep in short-term period (30 days) without affecting the growth performance, fibre digestibility and blood parameters.


Subject(s)
Animal Feed , Glycyrrhizic Acid , Methane , Rumen , Animals , Methane/metabolism , Glycyrrhizic Acid/pharmacology , Male , Sheep , Rumen/microbiology , Rumen/metabolism , Animal Feed/analysis , Diet/veterinary , Digestion/drug effects
2.
J Anim Sci ; 1012023 Jan 03.
Article in English | MEDLINE | ID: mdl-37155664

ABSTRACT

Dairy calves are highly susceptible to the negative effects of heat stress, which can cause organ hypoxia after blood redistribution, damage the intestinal barrier, and trigger intestinal oxidative stress. This study aimed to investigate the antioxidant effects of monoammonium glycyrrhizinate (MAG) on calf small intestinal epithelial cells under heat stress in vitro. Small intestinal epithelial cells were isolated from a 1-d-old healthy calf and purified by differential enzymatic detachment. The purified cells were divided into seven groups. The control group was cultured with DMEM/F-12 at 37 °C for 6 h, and the treatment groups were cultured with 0, 0.1, 0.25, 0.5, 1, or 5 µg/mL MAG at 42 °C for 6 h. Heat stress causes oxidative damage to cells. Adding MAG to the medium can significantly improve cell activity and reduce cellular oxidative stress. MAG significantly increased the total antioxidant capacity and superoxide dismutase activity caused by heat stress, and significantly decreased malondialdehyde and nitric oxide levels. The MAG treatment also reduced lactate dehydrogenase release, increased mitochondrial membrane potential, and decreased apoptosis under heat stress. MAG also upregulated the expression of the antioxidant-related genes, Nrf2 and GSTT1, in heat-stressed intestinal epithelial cells and significantly downregulated the expression of the heat shock response-related proteins, MAPK, HSP70, HSP90, and HSP27. From the above results, we conclude that 0.25 µg/mL MAG improves the capability of the antioxidant system in small intestinal epithelial cells to eliminate reactive oxygen species by activating antioxidant pathways, improving the oxidant/antioxidant balance, lowering excessive heat shock responses, and reducing intestinal oxidative stress.


In this study, we investigated the antioxidant effect of monoammonium glycyrrhizinate (MAG) on calf intestinal epithelial cells (CIECs) exposed to heat stress in vitro. Calves are sensitive to heat stress, and high temperatures can stimulate heat stress and produce a large number of reactive oxygen species (ROS) to induce oxidative stress. The intestinal tract plays a very important role in the immune defense system of dairy calves. The large amount of ROS can lead to the death of intestinal epithelial cells and damage to intestinal barrier. In order to investigate the antioxidant function of MAG, different concentrations of MAG were added to the culture medium of CIECs and the cells were subsequently exposed to heat stress. The results showed that MAG could effectively relieve oxidative stress and reduce the apoptosis of CIECs exposed to heat stress.


Subject(s)
Antioxidants , Oxidative Stress , Animals , Cattle , Antioxidants/pharmacology , Antioxidants/metabolism , Heat-Shock Response , Reactive Oxygen Species/metabolism , Epithelial Cells/metabolism
3.
J Anim Physiol Anim Nutr (Berl) ; 107(2): 475-484, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35989475

ABSTRACT

This study was conducted to evaluate the antioxidant capability of dietary supplementation with monoammonium glycyrrhizinate (MAG) in perinatal cows. Glycyrrhizic acid has been shown to have strong antioxidant activity and we hypothesised that the aglycone of glycyrrhizin and MAG, could reduce damage from oxidative stress in perinatal cows by enhancing antioxidant capacity. Blood and milk samples were collected from three groups of healthy perinatal cows that were similar in body weight, parity, milk yield in the last milk cycle, etc., receiving dietary MAG supplementation ([Day 0 = parturition]: 0 g/day, [n = 13)] 3 g/day [n = 13] or 6 g/day [n = 11]) from -28 to 56 day (0 day = parturition). Compared with 0 g/day controls (CON), milk fat was significantly decreased in cows fed with MAG, and 3 g/day had the greatest effect. A diet containing 3 g/day MAG decreased the serum alanine aminotransferase (ALT) level compared with CON at -7 day post-partum. ALT was also lower at 5 day post-partum in cows fed with 3 g/day MAG compared to 6 g/day. The administration of 3 g/day and 6 g/day MAG decreased serum aspartate transaminase (AST) at 3 day post-partum. Supplementation of MAG in cows increased total antioxidant capacity (T-AOC) in serum, and cows given 3 g MAG per day had higher T-AOC than controls on post-partum 7 day. At the end of the experiment, we isolated and cultured primary hepatocytes to determine the effect of MAG on oxidative stress caused by incubation with the sodium oleate (SO). SO increased lipid synthesis, but pre-treatment with MAG prevented the fatty buildup. SO treatment increased AST and ALT levels and malondialdehyde concentration, but decreased T-AOC and superoxide dismutase (SOD). Incubation with MAG increased antioxidant capacity and inhibited oxidant damage in bovine hepatocytes. SO stimulated expression of the antioxidant genes, NAD(P)H quinone dehydrogenase 1 (NQO1) and SOD1, in the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, and catalase 1 (CAT1); this increase was accentuated by MAG pre-treatment. The results suggest that MAG can alleviate the damage caused by oxidative stress in perinatal cows by enhancing antioxidant activity.


Subject(s)
Antioxidants , Glycyrrhetinic Acid , Pregnancy , Female , Cattle , Animals , Antioxidants/metabolism , Glycyrrhizic Acid/metabolism , Glycyrrhizic Acid/pharmacology , Oxidative Stress , Parturition , Diet/veterinary , Milk/metabolism , Glycyrrhetinic Acid/metabolism , Glycyrrhetinic Acid/pharmacology , Dietary Supplements , Lactation
4.
Res Vet Sci ; 150: 213-223, 2022 Dec 05.
Article in English | MEDLINE | ID: mdl-35868152

ABSTRACT

In this study we investigated the effect of MAG on fatty deposit-induced degeneration of primary calf hepatocytes induced by sodium oleate. Primary hepatocytes were isolated from dairy calves and cultured before allocation to the following treatment groups: control (untreated), model (starved for 12 h before treatment with 0.25 mM sodium oleate to induce steatosis-like changes, and the MAG group pretreated with MAG (0.1, 0.25, 0.5, and 1.5 mM) for 12 h before sodium oleate treatment (0.25 mM) for 12 h). To evaluate the effect of MAG on fat-induced degradation of primary hepatocytes, we evaluated lipid deposition, cell viability, apoptosis rate, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the culture supernatant, and expression of oxidant and antioxidant enzymes (LDH, MDA, GSH, and CAT), as well as the expression of lipid metabolism-related genes (PPARα, SREBP-1c, ChREBP, CPT1, CPT2, and MTP) and apoptosis-related genes (Cyt-c, Caspase 9, Caspase 8, Caspase 3, Bax, and Bcl-2). MAG significantly reduced lipid accumulation in hepatocytes induced by sodium oleate (P < 0.05), increased cell viability, decreased the apoptosis rate (P < 0.05), and significantly decreased ALT and AST activity in the culture supernatant (P < 0.05). MAG significantly decreased MDA levels in cells and LDH levels in the culture supernatant, while GSH and CAT levels were increased (P < 0.05). MAG significantly increased the expression of the lipid transport- and metabolism-related genes MTP, PPARα, CPT1 and CPT2, and decreased ChREBP expression (P < 0.05). At concentrations higher than 0.25 mM, MAG significantly decreased SREBP-1c expression (P < 0.05). MAG significantly decreased the expression of the apoptosis-related genes Cyt-c, Caspase 9, Caspase 8, Caspase3 and Bax, while Bcl-2 expression was increased (P < 0.05). These findings demonstrate that MAG improves the antioxidant capacity of hepatocytes and effectively reduces lipid deposition by inhibiting the expression of lipid metabolism- and apoptosis-related genes.


Subject(s)
Antioxidants , PPAR alpha , Animals , Antioxidants/pharmacology , Apoptosis , Caspase 8/metabolism , Caspase 8/pharmacology , Caspase 9/metabolism , Caspase 9/pharmacology , Cattle , Hepatocytes/metabolism , Liver/metabolism , Oleic Acid/metabolism , Oleic Acid/pharmacology , PPAR alpha/genetics , PPAR alpha/metabolism , PPAR alpha/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , bcl-2-Associated X Protein/metabolism
5.
J Pharm Pharmacol ; 74(5): 730-739, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35355074

ABSTRACT

OBJECTIVES: Acetaminophen (APAP) overdose has been the primary cause of drug-induced liver injury (DILI) in western countries. Monoammonium glycyrrhizinate (MG) is a primary active ingredient from glycyrrhiza. Cysteine hydrochloride (CH) is a component of glutathione (GSH). The study aimed to explore the therapeutical effect of MG-CH against DILI incurred by intragastric APAP. METHODS: Mice were randomized into eight groups: control, APAP, three groups accepted APAP and the combination of MG and CH (15, 30, 60 mg/kg), two groups accepted APAP and MG (40 mg/kg) or CH (20 mg/kg), moreover, one group received MG-CH (60 mg/kg) without APAP. After pretreatment with MG-CH or MG and CH alone for 3 days, mice were administered APAP by oral gavage. The serum and tissue were collected to detect the activities of liver enzymes and evaluate the change of histomorphology and explore the possible mechanism of MG-CH in protecting against DILI. KEY FINDINGS: MG-CH pretreatment remarkably alleviated hepatic injury and decreased the activities of ALT, AST, ALP and LDH. The hepatic ROS and MDA contents were decreased, and the level of GSH and GSH-PX activities was increased in the serum. Furthermore, MG-CH improved the expression of Nrf2, HO-1, GCLM and NQO1 to increase antioxidant ability and induce detoxification. The expression of IL-10 suppressing excessive inflammatory responses was enhanced. CONCLUSION: The study demonstrated that MG-CH had protective effects against DILI induced by APAP and the potential mechanisms were based on inhibiting oxidative stress and activating the Keap1/Nrf2/ARE pathway.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Chemical and Drug Induced Liver Injury , Acetaminophen/metabolism , Acetaminophen/toxicity , Animals , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Cysteine/metabolism , Cysteine/pharmacology , Glutathione/metabolism , Glycyrrhizic Acid/pharmacology , Kelch-Like ECH-Associated Protein 1/metabolism , Liver , Mice , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Signal Transduction
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(1): 22-29, 2022 Feb.
Article in Chinese | MEDLINE | ID: mdl-35123599

ABSTRACT

OBJECTIVE: To investigate the effect of monoammonium glycyrrhizinate on the stem cell-like characteristics, oxidative stress and mitochondrial function of acute promyelocytic leukemia cells NB4. METHODS: CCK-8 method was used to detect the viability of acute promyelocytic leukemia cells NB4, and the appropriate dose was screened; Cloning method was used to detect the proliferation rate of NB4 cell; Western blot was used to detect the expression of cell cycle-related protein; flow cytometry was used to detect cell apoptosis and sort NB4 stem cells positive (CD133+); Stem cell markers (Oct4, ABCG2, Dclk1) were detected by RT-PCR; ROS was detected by fluorescence; The kit was used to detect the level of oxidative stress markers (MDA); The flow cytometry was used to detect the change of mitochondrial membrane potential; Western blot was used to detect the expression of mitochondrial damage index-related proteins (Bax/BCL-2). RESULTS: Compared with the control group, if the concentration of MAG was less than 5 µmol/L, the cell NB4 viability showed no significant difference; if the concentration was higher than 5 µmol/L, the inhibitory effect on the growth of cell NB4 increased and showed significant difference (P<0.05), according to the results of CCK-8 experiment, four groups were set based on the concentration of MAG 0 µmol/L, MAG 5 µmol/L, MAG 10 µmol/L, and MAG 20 µmol/L; compared with the control group (MAG 0 µmol/L), the cells in MAG 5 µmol/L group showed no significant difference, while the proliferation rate, cyclin expression, mitochondrial membrane potential, stem cell CD133+ ratio, and marker mRNA level ( Oct4, ABCG2, Dclk1) of NB4 cell were significantly reduced (P<0.05); the apoptosis rate, reactive oxygen species, MDA content and Bax/BCL-2 expression of NB4 cell significantly increased (P<0.05). CONCLUSION: Monoammonium glycyrrhizinate has a significant inhibitory effect on acute promyelocytic leukemia cells NB4, which may be related to the regulation of stem cell-like characteristics, oxidative stress and mitochondrial function.


Subject(s)
Leukemia, Promyelocytic, Acute , Apoptosis , Cell Line, Tumor , Doublecortin-Like Kinases , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Mitochondria , Oxidative Stress , Protein Serine-Threonine Kinases , Stem Cells
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-928665

ABSTRACT

OBJECTIVE@#To investigate the effect of monoammonium glycyrrhizinate on the stem cell-like characteristics, oxidative stress and mitochondrial function of acute promyelocytic leukemia cells NB4.@*METHODS@#CCK-8 method was used to detect the viability of acute promyelocytic leukemia cells NB4, and the appropriate dose was screened; Cloning method was used to detect the proliferation rate of NB4 cell; Western blot was used to detect the expression of cell cycle-related protein; flow cytometry was used to detect cell apoptosis and sort NB4 stem cells positive (CD133+); Stem cell markers (Oct4, ABCG2, Dclk1) were detected by RT-PCR; ROS was detected by fluorescence; The kit was used to detect the level of oxidative stress markers (MDA); The flow cytometry was used to detect the change of mitochondrial membrane potential; Western blot was used to detect the expression of mitochondrial damage index-related proteins (Bax/BCL-2).@*RESULTS@#Compared with the control group, if the concentration of MAG was less than 5 μmol/L, the cell NB4 viability showed no significant difference; if the concentration was higher than 5 μmol/L, the inhibitory effect on the growth of cell NB4 increased and showed significant difference (P<0.05), according to the results of CCK-8 experiment, four groups were set based on the concentration of MAG 0 μmol/L, MAG 5 μmol/L, MAG 10 μmol/L, and MAG 20 μmol/L; compared with the control group (MAG 0 μmol/L), the cells in MAG 5 μmol/L group showed no significant difference, while the proliferation rate, cyclin expression, mitochondrial membrane potential, stem cell CD133+ ratio, and marker mRNA level ( Oct4, ABCG2, Dclk1) of NB4 cell were significantly reduced (P<0.05); the apoptosis rate, reactive oxygen species, MDA content and Bax/BCL-2 expression of NB4 cell significantly increased (P<0.05).@*CONCLUSION@#Monoammonium glycyrrhizinate has a significant inhibitory effect on acute promyelocytic leukemia cells NB4, which may be related to the regulation of stem cell-like characteristics, oxidative stress and mitochondrial function.


Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Doublecortin-Like Kinases , Intracellular Signaling Peptides and Proteins/metabolism , Leukemia, Promyelocytic, Acute , Mitochondria , Oxidative Stress , Protein Serine-Threonine Kinases , Stem Cells
8.
Eur J Pharmacol ; 913: 174628, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34774851

ABSTRACT

Combination of monoammonium glycyrrhizinate and cysteine hydrochloride (MG-CH) has been used in the treatment of chronic liver disease for decades, however, its mechanism is still unclear. Our previous studies showed that MG-CH confers the optimal therapeutic effect at the ratio of 2:1 to against acute liver damage. In this study, it was used to investigate the anti-fibrotic effect induced by CCl4. The results showed that injection of MG-CH produced anti-fibrotic effect ranged from 30 mg/kg to 60 mg/kg, evidenced by decreased the collagens deposition and inhibited the production of hydroxyproline. Mechanism study found that Nrf2/ARE signaling pathway was activated by MG-CH, whereas loss of hepatocytic Nrf2 abolished its anti-fibrotic effect significantly. Furthermore, it was demonstrated that MG-CH is a non-canonical NRF2 inducer, which promoted the autophagy activity and release the Nrf2 from keap 1 by promoting the phosphorylation of p62 at Ser351. Knockdown of p62 abolished the enhancement of nuclear accumulation of Nrf2 by MG-CH. All of these results suggested that up-regulation of Nrf2/P62/Keap1 involves in the anti-fibrotic effect of MG-CH, which provide a rational explanation for the usage of MG-CH in the treatment of fibrosis.


Subject(s)
Antifibrotic Agents/pharmacology , Cysteine/pharmacology , Glycyrrhizic Acid/pharmacology , Liver Cirrhosis/drug therapy , Animals , Antifibrotic Agents/therapeutic use , Carbon Tetrachloride/administration & dosage , Carbon Tetrachloride/toxicity , Cysteine/therapeutic use , Disease Models, Animal , Gene Knockdown Techniques , Gene Knockout Techniques , Glycyrrhizic Acid/therapeutic use , Hep G2 Cells , Hepatocytes , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/pathology , Male , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Rats , Sequestosome-1 Protein/genetics , Sequestosome-1 Protein/metabolism , Signal Transduction/drug effects , Up-Regulation/drug effects
9.
Anim Biotechnol ; 32(6): 688-698, 2021 Dec.
Article in English | MEDLINE | ID: mdl-32213006

ABSTRACT

Cattle fatty liver has caused mass damage in milk production during the past few years. In our study, to identify different miRNAs involved in cell physiological regulation in fatty liver, we performed miRNA deep sequencing on a normal liver cell (S01), fatty liver cell (S02) and processed cell by monoammonium glycyrrhizinate (S03). As a result, a total of 15,277,462, 14,190,360 and 13,771,060 raw reads representing 13,904,074, 12,784,128 and 11,017,604 clean reads per library were obtained separately. Through bioinformatics analysis, a total of 511 known miRNAs were identified when they were aligned with the known animal miRNAs, and 197 novel miRNAs were predicted using mirDeep2 software. A total of 511 miRNAs including 101 known and 51 novel miRNAs were expressed significantly different. Additionally, expression levels of eight randomly selected miRNAs were confirmed using the stem-loop qPCR, and their expression profiles were consistent with the deep sequencing results. For better understanding the functions of miRNAs, a total of 14,231 targets were predicted. These predicted target genes were further analyzed by function annotation and enrichment pathways, the results showed that these targets of the identified miRNAs are involved in a broad range of physiological functions.


Subject(s)
Cattle Diseases , Cattle , Fatty Liver , MicroRNAs , Animals , Cattle/genetics , Cattle Diseases/genetics , Computational Biology , Fatty Liver/genetics , High-Throughput Nucleotide Sequencing , MicroRNAs/genetics
10.
Eur J Pharmacol ; 882: 173258, 2020 Sep 05.
Article in English | MEDLINE | ID: mdl-32544505

ABSTRACT

Combination of monoammonium glycyrrhizinate and cysteine hydrochloride (MG-CH) has been used for treatment of chronic liver damage in clinic for several years, however, the effect of MG-CH on acute liver injury (ALI) is still obscure. In this study, we aimed to investigate the effect of MG-CH on ALI induced by co-injection of lipopolysaccharide (LPS) and d-galactosamine (GalN). Our results found that MG-CH produced the optimal therapeutic effect at the ratio of 2:1, as manifested by the increased survival percentage, decreased ALT and AST level and improved hepatic pathology. Both oxidative stress and inflammation induced by LPS/GalN were attenuated by MG-CH. Mechanism study showed that MG-CH promoted the nuclear accumulation of Nrf2 and its transcriptional activity, as well as improved Nrf2-target genes' expression. It was also found that activation of Nrf2 is dependent on the MG, not CH. Blockade of Nrf2 abolished the anti-inflammatory effect of MG-CHinduced by LPS/GalN, while inhibition of NFκB showed no effect on its anti-oxidative effect, though the inhibited phosphorylation of IκB and NFκB were detected in liver. The protective effect of MG-CH against ALI was abolished in Nrf2-/- mice. All of these results suggested that MG-CH ameliorated LPS/GalN induced ALI through Nrf2/ARE pathway.


Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Cysteine/therapeutic use , Glycyrrhizic Acid/therapeutic use , NF-E2-Related Factor 2/metabolism , Animals , Antioxidant Response Elements , Cells, Cultured , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/metabolism , Cysteine/pharmacology , Cytokines/genetics , Drug Combinations , Galactosamine , Glutathione/metabolism , Glycyrrhizic Acid/pharmacology , Heme Oxygenase-1/genetics , Hepatocytes/drug effects , Hepatocytes/metabolism , Lipopolysaccharides , Liver/drug effects , Liver/metabolism , Male , Malondialdehyde/metabolism , Mice, Inbred C57BL , Mice, Knockout , NF-E2-Related Factor 2/genetics , Peroxidase/metabolism , Signal Transduction/drug effects , Superoxide Dismutase/metabolism
11.
Clin Exp Pharmacol Physiol ; 47(5): 809-820, 2020 05.
Article in English | MEDLINE | ID: mdl-31944346

ABSTRACT

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it unavoidable. It is implicated in the aetiology of different neurodegenerative diseases and can induce liver injury. In addition, insulin resistance (IR) plays an essential role in the pathogenesis and the progression of liver disorders. The increased consumption of fructose contained in soft drinks and western pattern diet results in IR that along with the wide distribution of aluminium make the concurrent exposure conceivable and increase the risk of liver injury. Therefore, the present study explores the hepatotoxic effects of aluminium and fructose administered concurrently and evaluates the possible protection by monoammonium glycyrrhizinate (MAG). Liver injury was induced by the administration of aluminium chloride (34 mg/kg/d) plus 10% (w/v) fructose in drinking water. Male rats were treated with either MAG (40 mg/kg/d) or silymarin (SIL, 100 mg/kg/d). The concurrent administration of aluminium and fructose (FRUAL) induced liver injury manifested as a significant elevation of serum liver enzymes activities, bilirubin level, and prothrombin time, as well as reduction of albumin level. On the other hand, the administration of MAG improved the FRUAL-induced aberrations of liver function tests and hepatic cytoarchitecture. We assume that the MAG-induced suppression of oxidative stress, toll-like receptor 4 pathway activation, inflammation, and apoptosis might play a crucial role in the hepatoprotective effect of MAG in this model. Intriguingly, the hepatoprotective effect MAG against FRUAL-induced liver injury surpasses that of the gold standard SIL, suggesting MAG as a better alternative to SIL.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Glycyrrhizic Acid/pharmacology , Liver/drug effects , Protective Agents/pharmacology , Silymarin/pharmacology , Aluminum Chloride , Animals , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Disease Models, Animal , Fructose , Glycyrrhizic Acid/analogs & derivatives , Inflammation Mediators/metabolism , Liver/metabolism , Liver/pathology , Male , Oxidative Stress/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats, Wistar , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Triglycerides/blood
12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-850956

ABSTRACT

Objective To investigate the effects of the three methods of decocting with deslag, decocting without deslag, and double decocting on the content of nine ingredients baicalin, baicalein, ginsenoside Re, ginsenoside Rb1, monoammonium glycyrrhizinate hydrate, liquiritin, 6-gingerol, berberine hydrochloride, palmatine hydrochloride, and total flavonoids in Banxia Xiexin Decoction (BXD). Methods Nine index components were determined by HPLC. The HPLC analysis was performed on Welch Ultimate XB-C18 column (250 mm × 4.6 mm, 5 μm) with mobile phase of acetonitrile-0.1% phosphate aqueous solution for gradient elution; And carried out at column temperature of 28 ℃, volume flow of 0.9 mL/min, and detection wavelength of 203, 252, 280, and 355 nm. The total flavonoids were determined by colorimetry. Results Nine kinds of ingredients and total flavonoids could be detected in three different decoctions. In the method of decocting with deslag, baicalin, baicalein, ginsenoside Rb1, monoammonium glycyrrhizinate hydrate, and liquiritin increased by 10.01%, 12.88%, 29.09%, 16.75%, and 15.02%, respectively, compared with decocting without deslag; It decreased by 5.54%, 4.15%, 14.49%, 7.85%, and 9.18%, respectively compared with double decocting; Ginsenoside Re, 6-gingerol, berberine hydrochloride, and palmatine hydrochloride increased by 37.90%, 3.78%, 5.33%, and 5.99% compared with decocting without deslag, respectively; compared to the double decocting methods, it increased by 1.07%, 11.57%, 3.41%, and 1.93%. The total flavonoids increased 22.61% higher than decocting without deslag and 6.54% higher than double decocting. Conclusion: The results can effectively reflect the quality difference of different decocting methods. Among the three methods of decoction, the method of decocting without deslag has significantly improved the dissolution of the active ingredients of each component in the decoction, and improve the clinical efficacy of BXD to a certain extent. It provides a good experimental basis for the decocting without deslag method used in Zhang Zhongjing’s Treatise on Febrile Diseases.

13.
Saudi Pharm J ; 24(2): 153-64, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27013908

ABSTRACT

CONTEXT: Medicated chewing gum (MCG) of Domperidone Maleate (DM) was developed by direct compression method with the goal to achieve quick onset of action and to improve patient compliance. OBJECTIVE: Formulation development of MCG of DM and optimization of the formulation by screening of different excipients. MATERIAL AND METHODS: MCG containing DM was prepared by screening different concentrations of sweeteners, flavouring agents, softening agents, lubricants and anti-adherents by changing one variable at a time. Performance evaluation was carried out by evaluating size, shape, thickness, taste, scanning electron microscopy, texture analysis, in vivo drug release study, ex vivo buccal permeation study and by studying statistical analysis for quality. RESULTS AND DISCUSSION: The statistical analysis showed significant improvement in organoleptic properties such as chewable mass, product taste, product consistency, product softness, total flavour lasting time and pharmaceutical properties like micromeritic properties after incorporation of appropriate excipients in an optimum amount in final optimized MCG formulation. In vivo drug release study showed 97% DM release whereas ex vivo buccal permeation study through goat buccal mucosa exhibited 11.27% DM permeation within 15 min indicating its potential for increasing bioavailability by decreasing time of onset. The optimized formulation showed good surface properties and the peak load required for drug release was found to be acceptable for crumbling action. CONCLUSION: The developed formulation of medicated chewing gum can be a better alternative to mouth dissolving and conventional tablet formulation. It may be proved as a promising approach to improve the bioavailability as well as to improve patient compliance.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-853550

ABSTRACT

Objective: Taking thewater extraction of Compound Banlangen Liyan Granules (IsatidisRadix, ScrophulariaeRadix, PlatycodiRadix, GlycyrrhizaeRadix, etc.)as the research object to explore the dynamic migration regular of the active ingredient population of compoundChinesemateriamedica in different apertures in ceramic membrane separation process and compare its membrane filtration flux and solid inclusion removal rate. Methods: The water extraction of Compound Banlangen Liyan Granules was separated with 200 nm and 50 nm aperture of ceramic membrane, respectively. Continuously sampling for many times was done in the ceramic membrane separation process. The optimized HPLC methods were as follows: chromatographic column was Agilent Zorbox Eclipse XDB-C18, mobile phase was acetonitrile-0.05% phosphoric acid in gradient elution at flow rate of 1 mL/min, detection wavelength was wavelength switching, injection volum was 10 μL, the column temperature was 30 ℃. The contents of sixactive ingredients[adenosine, (R,S)-goitrin, liquiritin, harpagosid, platycodinD, and monoammonium glycyrrhizinate]were determined in thecompound at the same time, and the dynamic migration rates were investigated. Results:The simultaneous determination of the sixactive ingredient in thecompound was done with HPLC method. For the water extraction in Compound Banlangen Liyan Granules, in the 200 nm ceramic membrane separation process, the dynamic migration rates of the sixactive ingredientsranged between 71%-104%, the average migration rate was 85%, the membrane filter flux attenuation was smaller, the stable flux was in 426-340 L/(m2∙h), solid inclusion removal rate was 21.0%. But in 50 nm ceramic membrane, the dynamic migration rates of the sixactiveingredients ranged between 83%-107%, the average migration rate was83%, the membrane filter flux attenuation was larger, the stable flux was in 258-228 L/(m2∙h), and solid inclusion removal rate was23.9%. Conclusion :The experiment preliminarily reflects the dynamic migration regular of the active ingredient population of compoundChinesemateriamedica in two different aperture ceramic membrane separation process. It lays a migration theoretical foundation of effective materials for popularization and application of modern ceramic membrane technology in Chinese materiamedica refining.

15.
J Ethnopharmacol ; 166: 149-56, 2015 May 26.
Article in English | MEDLINE | ID: mdl-25794808

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin decoction (BXD), one of a traditional Chinese medicine chronicled in Shang Han Lun, is commonly used to treat gastroenteritis, ulcerative colitis and diarrhea. In our study, we used current biomedical approaches to investigate the therapeutic efficacy of BXD and possible protective mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced chronic ulcerative colitis model. MATERIALS AND METHODS: Chronic DSS colitis was induced in C57BL/6 male mice by three cycles of 5 days of 2% DSS in drinking water, alternating with 5 days of normal water, totaling 30 days. In BXD group, the mice were administered at a dose of 8.7g/kg BXD for 5 days before and during DSS treatment via oral gavage per day. Mice in vehicle group and DSS group were given orally the same volume of drinking water, instead. Body weight, stool characters and hematochezia were observed everyday. The colorectal tissues were used to detect levels of TNF-α, IL-4, IL-10, IL-1ß, IL-17, IL-23 and MPO by ELISA or qRT-PCR. The expression of COX-2, 8-Oxoguanine and Nrf2 were examined by IHC, and p-p65 was examined by western blotting. ThOD and the content of MDA were measured according to kits respectively. RESULTS: BXD significantly protected against DSS-induced chronic ulcerative colitis by amelioration of body weight loss, DAI and histology score. The level of TNF-α, IL-1ß, IL-17, IL-23, COX-2 and p-p65 were decreased significantly, while the level of IL-10 improved with the treatment of BXD. MDA, MPO and 8-Oxoguanine were decreased, meanwhile SOD activity and Nrf2 expression were elevated significantly by BXD. CONCLUSIONS: BXD possesses the potential of anti-inflammation and anti-oxidation to treat colitis. The protective mechanism of BXD may involve in inhibition of NF-κBp65 activation and increasement of Nrf2 expression in colorectums of mice.


Subject(s)
Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Dextran Sulfate/pharmacology , Drugs, Chinese Herbal/pharmacology , Plant Extracts/pharmacology , Animals , Body Weight/drug effects , Colitis, Ulcerative/metabolism , Colon/drug effects , Colon/metabolism , Cyclooxygenase 2/metabolism , Guanine/analogs & derivatives , Guanine/metabolism , Interleukins/metabolism , Male , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , Transcription Factor RelA/metabolism , Tumor Necrosis Factor-alpha/metabolism
16.
Colloids Surf B Biointerfaces ; 125: 291-9, 2015 Jan 01.
Article in English | MEDLINE | ID: mdl-25524220

ABSTRACT

In the present paper physical gels, prepared with two polysaccharides, Xanthan and Locust Bean Gum, and loaded with non-ionic surfactant vesicles, are described. The vesicles, composed by Tween20 and cholesterol or by Tween85 and Span20, were loaded with Monoammonium glycyrrhizinate for release experiments. Size and zeta (ζ)-potential of the vesicles were evaluated and the new systems were characterized by rheological and dynamo-mechanical measurements. For an appropriate comparison, a Carbopol gel and a commercial gel for topical applications were also tested. The new formulations showed mechanical properties comparable with those of the commercial product indicating their suitability for topical applications. In vitro release experiments showed that the polysaccharide network protects the integrity of the vesicles and leads to their slow release without disruption of the aggregated structures. Furthermore, being the vesicles composed of molecules possessing enhancing properties, the permeation of the loaded drugs topically delivered can be improved. Thus, the new systems combine the advantages of matrices for a modified release (polymeric component) and those of an easier permeability across the skin (vesicle components). Finally, shelf live experiments indicated that the tested gel/vesicle formulations were stable over 1 year with no need of preservatives.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Galactans/chemistry , Glycyrrhizic Acid/chemistry , Liposomes/chemistry , Mannans/chemistry , Plant Gums/chemistry , Polysaccharides, Bacterial/chemistry , Acrylic Resins/chemistry , Administration, Topical , Delayed-Action Preparations , Drug Liberation , Gels , Hexoses/chemistry , Kinetics , Polysorbates/chemistry , Solutions , Surface-Active Agents/chemistry
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-579869

ABSTRACT

AIM: To establish the methods of identifing and determining Yiganjian Tables. METHODS: Herba Halenia,extract of Radix et Rhizoma Glycyrrhizale,Radix Astragali were identified by TLC.The content of 1-hydroxy-3,4,5-trimethoxyxanthon in Herba Halenia was determined by HPLC on Hypersil-ODS2 column with the mobile phase of methanol-0.2%H_3PO_4(55∶45).The detective wavelength was set at 243 nm and monoammonium glycyrrhizinate was determinad by HPLC on Hypersil-ODS2 column with the mobile phase of acetonitrile-2% aceacid(60∶40).The detective wavelength was set at 250 nm. RESULTS: The linear range of 1-hydroxy-3,4,5-trimethoxyxanthon was from 0.173 2 to 0.866 0 ?g.The average recovery was 100.56%,RSD was 2.7%(n=9).The linear range of monoammonium glycyrrhizinate was from 0.55 to 2.75 ?g.The average recovery was 98.29%,RSD was 1.7%(n=9). CONCLUSION: The method is simple,accurate and sensitive,so it can be used for the quality control of Yiganjian Tablets.

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