Delving into the Latest Updates on Diammonium glycyrrhizinate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ADiammonium Glycyrrhizinate, Diammomium Glycyrrhizinate, Diammonium Glycrrhizinate

+ [6]

Target

11β-HSD1

Mechanism

11β-HSD1 inhibitors(Corticosteroid 11-beta-dehydrogenase isozyme 1 inhibitors)

Therapeutic Areas

Digestive System Disorders

Active Indication

Acute hepatitisHepatitis, Chronic

Inactive Indication-

Originator Organization

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Active Organization

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (01 Jan 1994),

Acute hepatitisHepatitis, Chronic

Regulation-

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Structure

Molecular FormulaC42H68N2O16

InChIKeySPPIIOPGDLITJE-VLQRKCJKSA-N

CAS Registry79165-06-3

Alcohol-induced liver injury (ALI) is a serious global health issue. Diammonium glycyrrhizinate (DG), a pharmaceutical form of glycyrrhizic acid, has been reported to have anti-inflammatory and anti-oxidative stress properties. We investigated the potential hepatoprotective effects of DG against ALI and explored the mechanisms of it. In vivo, C57BL/6J mice were used to investigate the protective effect of DG on ALI induced by chronic plus binge alcohol exposure. In vitro, AML-12 cells were applied to evaluate the role of DDX5 in the hepatic protection of DG and explore the possible mechanism of STAT1 activation regulated by DDX5. The results showed that DG significantly alleviated liver injury, inflammation, and lipid deposition in hepatocytes. It also beneficially influenced oxidative stress dysregulation. RNA-seq expression in mouse liver tissue indicated that Dead-box helicase 5 (DDX5) might be a potential target of DG. Compared with the control group, the expression of DDX5 decreased significantly in the ethanol-fed group, while DDX5 was restored in the DG treatment group. In addition, the protective effects of DG against ALI were impaired by DDX5 deficiency. DDX5 inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1) by recruiting the protein inhibitor of activated STAT1 (PIAS1) to STAT1. The protective effect of DG against ALI associated with oxidative stress, steatosis, and inflammation was probably via regulating the DDX5/STAT1 axis.

01 Aug 2024·Toxicon

Hepatoprotective effect of diammonium glycyrrhizinate and neuroprotective effect of piperazine ferulate on AmB-induced liver and kidney injury by suppressing apoptosis in vitro and in vivo

Article

Author: Huo, Jian ; Peng, Xiuhong ; Yang, Tianfeng ; He, Xu ; Zhang, Suyu ; Zhang, Yanmin

Amphotericin B (AmB) induced liver and kidney injury is often responsible for hepatic and renal dysfunction. Therefore, the protection strategy on liver and renal functions in patients treated with AmB should be emphasized. In this paper, diammonium glycyrrhizinate (DG) and piperazine ferulate (PF) were taken as the research object to study its hepatoprotective and neuroprotective effect on AmB-induced liver and kidney damage in vitro and in vivo. The microplate method and ELISA kits were employed for the biochemical detection in the serum and urine of mice. Flow cytometric analysis and western blotting analysis were conducted to study the mechanism of DG and PF. Our results confirmed the prevention capacity of DG and PF on AmB-induced liver and kidney injury through the alleviation of pathological changes and enzyme reducing action. Furthermore, DG and PF suppressed ROS-mediated mitochondrial apoptosis in AmB-treated mice and cells through Caspase pathway and Caspase-independent AIF pathway. In summary, DG and PF could protect AmB-induced hepatotoxicity and nephrotoxicity by disrupting oxidative stress and apoptosis.

01 Jun 2024·Shock

DIAMMONIUM GLYCYRRHIZINATE INHIBITED INFLAMMATORY RESPONSE AND MODULATED SERUM METABOLISM IN POLY(I:C)-INDUCED PNEUMONIA MODEL MICE

Article

Author: Du, Wenjing ; Cai, Xuanlin ; Luo, Li ; Cong, Shan ; Ma, Xiumin ; Sun, Jiao ; Wang, Li ; Meng, Yan ; Cui, Huantian

ABSTRACTCurrently, the coronavirus disease 2019 (COVID-19) is becoming a serious threat to human health worldwide. Therefore, there is a great need to develop effective drugs against viral pneumonia. Diammonium glycyrrhizinate (DG), derived from Glycyrrhiza glabra L., has been demonstrated with significant anti-inflammatory properties. However, the therapeutic effects and mechanisms of DG on pneumonia require further clarification. In this study, mice received intratracheal injection of polyinosinic–polycytidylic acid (poly(I:C)) to induce pneumonia and were treated with DG. First, we evaluated the therapeutic potential of DG on poly(I:C)-induced pneumonia. Second, the anti-inflammatory and antioxidative activities and the impact of DG on the toll-like receptor 3 (TLR3) pathway were investigated. Third, the mechanism of DG was analyzed through untargeted metabolomics techniques. Our results revealed that DG intervention decreased permeability and reduced abnormal lung alterations in poly(I:C)-induced pneumonia model mice. DG intervention also downregulated cytokine levels in bronchoalveolar lavage fluid. Moreover, DG treatment inhibited the activation of TLR3 pathway. Furthermore, untargeted metabolomics analysis revealed that DG intervention could modulate serum metabolites involved in amino and nucleotide sugar metabolism, fructose and mannose metabolism, tyrosine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, our study showed that DG could ameliorate poly(I:C)-induced pneumonia by inactivating the TLR3 pathway and affecting amino and nucleotide sugar, fructose and mannose metabolism, as well as tryptophan, phenylalanine, and tyrosine biosynthesis.

100 Deals associated with Diammonium glycyrrhizinate

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External Link

KEGG	Wiki	ATC	Drug Bank
D02028	-	A05A	-

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Acute hepatitis	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	01 Jan 1994
Hepatitis, Chronic	CN	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	01 Jan 1994