Magnesium Isoglycyrrhizinate Research Articles

Effectiveness and Economic Evaluation of Polyene Phosphatidyl Choline in Patients With Liver Diseases Based on Real-World Research.

Aims: Liver disease has high prevalence, number, and disease burden in China, and polyene phosphatidyl choline (PPC) is a widely used liver protective drug. We aim to explore the effectiveness and economy of PPC in patients with liver diseases based on real-world research and compare with other hepatoprotective drugs. Methods: This is a “three-phase” study from three medical centers, including descriptive study of patients using PPC injection, self-control case study of patients using PPC injection, and specific-disease cohort study of patients using PPC injection or control drugs. The major measurements of liver function for effectiveness analysis were the alanine transaminase (ALT) level changes and recovery rate. The main statistical methods were Wilcoxon signed rank test, χ 2 test, and Mann–Whitney U test. Propensity score matching was applied to reduce bias. Cost-effectiveness analysis, cost minimization analysis, and sensitivity analysis were used for economic evaluation. Results: PPC alone or in combination with glutathione and magnesium isoglycyrrhizinate shows less total hospitalization cost (p < 0.05) and smaller cost-effectiveness ratio and was effective in protecting liver function, especially in patients with liver transplantation or postoperation of nontumor liver disease (ALT decreased significantly after PPC treatment; p < 0.05). Glutathione and magnesium isoglycyrrhizinate combined with PPC could enhance the protective function of liver. Conclusion: PPC was an effective and economic liver protective drug in patients with specific liver diseases, and PPC could enhance the liver protective function of glutathione and magnesium isoglycyrrhizinate.

Nephroprotective effect of magnesium isoglycyrrhizinate against arsenic trioxide-induced acute kidney damage in mice.

Magnesium isoglycyrrhizinate (MgIG) has anti-inflammatory, antioxidative, antiviral and anti-hepatotoxic effects. However, protective effects of MgIG against renal damage caused by arsenic trioxide (ATO) have not been reported. The present study aimed to clarify the protective function of MgIG on kidney damaged induced by ATO. Other than the control group and the group treated with MgIG alone, mice were injected intraperitoneally with ATO (5 mg/kg/day) for 7 days to establish a mouse model of kidney damage. On the 8th day, blood and kidney tissue were collected and the inflammatory factors and antioxidants levels in the kidney tissue and serum were measured. The expression of protein levels of caspase-3, Bcl-2, Bax, Toll-like receptor-4 (TLR4) and nuclear factor-κB (NF-κB) were determined via western blot analysis. In the renal tissue of mice, ATO exposure dramatically elevated markers of oxidative stress, apoptosis and inflammation. However, MgIG could also restore the activities of urea nitrogen and creatinine to normal levels, decrease the malondialdehyde level and reactive oxygen species formation and increase superoxide dismutase, catalase and glutathione activities. MgIG also ameliorated the morphological abnormalities generated by ATO, reduced inflammation and apoptosis and inhibited the TLR4/NF-κB signaling pathway. In conclusion, MgIG may mitigate ATO-induced kidney damage by decreasing apoptosis, oxidative stress and inflammation and its mechanism may be connected to the inhibition of TLR4/NF-κB signaling.

Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review.

Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.

Comparative effectiveness of glycyrrhizic acid preparations aimed at preventing and treating anti-tuberculosis drug-induced liver injury: A network meta-analysis of 97 randomized controlled trials

Background and objectivesClinical guidelines and expert consensus do not yet recommend glycyrrhizic acid (GA) preparations, such as compound glycyrrhizin, diammonium glycyrrhizin, magnesium isoglycyrrhizinate (MGIG), et al., for the prevention of anti-tuberculosis(anti-TB) drug-induced liver injury (DILI) due to insufficient evidence. Although these GA preparations are recommended for the treatment of anti-TB DILI, which one performs best is unclear. Previous conventional meta-analyses did not summarize the results of simultaneous comparisons of different glycyrrhizinate preparations. Therefore, we aimed to compare and rank different GA preparations on preventing and treating the anti-TB DILI by network meta-analysis (NMA). MethodsA systematic search on PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, SinoMed, Chongqing VIP and, the Wanfang Database was performed up to December 19, 2020. The literature was screened according to predefined inclusion and exclusion criteria to extract important information. The outcomes were the incidence of liver injury (prevention section) and treatment response rate (treatment section). The NMA was conducted with a random-effects model under the Bayesian framework to calculate risk ratios (RRs) with 95% credible intervals (95% CrIs) using R software (version 3.6.1). ResultsFrom 1,411 publications, we included 97 relevant randomized clinical trials (RCTs) (10,923 participants). In terms of preventing anti-TB DILI (33 RCTs, comprising 5,762 patients), CGC, DGC, DGEC, and DGI, but not CGI, significantly reduced the incidence of liver injury than control group (RRs ranged from 0.26 to 0.58); CGC and DGEC were superior to DGC (RRs = 0.50 and 0.58, respectively). In terms of treating anti-TB DILI (64 RCTs, comprising 5,161 patients), MGIG was most effective among all regimens (RRs ranged from 1.15 to 1.72) while DGC ranked last (RRs ranged from 0.58 to 0.83). ConclusionsAll GA preparations except for CGI were effective in preventing the incidence of anti-TB DILI and CGC was superior to DGC. MGIG seems to be the best choice among all GA preparations for the treatment of anti-TB DILI. Future clinical practice guidelines should factor in these novel findings to improve patient outcomes; however, further high-quality trials are needed to validate these results.

Magnesium Isoglycyrrhizinate Ameliorates Concanavalin A-Induced Liver Injury by Inhibiting Autophagy.

Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury. Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry. Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy. Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.

Magnesium isoglycyrrhizinate inhibits airway inflammation in rats with chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a kind of chronic lung diseases with the characteristics of airway remodeling and airflow obstruction. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating hepatitis. However, whether MgIG can treat other diseases and its action mechanism is still obscure. In this study, we evaluated the anti-inflammatory effect of MgIG in rats with COPD and investigated the underlying mechanisms.MethodsRat model of COPD was constructed by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction. Rats were randomly divided into 5 groups: control group, COPD model group, salmeterol fluticasone comparator group, low dose of MgIG group, and high dose of MgIG group. Except for normal control group, the other four groups received sensitization treatment by cigarette smoking and endotracheal-atomization of endotoxin lipopolysaccharide to construct COPD rats model. After model established successfully, the COPD rats in each group received corresponding dose of endotracheal-atomized normal saline, salmeterol fluticasone, and MgIG every day prior to exposure of cigarette smoke from days 30 to 45. Normal control group were treated with normal saline. Finally, All rats were euthanatized. Pulmonary function was measured. Cells in bronchoalveolar lavage fluid were classified, inflammatory factors IL-6 and TNF-α were determined, histopathological analysis was performed by HE staining, and expression of NLRP3 and cleaved caspase-1 in the lung tissue was also determined by Western blotting.ResultsIt showed that MgIG treatment (0.40 or 0.80 mg/kg/day) could recover the weight and the clinical symptoms of rats with COPD, accompanied with lung inflammation infiltration reduction, airway wall attenuation, bronchial mucus secretion reduction. Additionally, MgIG administration reduced inflammatory cells (white blood cells, neutrophils, lymphocytes and monocytes) accumulation in bronchoalveolar lavage fluid and decreased IL-6 and TNF-α production in the serum of COPD rats. Furthermore, MgIG treatment also reduced the expression level of NLRP3 and cleaved caspase-1.ConclusionIt indicate that MgIG might be an alternative for COPD treatment, and its mechanism of action might be related to the suppression of NLRP3 inflammasome.

Magnesium isoglycyrrhizinate prevents cadmium-induced activation of JNK and apoptotic hepatocyte death by reversing ROS-inactivated PP2A.

Cadmium (Cd) induces reactive oxygen species (ROS)-mediated hepatocyte apoptosis and consequential liver disorders. This study aimed to investigate the effect of magnesium isoglycyrrhizinate (MgIG) on Cd-induced hepatotoxicity. L02 and AML-12 cells were used to study MgIG hepatoprotective effects. Cd-evoked apoptosis, ROS and protein phosphatase 2A (PP2A)/c-Jun N-terminal kinase (JNK) cascade disruption were analysed by cell viability assay, 6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, ROS imaging and Western blotting. Pharmacological and genetic approaches were used to explore the mechanisms. We show that MgIG attenuated Cd-evoked hepatocyte apoptosis by blocking JNK pathway. Pre-treatment with SP600125 or ectopic expression of dominant-negative c-Jun enhanced MgIG's anti-apoptotic effects. Further investigation found that MgIG rescued Cd-inactivated PP2A. Inhibition of PP2A activity by okadaic acid attenuated the MgIG's inhibition of the Cd-stimulated JNK pathway and apoptosis; in contrast, overexpression of PP2A strengthened the MgIG effects. In addition, MgIG blocked Cd-induced ROS generation. Eliminating ROS by N-acetyl-l-cysteine abrogated Cd-induced PP2A-JNK pathway disruption and concurrently reinforced MgIG-conferred protective effects, which could be further slightly strengthened by PP2A overexpression. Our findings indicate that MgIG is a promising hepatoprotective agent for the prevention of Cd-induced hepatic injury by mitigating ROS-inactivated PP2A, thus preventing JNK activation and hepatocyte apoptosis.

Exploring the efficacy and safety of polyene phosphatidylcholine for treatment of drug-induced liver injury using the Roussel Uclaf causality assessment method: a propensity score matching comparison.

Objective In China, polyene phosphatidylcholine (PPC) is widely used to treat alanine aminotransferase (ALT) elevation associated with various liver diseases. Here, we assessed the efficacy and safety of PPC in treating drug-induced liver injury (DILI).Methods Data from a multicenter retrospective cohort study (DILI-R) were analyzed to compare PPC and magnesium isoglycyrrhizinate (MgIG) for treatment of DILI. We used the Roussel Uclaf causality assessment method (RUCAM) to evaluate patients with DILI. Patients with RUCAM scores ≥6 were included in the study, while those with RUCAM scores <6 were further evaluated by a panel of hepatologists. The primary outcome was the proportion of patients with ALT normalization at discharge. Propensity score matching was used to identify 183 matched pairs of patients (366 patients in total) from 25,927 patients with DILI.Results Among the DILI patients, 64 of 183 (34.97%) achieved normal ALT levels after treatment in both the PPC and the MgIG groups.Conclusion There were no significant differences in safety biomarkers including serum creatinine, blood urea nitrogen, white blood cells, platelets, hemoglobin, and albumin between patients treated with PPC or MgIG. The safety and efficacy of these two agents for treatment of DILI were comparable.

Magnesium Isoglycyrrhizinate Reduces Hepatic Lipotoxicity through Regulating Metabolic Abnormalities.

The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis.

Exploration of the hepatoprotective effect and mechanism of magnesium isoglycyrrhizinate in mice with arsenic trioxide‑induced acute liver injury.

Arsenic trioxide (ATO)-induced hepatotoxicity limits the therapeutic effect of acute myelogenous leukemia treatment. Magnesium isoglycyrrhizinate (MgIG) is a natural compound extracted from licorice and a hepatoprotective drug used in liver injury. It exhibits anti-oxidant, anti-inflammatory and anti-apoptotic properties. The aim of the present study was to identify the protective action and underlying mechanism of MgIG against ATO-induced hepatotoxicity. A total of 50 mice were randomly divided into five groups (n=10/group): Control; ATO; MgIG and high- and low-dose MgIG + ATO. Following continuous administration of ATO for 7 days, the relative weight of the liver, liver enzyme, histological data, antioxidant enzymes, pro-inflammatory cytokines, cell apoptosis and changes in Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) signaling pathway were observed. MgIG decreased liver injury, decreased the liver weight and liver index, inhibited oxidative stress and decreased the activity of glutathione, superoxide dismutase and catalase, production of reactive oxygen species and levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Western blotting showed a decrease in Bax and caspase-3. There was decreased cleaved caspase-3 expression and increased Bcl-2 expression. MgIG notably activated ATO-mediated expression of Keap1 and Nrf2 in liver tissue. MgIG administration was an effective treatment to protect the liver from ATO-induced toxicity. MgIG maintained the level of Nrf2 in the liver and protected the antioxidative defense system to attenuate oxidative stress and prevent ATO-induced liver injury.

A narrative review of COVID-19: magnesium isoglycyrrhizinate as a potential adjuvant treatment.

Coronavirus disease 2019 (COVID-19) has become a global pandemic affecting more than 200 countries with 87 million patients worldwide as of January 7, 2021. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replicates in a large amount and reaches high-titer levels in a short time after the infection. COVID-19 caused by SARS-CoV-2 shows clinical symptoms mainly including fever, fatigue, dry cough, and dyspnea. In more severe COVID-19 patients, viral pneumonia characterized by bilateral ground glass or patchy opacity, may lead to acute respiratory distress syndrome (ARDS), cytokine storm, multi-organ damage, and even death. Unfortunately, there is no effective therapy for COVID-19 until now. Magnesium isoglycyrrhizinate (MgIG), a magnesium salt of 18-α glycyrrhizic acid stereoisomer, belongs to the fourth generation of glycyrrhizic acid preparation. MgIG has various pharmacological activities including anti-inflammation, anti-oxidation, anti-virus, and immunoregulation, showing the protection against the injury of the vital organs (such as kidney, heart, and lung). Clinically, MgIG injection is usually used as a hepatoprotective agent to treat liver diseases. This narrative review summarizes the research and application of MgIG, and provides the evidence supporting the recommended MgIG as supportive therapy in the "Management Standard for Mild and Common Patients of Coronavirus Disease 2019 (COVID-19) (Second Edition)", which is jointly issued by National Health Commission of People's Republic of China and National Administration of Traditional Chinese Medicine.

Differential proteomic screening of plasma exosomes before and after magnesium isoglycyrrhizinate treatment in chronic hepatitis B

Objective: To screen the differential proteomic of plasma exosomes before and after magnesium isoglycyrrhizinate (MgIG) treatment in chronic hepatitis B patients. Methods: Plasma samples were collected from 36 cases with chronic hepatitis B before and after MgIG treatment (2 ml/case). Plasma exosomes were extracted by ultracentrifugation. Exosomal particles concentration and inner diameter were detected by Nanosight NS300 particle size analyzer. Three cases of plasma exosomes were randomly selected before and after MgIG treatment. Proteins were extracted after lysis and digested with trypsin. Label-free differential proteomics analysis was performed by liquid chromatography-tandem mass spectrometry to screen out differential proteins that changed more than 1.5 times. Enzyme linked immunosorbent assay (ELISA) was used to verify the quantitative differential protein expression (n = 30). Measurement data were compared by paired sample t-test. Results: The average particle concentration of the extracted exosomes was 2.2×10(9)/ml, and the average size was (107 ± 52) nm, which was consistent with the theoretical value of plasma exosome size, proving that the plasma exosomes were successfully extracted. Proteomics results showed that before and after MgIG treatment in chronic hepatitis B patients, a total of 153 differentially expressed proteins were screened, including 85 up-regulated and 68 down-regulated proteins. Enzyme-linked immunosorbent assay results showed that compared with the MgIG before and after treatment group of chronic hepatitis B patients, the differences in the concentrations of hepatocyte growth factor activator and hepatocyte growth factor like protein in plasma exosomes were statistically significant (P < 0.05). Hepatocyte growth factor activator concentration in the plasma exosomes before and after MgIG treatment group was (45.9 ± 9.4) μg/ml and (13.9 ± 2.0) μg/ml, respectively, and it was down-regulated by about 3 times. Hepatocyte growth factor-like protein concentration in the plasma exosomes before and after MgIG treatment group was (23.4 ± 4.9) μg/ml and (13.8 ± 2.2) μg/ml, respectively, and it was down-regulated by about 2 times. Enzyme-linked immunosorbent assay results had consistency with the proteomics results. Conclusion: This study successfully screened the differential proteomic of plasma exosomes before and after MgIG treatment in chronic hepatitis B, and provided experimental basis for studying the molecular mechanism of MgIG treatment for chronic hepatitis B.

Magnesium Isoglycyrrhizinate Alleviates Arsenic Trioxide-Induced Cardiotoxicity: Contribution of Nrf2 and TLR4/NF-κB Signaling Pathway.

PurposeMagnesium isoglycyrrhizinate (MgIG), a single stereoisomer magnesium salt of glycyrrhizic acid, has beneficial effects on the cardiovascular system through anti-inflammatory, anti-oxidation, and anti-apoptotic actions. However, MgIG has not been shown to provide protection against cardiotoxicity induced by arsenic trioxide (ATO). This study aims to demonstrate the protection of MgIG against ATO-induced cardiac toxicity in mice and to investigate the underlying mechanism.MethodsA mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection.ResultsMgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid-2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-κB) and toll-like receptor-4 (TLR4) were significantly decreased.ConclusionOur data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-κB pathway.

Improvement of magnesium isoglycyrrhizinate on DSS-induced acute and chronic colitis

Inflammatory bowel disease (IBD) is a worldwide prototypical complex disease, owing to its multifactorial causes, relapsing and remitting condition and high incidence. Thus, effective therapeutic approaches need to be developed for patients with IBD. Currently, we reported the improving effect of magnesium isoglycyrrhizinate on colitis induced by dextran sulfate sodium (DSS). We found that magnesium isoglycyrrhizinate treatment significantly alleviated DSS-induced acute and chronic colitis by inhibiting the inflammatory response characterized by reduce of the infiltrations of immune cell and the level of pro-inflammatory cytokines. Besides, magnesium isoglycyrrhizinate treatment significantly inhibited the level of ROS and decreased the gut barrier destruction after DSS treatment. Furthermore, the results also showed that administration of magnesium isoglycyrrhizinate significantly reduced the colonic fibrosis. Taken together, these results revealed the potency of magnesium isoglycyrrhizinate on the intestinal inflammation, by which points to the possible use of magnesium isoglycyrrhizinate for IBD therapy in clinical applications.

Magnesium isoglycyrrhizinate ameliorates concanavalin A-induced liver injury via the p38 and JNK MAPK pathway

Context Acute liver failure is a serious disease caused by a variety of factors, and immunological injury is an important pathological process. Comprehensive liver treatment efficacy is poor, and the mortality rate is high. Magnesium isoglycyrrhizinate (MgIG) is a new glycyrrhizin drug extracted from the traditional Chinese medicine licorice. The mechanism by which MgIG regulates ConcanavalinA (ConA)-induced immunological liver injury in mice is not completely clear. Materials and methods Immunological liver injury was induced in mice by ConA injection, and the inflammatory macrophages model was induced by lipopolysaccharide (LPS). MgIG was administered 30 min prior to ConA and LPS treatment. The mice in the different groups were sacrificed 12 h after treatment, and macrophages were measured at 30 min, 1 h, and 2 h after induction. Macrophages, liver, and blood samples were then collected for analysis. Results After drug administration, the MgIG group showed a marked decrease in serum transaminase levels, reduced apoptosis and hepatic inflammatory responses compared to the ConA group. Furthermore, there was a significant reduction in inflammatory cytokine levels in the serum and liver tissue. In vitro, the expression of inflammatory cytokines was distinctly reduced after MgIG administration. In addition, MgIG pretreatment reduced the expression of inflammatory cytokines and regulated the phosphorylation of p38 and JNK proteins in the MAPK pathway. Conclusion These findings demonstrated that MgIG protects against ConA-induced immunological liver injury by markedly alleviating liver inflammation, and this provides guidance for the clinical amelioration of liver inflammation induced by immunological factors.

Magnesium isoglycyrrhizinate alleviates fructose-induced liver oxidative stress and inflammatory injury through suppressing NOXs

Excessive fructose intake is a risk factor for liver oxidative stress injury. Magnesium isoglycyrrhizinate as a hepatoprotective agent is used to treat liver diseases in clinic. However, its antioxidant effects and the underlying potential mechanisms are still not clearly understood. In this study, magnesium isoglycyrrhizinate was found to alleviate liver oxidative stress and inflammatory injury in fructose-fed rats. Magnesium isoglycyrrhizinate suppressed hepatic reactive oxygen species overproduction (0.97 ± 0.04 a.u. versus 1.34 ± 0.07 a.u.) in fructose-fed rats by down-regulating mRNA and protein levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 1, NOX2 and NOX4, resulting in reduction of interleukin-1β (IL-1β) levels (1.13 ± 0.09 a.u. versus 1.97 ± 0.12 a.u.). Similarly, magnesium isoglycyrrhizinate reduced reactive oxygen species overproduction (1.07 ± 0.02 a.u. versus 1.35 ± 0.06 a.u.) and IL-1β levels (1.14 ± 0.09 a.u. versus 1.66 ± 0.07 a.u.) in fructose-exposed HepG2 cells. Furthermore, data from treatment of reactive oxygen species inhibitor N-acetyl-L-cysteine or NOXs inhibitor diphenyleneiodonium in fructose-exposed HepG2 cells showed that fructose enhanced NOX1, NOX2 and NOX4 expression to increase reactive oxygen species generation, causing oxidative stress and inflammation, more importantly, these disturbances were significantly attenuated by magnesium isoglycyrrhizinate. The molecular mechanisms underpinning these effects suggest that magnesium isoglycyrrhizinate may inhibit NOX1, NOX2 and NOX4 expression to reduce reactive oxygen species generation, subsequently prevent liver oxidative stress injury under high fructose condition. Thus, the blockade of NOX1, NOX2 and NOX4 expression by magnesium isoglycyrrhizinate may be the potential therapeutic approach for improving fructose-induced liver injury in clinic.

Magnesium isoglycyrrhizinate prevents the nonalcoholic hepatic steatosis via regulating energy homeostasis.

Non‐alcoholic fatty liver disease is a public health problem worldwide associated with high morbidity and hepatic steatosis, but no effective therapeutic interventions. Magnesium isoglycyrrhizinate (MGIG), a derivative of an active component of Glycyrrhiza glabra, is widely used for the treatment of inflammatory liver diseases due to its potent anti‐inflammatory and hepatoprotective activities. Hence, this study aimed to study the effects of MGIG on hepatic steatosis in mice fed a high‐fat diet (HFD). Oil Red O staining and transmission electron microscopy revealed a decrease in lipid accumulation in the liver after MGIG treatment along with improved mitochondrial ultramicrostructures. Metabonomic analysis demonstrated that MGIG intervention increased glutamate utilization in mitochondria by promoting the uptake of glutamate into the tricarboxylic acid (TCA) cycle. The NAD+/NADH ratio and the expression of other lipid‐metabolism‐related genes were increased in MGIG‐treated livers. Transcriptome sequencing showed that the expression of TLR4, an isoform of the innate immunity Toll‐like receptors (TLRs), was significantly decreased after MGIG treatment, suggesting a link between the anti‐inflammatory effects of MGIG and its suppression of lipidation. Our results reveal the potent effects of MGIG on lipid metabolism and suggest that hepatic TLR4 might be a crucial therapeutic target to regulate energy homeostasis in hepatic steatosis.

Characterization of binding interaction between magnesium isoglycyrrhizinate and human serum albumin.

Magnesium isoglycyrrhizinate (MgIG) is the magnesium salt of 18β-glycyrrhizic acid extracted from licorice, a Chinese traditional medicine. The pharmacokinetic characteristics of MgIG have been widely studied; nevertheless, its target protein and mechanism of action remain unclear. Therefore, the objective of present work was to determine the characteristics of binding between human serum albumin (HSA) and MgIG. The formation of HSA-MgIG complex was studied using spectrometric techniques, LC-MS/MS, and molecular docking calculations. The results of fluorescence study demonstrated the quenching mechanism is definitely static. The negative thermodynamic parameters suggested that the interaction is enthalpically driven and occurs spontaneously. Binding density and probe displacement analysis suggested that MgIG bound to HSA at a single site, determined to be site I. The mean albumin binding rate of MgIG with HSA concentration ranged from 35 to 50g·L-1 reached 85.6%. Molecular docking analysis revealed the major residues and interaction forces involved in formation of HSA-MgIG complex, corresponding with the experimental results.

Meta-Analysis Based on Clinical RCTs: The Effect of Molecular Epimerism on the Safety of Glycyrrhizic Acid.

Objective To carry out the meta-analysis on the clinical safety of glycyrrhizic acid and the influencing factors between 18α-glycyrrhizinate (18α-GL) and 18β-glycyrrhizinate (18β-GL). Methods Magnesium isoglycyrrhizinate injection was used as the representative preparation of 18α-GL, and compound glycyrrhizin injection was used as the representative preparation of 18β-GL. The clinical control trial of magnesium isoglycyrrhizinate injection and compound glycyrrhizin injection was searched in a computer, which was published from January 2006 to December 2019 on the databases such as PubMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CSTJ), and Wanfang Medical Network (Wanfang Data). The data associated with adverse drug reactions (ADRs) were extracted. RevMan5.3 was used for statistical analysis. Results Finally, 24 studies were included, and 2757 patients were involved, of which the experimental group was mainly treated with magnesium isoglycyrrhizinate, while the control group was mainly treated with compound glycyrrhizin. The results showed that the occurrence of ADRs was significantly lower in the experimental group than that in the control group, and the difference between two groups was statistically significant (RR = 0.26, 95% CI = (0.18, 0.38), P < 0.00001). There was no heterogeneity among the studies (I2 = 0%, P=1.00). Conclusion Compared with 18β-GL, 18α-GL had a lower incidence of adverse reactions and better clinical safety.

Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug‐induced liver injury: A phase II trial

Drug-induced liver injury (DILI) is the most common reason for a drug to be withdrawn from the market. Apart from stopping the offending drug, no regimens are available for treating idiosyncratic DILI in clinical practice. We carried out a randomized, double-blind, multidoses, active drug controlled, multicentre phase II trial to assess the safety and efficacy of the study drug, magnesium isoglycyrrhizinate (MgIG), as compared to tiopronin, a standard therapy for DILI in China. The primary outcome was the proportion of alanine aminotransferase (ALT) normalization at week 4 after study drug administration. Logistic regression was used to examine the odds of ALT normalization between low dose (Group A) and high dose (Group B) vs active control (Group C). One hundred and seventy-four eligible subjects were randomized and enrolled into three groups: 59 in group A, 56 in group B and 59 in group C. It was shown that group A and group B lowered ALT level even at early stage of study drug administration; when compared with Group C (61.02%), the proportions of ALT normalization at week 4 were significantly greater in Group A (84.75%, P=.0029) and Group B (85.71%, P=.0037) respectively. The results from the univariate logistic model showed that the odds of ALT normalized among subjects in Group A were about 3.6 times greater (OR=3.55, 95% CI: 1.47-8.57, P=.0049) than subjects in Group C. Similar effect was observed among subjects in Group B (OR=3.83, 95% CI: 1.54-9.55, P=.0039). This trial provided preliminary evidence that MgIG is an effective and safe treatment for patients with acute DILI.